Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications

Purpose: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." Methods: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. Results: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p =.698), but different in male/female ratio (81/173 vs 226/696, p =.019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p <.001). Conclusions: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure

Osteoporosis in men with hypogonadism because of ApoA-I Leu75Pro amyloidosis under long-term testosterone therapy

Background: Apo A-I Leu75Pro amyloidosis is a rare systemic hereditary disease, whose hallmark and earliest involvement is testicular impairment, characterized by hypogonadism and macrorchidism; renal and hepatic involvement are the other characteristics. Objective: To evaluate for the first time the prevalence of osteopenia, osteoporosis and vertebral fractures (VFs) in men with this form of amyloidosis affected by hypogonadism and under long-term testosterone replacement therapy (TRT). Materials and methods: Retrospective study on 50 men >50 years (median age 64.5) with dual-energy X-ray absorptiometry (DXA), hormonal, and biochemical data available at least 3 years after the start of TRT. Serum gonadal hormones and bone markers, lumbar and femoral DXA-scan with morphometric assay for evaluation of VFs were assessed. Results: At 7.5 years from start of TRT, lumbar and/or femoral osteopenia and osteoporosis were found in 54% and 10% of patients, respectively. Of the men who had the morphometric assay performed, five of 34 (14.7%) had VFs. Compared to patients with normal bone mineral density, men with osteopenia and osteoporosis were older, had lower body mass index, higher sex hormone binding globulin and showed more frequently renal involvement. Multiorgan involvement, without different TRT dosage, was associated with lower testosterone levels. Discussion and conclusion: Men with hypogonadism because of Apo A-I Leu75Pro amyloidosis under long-term TRT had a high burden of low bone mass (64%) and VFs (almost 15%). Osteopenia-osteoporosis was more frequently observed in older patients with multi-organ disease, which might contribute to impair bone health beyond hypogonadism

Klinefelter syndrome: The altered bone

Low bone mass is present in up to 50% of subjects with Klinefelter syndrome (KS) and has usually been attributed to low testosterone levels. Indeed, hypogonadism represents one of the most important causes of male osteoporosis and testosterone is known to regulate male bone metabolism both indirectly by aromatization to oestrogens and directly through the androgen receptor (AR). Early onset of testosterone deficiency, as observed in KS, is an important risk factor for precocious osteoporosis. However, reduced bone mass might be present also in KS men with normal testosterone levels and testosterone replacement therapy does not always restore bone density in KS patients. Possible other determinants for osteoporosis in KS might be related to low insulin-like factor 3 (INSL3), 25-hydroxyvitamin D, oestrogen levels, unfavourable fat/muscle ratio, CAG length and inactivation pattern of the AR and high FSH, with different levels of evidence. Although the exact fracture rates in KS are unknown, some epidemiologic studies have shown a correlation between fractures and increased morbidity and mortality in KS. Therefore, it is essential to assess bone density and bone fracture risk in KS patients from a young age, keeping in mind that KS men are at risk of low bone mineral density and fractures regardless of testosterone levels

Usefulness of routine assessment of free testosterone for the diagnosis of functional male hypogonadism

Objective: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional hypogonadism. Methods: Total and free testosterone (calculated on SHBG levels) were determined in 188 patients with sexual symptoms and 184 with infertility. Results: Hypogonadism (calculated free testosterone <63 pg/ml) was found in 47/188 (25.0%) patients with sexual symptoms and in 21/184 (11.4%) with infertility. Total testosterone determination misdiagnosed hypogonadism in 8.4% (12/143) of men with sexual symptoms and in 2% (3/152) with infertility. In subjects with borderline total testosterone, only 24.7% (19/77) had hypogonadism confirmed by free testosterone levels. Free testosterone levels significantly correlated with age, haematocrit, gonadotropins, gynecomastia, BMI, and number of co-morbidities, whereas total testosterone associated only with the latter two. Furthermore, age, haematocrit, BMI, and the presence of erectile dysfunction and of low libido were significantly different between men with normal and low free testosterone, whereas only BMI and low libido were significantly different between patients with normal and low total testosterone. Conclusion: Routine assessment of free testosterone allows a more accurate diagnosis of functional hypogonadism, especially in men with sexual symptoms. Free testosterone levels associate with clinical and biochemical parameters of androgen deficiency better than total testosterone levels

Thyroid scintigraphy in the era of fine-needle aspiration cytology

none8Purpose: To evaluate whether thyroid scintigraphy would alter the clinical management of patients referred for fine-needle aspiration cytology (FNA). Methods: We reviewed the medical and imaging records of patients referred to our Department between 2016 and 2019. All the patients had to take a serum thyrotropin test administered in our hospital at least two months before the FNA; where the TSH level was ≤1.5 mIU/L, the patients were subjected to a scan and subsequently to FNA, where indicated. We selected only healthy patients with no previous history of thyroid disease, who were not taking any drugs and who had a TSH level of ≤1.5 mIU/L. We excluded patients with multinodular goitre. Results: A total of 176 patients were analysed. A total of 67/176 patients (38%) showed a serum of TSH ≤ 0.27 mIU/L. Scintigraphy identified a hot nodule in 142 lesions (80.7%), a warm nodule in 8 lesions (4.5%) and a cold nodule in 26 lesions (14.8%). The ROC curve analysis indicated that a TSH value of ≤0.42 mIU/L identified patients with hyperfunctioning nodules with a sensitivity of 65% and a specificity of 77%. All patients with cold and warm nodules were submitted to FNA: 22/26 (85%) and 5/8 (63%) lesions showed suspected malignancy or were compatible with malignancy, respectively. Conclusion: Speculating on our data, if we had subjected our patients to FNA as indicated by the 2015 ATA guidelines, we would have subjected 117 patients to cytology, from whom 83 had undetected hot nodules. Conversely, by adopting scintigraphy for all patients with TSH ≤ 1.5 mIU/L, 109 patients have avoided FNA. However, our study was performed in a region with a history of mild iodine deficiency. Therefore, we cannot claim that our observation is valid for patients born and living in areas with sufficient iodine uptake. We recommend thyroid scintigraphy for treating single thyroid nodules in euthyroid patients born and living in regions with an iodine deficiency, when TSH levels are below 1.5 mIU/L before FNA.nonePirola I.; Di Lodovico E.; Casella C.; Pezzaioli L.; Facondo P.; Ferlin A.; Lombardi D.; Cappelli C.Pirola, I.; Di Lodovico, E.; Casella, C.; Pezzaioli, L.; Facondo, P.; Ferlin, A.; Lombardi, D.; Cappelli, C

The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis

Background: Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. Objectives: To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. Materials and methods: A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. Results: The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. Discussion: DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. Conclusion: Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study

ObjectiveHypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis. Research design and methodsConsecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy. ResultsA total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT. ConclusionTestosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life

Hypogonadism and liver fibrosis in HIV-infected patients

none10Purpose: Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods: We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results: Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion: Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.noneQuiros-Roldan E.; Porcelli T.; Pezzaioli L. C.; Degli Antoni M.; Paghera S.; Properzi M.; Foca E.; Carriero C.; Castelli F.; Ferlin A.Quiros-Roldan, E.; Porcelli, T.; Pezzaioli, L. C.; Degli Antoni, M.; Paghera, S.; Properzi, M.; Foca, E.; Carriero, C.; Castelli, F.; Ferlin, A

Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men

Purpose: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function. Methods: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score 64 \u2013 2.5SD and T-score between \u2013 1 and \u2013 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH)\ua0and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels. Results: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs. Conclusion: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD

Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome

Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS