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Although selective estrogen receptor modulators (SERMs) have been proposed as a treatment for men with central functional hypogonadism, only few data have been produced in men with obesity-related functional androgen deficiency (ORFAD).To determine whether and to what extent SERMs are an effective and safe therapy in men with ORFAD.A thorough search of PubMed, Web of science, Scopus and Cochrane Library databases was performed to identify studies comparing testosterone (T) levels before and after treatment with SERMs in men with ORFAD. Mean differences (MDs) with 95% coefficient intervals (CIs) were combined using random effects models. Funnel plot, Egger's test and trim-and-fill analysis were used to assess publication bias.Seven studies met the inclusion criteria providing information on 292 men with ORFAD treated with clomiphene citrate (CC, 12.5-50 mg daily) or enclomiphene citrate (EC, 12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in T levels both with CC (MD: 11.56 nmol/L; 95% CI: 9.68, 13.43; ITreatment with CC and EC may be an effective and safe alternative to T replacement therapy in men with ORFAD. Further long-term studies are warranted to define clinical reflections of the SERMs-induced increase in T levels and to better clarify the safety profile. This article is protected by copyright. All rights reserved.

Background: Autoimmune diseases tend to cluster in the same individual or in families. Four types of autoimmune polyglandular syndromes (APS) have been described based on the combination of endocri...

Purpose: Conventional (CONV) treatment of adrenal insufficiency (AI) is associated with risk of overtreatment: glyco-metabolic impairment, bone loss, and reduced quality of life. Recent findings suggest that modified-release hydrocortisone (MOD) may restore a more physiological cortisol profile. Our aims were: (1) to compare the gene expression profile of peripheral blood mononuclear cells derived from patients, with secondary AI (SAI), under CONV (cortisone acetate or hydrocortisone) or MOD versus healthy controls; and (2) to evaluate MOD effects on serum cortisol profile, glucose, lipid, bone, and clinical parameters. Methods: Thirteen patients with SAI were switched from CONV to MOD at equivalent dose. Area under curve (AUC) of both formulations was calculated in six patients. Clinical, metabolic and bone parameters were measured at baseline and 3 months after MOD in all patients. In six patients and six age- and sex-matched healthy controls, a whole-genome expression analysis was performed at baseline, 1 month, and 3 months after MOD. Results: (1) The number of genes differentially expressed (n = 235; mainly involved in immune response and metabolism) in SAI patients compared to controls progressively and significantly decreased switching from CONV to MOD (n = 78 at 3 months). (2) Under MOD: AUC of cortisol exposure tended to be smaller and cortisol levels showed a more physiological profile; no significant changes of clinical, metabolic and bone parameters were observed, likely due to the short follow-up, but triglycerides tended slightly to increase. Conclusions: MOD may restore a normal gene expression profile as soon as 1 month after switching from CONV.

Context Long-term studies evaluating the treatment of toxic multinodular goiter (TMNG) with fixed activities of radioiodine (RAI) are lacking. Objective The objective of this work is to describe the effects of 15 mCi on thyroid volume, function, and autoimmunity in the long term. Design and Setting A population-based, retrospective analysis with up to 12 years of follow-up was conducted in Siena, Italy. Participants Adult patients (n = 153) with TMNG, naive to RAI, were included. Methods Evaluation was performed of thyroid function, antithyroid antibodies, and ultrasound scans before and yearly after RAI. Main Outcome Measures Evaluations included hyperthyroidism cure, hypothyroidism, volume reduction, nadir and regain, and antibody titer change. Results The study revealed mean volume reductions greater than or equal to 50% at 3 years after RAI; the greatest annual reduction was observed during the first year (30 ± 17.8%; P < .001). Most patients (60%) achieved their volume nadir 3 to 6 years after RAI. Although 22% patients showed volume regain, the net reduction was statistically significant as late as 9 years after RAI (P = .005). The mean time to hypothyroidism was 2.7 ± 2.4 years, and it was associated with greater reductions in volume (P = .01). During the first 3 years after treatment, hyperthyroid patients decreased approximately by 50% per year without additional RAI. There was no statistically significant association of antibody titers with thyroid function except for antithyrotropin receptor antibodies and hyperthyroidism (P = .004). At the end of follow-up there were 61.6% euthyroid patients, 11% hyperthyroid (4.8% overt), and 27.4% hypothyroid patients (2.7% overt). Hyperthyroidism was cured in 89%. Conclusions The treatment of TMNG with 15 mCi of RAI induced low hypothyroidism rates while providing high cure rates and significant volume reduction, which was maintained in the long term.

Objective Coronavirus disease-2019 (COVID-19) causes acute respiratory distress syndrome. Patients with adrenal insufficiency (AI) may develop severe complications due to this infection and should undergo COVID-19 vaccination; however, there is no consensus about the management of their replacement therapy. The aim of our study was to evaluate the tolerability and need for glucocorticoid dose adjustment related to COVID-19 mRNA vaccines in a cohort of patients with AI. Design and methods We prospectively administered to 88 patients (51 M/37 F; mean age: 62.3 ± 16 years), with AI (28 primary and 60 secondary AI), a questionnaire about the occurrence, severity and duration of the side effects and the need for glucocorticoid dose adjustment within 1 week after the first and the second dose of COVID-19 mRNA vaccines (Pfizer–BioNTech and Moderna). Results Side effects of mild to moderate severity occurred in about 70% of patients after both vaccine doses. The most common adverse events were pain at the injection site, fatigue, fever and flu-like symptoms. The occurrence and severity of the side effects were not correlated to gender, type of AI and mRNA vaccine, but their total number was higher after the second vaccine dose. Doubling the oral glucocorticoid dose was needed in up to 8% of patients, especially after the second vaccine dose, but no parenteral administration was required. Conclusions COVID-19 mRNA vaccines were well tolerated in patients with AI. Side effects were similar to those observed in the general population, and increasing glucocorticoid replacement therapy before vaccine administration was not needed.

Background: The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be perf...