Increased cardiovascular morbidity and reduced life expectancy in a large Italian cohort of patients with resistance to thyroid hormone β (RTHβ).

Objective: Decreased survival and higher cardiovascular morbidity have been recently reported in a UK cohort of 61 RTHβ patients, but there is no evidence from other countries.

Design: Retrospective cohort study from an historical group of 284 Italian RTHβ patients, diagnosed between 1984 and 2023.

Methods: We collected data on diagnosis of 284 cases and longitudinal data of 249 RTHβ who carried heterozygous pathogenic variants in the THRB gene.

The role of male hypogonadism, aging, and chronic diseases in characterizing adult and elderly men with erectile dysfunction: a cross-sectional study.

Background: Erectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019.

Exploring the human chorionic gonadotropin induced steroid secretion profile of mouse Leydig tumor cell line 1 by a 20 steroid LC-MS/MS panel.

The canonical androgen synthesis in Leydig cells involves Δ5 and Δ4 steroids. Besides, the backdoor pathway, eompassing 5α and 5α,3α steroids, is gaining interest in fetal and adult pathophysiology. Moreover, the role of androgen epimers and progesterone metabolites is still unknown.

Adrenal Insufficiency with Anticancer Tyrosine Kinase Inhibitors Targeting Vascular Endothelial Growth Factor Receptor: Analysis of the FDA Adverse Event Reporting System.

: We described clinical features of adrenal insufficiency (AI) reported with tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) in the Food and Drug Administration Adverse Event Reporting System (FAERS). : Reports of AI recorded in FAERS (January 2004-March 2022) were identified through the high-level term "adrenal cortical hypofunctions". Demographic and clinical features were inspected, and disproportionality signals were detected through the Reporting Odds Ratio (ROR) and Information Component (IC) with relevant 95% confidence/credibility interval (CI), using different comparators and adjusting the ROR for co-reported corticosteroids and immune checkpoint inhibitors (ICIs).

The Effects of the New Therapeutic Treatments for Diabetes Mellitus on the Male Reproductive Axis.

One of the complications of chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men, is the high prevalence of hypogonadotropic hypogonadism, which has been recently defined as functional hypogonadism, characterized by low testosterone associated with inappropriately normal gonadotropin levels. Although the pathophysiology of this hormonal imbalance may be related to several factors, including glycemic control, concomitant sleep apnea, insulin resistance, the main role is determined by the degree of central or visceral obesity and the consequent inflammatory state. Several drugs have been developed to treat T2DM such as glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium-glucose co-transporter 2 inhibitors.

Overall Sexual Function in Dysmetabolic Obese Men with Low Testosterone Levels Treated with Clomiphene Citrate.

Background: Sexual disorders are the most common clinical manifestations of hypogonadism. Functional hypogonadism is the most frequent form, and clomiphene citrate (CC) has been recently introduced as a possible off-label therapeutic option for these patients.

Objectives: This study aimed to evaluate the effects of CC on the overall sexual function in dysmetabolic obese men with low testosterone (T) levels.

Immune-related adverse events in the treatment of non-Hodgkin lymphoma with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) show efficacy in the treatment of non-Hodgkin lymphomas (NHL). However, these agents are associated with a unique group of side effects called immune-related adverse events (irAEs). We conducted an observational retrospective/prospective study on patients with relapsed/refractory NHL treated with ICI to determine the incidence of irAEs assessing the type, severity, and timing of onset, outcome and relationship with study drugs of these events.

Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors.

Objective: Patients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency.

Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels.

Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis.

Steroid reference intervals in women: influence of menopause, age and metabolism.

Objective: To investigate the impact of age, obesity and metabolic parameters on 13 circulating steroids in reproductive and menopausal age. To define reference intervals (RIs).

Design: Cross-sectional.

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome.

Objective: Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism.

Age-related changes in human Leydig cell status.

Study Question: What are the consequences of ageing on human Leydig cell number and hormonal function?

Summary Answer: Leydig cell number significantly decreases in parallel with INSL3 expression and Sertoli cell number in aged men, yet the in vitro Leydig cell androgenic potential does not appear to be compromised by advancing age.

What Is Known Already: There is extensive evidence that ageing is accompanied by decline in serum testosterone levels, a general involution of testis morphology and reduced spermatogenic function. A few studies have previously addressed single features of the human aged testis phenotype one at a time, but mostly in tissue from patients with prostate cancer.

Effects of acute hCG stimulation on serum INSL3 and 25-OH vitamin D in Klinefelter syndrome.

Background: It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se, but mainly to an altered testosterone (T) secretion into the bloodstream. However, the Leydig cell functionality remains incompletely studied in KS, and new markers should be considered. Previous data indicated that chronic hCG stimulation influences the production of both insulin-like peptide 3 (INSL3) and 25-hydroxy-vitamin D (25-VD) in eugonadal men.

Prevalence and Incidence of Atrial Fibrillation in a Large Cohort of Adrenal Incidentalomas: A Long-Term Study.

Context: Chronic glucocorticoids excess leads to morphological and functional cardiac alterations, a substrate for arrhythmias. Autonomous cortisol secretion (ACS) in adrenal incidentalomas is a model of chronic endogenous hypercortisolism.

Objective: To investigate prevalence and incidence of atrial fibrillation (AF) in a large cohort of patients with ACS.

Impact of age, body weight and metabolic risk factors on steroid reference intervals in men.

Objective: To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men.

Design: Cross-sectional study.

Methods: Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation.

Weight loss more than glycemic control may improve testosterone in obese type 2 diabetes mellitus men with hypogonadism.

Background: Functional hypogonadism is a common disorder among patients with obesity and type 2 diabetes mellitus and could be managed by first treating the underlying causes.

Objective: The present study was undertaken to investigate the contribution of body weight and glycemic control to the reversibility of hypogonadism to eugonadism in a real-life setting.

Materials And Methods: Adult obese male patients with uncontrolled type 2 diabetes mellitus, complaining of mild to moderate erectile dysfunction and suspected of functional hypogonadism evaluated at our institution from 2015 to 2017, were retrospectively included.

The Role of Diet and Weight Loss in Improving Secondary Hypogonadism in Men with Obesity with or without Type 2 Diabetes Mellitus.

Despite growing recognition of the issue, obesity represents one of the most common public health problems, and its rates are still increasing globally. Among the number of comorbidities and complications associated with obesity, hypogonadism is listed, and this disorder, although frequently neglected, is characterized by a relevant impact on both quality of life and life expectancy. It is generally accepted that hypogonadism secondary to obesity is functional since it is reversible following weight loss.

Female and male serum reference intervals for challenging sex and precursor steroids by liquid chromatography - tandem mass spectrometry.

Measuring some sex and precursor steroids is still challenging even by liquid chromatography - tandem mass spectrometry (LC-MS/MS), and few normal values are available. We developed a LC-MS/MS method for estradiol, estrone, dihydrotestosterone and 17-hydroxypregnenolone measurement, compared it with direct immunoassays, and generated sex, age, menopausal and menstrual status specific reference intervals. Liquid-liquid extraction was optimized on 300 μL serum spiked with isotopic internal standards.

Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels.

Background: Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function.

Aim: To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment.

Androgens, Body Composition, and Their Metabolism Based on Sex.

Differences between males and females are commonly attributed to sexual hormones. Androgens are responsible for the development of primary and secondary sexual characteristics in males, whereas they influence sexual behaviour, glycaemic control, lipid profile, bone metabolism and erythropoiesis in both sexes. In this chapter, we discuss preclinical and clinical data on sex-specific androgen metabolism and androgen effect on body composition.

The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk.

Context: Steroid profiling by mass spectrometry has shown implications for diagnosis and subtyping of adrenal tumors.

Objectives: To investigate steroid profiles and their cardiovascular correlates in a large cohort of patients with nonsecreting (NS) adrenal incidentalomas and autonomous cortisol secretion (ACS).

Design: Cohort study.

Sex hormones, obesity and type 2 diabetes: is there a link?

An imbalance in sex hormones has an important impact on type 2 diabetes (T2DM) mainly through the involvement of visceral adipose tissue. Androgens have an interesting sex-dimorphic association with T2DM, since hyperandrogenism in females and hypogonadism in males are risk factors for T2DM. Thus, treatments aimed at correcting hyperandrogenism in females and hypogonadism in males may prevent the development of T2DM or help in its treatment.

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

Context: Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate.

Objective: To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET).

Design: Cross-over, randomized, double-blind, placebo-controlled study.

Retinal Photoreceptor Functions Are Compromised in Patients With Resistance to Thyroid Hormone Syndrome (RTHβ).

Context: In animal models, disruption of thyroid hormone (TH) receptor-β (TRβ) reduces the long/medium wavelength (L/M) and increases the short-wavelength (S) cones. Retinal photoreceptor (RP) functions are unknown in patients with resistance to TH syndrome (RTHβ) with dominant-negative TRβ mutations.

Objective: To investigate RP functions in RTHβ.