Paolo Facondo

Background: Erectile dysfunction (ED) is a multidimensional condition commonly affecting men living with HIV. The structured interview of erectile dysfunction (SIEDY) is the only validated tool assessing organic, relational, and psychological factors contributing to ED, while dynamic penile color Doppler ultrasound (dPCDU) is a reliable method for evaluating vascular causes of ED. Objectives: This monocentric cross‐sectional study aims to assess the reliability of the SIEDY questionnaire in determining the underlying causes of ED in young men living with HIV. Materials and Methods: Young men (<50 years) living with HIV, on antiretroviral therapy for at least the last 12 months, and reporting symptoms of ED were enrolled. The degree of sexual dysfunction was assessed with the International Index of Erectile Function‐5 (IIEF‐5), while SIEDY was used to explore the pathogenetic components of ED. dPCDU was performed to assess vascular damage in the penile district. Univariate binomial logistic regression models were used to evaluate the association between ultrasound parameters and SIEDY results. Results: A total of 50 young men living with HIV were enrolled, of whom 40 (80%) had at least one altered SIEDY scale, most frequently Scale 3 (70%). Forty‐five (90%) participants presented with at least one abnormal ultrasound parameter, with intima‐media thickness being the most common (76%). No correlation was found between ultrasound parameters and the SIEDY Scale 1, while logistic regression identified IMT as the only variable significantly associated with SIEDY Scales 2 (relational) and 3 (psychological). Discussion and Conclusions: SIEDY may have limited reliability in detecting vascular causes of ED in this population, particularly underestimating organic causes. The lack of correlation with objective vascular findings highlights the importance of including tools like dPCDU for vascular assessment in routine clinical evaluations of the ED.

Background: Erectile dysfunction in people living with HIV is a multifactorial disease, but the role of penile vascular status assessed by dynamic penile color Doppler echography is underexplored. Objectives: This study assessed penile vascular status in young males living with HIV experiencing erectile dysfunction, comparing them to HIV‐negative controls stratified into young (12 months and HIV‐negative individuals presenting with erectile dysfunction. We used dynamic penile color Doppler echography to evaluate penile vascular parameters such as peak systolic velocity, intima‐media thickness, and end‐diastolic velocity. Statistical analyses, including k ‐means clustering and stepwise multivariate logistic regression, assessed associations between clinical variables and vascular parameters. Results: Of 310 young males living with HIV screened, 50 (16.1%) reported erectile dysfunction and were enrolled, with 97 HIV‐negative individuals included as controls. Pathological intima‐media thickness was significantly higher ( p = 0.004) in young males living with HIV (76%) than in young controls (49%) but comparable to middle‐aged controls (76.1%). Stepwise multivariate logistic regression identified belonging to the young control group, compared to young males living with HIV, as a protective factor against pathological intima‐media thickness (OR 0.353, 95% CI 0.138–0.902, p = 0.0295), while increasing age was a significant risk factor (OR 1.09, 95% CI 1.01–1.18, p = 0.0247). Relative inhomogeneity of clusters was tested demonstrating that membership in either the people living with HIV or HIV‐negative group was a significant predictor of cluster assignment based on dynamic penile color Doppler echography parameters, independent of age ( p = 0.0025). Discussion and conclusions: This study is the first to utilize dynamic penile color Doppler echography to evaluate erectile dysfunction in young males living with HIV, highlighting the association between HIV and early vascular alterations. Clinicians should incorporate routine sexual health evaluations into routinary out‐patients visits, using erectile dysfunction as a potential indicator for further vascular screening and early intervention.

Background: The potential impact of diabetes mellitus type 1 (DM1) on male fertility is currently poorly defined. Hyperglycaemia and insulin deficiency may affect spermatogenesis. Some evidence suggests that men with DM1 have a significant reduction in progressive sperm motility, sperm morphology and semen volume, without significant changes in sperm concentration and count, but definite data are lacking.Objectives: To evaluate the impact of DM1 on clinical parameters related to male fertility and semen analysis.Materials and methods: We compared a court of 42 male DM1 patients with 43 nondiabetic subjects overlapping in age and remaining clinical data in an observational case‐control study. All subjects underwent a comprehensive andrological reproductive evaluation, including medical history, physical examination, and semen analysis. We collected biochemical data in all patients with DM1, while diabetic patients with any alteration in semen parameters underwent sperm culture and scrotal ultrasound. In addition, all men completed the IIEF‐5 questionnaire (International Index of Erectile Function‐5) and the AMS (Aging Male Symptom score) questionnaire.Results: Patients with DM1 had a higher prevalence of infertility, erectile dysfunction and worse semen parameters compared with controls. In particular, semen volume, total sperm count, and total and progressive sperm motility were significantly lower (p < 0.001, p = 0.003, p = 0.048, and p = 0.022 respectively). In addition, the rate of semen anti‐sperm antibody positivity, the AMS score and FSH levels were higher.Discussion and conclusion: Several mechanisms may contribute to these semen alterations in DM1 patients, such as oxidative damage to spermatogenesis, seminal infections and pelvic neurological changes. These data suggest that patients with DM1 should be counselled from an andrological‐reproductive point of view.

SUMMARY Treating hypothyroidism can be challenging in patients with malabsorption, as they require a higher daily dose of oral levothyroxine (L-T4). Oral L-T4 absorption occurs mainly in the jejunum and the ileum and is affected by gastric acidity. As a result, absorption can be impaired by bariatric surgery. This paper presents a case of myxedema in a young man who had previously undergone biliopancreatic diversion. He was referred to the Emergency Department with deteriorated mental state, hypotension, bradycardia and hypothermia. [...] SUMMARY Treating hypothyroidism can be challenging in patients with malabsorption, as they require a higher daily dose of oral levothyroxine (L-T4). Oral L-T4 absorption occurs mainly in the jejunum and the ileum and is affected by gastric acidity. As a result, absorption can be impaired by bariatric surgery. This paper presents a case of myxedema in a young man who had previously undergone biliopancreatic diversion. He was referred to the Emergency Department with deteriorated mental state, hypotension, bradycardia and hypothermia.

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.

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.

Male hypogonadism is defined as low circulating testosterone level associated with signs and symptoms of testosterone deficiency. Although the bidirectional link between hypogonadism and cardiovascular disease has been clarified, the association between testosterone and chronic heart failure (HF) is more controversial. Herein, we critically review published studies relating to testosterone, hypogonadism, and HF and provide practical clinical information on proper diagnosis and treatment of male hypogonadism in patients with HF. In general, published studies are extremely heterogeneous, frequently have not adhered to hypogonadism guidelines, and suffer from many intrinsic methodological inaccuracies; therefore, data provide only low-quality evidence. Nevertheless, by selecting the few methodologically robust studies, we show the prevalence of testosterone deficiency (30%–50%) and symptomatic hypogonadism (15%) in men with HF is significant. Low testosterone correlates with HF severity, New York Heart Association class, exercise functional capacity, and a worse clinical prognosis and mortality. Interventional studies on testosterone treatment in men with HF are inconclusive but do suggest beneficial effects on exercise capacity, New York Heart Association class, metabolic health, and cardiac prognosis. We suggest that clinicians should measure testosterone levels in men with HF who have symptoms of a testosterone deficiency and conditions that predispose to hypogonadism, such as obesity and diabetes. These patients—if diagnosed as hypogonadal—may benefit from the short- and long-term effects of testosterone replacement therapy, which include improvements in both cardiac prognosis and systemic outcomes. Further collaborative studies involving both cardiologists and endocrinologists are warranted.

Purpose: 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.

This article reviews the role of INSL3 as biomarker of Leydig cell function and its systemic action in testis-bone-skeletal muscle crosstalk in adult men. Insulin-like factor 3 (INSL3) is a peptide hormone secreted constitutively in a differentiation-dependent mode by testicular Leydig cells. Besides the role for the testicular descent, this hormone has endocrine anabolic functions on the bone-skeletal muscle unit. INSL3 levels are low in many conditions of undifferentiated or altered Leydig cell status, however the potential clinical utility of INSL3 measurement is not yet well defined. INSL3 levels are modulated by the long-term cytotropic effect of the hypothalamicpituitary- gonadal axis, unlike testosterone that is acutely sensitive to the stimulus by luteinizing hormone (LH). INSL3 directly depends on the number and differentiation state of Leydig cells and therefore it represents the ideal marker of Leydig cell function. This hormone is more sensitive than testosterone to Leydig cell impairment, and the reduction of INSL3 in adult men can precociously detect an endocrine testicular dysfunction. Low INSL3 levels could cause or contribute to some symptoms and signs of male hypogonadism, above all sarcopenia and osteoporosis. The measurement provided suggested that the measurement of INSL3 levels should be considered in the clinical management of male hypogonadism and in the evaluation of testicular endocrine function. The monitoring of INSL3 levels could allow an early detection of Leydig cell damage, even when testosterone levels are still in the normal range.

Context: Apo A-I Leu75Pro is a rare hereditary form of amyloidosis that mainly involves the kidney, the liver, and the testis. Objective: To define the characteristics of organ damage and testis impairment in the largest cohort collected to date of men with Apo A-I Leu75Pro amyloidosis. Design, Setting, and Patients: Retrospective study from a prospectively collected database of 129 male subjects >18 years with Apo A-I Leu75Pro amyloidosis from a reference center at the University Hospital of Brescia, Italy. Main outcome measures: We evaluated liver and renal function, scrotal ultrasound, reproductive hormone levels, testis biopsy, hypogonadal symptoms, and fertility. Results: Progressive involvement of testis, kidney, and liver was observed in 96/129 (74.4%) cases. Testis impairment was found in 88/129 patients (68.2%), liver in 59 (45.7%) and renal in 50 (38.8%). Testis damage was often the first manifestation of the disease and the only dysfunction in 30% of younger patients (<38 years). Testicular involvement was characterized mainly by primary (73/88 patients, 83.0%) and subclinical (8/88, 9.1%) hypogonadism. Almost all (85/88, 96.6%) also had high follicle-stimulating hormone, suggesting a primary global damage of endocrine and spermatogenic functions, and 30% of them did not conceive. Macroorchidism was found in 53/88 (60.2%) patients, especially in men <54 years (30/33, 90.9%). Apo A-I amyloid deposits were found in Sertoli cells, germinal epithelium, and vessel walls. Conclusion: In men with Apo A-I Leu75Pro amyloidosis, testicular involvement is the hallmark of the disease, characterized by global primary testicular dysfunction and macroorchidism due to amyloid deposits.