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CHIARA DIAZZI

Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede ex-Medicina, Endocrinologia, Metabolismo e Geriatria

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Pubblicazioni

2022 - Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay [Articolo su rivista]
De Vincentis, Sara; Decaroli, Maria Chiara; Fanelli, Flaminia; Diazzi, Chiara; Mezzullo, Marco; Tartaro, Giulia; Tagliavini, Simonetta; De Santis, Maria Cristina; Roli, Laura; Milic, Jovana; Trenti, Tommaso; Pagotto, Uberto; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged < 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p < 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p < 0.0001) or cFT (9.5% vs 7%, p < 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency.

2021 - Ruolo diagnostico del dosaggio della calcitonina su liquido di lavaggio da agoaspirato tiroideo nel carcinoma midollare della tiroide [Articolo su rivista]
Brigante, Giulia; Madeo, Bruno; Diazzi, Chiara; Simoni, Manuela; Rochira, Vincenzo
abstract

2021 - Sexual dysfunction: a neglected and overlooked issue in adult GH deficiency: the management of AGHD study. [Articolo su rivista]
Monzani, M. L.; Pederzoli, S.; Volpi, L.; Magnani, E.; Diazzi, C.; Rochira, V.
abstract

Context: Although sexuality influences well-being and quality of life (QoL), studies on sexual dysfunction (SD) in adult growth hormone deficiency (AGHD) patients are lacking. Objective: To investigate the prevalence of SD in AGHD patients grouped according to recombinant human growth hormone (r-hGH) therapy. Design: Prospective, cross-over, 24 months, monocentric study. Setting: Real-life clinical setting in a tertiary, endocrinological center. Patients: 83 AGHD patients (31 women, 52 men, mean age 56.3 ± 14.7 years) were enrolled according to stringent criteria. Interventions: Patients already on long-term r-hGH therapy (Group 1, n = 32) vs untreated (Group 2, n = 51). Main outcome measures: Serum hormones, QoL Satisfaction in Hypopituitarism (QLS-H) and QoL Assessment of GHD in Adults (QoL-AGHDA) questionnaires for QoL, Index for Erectile Function-15 (IIEF-15) in men, and Female Sexual Function Index (FSFI) in women for SD. Results: The overall prevalence of SD was 71.2% (60% men, 89% women). All IIEF-15 scores were lower (P = 0.001) and erectile dysfunction was more prevalent in Group 2 (75%) than Group 1 (35%). IGF-1 was correlated to scores of all IIEF-15 domains, particularly with that of erectile function (EF) (R2=0.123, P = 0.019). EF domain score correlated with QLS-H (P < 0.005) and QoL-AGHDA (P = 0.001). Despite the high prevalence of female SD also in untreated AGHD women, FSFI scores did not correlate with IGF-1 levels and QoL scores. Conclusions: SD is highly prevalent in AGHD patients, especially in those untreated. SD represents an overlooked and neglected issue in AGHD, regardless the contribution of sexual life on QoL. The evaluation of sexual function should be integrated in the global assessment of AGHD patients

2020 - Effect of a standard schema of self-monitoring blood glucose in patients with poorly controlled, non-insulin-treated type 2 diabetes mellitus: A controlled longitudinal study [Articolo su rivista]
Madeo, B.; Diazzi, C.; Granata, A. R. M.; Ghoch, M. E.; Greco, C.; Romano, S.; Scaltriti, S.; Rochira, V.
abstract

The effect of self-monitoring of blood glucose (SMBG) on glycemic control with regard to non-insulintreated Type 2 diabetes mellitus (NIT-Type 2 DM) is still a controversial topic. Against this backdrop, we sought to compare the effect of a continuous short-term SMBG schema with as-usual treatment, based on changes in oral antidiabetic treatment in patients with poorly controlled Type 2 DM. We reviewed 492 NIT-Type 2 DM record charts, selecting 27 patients, with poor glycemic control, who were thought to self-monitor their blood glucose levels (SMBG group). We then compared them with 27 patients treated with modifying drugs or diets to achieve and maintain the glycemic target (Control Group). Haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were evaluated at baseline, after 3 and 6 months. HbA1c values decreased after 3 and 6 months in the SMBG group (P < 0.001 on both occasions) and in the control group (P < 0.05 and P < 0.01, respectively), but without a significant difference between the two groups when compared at the same time. The FPG progressively decreased in both groups, reaching a significant difference in the SMBG group after 3 months and in the control group after 6 months, and without a significant difference between the two groups. The SMBG schema used in our study could be adopted for target groups before proceeding to the next therapeutic enhancement drug step, representing a useful tool that can help diabetic patients in raising awareness of and treating their disease.

2020 - Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV. [Articolo su rivista]
De Vincentis, S.; Decaroli, M. C.; Fanelli, F.; Diazzi, C.; Mezzullo, M.; Morini, F.; Bertani, D.; Milic, J.; Carli, F.; Cuomo, G.; Santi, D.; Tartaro, G.; Tagliavini, S.; De Santis, M. C.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

Objective: Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. Design: Prospective, cross-sectional, observational study. Methods: HIV-infected men aged<50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. Results: A total of 316 HIV-infected men aged 45.3±5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/T ratio. Patients with MM had lower cFT (p<0.0001) and TT (p=0.036), and higher E1 (p<0.0001) and E2/T ratio (p=0.002). Frailty was inversely related to cFT (R2=0.057, p<0.0001) and TT (R2=0.013, p=0.043), and directly related to E1 (R2=0.171, p<0.0001), E2 (R2=0.041, p=0.004) and E2/T ratio (R2=0.104, p<0.0001). Conclusions: Lower TT and cFT, higher E1, E2/T ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.

2020 - Importance of Sexual Function Assessment in Multidimensional Evaluation of AGHD Patients: Results from the MAGHD Study. [Abstract in Atti di Convegno]
Monzani, M. L.; Pederzoli, S.; Volpi, L.; Magnani, E.; Diazzi, C.; Rochira, V.
abstract

Background: Adult growth hormone deficiency (AGHD) is a debilitating clinical condition leading to decreased quality of life (QoL). The impact of reduced muscle mass, weakening and loss of vitality on QoL have been well characterized in AGHD. The impact of AGHD on sexual function, a recognized factor able to modify well-being, has never been investigated. Aim: To investigate the prevalence of sexual dysfunction in AGHD patients referring to a single endocrinological center and grouped according to their his- tory of r-hGH therapy.Methods: The Management of Adult Growth Hormone Deficiency (MAGHD) Study is a pro- spective, real-life trial aiming to improve management of AGHD patients through a smartphone app (MAGHD App)and a wearable device. The 83 AGHD enrolled patients (31 Females, 52 Males, mean age 56.27 + 14.68 years) were divided in 3 groups (G) according to r-hGH therapy: on long-term r-hGH therapy (G1, n=32), previously treated with r-hGH (G2, n=20), never treated (G3, n=31). Within the first phase of the study, a large database was created collecting clinical, biochemical and psychological data. In addition to QLS-H and QoL-AGHDA routinely used to as- sess QoL, IIEF-15 and FSFI were employed to evaluate sexual function in males and females, respectively. The nonparametric Kruskal-Wallis test was used for compar- ison among 3 groups.Results: Here only baseline data of the MAGHD Study are presented.According to IIEF-15 results, the prevalence of erectile dysfunction (ED) in male AGHD cohort was 60%. Erectile function (EF) score was signifi- cantly higher in G1 compared to both G2 and G3 (p < 0.05) with an ED prevalence of 35% in G1, 75% in G2 and 75% in G3. Even excluding patients with serum testosterone lower than 2 ng/ml and older than 65 years, ED prevalence did not change significantly in the 3 groups. Moreover, EF do- main was inversely and directly correlated to age (R20.130, β-0.360) and IGF1 levels (R20.156, β0.395), respectively. The prevalence of female sexual dysfunction according to FSFI was 89.3%. Even though desire, arousal, lubrication and overall scores were significantly higher (better results) in G1 compared to G2 and G3 (p < 0.05), no correlation resulted between FSFI domains and IGF1 levels. Instead an inverse correlation resulted between desire domain and age.Conclusions: This study, performed in a real-life clinical setting, demonstrates a high prevalence of sexual dysfunc- tion in AGHD patients and that r-hGH treatment seems to be associated to better sexual outcomes. These results suggest that the evaluation of sexual function should be in- tegrated in the global assessment of AGHD patients since sexual activity is a fundamental domain able to influence both well-being and QoL.

2020 - Importance of sexual function assessment in multidimensional evaluation of AGHD patients: Baseline results from the management of adult growth hormone deficiency (MAGHD) study. [Abstract in Atti di Convegno]
Monzani, M. L.; Pederzoli, S.; Volpi, L.; Magnani, E.; Diazzi, C.; Rochira, V.
abstract

Background Patients with adult growth hormone deficiency (AGHD) have impaired health-related quality of life (QoL). While the effects of reduced muscle mass and vitality-loss on QoL have been well characterized in AGHD, the impact of AGHD on sexual function, a recognized factor influencing well-being, has never been deepened. Aim To investigate the prevalence of sexual dysfunction in AGHD patients re- ferring to a single endocrinological center and grouped according to their history of r-hGH therapy. Methods The MAGHD Study aims to improve management of AGHD patients through a smartphone app (MAGHD-App) and a fit-watch. The 83 enrolled patients (31 Females, 52 Males, mean age 56.27 ± 14.68 years) were divided in 3 groups (G) according to r-hGH therapy: on long-term treatment (G1, n=32), previously treated (G2, n=20), never treated (G3, n=31). At the baseline visit, besidesclinical and biochemical data, a psychological assess- ment was performed. IIEF-15 (for males) and FSFI (for females) were em- ployed to evaluate sexual function in addition to QLS-H and QoL-AGHDA routinely used to assess QoL. The nonparametric Kruskal-Wallis test was used for comparison among 3 groups. Results According to IIEF-15 results, the prevalence of erectile dysfunction (ED) in AGHD males was 60%. Erectile function (EF) score was significantly high- er in G1 compared to G2 and G3 (P < 0.05) with an ED prevalence of 37.5% in G1, 75% in G2 and 75% in G3. Even excluding interfering factors (serum testosterone <2ng/ml and age ≥65 years), ED prevalence did not change significantly. Moreover, EF domain was inversely and directlycorrelated to age (R2 0.130, β–0.360) and IGF1 levels (R2 0.156, β 0.395), respectively. The prevalence of female sexual dysfunction according to FSFI was 89%. Even though desire, arousal, lubrication and overall scores were significant- ly higher (better results) in G1 compared to G2 and G3 (P<0.05), no cor- relation resulted between FSFI domains and IGF1 levels. Only an inverse correlation resulted between desire domain and age. Conclusions This real-life study documents a high prevalence of sexual dysfunction in AGHD patients, especially in untreated ones, and that r-hGH treatment seems to be associated to better sexual outcomes. These results suggest that the evaluation of sexual function should be integrated into global assessment of AGHD patients since sexual activity is able to influence both well-being and QoL.

2020 - Low Serum Testosterone (T) Is Associated with Poor Health Status in Young to Middle-Aged Human Immunodeficiency Virus (HIV)-Infected Men. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

BACKGROUND: The relationship between health status, defined by frailty and comorbidities, and serum T levels has been widely demonstrated in general population, while only one previous retrospective study has explored it in HIV-infected men1. AIM: To investigate the association between frailty and go- nadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS: Prospective, cross-sectional, observational study on HIV-infected men (age <50 years) with on- going Highly Active Antiretroviral Therapy. Serum TT was assessed by the gold standard ID-LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chem- iluminescent immunoassay. Calculated free T (cFT) was obtained by Vermeulen equation. Multimorbidity was de- fined as at least 3 comorbid conditions, including: hyperten- sion, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, osteoporosis, chronic viral hepatitis and cancers. Frailty was calculated through the validated 37-item frailty index (FI)2. Patients with FI>0.21 were considered frail. Statistical ana- lysis: Mann-Whitney U test was used to compare contin- uous variables. Correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.3±5.3 years; average duration of HIV-infection 16.3±8.8 years). 128 patients (40.5%) were co- morbid and 207 (64.9%) were frail. Either cFT (p=0.001) or TT (p<0.001) were lower in comorbid patients than others. FT was inversely related to the number of comorbidities (p<0.001, R2=0.045). Accordingly, cFT (p=0.003) and TT (p<0.001) were significantly lower in frail patients.Frailty score was inversely correlated with cFT (p<0.001, R2=0.058), TT (p=0.041, R2=0.014) and SHBG (p=0.003, R2=0.029). However, after adjustment for age and duration of HIV-infection, cFT, TT and SHBG were excluded from the regression model. CONCLUSIONS: Low cFT and TT levels are associated with multimorbidity and poor health status in HIV infected men. The bidirectional nature of this relationship leads to the figuration of an intriguing vicious circle where T de- ficiency triggers the onset of comorbidities or, vice versa, poor health status induces hypogonadism. At the same time, notwithstanding the inverse relation between FT and frailty, it seems that other stronger predictive factors, and in particular the duration of infection, are involved in de- termining the health outcome in this clinical setting.

2020 - Testosterone (T) is poorly related to sexual desire and Erectile Dysfunction (ED) in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

Background ED is highly prevalent in HIV-infected men. T leads sexual behavior in men, but preliminary data suggests that ED is poorly related to serum T in HIV- infected men. Aim To explore the relationship between sexual function and gonadal function in young/middle-aged HIV-infected men. Methodology Prospective, cross-sectional, observational study on HIV-infected men (age <50 years). Serum TT was assessed by the gold standard LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent im- munoassay and calculated free T (cFT) was obtained by Vermeulen equa- tion. Biochemical hypogonadism was defined as TT levels below 320ng/ dl and/or cFT levels below 64pg/ml. The validated International Index of Erectile Function (IIEF)-15 questionnaire was used to identify the presence of ED (score <25) and its degree. IIEF-5 was performed to check if it is reliable as IIEF-15 in this setting. Statistical analysis Continuous and categorical variables were compared using ANOVA univari- ate and Chi-Square test. Correlations were performed using linear regression models.Results 315 consecutive HIV-infected men were enrolled (mean age 45.3 ± 5.3 years; mean duration of HIV-infection 16.3 ± 8.8 years). A total of 187 patients (59.7%) had ED at IIEF-15; 59 patients (31.5%) presented a severe form of ED (score <10). Considering gonadal function, 35 patients (11.1%) had T deficiency. Scores of EF (P=0.039) and sexual desire (P=0.015) domains were higher in hypogonadal than eugonadal men. Accordingly, the prev- alence of ED raised to 71.4% among hypogonadal men. By considering ED severity, patients with severe ED showed a longer duration of infection (P = 0.039) and lower cFT levels (P = 0.041) than patients with mild ED. No difference was found for age (P = 0.224) and TT levels (P = 0.110). IIEF-15 score was inversely related to duration of infection (R2 = 0.030, beta = –0.173, P = 0.002) and patients’ age (R2 = 0.020, beta = –0.140, P = 0.013).No signif- icant correlation was found between IIEF-15 score and total T (P = 0.236) and cFT (P = 0.126). The erectile function domain at IIEF-15 directly cor- related with IIEF-5 score (R2 = 0.545, beta = 0.778, P < 0.001). Conclusions In our HIV-cohort of young/middle-aged men, the prevalence of ED and T deficiency were high being of 60% and 11%, respectively. Serum TT and cFT did not correlate with sexual function parameters, even though sexual desire was lower in men with hypogonadism. ED seems to be better predict- ed by other factors, such as the duration of infection in this clinical setting, rather than the gonadal status. Furthermore, IIEF-5 seems to be as reliable as IIEF-15 for ED diagnosis in HIV-infected men

2019 - Abacavir, nevirapine, and ritonavir modulate intracellular calcium levels without affecting GHRH-mediated growth hormone secretion in somatotropic cells in vitro [Articolo su rivista]
Brigante, G; Riccetti, L; Lazzaretti, C; Rofrano, L; Sperduti, S; Potì, F; Diazzi, C; Prodam, F; Guaraldi, G; Lania, Ag; Rochira, V; Casarini, L
abstract

Growth Hormone (GH) deficiency is frequent in HIV-infected patients treated with antiretroviral therapy. We treated GH3 cells with antiretrovirals (nevirapine, ritonavir or abacavir sulfate; 100 pM-1 mM range), after transfection with human growth hormone releasing hormone (GHRH) receptor cDNA. Cells viability, intracellular cAMP, phosphorylation of CREB and calcium increase, GH production and secretion were evaluated both in basal condition and after GHRH, using MTT, bioluminescence resonance energy transfer, western blotting and ELISA. Antiretroviral treatment did not affect GHRH 50% effective dose (EC50) calculated for 30-min intracellular cAMP increase (Mann-Whitney's U test; p ≥ 0.05; n = 4) nor 15-min CREB phosphorylation. The kinetics of GHRH-mediated, rapid intracellular calcium increase was perturbed by pre-incubation with drugs, while GHRH failed to induce the ion increase in ritonavir pre-treated cells (ANOVA; p < 0.05; n = 3). Antiretrovirals did not impact 24-h intracellular and extracellular GH levels (ANOVA; p ≥ 0.05; n = 3). We demonstrated the association between antiretrovirals and intracellular calcium increase, without consequences on somatotrope cells viability and GH synthesis. Overall, these results suggest that antiretrovirals may not directly impact on GH axis in HIV-infected patients.

2019 - Free Testosterone (FT) is inversely related to frailty in Human Immunodeficiency Virus (HIV)-Infected Men [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Free testosterone (FT) is inversely related to frailty in human immunodeficiency virus (HIV)-infected men. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

BACKGROUND HIV-infection is associated to several age-related comorbidities, such as a premature decline of serum testosterone (T). There is evidence about the relationship between health status, represented by frailty and comorbidities, and serum T levels in general population, while only one previous retrospective study investigated it in HIV-infected men. AIM To investigate the association between frailty and gonadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS Prospective, cross-sectional, observational study on HIV-infected men (age years) with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT was assessed by the gold standard ID- LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent immunoassay. Free T (FT) was calculated by Vermeulen equation. Frailty was calculated through -items multimorbidity frailty index. Saca aa Parameters were not normally distributed and Mann- Whitney U test was used to compare continuous variables. Correlations were performed using linear regression models. RESULTS consecutive HIV-infected men were enrolled (mean age .. years; average duration of HIV-infection .. years). patients (.) had TT below ng/dL and patients (.) had calculated FT below pg/mL. Overall, patients (.) had T deficiency defined by low TT levels and/or low FT. patients (.) showed SHBG above the normal range (. nmol/L). Frailty score (p.), age (p.), duration of HIV-infection and of HAART (p.) significantly differed between eugonadic and hypogonadic patients, while no difference was found for BMI (p.). FT inversely correlated with frailty score (p., R.), while TT did not (p.). At stepwise multivariate regression analysis, FT showed an inverse relation with age (p.,R.), years of infection (-.,p.,R.) and years of HAART (-.,p.,R.), but not with frailty score and BMI of patients. CONCLUSIONS To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the relationship between general health status and gonadal function in a cohort of HIV-infected men. FT is inversely related to frailty score, suggesting an impairment of gonadal function in those patients affected by more multimorbidities in this setting as well as in general population. At the same time, the age of patient and the duration of HIV-infection seem to be more potent predictive factors for serum FT levels than frailty score. In clinical practice it is important to check for testosterone in these patients due to frequent alterations of SHBG.

2019 - Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men Assessed by Isotopic Dilution-Liquid Chromatography-Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men: comparison between Isotopic Dilution-Liquid Chromatography- Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay (CI). [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Fanelli, F.; Mezzullo, M.; Diazzi, C.; Morini, F.; Bertani, D.; Santi, D.; Baraldi, E.; Tagliavini, S.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Gonadal function in human immunodeficiency virus (HIV)-infected men: comparison between isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and chemiluminescent immunoassay (CI) [Abstract in Atti di Convegno]
Decaroli, M. C.; De Vincentis, S.; Fanelli, F.; Mezzullo, M.; Diazzi, C.; Morini, F.; Bertani, D.; Santi, D.; Baraldi, E.; Tagliavini, S.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

2019 - Importanza della valutazione della funzione sessuale nei pazienti adulti con deficit di GH: risultati preliminari dello studio Management of Adult Growth Hormone Deficiency (MAGHD) [Abstract in Atti di Convegno]
Monzani, M. L.; Pederzoli, S.; Volpi, L.; Magnani, E.; Diazzi, C.; Rochira, V.
abstract

2019 - Prevalence of thyroid disfunctions in a large cohort of Human Immunodeficiency Virus (HIV)-Infected Patients [Abstract in Atti di Convegno]
Tartaro, G.; De Vincentis, S.; Brigante, G.; Diazzi, C.; Malagoli, A.; Guaraldi, G.; Rochira, V.
abstract

2019 - Serum Sodium Is Inversely Related to Frailty and Bone Mineral Density (BMD) in Human Immunodeficiency Virus (HIV)-Infected Patients [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Santi, D.; Carli, F.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

2019 - Trunk Fat Increase Is Prevented Both in Patients Undergoing Long-Lasting Continuous r-hGH Therapy and in Those Who Discontinued r-hGH Compared to Untreated Patients: Results from Baseline Data of the MAGHD Study [Abstract in Atti di Convegno]
Monzani, M. L.; Magnani, E.; Diazzi, C.; Volpi, L.; Rochira., V.
abstract

2019 - Trunk fat increase is prevented both in patients undergoing long- lasting continuous r-hGH therapy and in those who discontinued r-hGH compared to untreated patients: results from baseline data of the MAGHD study [Abstract in Atti di Convegno]
Monzani, M. L.; Magnani, E.; Diazzi, C.; Pederzoli, S.; Volpi, L.; Rochira, V.
abstract

2019 - Trunk fat increase is prevented both in patients undergoing long-lasting continuous r-hGH therapy and in those who discontinued r-hGH compared to untreated patients: results from baseline data of the MAGHD study [Abstract in Atti di Convegno]
Monzani, M. L.; Magnani, E.; Diazzi, C.; Pederzoli, S.; Volpi, L.; Rochira, V.
abstract

2018 - A comparison of pituitary function in primary and secondary empty sella: preliminary data [Abstract in Rivista]
Magnani, E.; Decaroli, M. C.; Leoni, L.; Diazzi, C.; Rochira, V.
abstract

Background Empty sella (ES), the herniation of the subarachnoid space within sella associated with a variable flattening of the pituitary gland, is classified as primary (PES) or secondary (SES) on the basis of etiological factors. Aim To assess the differences between PES and SES in terms of pituitary function. Methods Clinical, radiological and hormonal data were retrospectively extrapolated from the records of 85 patients with a diagnosis of ES made between 1990 and 2016, attending to the Pituitary Unity of Azienda Ospedaliero-Universitaria of Modena, Italy. The pituitary function was assessed by basal hormonal measurements and dynamic tests in an appropriate clinical context. Chi square was used for comparison of categorical variables. Results Fifty-nine patients with PES (male/female ratio:1/2) and 26 with SES (male/female ratio:1.4/1) were considered. The mean age at diagnosis was 54G17 years in PES and 45G15 years in SES. Among PES 54% of patients had a normal pituitary function and 64% didn’t take replacement treatment, while in SES the percentages decreased to 28% and 35% respectively (Chi-squareZ16.8, P!0.0001). Accordingly, the overall number of pituitary deficits was higher in SES than in PES and even each single pituitary deficit occurred more frequently in SES (P!0.05). Mild hyperprolactinemia was present in 24% of PES and 22% of SES. A variable degree of hypopituitarism was found in 36% of PES and 58% of SES. Hypogonadism and growth hormone deficiency were the prevalent deficits among PES (61%) and SES (80%) respectively. The radiological degree of ES (partial vs total) didn’t influence the pituitary function. Discussion Our preliminary results confirm a higher prevalence of endocrine alterations in SES compared to PES but, in contrast with previous reports in literature, hypogonadism is the most frequent alteration in our PES patients. These data suggest that SES requires a more accurate endocrine screening and follow-up and, if confirmed by prospective studies, may open new insights on the management of ES.

2018 - CONFRONTO DELLA FUNZIONALITÀ IPOFISARIA NELLA SELLA VUOTA PRIMARIA E SECONDARIA: DATI PRELIMINARI [Abstract in Atti di Convegno]
Magnani, E.; Decaroli, M. C.; Leoni, L.; Diazzi, C.; Rochira, V.
abstract

Analisi comparativa di dati clinici in pazienti con sella vuota primaria e secondaria

2018 - Gonadal function in human immunodeficiency virus (HIV)-infected men assessed by isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and chemiluminescent assay. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, Vincenzo
abstract

BACKGROUND: HIV infection is associated to premature decline of serum T1,2. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined1,2. AIM OF THE STUDY: We evaluated the gonadal status in young to middle aged HIV-infected men in order to characterize hypogonadism by assessing circulating total T (TT) with either Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) or chemiluminescent immunoassay. METHODS: Prospective, cross-sectional, observational study on 315 consecutive HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Metabolic Clinic of Infectious Diseases. Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay. Serum TT was also assessed by the gold standard LC-MS/MS in 233 patients. Free T (FT) was calculated by using Vermeulen equation3. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml4. Statistical analysis: Categorical variables were compared using Chi-Square test, while correlations were performed using Spearman’s Rho coefficient and linear regression models. RESULTS: 315 HIV-infected patients were enrolled (mean age 45.56±5.61 years) with average duration of HIV-infection of 16.57±10.45 years. Considering serum total T levels assessed by LC-MS/MS and immunoassay, 11 patients out of 233 (4.8%) and 10 patients out of 315 (3.2%) had T deficiency, respectively. TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism (Table 1). No difference was found among subgroups comparing the two methodologies used for TT measurement (p=0.914). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the incidence of hypogonadism raised to 6.9% using either immunoassay or LC-MS/MS, respectively (Table 1), with no difference between methodologies (p=0.895). Including compensated form oh hypogonadism, the prevalence raised to 13% for TT and to 15% for FT. Patients with low FT were older than eugonadal patients (p=0.005) and showed a significantly longer duration of HIV-infection (p<0.0001) and HAART (p=0.002), while they did not differ for body mass index (p=0.231). FT showed an inverse relation with age (-0.340, p<0.0001, R2=0.116), years of infection (-0.339, p<0.0001, R2=0.120) and years of HAART (-0.346, p<0.0001, R2=0.117), but not with BMI of patients. CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the gonadal status of HIV-infected men with both LC-MS/MS and chemiluminescent assay. In HIV-infected patients a) the two methodologies have equivalent reliability in TT measurement; b) SHBG for calculated FT is essential for the detection of T deficiency, revealing the real prevalence of hypogonadism in this context; c) duration of HIV-infection and HAART seem to be potent predictive factors for serum FT levels, suggesting a concomitant negative effect of virus per se and antiretroviral drugs on gonadal function. References 1Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 2Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30. 3Vermeulen A et al. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84:3666–3672 4Bhasin S et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 May 1;103(5):1715-1744.

2018 - IL SODIO SIERICO È INVERSAMENTE CORRELATO ALLA FRAILTY E ALLA DENSITÀ MINERALE OSSEA (BMD) NEI PAZIENTI CON INFEZIONE DA HUMAN IMMUNODEFICIENCY VIRUS (HIV) [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, MARIA CHIARA; Diazzi, C.; Santi, D.; Menozzi, M.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

L'iponatriemia si associa alla frailty nei pazienti con infezione da HIV

2018 - Serum sodium is inversely related to frailty and bone mineral density (BMD) in human immunodeficiency virus (HIV)-infected patients [Abstract in Rivista]
De Vincentis, S.; Decaroli, MARIA CHIARA; Diazzi, C.; Santi, D.; Carli, F.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

Background HIV-infected patients are predisposed to an increased risk of hyponatremia. In healthy population, low sodium is associated with impaired health status and reduced BMD, but less is known about this association in HIV-infection. Aim To investigate the relationship between serum sodium, frailty and BMD in a large cohort of HIV-infected patients. Methodology A retrospective, observational, cohort study on adult HIV-infected patients (age R18 years), attending the Multidisciplinary Metabolic Clinic of Modena, was carried out including all sodium examinations performed at the Modena lab from 2007 to 2017 available in a large database. Laboratory ranges of normality for sodium (136–146mEq/l) were used to subdivide records in hyponatremic (HypoNa), hypernatremic (HyperNa) and normonatremic (NormoNa) groups. BMD was measured at total body, lumbar spine (L1–L4) and total hip using a Hologic QDR-2000 densitometer (DXA). Frailty was calculated through 38-item multimorbidity frailty index. Statistical analysis Parameters were not normally distributed and Kruskal-Wallis test, followed by Dunn’s test, was used to compare continuous variables. Correlations were performed using linear regression models. Results 8101 records (5454 from males and 2647 from females) of serum sodium (mean 139.4G3.1 mEq/l) evaluated in HIV-infected patients (mean age 49.0G7.9 years) were considered. 617 (7.6%), HypoNa, 44 (0.5%) HyperNa and 7440 (91.8%) NormoNa were found. Frailty score was inversely related to serum sodium (rZK0.174, R2Z0.03, P!0.0001), even after the exclusion of HyperNa group (RZK0.191, R2Z0.036, P!0.0001). Frailty was significantly higher in HypoNa than NormoNa (P!0.001). Considering results at DXA examination, BMD was normal in 30.3% and reduced in 69.7% (54.8% osteopenia, 14.9% osteoporosis). Total body BMD, but not femoral nor lumbar, directly correlated with serum sodium (RZ0.049, P!0.001) and it was significantly lower in HypoNa compared to NormoNa (PZ0.029). Conclusions This study shows that serum sodium is inversely related to frailty, suggesting its potential role as reliable and cheap marker in the HIV-infection follow-up. Furthermore, we demonstrate a direct correlation between sodium and body BMD in HIV-infected patients, similarly to general population. DOI: 10.1530/endoabs.56.P745

2018 - Testosterone (T) and estradiol (E2) are poorly associated to the reduction of bone mineral density (BMD) in Young/Middle Aged Men with Human immunodeficiency virus (HIV). [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, Federica; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Pagotto, U.; Guaraldi, G.; Rochira, Vincenzo
abstract

Background: Osteopenia and osteoporosis, as well as hypogonadism, are common findings in men with HIV- infection and they occur at a younger age than healthy subjects. The reduction of BMD is due to both HIV-related and HIV-unrelated factors. Previous studies suggest that T deficiency is not or poorly associated with reduced BMD in HIV context. On the other hand, estrogens are consid- ered more important than androgens for bone health in general population, but data about their role in HIV- infected men are still scanty. Objective: To investigate the relationship between BMD and circulating sex steroids assessed by Liquid Chro- matography tandem Mass Spectrometry (LC-MS/MS) in a cohort of young/middle aged HIV-infected men. Methods: Prospective, cross-sectional, observational study on 233 consecutive HIV-infected male patients with ongo- ing Highly Active Antiretroviral Therapy (HAART), attend- ing the Multidisciplinary Metabolic Clinic of Modena. Body composition and BMD at total body, lumbar spine (L1 to L4) and total hip were measured using a Hologic QDR-2000 densitometer (DXA). LC-MS/MS was used for hormonal assays. Statistical analysis: The nonparametric Mann–Whitney U test was used for group comparisons because variables were not normally distributed at the Kolmogorov-Smirnov test. Correlations were performed using linear regression models. Results: Two hundred and thirty-three HIV-infected patients were enrolled (mean age 45.29 ! 5.33 years) with average duration of HIV-infection of 190.8 ! 102.8 months. Eight patients (3.4%) had hypogonadism, defined as total T serum levels below 300 ng/dL. Considering results at DXA examination, BMD was normal in 36.5% and reduced in 63.5% (55.8% osteopenia, 7.7% osteoporo- sis). Both total T and E2 did not significantly differ com- paring patients with normal BMD to patients with reduced BMD. Body and lumbar BMD did not show any significant difference between eugonadal patients and patients with low T and/or low E2, while both femoral BMD and femoral T-score were significantly higher in patients with E2 above 20 pg/mL than in those with E2 below 20 pg/mL (p = 0.043 and p = 0.033, respectively). At linear and step- wise multiple regression analyses, BMD was positively associated with total lean mass (R2 = 0.154, p < 0.0001); apart from it, neither T nor E2 correlated with BMD and T- score at any site. Conclusion: Classical factors associated to BMD as E2 and T seem to be less relevant in this model of male osteoporo- sis. Other specific HIV-related factors, such as changes in body composition and consequent lipodystrophy, could be more deeply involved than sex steroids as potential mecha- nisms in bone loss in this setting. Finally, we confirm the high prevalence of reduced BMD in young/middle aged HIV-infected men, representing one of the clinical hallmarks of the premature aging process related to HIV infection.

2017 - Pituitary growth hormone (GH) secretion is partially rescued in HIV-infected patients with GH deficiency (GHD) compared to hypopituitary patients [Articolo su rivista]
Diazzi, Chiara; Brigante, Giulia; Ferrannini, G.; Ansaloni, Anna; Zirilli, Lucia; De Santis, M. C.; Zona, Stefano; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Biochemical growth hormone deficiency is prevalent among human immunodeficiency virus-infected patients, but if this condition is clinically relevant remains challenging. The aim is to prospectively compare the growth hormone deficiency/insulin-like growth factor-1 status of 71 human immunodeficiency virus-infected patients with impaired growth hormone response to growth hormone releasing hormone + Arginine with that of 65 hypopituitary patients affected by a true growth hormone deficiency secondary to pituitary disease. The main outcomes were: basal serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein 3, growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine test, body mass index, waist and hip circumference, and body composition by dual energy X-ray absorptiometry. Insulin-like growth factor-1 binding protein 3, basal growth hormone (p < 0.005), growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine, waist to hip ratio, insulin-like growth factor-1, fasting glucose, insulin, and triglycerides (p < 0.0001) were lower in hypopituitary than human immunodeficiency virus-infected patients. Total and trunk fat mass by dual energy X-ray absorptiometry were higher in hypopituitary than in human immunodeficiency virus-infected patients (p < 0.0001). In all the patients total body fat was associated with both growth hormone peak and area under the curve at stepwise linear regression analysis. The degree of growth hormone deficiency is more severe in hypopituitary than in human immunodeficiency virus-infected patients, suggesting that the function of growth hormone/insulin-like growth factor-1 axis is partially rescued in the latter thanks to a preserved pituitary secretory reserve. Data from the current study suggest that human immunodeficiency virus-infected patients with peak growth hormone < 9 mg/L may have partial growth hormone deficiency and clinicians should be cautious before prescribing recombinant human growth hormone replacement treatment to patients living with human immunodeficiency virus.

2017 - Psychological rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle aged human immunodeficiency virus (HIV)-Infected Men. [Abstract in Rivista]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

Background HIV-infection is associated to an increased prevalence of erectile dysfunction (ED). In HIV-infected men ED seems to be less related to serum Testosterone (T), depending from other factors. Aim To investigate the role of different components (organic, relational, psycho- logical) of erectile function by using validate questionnaires in HIV-infected men with normal serum T. Methodology Prospective, cross-sectional, observational study on eugonadal HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to assess sexual function. Sexual desire was further evaluated through a direct question during the visit. LC-MS/MS was used to assess gonadal status. Results 225 HIV-infected patients were enrolled (mean age 45.19G5.36 years). SIEDY scores at appendix and scale 3 were significantly higher in patients with ED at IIEF- 15 (nZ136, 60.4%) compared with those without ED (P!0.001 and PZ0.015, respectively). Conversely, scale 1 (PZ0.448) and 2 (PZ0.503) of SIEDY did not differ between patients with or without ED, suggesting a predominance of the psychological basis of ED in our cohort. The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, P!0.001). Similarly, the score at SIEDY appendix was significantly different among ED degrees at IIEF-15 (P!0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (P!0.001, PZ0.001, and P!0.001, respectively), confirming the reliability of these tools. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the specific item of IIEF-15 (P!0.001). Conclusions The psychological component impacts in a significant manner on ED in HIV- infection context. Despite the high prevalence of comorbidities in these patients, the organic component does not affect erectile function. All the three validated questionnaires seem to be trustworthy in the diagnosis of ED in this setting.

2017 - Psychological rather than organic and/or relational components are involved in sexual dysfunction in young/middle aged human immunodeficiency virus (HIV)-infected men. [Abstract in Atti di Convegno]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED). In HIV-infected men ED seems to be less related to serum Testosterone (T), depending from other factors. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using validate questionnaires in HIV-infected men with normal serum T. METHODOLOGY: Prospective, cross-sectional, observational study on eugonadal HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to assess sexual function. Sexual desire was further evaluated through a direct question during the visit. LC-MS/MS was used to assess gonadal status. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36years). SIEDY scores at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (p<0.001 and p=0.015, respectively). Conversely, scale 1 (p=0.448) and 2 (p=0.503) of SIEDY did not differ between patients with or without ED, suggesting a predominance of the psychological basis of ED in our cohort. The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001). Similarly, the score at SIEDY appendix was significantly different among ED degrees at IIEF-15 (p<0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p<0.001, p=0.001, and p<0.001, respectively), confirming the reliability of these tools. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the specific item of IIEF-15 (p<0.001). CONCLUSIONS: The psychological component impacts in a significant manner on ED in HIV-infection context. Despite the high prevalence of comorbidities in these patients, the organic component does not affect erectile function. All the three validated questionnaires seem to be trustworthy in the diagnosis of ED in this setting.

2016 - Estrogens and male reproduction [Capitolo/Saggio]
Rochira, Vincenzo; Madeo, Bruno; Diazzi, Chiara; Zirilli, Lucia; Santi, Daniele; Carani, Cesare
abstract

n males, estrogens exert pleiotropic effects by acting on several tissue and organs, including the male reproductive system. The action of estrogens is manifest from prenatal life during which the exposure to estrogen excess might influence the development of some structures of the male reproductive tract. Male fertility is under the control of estrogens, especially in rodents. The loss of function of estrogen receptor alpha and/or of the aromatase enzyme leads to infertility in mice. In men, estrogens are able to exert their actions at several levels through the reproductive tract and on several different reproductive cells. However, the regulation of human male reproduction is more complex and the role of estrogens is less clear compared to mice. During fetal and perinatal life, estrogen acts on the central nervous system by modulating the development of some areas within the brain that are committed to controlling male sexual behavior in terms of setting gender identity, sexual orientation development and the evolution of normal adult male sexual behavior. This organizational, central effect of estrogens is of particular significance in other species (especially rodents and rams), being probably less important in men where psychosocial factors become more determining. Other relevant, non-reproductive physiological events depend on estrogen in men and they involve bone maturation and mineralization as well as metabolic functions. In this chapter we provide an update of estrogen’s role in male reproductive function by reviewing the physiological actions of estrogen on male reproduction and the pathophysiology related to estrogen deficiency and estrogen excess. Phenotypes associated with estrogen deficiency and excess in rodents and in man have shed new light on the mechanisms involved in male reproduction, challenging the perception of the predominant importance of androgens in men. It is now clear that the imbalance between estrogen and androgen in men might affect male reproductive function even in presence of normal circulating androgens. Some uncertainties still remain, especially regarding the impact of abnormal serum estrogen levels on male health, particularly due to the fact that estrogen is not routinely measured in men in clinical practice. Advancements in methods to precisely measure estrogens in men, together with a reduction of their costs, should provide better evidence on this issue and inform clinical practice. New basic and clinical research is required to improve our knowledge on the role of estrogen in male reproductive function and men’s health in general. For complete coverage of all related areas of Endocrinology, please see our online FREE web-book, www.endotext.org.

2016 - Psychological, rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men. [Abstract in Atti di Convegno]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED)1,2. In HIV- infected men ED seems to be less related to serum Testosterone (T)2-4, ED and sexual dysfunction mainly depending from other factors1,2. However, data on other components of sexual dysfunction in HIV are scanty2. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using different validate questionnaire in HIV-infected men with normal serum T who are mainly homosexual (70%). METHODOLOGY: Prospective, cross-sectional, observational study on 225 eugonadal, HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used for the evaluation of sexual function. Moreover, the sexual desire was further evaluated using a direct question during the visit. Statistical analysis: comparison of continue variables among groups was performed using Kruskal-Wallis test and Dunnet test for post-hoc analyses. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36 years) with average duration of HIV- infection and of HAART treatment of 187.62±101.71 and 156.38+89.81 months, respectively. Table 1 summarizes the score obtained in each item evaluated by questionnaires.The SIEDY scores obtained at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (appendix: 7.64+4.39 vs 4.35+3-14, p&lt;0.001) (scale 3: 2.72+4.39 vs 2.07+1.86, p=0.015). Conversely, scale 1 (2.76+2.16 vs 2.46+2.10, p=0.448) and 2 (0.53+1.02 vs 0.61+1.47, p=0.503) of SIEDY did not differ between patients with or without ED. This suggests that the psychological basis of ED was predominant in HIV-infected men. However, when patients were grouped according to the severity of ED at IIEF-15 all SIEDY items did not differ among the 3 groups (p&gt;0.05). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p&lt;0.001). Similarly, the score at SIEDY appendix was significantly different among the ED degree found at IIEF-15 (p&lt;0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p&lt;0.001, p=0.001, and p&lt;0.001, respectively), confirming the reliability of these tools. Sexual desire was evaluated using IIEF-15 appropriate domain and during the interview through direct question performed by the clinician. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the item of IIEF-15 on sexual desire (p&lt;0.001). CONCLUSIONS: The psychological component of ED impacts in a significant manner on ED in men with HIV. Despite the high prevalence of comorbidities in these patients the organic component does not affect erectile function. Similarly, the relational component seems to play a not significant role probably because of the high percentage of men not in a stable relationship. All the three validated questionnaires well describe the degree of erectile dysfunction, with a good correlation index, suggesting that they are all reliable and accurate for the diagnosis of ED in this peculiar population. REFERENCES 1Zona S et al. Erectile dysfunction is more common in young to middle-aged HIV-infected men than in HIV-uninfected men. J Sex Med. 2012 Jul;9(7):1923-30. 2Santi D et al. Male sexual dysfunction and HIV--a clinical perspective. Nat Rev Urol. 2014 Feb;11(2):99-109. 3Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 4Rochira V &amp; Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30.

2015 - Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study [Articolo su rivista]
Rochira, Vincenzo; Diazzi, Chiara; Santi, Daniele; Brigante, Giulia; Ansaloni, Anna; Decaroli, Maria Chiara; De Vincentis, Sara; Stentarelli, Chiara; Zona, Stefano; Guaraldi, Giovanni
abstract

Men with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated non-acquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r(2) = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail.

2015 - Primary hypoparathyroidism is common in adult patients with b-thalassemia and protect patients from osteoporosis. [Abstract in Rivista]
Ansaloni, Anna; Ferrara, F.; Diazzi, Chiara; Pietrangelo, Antonello; Simoni, Manuela; Rochira, Vincenzo
abstract

Introduction b-thalassemia (bT) is associated to several endocrine abnormalities mainly due to iron overload. With the increase in bT-patients life expectancy, due to progresses in iron chelation therapy, more patients enter into adulthood than in the past and the prevalence of endocrine diseases is being reconsidered. The aim of the study is to investigate the prevalence of primary hypoparathyroidism (pHPT) in adult bT-patients and to characterize the relative clinical phenotype with particular regard to bone health. Methods We enrolled 26 adult patients with major or intermedia bT (12M and 14F; mean ageGS.D. of 38.1G7.5 years). Serum PTH, 25-hydroxyvitamin D (25OHD), calcium, phosphorous, albumin, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry (Hologic) at lumbar and femoral site were measured. Results pHPT (PTH !15 pg/ml) was found in seven of the 26 patients (27%). Of them, four patients (57%) had hypocalcemia and two were on chronic calcium therapy. Lumbar BMD was significantly higher in patients with pHPT (0.884G 0.189 g/cm2) than in patients without pHPT (0.731G0.124 g/cm2) (PZ0.023). No significant difference was found in femoral BMD, even though a trend for higher BMD was present in pHPT (0.704G0.117 vs 0.670G0.143 g/cm2 in pHPT and no-pHPT respectively) (PZ0.578). The prevalence of osteoporosis was higher in patients without pHPT (68%) than in patients with pHPT (29%). Two patients had a history of bone osteoporotic fractures and both of them did not present pHPT. Bone turnover markers were no different in the two groups. Conclusions The prevalence of pHPT in adult bT-patients is higher if compared to that observed in pediatric bT-patients, the latter ranging from 8 to 11%. Moreover we found an higher prevalence of pHPT compared to that reported in literature on adult bT patients. As expected, pHPT seems to exert a protective role on the development of osteoporosis in these patients.

2015 - Serum gonadotropins secretion is not reduced with advancing age in HIV-infected females: results of a case–control study in menopausal women. [Abstract in Rivista]
Diazzi, Chiara; Brigante, Giulia; Guaraldi, Giovanni; Simoni, Manuela; Rochira, Vincenzo
abstract

Introduction HIV infection treated with highly active antiretroviral therapy (HAART) seems to be associated with hypogonadism in men. Less is known in HIV-infected women gonadal status. The aim of this study is to investigate gonadal function, in menopausal HIV-infected women compared sex- and age-matched healthy subjects (HS). Methods We retrospectively compared 188 HIV-infected women with 192 HS selected reviewing record charts and laboratory database respectively. We considered only women older than 50 years and we grouped them according to their age (50–54; 55–59; and O60 years). Basal serum LH, FSH, estradiol, and testosterone were measured. The FSH cut-off of 40 UI/l for establishing menopausal status. Results The percentage of subjects with FSH levels O40 UI/l was higher in HIV-infected women (67.5%) than in healthy controls (59.4%). This difference was found also in the younger subgroup (38% vs 27%). FSH serum levels in HIV-infected women (54.08G31.47 mUI/ml) did not differ (PZ0.27) from HS (50.87G 31 mUI/ml). Accordingly, no significant differences were found in LH, estradiol, and testosterone levels. Conclusions Menopause seems to occur at a younger age than HS in HIV-infected women. Moreover, differently from what was documented in HIV-infected male counterpart, HIV-infected women seem to not develop hypogonadotropic hypogonadism, but have a tendency to higher serum FSH at a younger age (!54 years) suggesting premature hypergonadotropic hypogonadism. With this in view menopause may be considered an element of the process of premature aging associated with HIV infection and its comorbidities.

2014 - GH deficiency in HIV-infected patients compared to hypoopituitary patients [Abstract in Rivista]
Diazzi, Chiara; Brigante, Giulia; G., Ferrannini; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

The difference between HIV-infected patients with growth hormone deficiency (GHD) and GHD patients with hypopituitarism is in higher values go GH peak after GHRH+Arginine and IGF-1 in men with HIV.

2014 - GH deficiency in HIV-infected patients compared to hypopituitary patients [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; S., De Vincentis; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

Gh peak after GHR+Arginine and IGF-1 are lower in HIV-infected patients with biochemical growth hormone deficiency than in patients with hypopituitarism and GHD.

2014 - Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution [Articolo su rivista]
Brigante, Giulia; Diazzi, Chiara; Ansaloni, Anna; Zirilli, Lucia; Orlando, Gabriella; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

OBJECTIVE: Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. DESIGN AND METHODS: To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). RESULTS: Men had lower GH peak and AUC than women (P&lt;0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak &lt;7.5 μg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P&lt;0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P&lt;0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. CONCLUSIONS: These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.

2014 - Gonadal and sexual function in young/middle aged human immunodeficiency virus (HIV)-infected men [Abstract in Rivista]
Santi, Daniele; Brigante, Giulia; Diazzi, Chiara; S., De Vincentis; Zona, Stefano; Guaraldi, Giovanni; Simoni, Manuela; Rochira, Vincenzo
abstract

The study investigated male sexual function in men with HIV infection according with their gonadal status.

2014 - I pazienti con infezione da HIV hanno un reale deficit di GH (GHD) ? Confronto tra pazienti HIV positivi con documentato GHD biochimico e pazienti ipopituitarici HIV negativi con GHD [Abstract in Atti di Convegno]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

The response to GHRH+Arginine is higher in HIV-infected patients with GHD when compared to patients with GHD and hypopituitarism

2014 - Il volume tiroideo è ridotto in pazienti adulti affetti da beta-talassemia rispetto ai controlli [Abstract in Atti di Convegno]
Ansaloni, Anna; Diazzi, Chiara; Santi, Daniele; Brigante, Giulia; Ferrara, Francesca; Pietrangelo, Antonello; Simoni, Manuela; Rochira, Vincenzo
abstract

This study demonstrates that thyroid volume in adult patients with beta-thalassemia is reduced when compared with that of matched control subjects

2014 - Relationship between testosterone and HIV-related comorbidities: secondary hypogonadism is associated with a poor health status in HIV-infected men [Abstract in Atti di Convegno]
Rochira, Vincenzo; Diazzi, Chiara; Brigante, Giulia; Santi, Daniele; Maria Chiara De, Caroli; Sara De, Vincentis; Simoni, Manuela; Carani, Cesare; Guaraldi, Giovanni
abstract

ABSTRACT INTRODUCTION: Testosterone (T) deficiency is very common in men with Human Immunodeficiency Virus (HIV), and it is more often associated with inappropriately low/normal luteinizing hormone (LH). However, the underlying causes remain poorly understood. Moreover, the role of HIV and/or HIV infection treatments, as well as the role of the general health status on the gonadal axis have been rarely investigated. AIM: The aim of this study is to evaluate the association between gonadal function and health status in men with HIV infection. METHODS: We performed a cross-sectional, observational study on 1359 consecutive HIV male outpatients. Morning serum Total T (TT), LH, estradiol, HIV parameters were measured. Frailty Index and number of comorbidities were extracted from the Clinical Database in which all patients data are recorded. TT<300 ng/dL was used as the threshold for biochemical T deficiency. RESULTS: T deficiency was found in 212 subjects (15.6%), and most of them (n=183; 13.4%) had secondary hypogonadism. TT resulted inversely related to Frailty Index in all patients (r=0.302, r2=0.091), this correlation being strengthened in HIV- infected men with secondary hypogonadism (r=0.403, r2=0.162). The percentage of HIVinfected men with TT <300 ng/dL increased progressively in accordance with the increase in the number of comorbidities (0.5%, 2.8%, 8.5%, 22.7%, 25.5%, 40% in men with 0, 1, 2, 3, 4, and >5 comorbidities, respectively). CONCLUSION: Poor health status in HIV-infected men might be involved in the pathogenesis of hypogonadism. This mechanism could reflect an adaptive response to illness in unhealthy patients similarly to what happens in other clinical conditions such as anorexia nervosa. Thus, low TT could be considered a biomarker of frailty and might confer an advantage for both the sick patients (in terms of sparing energy) and the species (preventing fatherhood). Furthermore, frailty related hypogonadism could be part of the process of premature aging already demonstrated in HIVinfected patients.

2014 - Thyroid volume in adult beta-thalassemic patients is smaller than in controls [Abstract in Rivista]
Ansaloni, Anna; Diazzi, Chiara; Santi, Daniele; Brigante, Giulia; F., Ferrara; Pietrangelo, Antonello; Rochira, Vincenzo
abstract

Patients with beta-thalassemia have lower thyroid volume estimated at ultrasound than matched controls.

2014 - Thyroid volume in adult beta-thalassemic patients is smaller than in controls [Abstract in Rivista]
Ansaloni, Anna; Diazzi, Chiara; Santi, Daniele; Brigante, Giulia; Ferrara, Francesca; Carani, Cesare; Pietrangelo, Antonello; Simoni, Manuela; Rochira, Vincenzo
abstract

Thyroid volume is significantly reduced in adult patients with beta-thalassemia than in matched controls

2013 - Anterior panhypopituitarism due to neurosarcoidosis unmasked by sexual dysfunction in a young adult man [Abstract in Rivista]
Vezzani, Silvia; Diazzi, Chiara; Rochira, Vincenzo
abstract

A case of neurosarcoidosis with pituitary involvement is described. The rarity of disease and the peculiar onset characterized by male sexual dysfunction makes this case of interest.

2013 - Are pre-miR-146a and PTTG1 associated with papillary thyroid cancer? [Articolo su rivista]
Marino, Marco; Valentina, Cirello; Gnarini, Valentina; Carla, Colombo; Pignatti, Elisa; Casarini, Livio; Diazzi, Chiara; Rochira, Vincenzo; Katia, Cioni; Madeo, Bruno; Carani, Cesare; Simoni, Manuela; Laura, Fugazzola
abstract

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. The predisposition to developing this carcinoma by the heterozygous state of rs2910164 within the precursor of the miR-146a has been reported, but recently not confirmed. Interestingly, on the same chromosome, almost 50 kb separate the pre-miR-146a from the pituitary tumor-transforming gene 1 (PTTG1), a proto-oncogene involved in several tumors, including thyroid cancers. In this study, we analyzed, using a case–control design, the genetic association between PTC and the genomic region encompassing pre-miR-146a rs2910164 and PTTG1 rs1862391 and rs2910202. We enrolled 307 affected patients and 206 healthy controls. The possible presence of thyroid nodules in controls was excluded by ultrasonography. All the cases were submitted to single- nucleotide polymorphism (SNP) genotyping of pre-miR-146a and PTTG1, and risk association analyses were carried out. The genotypic and allelic frequencies of pre-miR-146a rs2910164 were not statistically different in the patients and controls, and this SNP was not in linkage disequilibrium with the investigated PTTG1 SNPs. Consistently, meta-analyses, the first including all the affected cases published to date, did not confirm the previously reported association of the heterozygous CG genotype with PTC. The PTTG1 SNPs exhibited the same allelic frequency in the patients and controls and were not associated with the disease. In conclusion, in a well-selected Italian population, neither pre-miR-146a rs2910164 nor PTTG1 rs1862391 and rs2910202 were found to be associated with the risk of developing PTC.

2013 - Association of pre-miR-146a rs2910164 GG genotype with papillary thyroid cancer: a new case control study on two adjacent genes on chromosome 5, pre-miR-146a and PTTG1 [Abstract in Rivista]
Marino, Marco; Valentina, Cirello; Gnarini, Valentina; Pignatti, Elisa; Casarini, Livio; Diazzi, Chiara; Rochira, Vincenzo; Katia, Cioni; Madeo, Bruno; Simoni, Manuela; Laura, Fugazzola
abstract

Role of the pre-miR-146a and PTTG1 on papilary thyroid cancer

2013 - Effects of gender and body composition on GH response to GHRH plus Arginine (GHRH+ARG) in HIV-lipodystrophic patients [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

GH-deficiency is more frequent in men with HIV than in HIV-infected women.

2013 - Effects of gender and body composition on GH response to GHRH plus Arginine (GHRH+Arg) in HIV-lipodystrophic patients: higher rate of GH deficiency in men. [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigates gender differences in the rate of GH-deficiency among hIV-infected men.

2013 - Effects of gender and body composition on GH response to GHRH+Arg in HIV-lipodystrophic patients: higher rate of GH deficiency in men [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; Giulia, Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigated the gender difference in GH secretion after GHRH+Arg in patients with HIV-related lipodystrophy showing hoe men are at higher risk to fail to respond copmared to females. In this group of patients with HIV that are at higher risk of GH deficiency, men have higher risk of GH deficiency than women.

2013 - Effects of treatment for acromegaly on Bone Mineral Density (BMD): is Pegvisomant protective on lumbar BMD? [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Diazzi, Chiara; S., De Vincentis; G., Ferrannini; Madeo, Bruno; Simoni, Manuela; Carani, Cesare; Rochira, Vincenzo
abstract

The abstract deals with the different effects of treatments for acromegaly on bone

2013 - Effects of treatment for acromegaly on bone mineral density (BMD): is pegvisomant protective on lumbar BMD? [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Diazzi, Chiara; S., De Vincetis; G., Ferrannini; Madeo, Bruno; Simoni, Manuela; Rochira, Vincenzo; Carani, Cesare
abstract

The type of medical therapy for acromegaly may have different effects on bone mineral density

2013 - Effects of treatment for acromegaly on bone mineral density: is pegvisomant protective on lumbar BMD? [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Diazzi, Chiara; Sara De, Vincentis; Giulia, Ferrannini; Madeo, Bruno; Carani, Cesare; Simoni, Manuela; Rochira, Vincenzo
abstract

The type of pharmacological treatment used for the control of acromegaly might have different effect in the prevention of bone loss.

2013 - Papillary thyroid cancer: a new case-control study involving pre-mir-146a and PTTG1 genes [Abstract in Rivista]
Marino, Marco; V., Cirello; Gnarini, Valentina; Pignatti, Elisa; Casarini, Livio; Diazzi, Chiara; Rochira, Vincenzo; K., Cioni; Madeo, Bruno; Simoni, Manuela; L., Fugazzola
abstract

Studio genetico dei carcinomi papillari della tiroide

2013 - The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer [Articolo su rivista]
Diazzi, Chiara; Madeo, Bruno; Taliani, Erica; Zirilli, Lucia; Romano, Stefania; Antonio R. M., Granata; Maria Cristina De, Santis; Simoni, Manuela; Katia, Cioni; Carani, Cesare; Rochira, Vincenzo
abstract

Objectives: The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy (FNAB) wash-out fluid (Ct-FNAB) for medullary thyroid cancer (MTC) remains to be determined. This prospective study aims to assess the diagnostic value of Ct-FNAB in thyroid nodules in comparison with basal serum calcitonin (Ct), Pentagastrin-stimulated Ct (Pg-sCt), and cytology. Methods: Among patients with goiter addressed to US-FNAB having initial clinical suggestion for thyroidectomy, 27 patients with thyroid nodule/s (n=60), normal, borderline or increased Ct, fulfilled criteria for thyroidectomy. All 27 patients (enrolled according to exclusion/inclusion criteria) underwent ultrasonography (US), Ct, Pg-sCt, US-assisted FNAB of each patient’s nodule for both cytology, and Ct-FNAB before thyroidectomy. Results: Ct-FNAB resulted always >1000 pg/mL in MTC nodules at histology. For values between 36 and 1000 pg/mL, MTCs and nodular or micronodular C-cell Hyperplasia (CCH) results overlapped. Most of the nodules without MTC and/or CCH had Ct-FNAB<17 pg/mL. Ct-FNAB diagnostic power was superior to and similar to other diagnostic procedures (Ct, Pg-sCt, and cytology) in identifying both MTC and CCH, and MTC alone, respectively. Conclusion: The diagnostic power of Ct-FNAB is valuable compared with other routine procedures. Ct-FNAB is highly reliable for the early detection and accurate localization of MTC in thyroid nodules, but it does not differentiate between MTC and CCH. Ct-FNAB is an extremely valuable diagnostic tool, especially considering that other diagnostic procedures do not provide a definitive diagnosis, and it can be included in the clinical work up of thyroid nodules when MTC is suspected.

2013 - Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy [Articolo su rivista]
Gnarini, Valentina; Brigante, Giulia; DELLA VALLE, Elisa; Diazzi, Chiara; Madeo, Bruno; Carani, Cesare; Rochira, Vincenzo; Simoni, Manuela
abstract

Background: Italy is characterized by high preva- lence of goiter. To date, only limited data about the preva- lence of goiter in the Italian adult population are available. Aim: To investigate the prevalence of thyroid ultrasound ab- normalities in adults unaware of any thyroid disease and eval- uate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. Methods: Ultrasound (US) thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. One hundred and thirty-five women and 66 men (no.= 201), unaware of any thyroid disease (mean age of 46±10.7 yr) underwent their first thyroid US scan. Results: US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associ- ated with positive auto-antibodies in 11 of them. Seventeen subjects (18%) with nodules underwent US-fine needle aspiration biopsy with the following cytological class (C) outcome: 14 patients C2 (82%), 1 patient C3 (6%), 2 patients had C4 (12%), the latter received histological confirmation. Conclu- sions: The prevalence of thyroid abnormalities is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goi- ter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thy- roid US screening could allow the detection of DTC in asymp- tomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases.

2012 - Clinical and radiological evidence of the recurrence of reversible pegvisomant-related lipohypertrophy at the new site of injection in two women with acromegaly: a case series [Articolo su rivista]
Rochira, Vincenzo; Zirilli, Lucia; Diazzi, Chiara; Romano, Stefania; Carani, Cesare
abstract

IntroductionPegvisomant-related lipohypertrophy may revert when changing the site of injection, but the lipohypertrophy may recur at the new site of injection. The strength of evidence, however, is weak and comes from information obtained from physical examination only.Case presentationWe studied two Caucasian women with acromegaly, aged 51 and 71 years, with pegvisomant-related lipohypertrophy. Our two patients were evaluated at baseline, when the site of pegvisomant injection was the periumbilical abdominal region, and then four months after switching the injection site from the abdomen to both thighs. Both physical examination and radiological studies (magnetic resonance imaging and dual energy X-ray absorptiometry) demonstrated that the abdominal lipohypertrophy progressively reverted in both patients after switching the site of injection to the thighs. However, lipohypertrophy reappeared at the new site of injection. The radiological outcome confirmed the reversibility of pegvisomant-related lipohypertrophy and strengthened the body of evidence on this issue.ConclusionIn clinical practice, physical examination of the injection site or sites leads to an early detection of lipohypertrophy during pegvisomant treatment. Radiological procedures may be of help to confirm subcutaneous fat changes and for a precise monitoring of fat redistribution. Patients should get appropriate information about lipohypertrophy before starting pegvisomant treatment since the rotation of the site of injection may prevent lipohypertrophy.

2012 - GH response to GHRH plus Arginine in lipodistrophic patients with human immunodeficiency virus: gender differences [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; Guaraldi, Giovanni; M., De Santis; L., Roli; Rochira, Vincenzo; Baraldi, Enrica
abstract

GH deficiency is more frequent in men with HIV than in HIV-infected women

2012 - GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls [Articolo su rivista]
Zirilli, Lucia; Orlando, Gabriella; Carli, Federica; Madeo, Bruno; Cocchi, Stefania; Diazzi, Chiara; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Objective: GH secretion is impaired in lipodystrophic human immunodeficiency virus (HIV) patients and inversely related to lipodystrophy-related fat redistribution in men. Less is known about the underlying mechanisms involved in reduced GH secretion in HIV-infected women.Design: A case–control, cross-sectional study comparing GH/IGF1 status, body composition, and metabolic parameters in 92 nonobese women with HIV-related lipodystrophy and 63 healthy controls matched for age, ethnicity, sex, and body mass index (BMI).Methods: GH, IGF1, IGF binding protein 3 (IGFBP3), GH after GHRH plus arginine (GHRHCArg), several metabolic variables, and body composition were evaluated.Results: GH response to GHRHCArg was lower in HIV-infected females than in controls. Using a cutoff of peak GH %7.5 mg/l, 20.6% of HIV-infected females demonstrated reduced peak GH response after GHRHCArg. In contrast, none of the control subjects demonstrated a peak GH response %7.5 mg/l. Bone mineral density (BMD), quality of life, IGF1, and IGFBP3 were lowest in the HIV-infected females with a GH peak %7.5 mg/l. BMI was the main predictive factor of GH peak in stepwise multiregression analysis followed by age, with a less significant effect of visceral fat in the HIV-infected females. Conclusions: This study establishes that i) GH response to GHRHCArg is lower in lipoatrophic HIV- infected women than in healthy matched controls, ii) BMI more than visceral adipose tissue or trunk fat influences GH peak in this population, and iii) HIV-infected women with a GH peak below or equal to 7.5 mg/l demonstrate reduced IGF1, IGFBP3, BMD, and quality of life.

2012 - Prevalence of differentiated thyroid cancer is relevant in patients with familial adenomatous polyposis: a case-control, prospective study [Abstract in Rivista]
Diazzi, Chiara; Benatti, Piero; Zirilli, Lucia; Gnarini, Valentina; Madeo, Bruno; Romano, Stefania; Rossi, Giuseppina; Carani, Cesare; PONZ DE LEON, Maurizio; Roncucci, Luca; Rochira, Vincenzo
abstract

Studio sulla prevalenza dei tumori differenziati della tiroide in pazienti con poliposi adenomatosa famigliare. Lo studio ha permesso di stabilire che la prevalenza di tumori della tiroide è aumentata in questi pazienti in confronto alla popolazione normale.

2012 - Propylthiouracil-induced interstitial pneumonia in a caucasian woman with amiodarone-induced thyrotoxicosis [Articolo su rivista]
Diazzi, Chiara; Brigante, Giulia; Rossi, Giulio; Rochira, Vincenzo
abstract

Background: Propylthiouracil (PTU) therapy is associated with a variety of adverse reactions, among the most rare being interstitial pneumonia. To date, this has been reported in four Asian patients with autoimmune hyperthyroidism. Here we describe a Caucasian woman who developed a bronchiolitis obliterans organizing pneumonia (BOOP)-like interstitial pneumonia after PTU administration for amiodarone-induced thyrotoxicosis. Patient Findings: The patient was a 68-year-old woman who had been treated with amiodarone for chronic atrial fibrillation starting in May 2004. She had been a heavy smoker with a history of hypertension but no dust exposures. In October 2006, amiodarone was stopped after she developed thyrotoxicosis. In January 2007 serum thyroid-stimulating hormone (TSH) was 0.01 mIU/L (0.35-4.94) and free T4 was 17.5 pg/mL (7 to 15). She was initially started on methimazole and then changed to PTU after she developed pruritus. She developed severe dyspnea 9 months after starting PTU. At the time she was also taking warfarin, enalapril, and sotalol. Chest X-ray showed diffuse interstitial peripheral opacities and transbronchial lung biopsy revealed subacute lung injury with organizing pneumonia with hyperplasia of the alveolar type 2 pneumocytes, and characteristics of BOOP-like interstitial pneumonia. Signs and symptoms progressively improved after PTU discontinuation as confirmed at X-ray and computed tomography (CT) scan of the chest and by respiratory function tests. She has been recurrence free for 4 years after stopping PTU. Summary: This woman of Caucasian ancestral origin developed BOOP-like interstitial pneumonia after PTU treatment for apparent amiodarone-induced thyrotoxicosis, with resolution of her lung disease after stopping PTU. Tests for TSH receptor antibodies, thyroid peroxidase antibodies, and antinuclear cytoplasmic autoantibody were negative. Thyroid ultrasound was consistent with thyroiditis without nodules. Conclusions: PTU-associated interstitial pneumonia is not limited to patients of Asian origin or those with autoimmune thyroid disease. PTU must be withdrawn in the presence of respiratory symptoms and documented interstitial pneumonia. X-ray films, CT-scan, respiratory function tests, and lung biopsy are needed to diagnose PTU-induced interstitial pneumonia with certainty and to monitor the evolution of the disease after PTU discontinuation.

2012 - The Value of Repeated US-Guided Fine-Needle Aspirations (US-FNAB) in the Follow-Up of Thyroid Nodules: Preliminary Results from the MoCyThy (Modena's Cytology of the Thyroid) Database [Abstract in Rivista]
Rochira, Vincenzo; Ansaloni, Anna; Belli, Serena; Vezzani, Silvia; Diazzi, Chiara; Zirilli, Lucia; Simoni, Manuela; Carani, Cesare; Madeo, Bruno
abstract

Repeating ultrasound guided fine needle aspiration might be useful for detecting thyroid malinìgnant nodules

2012 - Ultrasound (US) Features of Thyroid Nodules with Cytology Suspicious for Malignancy [Abstract in Rivista]
Rochira, Vincenzo; Taliani, Erica; Ansaloni, Anna; Diazzi, Chiara; Brigante, Giulia; Carani, Cesare; Madeo, Bruno
abstract

Several US features are associated with and predict thyroid malignancy

2012 - Ultrasound (US) features of thyroid nodules with cytology suspicious for malignancy [Abstract in Rivista]
Taliani, Erica; Ansaloni, Anna; Diazzi, Chiara; Antonio R. M., Granata; Carani, Cesare; Rochira, Vincenzo; Madeo, Bruno
abstract

Studio dell'associazione di determinate caratteristiche ecografie con la malignità dei noduli tiroidei.

2012 - Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid nodules: effects of the operator’s experience on adequacy of sampling: the MoCyThy (Modena’s Cytology of the Thyroid) DATABASE [Abstract in Rivista]
Vezzani, Silvia; Ansaloni, Anna; Zirilli, Lucia; Katia, Cioni; Diazzi, Chiara; Simoni, Manuela; Madeo, Bruno; Rochira, Vincenzo
abstract

Lo studio ha permesso di evidenziare come l'esperienza (in termini di anni e di numero di prestazioni eseguite) sia importante per i risultati dell'agoaspirato tiroideo ecoguidato dei noduli tiroidei

2011 - Lateralization of calcitonin measurements in the wash-out fluid from thyroid fine-needle aspiration: a useful tool for the diagnosis of C-cell-hyperplasia? [Articolo su rivista]
Rochira, Vincenzo; Diazzi, Chiara; Brigante, Giulia; L., Persani; L., Fugazzola; Rossi, Giulio; Carani, Cesare
abstract

The measurement of calcitonin in the wash-out fluid from fine-needle aspiration seems to be a reliable method for the detection of C-cell hyperplasia when an evident difference in calcitonin levels between the two lobes of the thyroid is present.

2011 - Premature Decline of Serum Total Testosterone in HIV-Infected Men in the HAART-Era [Articolo su rivista]
Rochira, Vincenzo; Zirilli, Lucia; Orlando, Gabriella; Santi, Daniele; Brigante, Giulia; Diazzi, Chiara; Carli, Federica; Carani, Cesare; Guaraldi, Giovanni
abstract

BackgroundTestosterone (T) deficiency remains a poorly understood issue in men with Human Immunodeficiency Virus (HIV). We investigated the gonadal status in HIV-infected men in order to characterize T deficiency and to identify predictive factors for low serum T.Methodology/Principal FindingsWe performed a cross-sectional, observational study on 1325 consecutive HIV male outpatients, most of them having lipodystrophy. Serum total T&lt;300 ng/dL was used as the threshold for biochemical T deficiency. Morning serum total T, luteinizing hormone (LH), estradiol, HIV parameters, and body composition parameters by CT-scan and Dual-Energy-X-ray-Absorptiometry were measured in each case. Sexual behavior was evaluated in a subset of 247 patients. T deficiency was found in 212 subjects, especially in the age range 40–59, but was frequent even in younger patients. T deficiency occurred mainly in association with low/normal serum LH. Adiposity was higher in subjects with T deficiency (p&lt;0.0001) and both visceral adipose tissue and body mass index were the main negative predictors of serum total T. Osteoporosis and erectile dysfunction were present in a similar percentage in men with or without T deficiency.Conclusions/SignificancePremature decline of serum T is common (16%) among young/middle-aged HIV-infected men and is associated with inappropriately low/normal LH and increased visceral fat. T deficiency occurs at a young age and may be considered an element of the process of premature or accelerated aging known to be associated with HIV infection. The role of HIV and/or HIV infection treatments, as well as the role of the general health state on the gonadal axis, remains, in fact, to be elucidated. Due to the low specificity of signs and symptoms of hypogonadism in the context of HIV, caution is needed in the diagnosis of hypogonadism in HIV-infected men with biochemical low serum T levels.

2011 - Premature decline of serum total testosterone in human immunodeficiency virus (HIV) infected men with HIV-related lipodystrophy in the highly active antiretroviral therapy (HAART) era: a cross-sectional observational study [Abstract in Rivista]
Rochira, Vincenzo; Zirilli, Lucia; Orlando, Gabriella; Santi, Daniele; Brigante, Giulia; Diazzi, Chiara; Carli, Federica; Zona, Stefano; Carani, Cesare; Guaraldi, Giovanni
abstract

Hypogonadism is common in HIV-infected men with HAART. The causes are both testicular failure and pituitary insufficiency, these two cause often coexist in a mixed form of hypogonadism.

2011 - Prevalence of secondary, primary, and compensated hypogonadism in HIV infected men in HAART era: a cross-sectional observational study [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Zirilli, Lucia; Diazzi, Chiara; Orlando, Gabriella; Simoni, Manuela; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigates the prevalence of male hypogonadism among patients with HIV infection paying particular attention to the different types of hypogonadism

2011 - Ruolo del dosaggio di calcitonina (Ct) nei liquidi di lavaggio da agoaspirato (FNA-B) nella diagnosi di carcinoma midollare della tiroide (MTC): confronto con la calcitonina basale, la citologia e il test di stimolo alla pentagastrina (Pg-test) [Abstract in Rivista]
Baraldi, Enrica; Rochira, Vincenzo; Maria Cristina De, Santis; Diazzi, Chiara; Laura, Roli; Madeo, Bruno; Carani, Cesare; Tommaso, Trenti
abstract

Ruolo diagnostico del dosaggio della calcitonina nel liquido di lavaggio ottenuto mediante agoaspirato ecoguidato dei noduli tiroidei sospetti per carcinoma midollare tiroideo.

2011 - Self-Monitoring of Blood Glucose in Type 2 Diabetes Mellitus: Effect on Glycemic Control in Non-Insulin-Treated Patients [Abstract in Rivista]
Madeo, Bruno; Scaltriti, Sara; Romano, Stefania; Diazzi, Chiara; El Goch, Marwan; Antonio R. M., Granata; Emma Rita, Cavani; Rochira, Vincenzo
abstract

Glucose self-monitoring improve glucose control

2011 - Self-monitoring of blood glucose in type 2 diabetes mellitus: effect on glycemic control in non-insulin-treated patients [Abstract in Rivista]
Madeo, Bruno; Scaltriti, Sara; Romano, Stefania; Diazzi, Chiara; Marwan El, Goch; Antonio RM, Granata; Emma Rita, Cavani; Carani, Cesare; Rochira, Vincenzo
abstract

The role of self-monitoring of blodd glucose on the control of the disease

2011 - Sex steroids and HIV-related osteoporosis in men: low circulating estrogens are associated with impaired bone mineral density (BMD) [Abstract in Rivista]
Santi, Daniele; Brigante, Giulia; Orlando, Gabriella; Ciccarese, Michela; Diazzi, Chiara; Guaraldi, Giovanni; Carani, Cesare; Rochira, Vincenzo; Madeo, Bruno
abstract

The study investigates the role of sex steroids on HIV-related osteoporosis, suggesting that relative estrogen deficiency might play a role even in this particular type of bone demineralization.

2011 - Testosterone Changes over Time in Men with Human Immunodeficiency Virus Infection: Preliminary Results [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Zirilli, Lucia; Diazzi, Chiara; Orlando, Gabriella; Gnarini, Valentina; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study explored the changes overtime of circulating testosterone

2011 - Testosterone changes over time in men with human immunodeficiency virus infection: preliminary results [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Zirilli, Lucia; Diazzi, Chiara; Orlando, Gabriella; Gnarini, Valentina; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigates the changes in circulating testosterone overtime in order to establish if hypogonadism in men with HIV is a reversal condition or not

2011 - Thyroid Disease in Patients with Type-1 Neurofibromatosis: A New Chapter? [Abstract in Rivista]
Diazzi, Chiara; Guidi, Alessandro; Luberto, Alessandra; Taliani, Erica; Madeo, Bruno; Rochira, Vincenzo; Carani, Cesare
abstract

The study explore the prevalence of thyroid diseases (mainly thyroid nodules) in patients with the neurofibromatosis.

2011 - Thyroid disease in patients with type-1 neurofibromatosis: an underestimated issue ? [Abstract in Rivista]
Diazzi, Chiara; Guidi, Alessandro; Luberto, Alessandra; Taliani, Erica; Madeo, Bruno; Rochira, Vincenzo; Carani, Cesare
abstract

The study deals with the incidence of medullary thyroid cancer in patients with type-1 neurofibromatosis

2011 - Thyroid disease in patients with type-1 neurofibromatosis: an underestimated issue? [Abstract in Rivista]
Diazzi, Chiara; Guidi, Alessandro; Luberto, Alessandra; Taliani, Erica; Madeo, Bruno; Rochira, Vincenzo; Carani, Cesare
abstract

The study investigates the prevalence of medullary thyroid cancer in Neurofibromatosis type 1

2011 - Ultrasound mirror artifact of a thyroid nodule by trachea mimicking a tracheal mass [Articolo su rivista]
Diazzi, Chiara; Gnarini, Valentina; Brigante, Giulia; Rochira, Vincenzo
abstract

The article show how a mirror artifact generated by a thyroid nodule could mimic a tracheal mass, thus leading if not recognized to unnecessary further clinical examinations.

2010 - Prevalence and characterization of hypogonadism among men with human immunodeficiency virus infection: preliminary results [Abstract in Rivista]
Rochira, Vincenzo; Santi, Daniele; Brigante, Giulia; Zirilli, Lucia; Diazzi, Chiara; Orlando, Gabriella; Carani, Cesare; Guaraldi, Giovanni
abstract

Preliminary results on the prevalence of male hypogonadism in HIV-infected men

2010 - Prevalence and characterization of hypogonadism among men with human immunodeficiency virus infection: preliminary results [Abstract in Rivista]
Brigante, Giulia; Santi, Daniele; Zirilli, Lucia; Diazzi, Chiara; G., Orlando; Simoni, Manuela; Guaraldi, Giovanni; Carani, Cesare; Rochira, Vincenzo
abstract

Preliminary data on the prevalence and type of male hypogonadism in men with HIV infection

2010 - Prevalence and characterization of hypogonadism among men with human immunodeficiency virus infection: preliminary results. [Abstract in Rivista]
Rochira, Vincenzo; Brigante, Giulia; Santi, Daniele; Zirilli, Lucia; Diazzi, Chiara; Orlando, Gabriella; Carani, Cesare; Guaraldi, Giovanni
abstract

According to the preliminary results of the study HIV-infected men present a higher prevalence of hypogonadism, at a younger age than general population

2010 - Role of Calcitonin (Ct) in wash-out fluid from fine-needle aspiration (FNAB) in the diagnosis of medullary thyroid cancer (MTC): comparison with basal calcitonin, citology and pentagastrin stimulation test (Pg-Test) [Abstract in Rivista]
Rochira, Vincenzo; Diazzi, Chiara; Zirilli, Lucia; Romano, Stefania; Carani, Cesare; Madeo, Bruno
abstract

The study provides evidence on the usefulness of measurement of calcitonin into the fine needle aspiration wash-out fluid of thyroid nodules for the diagnosis of medullary thyroid cancer.

2010 - Role of Calcitonin (Ct) in wash-out fluid from fine-needle aspiration (FNAB) in the diagnosis of medullary thyroid cancer (MTC): comparison with basal calcitonin, citology and pentagastrin stimulation test (Pg-Test) [Abstract in Rivista]
Rochira, Vincenzo; Diazzi, Chiara; Zirilli, Lucia; Romano, Stefania; Carani, Cesare; Madeo, Bruno
abstract

Preliminary results regarding the role of calcitonin measurement in the wash-out fluid of thyroid fine-needle aspiration samples for the diagnosis of medullary thyroid cancer

2010 - Sex steroids and HIV-related osteoporosis in men: low circulating estrogens are associated with impaired bone mineral density (BMD) [Abstract in Rivista]
Santi, Daniele; Brigante, Giulia; Orlando, Gabriella; Ciccarese, Michela; Diazzi, Chiara; Guaraldi, Giovanni; Carani, Cesare; Rochira, Vincenzo; Madeo, Bruno
abstract

Preliminary data on the effects of sex steroids on bone max in men with HIV

2009 - Deficit di GH in pazienti affetti da lipodistrofia HIV-correlata: dati preliminari sugli effetti del trattamento con r-hGH sulla composizione corporea [Abstract in Atti di Convegno]
Diazzi, Chiara; Brigante, Giulia; Orlando, Gabriella; Squillace, Nicola; Guaraldi, Giovanni; Carani, Cesare; Rochira, Vincenzo; Simoni, Manuela; Zirilli, Lucia
abstract

r-hGH treatment in HIV-infected patients with documented GH deficiency seems to improve fat distribution

2009 - Differentiated Thyroid Carcinoma (DTC) in a Young Woman with Peutz-Jeghers Syndrome: are these Two Conditions Associated? [Articolo su rivista]
Zirilli, Lucia; Benatti, Piero; Romano, Stefania; Roncucci, Luca; Rossi, Giuseppina; Diazzi, Chiara; Carani, Cesare; PONZ DE LEON, Maurizio; Rochira, Vincenzo
abstract

AIMS: Peutz-Jeghers Syndrome (PJS) is a rare dominantly inherited disease characterized by hamartomatous small bowel polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer. Differentiated thyroid cancers (DTCs) present mainly as sporadic, but they may have also a familial component. We present a case of PJS in a caucasian 25 years-old woman, who developed a DTC. METHODS: The patient had a palpable nodule in the right side of the thyroid region and an endocrinological evaluation, including hormonal assays, neck ultrasound (US) and fine needle aspiration (FNAB) of the nodule was performed. RESULTS: US confirmed a single nodular lesion in the right thyroid lobe (14 mm). Cytological analysis at FNAB revealed a pattern compatible with papillary thyroid carcinoma. The histological analysis after total thyroidectomy confirmed the diagnosis of a Hurtle cell variant of papillary thyroid carcinoma, with follicular architecture. CONCLUSION: Even though rare, the association between PJS and DTC can be possible. In clinical practice it must be borne in mind that the wide spectrum of possible cancer diseases occurring in PJS could also include DTC, that the latter can occur earlier in life in PJS population and with a more aggressive histological pattern. Furthermore, in patients with PJS, US of the thyroid should be performed whenever thyroid disease is suspected at physical examination or based on patient's medical history. Due to lack of established data allowing for a real esteem of the association between PJS and DTC, US of the thyroid, should not be recommended as a routine screening for all subjects with PJS.

2009 - GH deficiency in HIV-infected patients with lipodystrophy: preliminary data on the effects of r-hGH treatment on body composition [Abstract in Rivista]
Zirilli, Lucia; Orlando, Gabriella; Brigante, Giulia; Squillace, Nicola; Diazzi, Chiara; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Evaluation of GH deficiency in HIV-infected patients with lipodystrophy,with particular concern to preliminary data on the effects of r-hGH treatment on body composition

2009 - Sex steroids and HIV-related osteoporosis in men: low circulating estrogens are associated with impaired bone mineral density [Abstract in Atti di Convegno]
Rochira, Vincenzo; Orlando, Gabriella; Ciccarese, Michela; Squillace, Nicola; Diazzi, Chiara; Guaraldi, Giovanni; Carani, Cesare; Zirilli, Lucia
abstract

Low circulating estrogens, but not testosterone are associated with impaired bone mineral density in HIV-related osteoporosis in men, especially when serum estradiol falls below a threshold of about 15-20 pg/mL

2009 - Testosterone action on erythropoiesis does not require its aromatization to estrogen: insights from the testosterone and estrogen treatment of two aromatase-deficient men [Abstract in Atti di Convegno]
Rochira, Vincenzo; Zirilli, Lucia; Madeo, Bruno; Laura, Maffei; Diazzi, Chiara; Carani, Cesare
abstract

The study of testosterone and estrogen action on erythropoiesis of two aromatase-deficient men provides evidence that testosterone directly increases red cells count and that this action does not require testosterone aromatization into estradiol.

2008 - Association of serum vitamin D levels nd type 2 diabetes in HIV infection in the Modena cohort [Abstract in Rivista]
Zsofia, Szep; Guaraldi, Giovanni; Samir S., Shah; Orlando, Gabriella; Squillace, Nicola; Rochira, Vincenzo; Madeo, Bruno; Diazzi, Chiara; Baraldi, Enrica; Carani, Cesare; Esposito, Roberto; Pablo, Tebas
abstract

Metabolic complications, including type 2 diabetes mellitus and metabolic syndrome, are increasingly recognized among HIV-infected individuals. Low vitamin D levels increase the risk of type 2 diabetes mellitus. Our study demonstrates an association between vitamin D deficiency and type 2 diabetes mellitus.

2008 - GH response to GH-releasing hormone-arginine (GHRH+Arg) is impaired in women affected by human immunodeficiency virus (HIV)-related lipodystrophy [Abstract in Rivista]
Zirilli, Lucia; Orlando, Gabriella; Scaltriti, Sara; Squillace, Nicola; Diazzi, Chiara; Esposito, Roberto; Carani, Cesare; Guaraldi, Giovanni
abstract

This study suggests that relative GH deficiency is common among females with HIV-related lipodystrophy if compared with matched controls.

2008 - Higher prevalence of nodular goiter and thyroid carcinoma in patients with familial adenomatous poliposis (FAP) [Abstract in Atti di Convegno]
Zirilli, Lucia; Romano, Stefania; Roncucci, Luca; Benatti, Piero; Madeo, Bruno; Diazzi, Chiara; Scaltriti, Sara; Carani, Cesare; PONZ DE LEON, Maurizio; Rochira, Vincenzo
abstract

The evaluation of 46 patients with familial adenomatous poliposis showed that nodular goiter is very common, and the prevalence of thyroid cancer is higher than that of a control group.

2008 - Human models of aromatase deficiency. [Articolo su rivista]
Zirilli, Lucia; Rochira, Vincenzo; Diazzi, Chiara; Caffagni, Giovanni; Carani, Cesare
abstract

Estrogens exert a wide range of biological effects in both sexes also on non-reproductive systems andorgans. Human congenital estrogen deficiency, due to an inactivating mutation of the aromatase gene,leads to the lack of the estrogen synthesis, with gonadotropins and circulating testosterone ranging fromnormal to elevated. The aromatese-deficient females show hyperandrogenism and virilization at birthwith ambiguous genitalia. During childhood there are a dysfunction in the LHRH-LH/FSH axis and a progressivedelay in bone age. At puberty they showprimary amenorrhea, no breast development,worseningof the virilization and the absence of growth spurt. The clinical phenotype in the male affected subjectscomprises tall stature, persistent linear growth and delayed bone age, osteopenia/osteoporosis, eunuchoidbody proportion, different degrees of glucose–insulin and of fertility impairment. These phenotypes suggestthe physiological role of estrogens on the skeleton, on pituitary function, on the reproductive system,on glucose metabolism, being the precise mechanism on each of these functions not yet known in detail.The estradiol replacement treatment leads to a complete epiphyseal closure and to the skeletal maturation.Moreover, the increasing knowledge on the role of estrogen in several metabolic pathways could beimportant for a better management of several metabolic diseases.

2008 - Hypopituitarism and HIV-infection: a new comorbidity in the HAART era? [Articolo su rivista]
Zirilli, Lucia; Orlando, Gabriella; Diazzi, Chiara; Squillace, Nicola; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Several comorbidities are associatedwith the HIV infection and may involvealso the endocrine-metabolic system. Consistently,the recent development of the therapeuticregimen highly active antiretroviraltherapy (HAART) ruled out a significant improvementboth in the prognosis and life expectancyof HIV-infected patients, but disclosedalso new serious drug-related toxicity.Of these, the lipodystrophy syndrome isthe most frequent, occurring in up to 83% ofHIV-infected patients under HAART. The HIVrelatedlipodystrophy is associated with alterationsin GH dynamics, affecting bothbasal and stimulated GH secretion. This GHIGF-I secretive pattern resembles that of severeGH deficiency in adulthood due to pituitarydiseases, but without leading to IGF-Iserum levels below the normal range. The impairmentof pituitary GH secretion has beenascribed to the hormonal and metabolic inhibitoryeffect due to adipose tissue redistributionin HIV-infected males, since in thesepatients pituitary GH secretion appeared tobe inversely related to visceral adipose tissueaccumulation and waist to-hip-ratio. However,whether these patients suffer from a true GHdeficiency due to an intrinsic pituitary failureor display only a functional reduction of GHsecretion due to visceral adiposity remainsstill a matter of debate, especially in HIV-infectedfemales.

2007 - Estrogènes chez l’homme: le modèle du déficit en aromatase. [Abstract in Atti di Convegno]
Carani, Cesare; Diazzi, Chiara; Luberto, Alessandra; Rochira, Vincenzo
abstract

Estrogen role on adult male studied on the basis of human model of congenital estrogen deficiency: aromatase deficiency and estrogen resistance

2007 - Impairment of GH Secretion in Women Affected by HIV-Related Adipose Tissue Redistribution Syndrome (HARS) [Abstract in Atti di Convegno]
Zirilli, Lucia; Orlando, Gabriella; Caffagni, Giovanni; Squillace, Nicola; Diazzi, Chiara; Madeo, Bruno; Guaraldi, Giovanni; Carani, Cesare
abstract

This study suggests that relative GH deficiency is common among females with HIV-related lipodystrophy if compared with matched controls

2007 - Impairment of GH response to GHRH+Arginine in women affected by HIV-related adipose tissue redistribution syndrome (HARS) [Abstract in Rivista]
Rochira, Vincenzo; Zirilli, Lucia; Orlando, Gabriella; Caffagni, Giovanni; Squillace, Nicola; Diazzi, Chiara; Madeo, Bruno; Guaraldi, Giovanni; Carani, Cesare
abstract

This study suggests that relative GH deficiency is common among females with HIV-related lipodystrophy if compared with matched controls.

2007 - Le metastasi polmonari da tumori della tiroide: diagnosi e terapia. [Capitolo/Saggio]
Diazzi, Chiara; Zirilli, Lucia; Madeo, Bruno; Sanguanini, Alessia; Carani, Cesare; Rochira, Vincenzo
abstract

The chapter deals with the lung metastases due to thyroid cancer and particularly it regards the diagnostic and therapeutic aspects.

2007 - The osteoporotic male: overlooked and undermanaged? [Articolo su rivista]
Madeo, Bruno; Zirilli, Lucia; Caffagni, Giovanni; Diazzi, Chiara; Sanguanini, Alessia; Pignatti, Elisa; Carani, Cesare; Rochira, Vincenzo
abstract

Age-related bone loss in men is a poorly understood phenomenon, although increasing data on the pathophysiology of bone in men is becoming available. Most of what we know on bone pathophysiology derives from studies on women. The well-known association between menopause and osteoporosis is far from been disproven. However, male osteoporosis is a relatively new phenomenon. Its novelty is in part compensated for by the number of studies on female osteoporosis and bone pathophysiology. On the other hand, the deeper understanding of female osteoporosis could lead to an underestimation of this condition in the male counterpart. The longer life-span exposes a number of men to the risk of mild-to-severe hypogonadism which in turn we know to be one of the pathogenetic steps toward the loss of bone mineral content in men and in women. Hypogonadism might therefore be one among many corrigible risk factors such as cigarette smoking and alcohol abuse against which clinicians should act in order to prevent osteoporosis and its complications. Treatments with calcium plus vitamin D and bisphophonates are widely used in men, when osteoporosis is documented and hypogonadism has been excluded. The poor knowledge on male osteoporosis accounts for the lack of well shared protocols for the clinical management of the disease. This review focuses on the clinical approach and treatment strategy for osteoporosis in men with particular attention to its relationship with male hypogonadism.

2006 - Analisi di una serie di esami citologici da agoaspirato tiroideo ecoguidato eseguiti in bambini, adolescenti ed adulti in un’area geografica della Bielorussia contaminata dall’incidente di Chernobyl [Abstract in Atti di Convegno]
Madeo, Bruno; Andrei, Alekseev; Natalia, Antanovich; Zirilli, Lucia; Vaccari, Vittoria; Diazzi, Chiara; Scaltriti, Sara; Luberto, Alessandra; Rochira, Vincenzo; Carani, Cesare; Massimo Tosti, Balducci
abstract

Analysis of 285 FNAB of thyroid nodules in a population living in a rural area exposed to radiation after Chernobyl radiation accident.

2006 - Carcinoma papillare e Sindrome di Peutz-Jeghers: una rara associazione [Abstract in Atti di Convegno]
Rochira, Vincenzo; Romano, Stefania; Zirilli, Lucia; Madeo, Bruno; Caffagni, Giovanni; Diazzi, Chiara; Valeria, Pugni; Pignatti, Elisa; Roncucci, Luca; PONZ DE LEON, Maurizio; Carani, Cesare; Benatti, Piero
abstract

Case report of a patient with Peutz-Jeghers syndrome and concomitant papillary thyroid cancer that indicates that thyroid cancer might be more frequent in patients with Peutz-Jeghers

2006 - Hpothalamic Pituitary Gonadal Axis (HPG-A) in two men with aromatase deficiency: evidence of estrogen need for the integrity of negative feedback at hypothalamic level [Abstract in Atti di Convegno]
Zirilli, Lucia; Laura, Maffei; Antonio, Balestrieri; Claudio, Aranda; Bibiana, Fabre; Paula, Antunez; Diazzi, Chiara; Antonio R. M., Granata; Carani, Cesare; Rochira, Vincenzo
abstract

Estrogen administration to aromatase deficient men discloses a feedback modulation both at pituitary and hypothalamic level which was greater than that exerted by testosterone

2006 - Hypothalamic pituitary gonadal axis (HPG-A) in two men with aromatase deficiency: evidence of estrogen need for the integrity of negative feedback at hypothalamic level [Abstract in Atti di Convegno]
Carani, Cesare; Zirilli, Lucia; Laura, Maffei; Antonio, Balestrieri; Claudio, Aranda; Bibiana, Fabre; Paula, Antunez; Diazzi, Chiara; Antonio R. M., Granata; Rochira, Vincenzo
abstract

Estrogen administration to aromatase deficient men discloses a feedback modulation both at pituitary and hypothalamic level

2006 - Hypothalamic pituitary gonadal axis in two men with aromatase deficiency: evidence of estrogen need for the integrity of negative feedback at hypothalamic level [Abstract in Rivista]
Zirilli, Lucia; Laura, Maffei; Balestrieri, Antonio; Claudio, Aranda; Viviana, Fabre; Paula, Antunez; Diazzi, Chiara; Antonio R. M., Granata; Rochira, Vincenzo; Carani, Cesare
abstract

Estrogen administration to aromatase deficient men discloses a feedback modulation both at pituitary and hypothalamic level suggesting that estradion but not testosterone is the main sex steroid involved in the control of gonadotropins secretion

2006 - Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback [Articolo su rivista]
Rochira, Vincenzo; Zirilli, Lucia; Genazzani, Alessandro; A., Balestrieri; Claudio, Aranda; Bibiana, Fabre; Paula, Antunez; Diazzi, Chiara; Carani, Cesare; Laura, Maffei
abstract

Background: In men, the feedback of gonadotropins is regulated by estrogens that come from the aromatization of testosterone, but the relative contribution to the inhibition of LH and FSH secretion by the amount of locally produced estrogens within the hypothalamus and/or the pituitary, and the amount of circulating estrogens still remains unknown. Objective: In order to evaluate the effect of regulation induced by estradiol on the hypothalamic-pituitary-gonadal (HPG) axis, we studied the pulsatility of LH and FSH in two aromatase-deficient men (called subject 1 and subject 2), in which the production rate of estrogen (both local and circulating) is completely, or at least severely, impaired. Design: FSH and LH were evaluated in terms of their pulsated secretion and as GnRH-stimulated secretion in two phases: phase 1, before estrogen treatment; and phase 2, during estrogen treatment with 25 mu g transdermal estradiol twice weekly. Methods: Blood samples were taken during phase I and phase 2 at 0800 h for basal measurements of LH, FSH, inhibin B, testosterone, and estradiol. The analysis of the pulsatility of LH and FSH was performed by sampling every 10 min for 8 h in the two phases. Gonadotropin response to GnRH-stimulation test was studied by serial standard sampling after 100 mu g GnRH i.v. bolus in phases 1 and 2. Results: Estrogen treatment led to a significant reduction in both LH-pulsated frequency (7.5 +/- 0.7 in phase 1, 4.5 +/- 0.7 in phase 2) and amplitudes (3.5 +/- 0.006 in phase 1, 1.9 +/- 0.4 in phase 2) of peaks, whereas FSH showed only a conspicuous reduction in serum levels and a trend towards the reduction of the amplitudes of its peaks without modification of the frequency of the pulses. Both testosterone and gonadotropins decreased during phase 2, whereas estradiol reached the normal range in both subjects. Transdermal estradiol treatment significantly lowered the peaks of both serum LH and FSH after GnRH as well as the incremental area under the curve after GnRH administration in both subjects. Basal serum inhibin B levels were slightly higher before transdermal estradiol treatment (phase 1) than during estrogen treatment (phase 2) in both subjects. Conclusions: The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of the frequency of LH pulses. The present study, coupling the outcomes of basal, GnRH-stimulated and the pulsatile evaluation of LH and FSH secretion in two aromatase-deficient men, demonstrates that circulating estrogens play an inhibitory role in LH secretion by acting on the hypothalamus and the pituitary gland of men. The discrepancy among testosterone levels, the arrest of spermatogenesis and a slightly inappropriate respective increase of serum FSH (lower than expected) suggests a possible role of estrogens in the priming and the maturation of HPG axis in men, an event that has never occurred in these two subjects as a consequence of chronic estrogen deprivation.

2006 - Impaired GH secretion in women with HIV-related lipodystrophy [Abstract in Rivista]
Rochira, Vincenzo; Zirilli, Lucia; Diazzi, Chiara; Caffagni, Giovanni; Antonio, Balestrieri; Antonio R. M., Granata; Maria C., De Santis; Orlando, Gabriella; Squillace, Nicola; Guaraldi, Giovanni; Carani, Cesare
abstract

Women with HIV-related lipodystrophy show impaired GH after GHRH+Arginine

2006 - Impaired growth hormone secretion in women with HIV-related lipodystrophy [Abstract in Rivista]
Guaraldi, Giovanni; Orlando, Gabriella; Squillace, Nicola; Rochira, Vincenzo; Zirilli, Lucia; Diazzi, Chiara; Caffagni, Giovanni; Antonio, Balestrieri; Antonio R. M., Granata; Maria C., De Santis; Carani, Cesare
abstract

Women with HIV-related lipodystrophy show impaired GH secretion at the stimulation test with GHRH+Arginine

2006 - Prevalence of secondary causes of osteoporosis among HIV infected individuals [Abstract in Rivista]
Guaraldi, Giovanni; Orlando, Gabriella; Squillace, Nicola; Rochira, Vincenzo; Madeo, Bruno; Zirilli, Lucia; Diazzi, Chiara; Caffagni, Giovanni; Baraldi, Enrica; Carani, Cesare; Esposito, Roberto; Pablo, Tebas
abstract

Although osteopenia/osteoporosis is very frequent among HIV infected individuals. Vitamin D deficiency is frequent in this Italian population and might be a contrib- utor to this problem.

2006 - Ruolo degli estrogeni sull’asse ipotalamo-ipofisi-gonadi in due uomini affetti da deficit di aromatasi: gli estrogeni sono indispensabili per l’integrità del feedback negativo a livello ipotalamico [Abstract in Atti di Convegno]
Rochira, Vincenzo; Antonio, Balestrieri; Madeo, Bruno; Zirilli, Lucia; Diazzi, Chiara; Paula, Antunez; Laura, Maffei; Carani, Cesare
abstract

Estrogen administration to aromatase deficient men discloses a feedback modulation both at pituitary and hypothalamic level demonstrating that estrogens but not testosterone are the main modulator of gonadotropins in men

2006 - Skeletal effects of estrogen and testosterone in a man with aromatase deficiency: priming effect of estrogen for sex steroids action on bone strength [Abstract in Rivista]
Zirilli, Lucia; Rochira, Vincenzo; Madeo, Bruno; Pignatti, Elisa; Luberto, Alessandra; Caffagni, Giovanni; Diazzi, Chiara; Sanguanini, Alessia; Emile, Roldan; Laura E., Maffei; Carani, Cesare
abstract

The combined treatment with estradiol and testosteron led to optimal parameters of BMD suggesting that testosterone needs estrogens as a permissive factor for a direct androgen anabolic action on bone in men

2005 - Clinical phenotype of male estrogen deficiency [Abstract in Atti di Convegno]
Carani, Cesare; Rochira, Vincenzo; Caffagni, Giovanni; Diazzi, Chiara; Laura, Maffei
abstract

Description of the clinical phenotype of men with congenital estrogen deficiency caused by complete defect of estrogen receptor alpha or aromatase deficiency

2005 - Pituitary function in two adult men with congenital aromatase deficiency: evidences of impaired pituitary reserve which is not restored by different doses of transdermal estradiol (TE2) treatment [Abstract in Atti di Convegno]
Rochira, Vincenzo; Antonio, Balestrieri; Madeo, Bruno; Antonio R. M., Granata; Zirilli, Lucia; Diazzi, Chiara; Claudio, Aranda; Paula, Antunez; Laura E., Maffei; Carani, Cesare
abstract

Estrogen modulate pituitary function, particularly GH and prolactin secretion in men, Aromatase deficiency constitutes a model to study the effect of the lack of estrogen on pituitary function.

2005 - Pituitary function in two adult men with congenital aromatase deficiency: evidences of impaired pituitary reserve which is not restored by different doses of transdermal estradiol (TE2) treatment [Abstract in Rivista]
Rochira, Vincenzo; Antonio, Balestrieri; Madeo, Bruno; Antonio R. M., Granata; Zirilli, Lucia; Diazzi, Chiara; Laura, Maffei; Carani, Cesare
abstract

Estrogen modulates pituitary function, particularly GH and prolactin secretion in men, Aromatase deficiency constitutes a model to study the effect of the lack of estrogen on pituitary function. Men with aromatase deficiency have GH deficiency despite their increased height.

2005 - Sex steroids and sexual desire in a man with a novel mutation of aromatase gene and hypogonadism [Abstract in Atti di Convegno]
Laura E., Maffei; Antonio R. M., Granata; Diazzi, Chiara; Zirilli, Lucia; Claudio, Aranda; Paula B., Antunez; Madeo, Bruno; Rochira, Vincenzo; Carani, Cesare
abstract

Sexual behavior was investigated by a sexological interview in a man with aromatase deficiency and hypogonadism, suggesting that in men estrogens could play a role in sexual activity while are not necessary for the development of sexual identity and orientation.

2005 - Testosterone and sildenafil in hypogonadal men: evidence for a synergical effect [Abstract in Rivista]
Rochira, Vincenzo; Madeo, Bruno; Zirilli, Lucia; Diazzi, Chiara; Antonio R. M., Granata; Antonio, Balestrieri; Carani, Cesare
abstract

Randomized placebo-controlled, crossover study demonstrating a synergic effect of sildenafil and testosterone on sleep-related erections in hypogonadal men

2005 - Testosterone and sildenafil in hypogonadal men: evidence for a synergical effect [Abstract in Atti di Convegno]
Rochira, Vincenzo; Madeo, Bruno; Zirilli, Lucia; Diazzi, Chiara; Antonio R. M., Granata; Antonio, Balestrieri; Carani, Cesare
abstract

Randomized placebo-controlled, crossover study demonstrating a synergic effect of sildenafil and testosterone on sleep-related erections in hypogonadal men

2005 - Testosterone and sildenafil in hypogonadal men: evidence for a synergistic effect [Abstract in Atti di Convegno]
Rochira, Vincenzo; Madeo, Bruno; Zirilli, Lucia; Diazzi, Chiara; Antonio R. M., Granata; Antonio, Balestrieri; Carani, Cesare
abstract

Randomized placebo-controlled, crossover study evaluating a synergic effect of sildenafil and testosterone on sleep-related erections in hypogonadal men

2004 - Ruolo degli estrogeni nell’uomo e degli androgeni nella donna [Relazione in Atti di Convegno]
Diazzi, Chiara; Caffagni, Giovanni; Zirilli, Lucia; Rochira, Vincenzo; Carani, Cesare
abstract

Both estrogen and androgens are crucial in males and females respectively for bone mineralization and maintenance of bone mass