Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a β subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

Objective: To determine whether cardiac remodelling associated with mild autonomous cortisol secretion (MACS) is reversible after treatment and how trajectories compare with non-functioning adrenal incidentalomas (NFAI). Design: Five-year prospective cohort study (ITACA; NCT04127552). Methods: Sixty patients (35 MACS, 25 NFAI) underwent clinical, biochemical, and echocardiographic evaluations at baseline and after 1 and 5 years. MACS was managed with either active surveillance (AS, n = 22) or unilateral adrenalectomy (ADRX, n = 13). Longitudinal changes were analysed with linear mixed-effects models. Results: At baseline, MACS had a higher prevalence of left-ventricular (LV) hypertrophy (46% vs 16%, P = .013) and diastolic dysfunction (34% vs 12%, P = .050), and greater LV mass index (LVMi) (median 100 vs 85 g/m², P = .011). Over time, the change in LVMi differed between NFAI, MACS-AS and MACS-ADRX (P = .004). At 1 year, LVMi fell by −14.8 g/m² (95%CI −28.7 to −0.9) after ADRX and rose by 13.7 g/m² (0.8 to 26.5) under AS. By 5 years, LVMi returned to baseline in both MACS subgroups, whereas NFAI increased by 22.4 g/m² (12.3 to 32.5; P < .001). Right-ventricular systolic excursion (TAPSE) improved only in AS (3.6 mm, 1.8 to 5.4; P = .001). Global LV systolic and diastolic indices deteriorated similarly across groups. Major adverse cardiac events occurred in 13.3% of MACS-AS, 12.5% of ADRX, and 5.6% of NFAI patients. Conclusions: MACS is associated with early concentric LV remodelling that regresses after adrenalectomy but rebounds within 5 years, leaving surgical and surveillance patients with comparable cardiac geometry. Under AS, remodelling stabilizes, whereas NFA continue a slow, progressive hypertrophic course. These findings support serial echocardiographic monitoring and underscore the need to test other cortisol-lowering therapies, alone or in combination with surgery, for durable cardioprotection.

The growing burden of obesity and diabetes underscores the need for innovative strategies to identify secondary causes. While hypercortisolism is traditionally considered rare, its broader spectrum - from mild autonomous cortisol secretion to overt Cushing's syndrome (CS) - may be under-recognized in these populations. We systematically searched MEDLINE, Scopus and Web of Science for original studies assessing hypercortisolism in obesity or diabetes. We included first-line screening tests for hypercortisolism, particularly the dexamethasone suppression test (DST), and subsequent confirmed CS. Data were pooled using random-effects models and are presented as 95%CIs. Certainty of evidence was assessed with GRADE. Of 3038 articles, 39 (14,995 screened participants) were included. In a pooled cohort of 8705 individuals with obesity (19 studies), the prevalence of an abnormal DST was 4.6% (95%CI: 3.2-6.4), and CS confirmed in 0.8% [0.4-1.5]. Among 6638 patients with diabetes (22 studies), 14.3% (95%CI: 10.9-18.4) had an abnormal DST, increasing to 23.3% (95%CI: 22.2-24.5) after heterogeneity adjustment; 2.1% (95%CI: 1.3-3.3) had confirmed CS. Younger age, recent weight gain, and diabetes were significant predictors of CS. One in six abnormal DST led to CS confirmation. Exploratory economic analyses supported broadening screening in selected cohorts. GRADE certainty ranged from low to moderate. In a clinically relevant subset of patients with obesity and diabetes, underlying hypercortisolism remains undiagnosed. The implications of abnormal DST without confirmed CS warrant further investigation. Screening strategies for secondary causes of obesity and type 2 diabetes might require reassessment, pending confirmation in unbiased cohorts.

Arterial hypertension is characterised by elevated blood pressure (BP) leading to cardiovascular morbidity and mortality, and organ damage. Its prevalence in childhood is around 5% and children should be screened from 3 years of age. Hypertension in childhood or adolescence requires exclusion of a secondary cause. Adrenal disorders frequently underlie secondary hypertension. presenting with imbalances of BP and pleiotropic clinical presentations. Examples are rare genetic defects leading to increased mineralocorticoid activity such as Congenital Adrenal Hyperplasia (CAH) due to 11β-hydroxylase gene ( CYP11B1 ) or 17-hydroxylase gene (CYP17A1) mutation, and Familial Hyperaldosteronism (FH), due to 11β-hydroxylase 1 ( CYP11B1 ) and 11β-hydroxylase 2 ( CYP11B2 ) gene fusion, or to mutations of other genes involved in aldosterone production such as those codifying the chloride-voltage gated channel 2 ( CLCN2 ), the potassium inwardly rectifying channel subfamily J member 5 ( KCNJ5 ), and the calcium voltage-gated channel subunitsα1 H and D (CACNA1H and CACNA1D). The differential diagnosis of childhood hypertension also includes endogenous hypercortisolism (Cushing’s syndrome) or phaeochromocytomas/paragangliomas, neoplastic conditions potentially caused by germinal genetic alterations, in a specific familial syndrome. Lastly, peripheral glucocorticoid and mineralocorticoid pathway disorders due to germline mutations in HSD-11B2 , codifying the enzyme 11β-dehydrogenase type 2, NR3C1 and NR3C2 genes codifying the nuclear receptor subfamily 3 group C members 1 and 2 may also be responsible. A systematic diagnostic approach based on published guidelines is still lacking, and diagnostic suspicions with referral for gene sequencing need to be identified. This review discusses the known causes of endocrine hypertension in children and adolescents, with an emphasis on prevalence, clinical presentation, genetic predisposition and therapeutic strategies.