SARS-CoV-2, testosterone and frailty in males (PROTEGGIMI): A multidimensional research project.

Preliminary published data depict a much greater prevalence of males with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) referred for intensive care unit admission and severe sequelae in several countries. In this context, males seem to not only be more susceptible to the infection compared to female subjects, at least in Western countries, but their case fatality rate attributable to SARS-CoV-2 infection is also highest. Therefore, we may speculate that the different hormonal milieu could have a more profound pathophysiological role in association with SARS-CoV-2, with endogenous testosterone leaving men more prone to develop more serious complications related to the SARS-CoV-2 infection. Another option is that SARS-CoV-2 infection per se causes an acute stage of male hypogonadism, the depletion of androgenic action triggering serious or an even fatal course of the disease. Therefore, we strongly advocate the development of a prospective multidimensional andrological translational research project in men, which we called the PROTEGGIMI study. In this Opinion Article, we will not only highlight novel research activity in this area but also invite other researchers and learned scientific societies to join us in our efforts to understand an important and very newly discovered gap in knowledge, which may have serious implications for the lives of millions of men.

NAFLD in Some Common Endocrine Diseases: Prevalence, Pathophysiology, and Principles of Diagnosis and Management.

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.

MRI assessment of pituitary iron accumulation by using pituitary-R2 in ß-thalassemia patients.

Background Patients with thalassemia major (TM) require repeated blood transfusions, which leads to accumulation of iron in a wide variety of tissues. Accumulation of iron in the pituitary gland can lead to irreversible hypogonadotropic hypogonadism (HH) in this group of patients. Purpose To investigate the reliability of pituitary-R2 as a marker to estimate the extent of pituitary iron load by comparing the pituitary magnetic resonance imaging (MRI) findings with hepatic iron load and serum ferritin levels. Material and Methods A total of 38 ß-TM patients were classified into HH (group A, n = 18) and non-HH (group B, n = 17) groups. A third group, group C, consisted of 17 healthy participants. Each participant underwent 1.5-T MRI examinations. Pituitary gland heights (PGH), pituitary-R2 values, and liver-R2 values were measured by using multi-echo spin-echo sequences. Results Pituitary-R2 values were significantly higher in group A compared with group B ( P < 0.05). A positive correlation was detected between the pituitary-R2 values and serum ferritin levels in TM patients ( P < 0.01). A threshold value of 14.1 Hz for pituitary-R2 was found to give a high specificity and sensitivity in distinguishing the TM patients with HH from those with normal pituitary functions. PGH measurements were significantly lower in group A compared with group B ( P < 0.05). Conclusion MRI-assessed pituitary-R2 seems to be a reliable marker for differentiating the TM patients with normal pituitary function from those with secondary hypogonadism due to iron toxicity.

Assessment of possible effects for testosterone replacement therapy in men with symptomatic late-onset hypogonadism.

We herein report clinical assessments of efficacy and side effects of T replacement therapy (TRT) in men with late-onset hypogonadism (LOH). The study included 56 patients who were diagnosed with LOH and treated with TRT for at least 6 months at our institution. Age, ageing male symptom (AMS) scale, and androgen decline in the ageing male (ADAM) questionnaires were examined. Fasting blood samples were analysed for sex hormones, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), red blood cell count (RBC), haemoglobin (Hb), haematocrit (Ht), and prostate-specific antigen (PSA). Total and psychological symptoms scores were measured by the AMS scale and the ADAM questionnaire score, demonstrating that the sum of positive responses to the questions were significantly improved after TRT (P < 0.05). TC, HDL, and LDL cholesterol, TG, AST, ALT, γ-GTP, RBC, Hb, Ht, and PSA were not significantly different between before and after TRT. Although TRT for men with LOH may cause favorable changes in psychological conditions, it may not have effects on lipid metabolism, liver function, RBC, and PSA level.

The GnRH test in the assessment of patients with pituitary and parapituitary lesions: results of a 5-year retrospective study.

OBJECTIVE: To examine the utility of the GnRH (gonadotrophin-releasing hormone) test in the management of patients with pituitary and parapituitary lesions. PATIENTS AND METHODS: A 5-year retrospective study of LH (luteinizing hormone) and FSH (follicle stimulating hormone) responses to GnRH test in patients with HP (hypothalamic-pituitary) disease in a regional endocrine centre. Serum LH and FSH concentrations were measured at baseline and at 20 and 60 min after an intravenous bolus of 100 mcg (micrograms) of GnRH. The GnRH responses were categorised by tumour size, tumour type, and gonadal status. RESULTS: Of the 104 patients studied, 46 were male and 58 were female. There were 50 normal, 38 subnormal and 16 exaggerated LH responses compared with 34 normal 67 subnormal and three exaggerated responses for FSH. Seventy-four patients (71.2%) were hypogonadal. Normal LH responses were achieved in half of the hypogonadal subjects and normal FSH responses in more than a third. Furthermore, the LH responses were exaggerated in nine hypogonadal patients compared with three for FSH. The GnRH test could not differentiate between pituitary or parapituitary lesions either by size or type of lesion. An exception was the male non-functioning adenoma (NFA) sub-group (10 patients, all were hypopituitary, seven were hypogonadal), which demonstrated significant subnormal LH and FSH responses compared with other male and female tumour type sub-groups. CONCLUSIONS: The data from this study indicate that the GnRH test is unhelpful in the clinical assessment of the HP axis in patients with HP disease.

When is bioavailable testosterone a redundant test in the diagnosis of hypogonadism in men?

OBJECTIVES: Total testosterone (TT) is frequently prescribed with an SHBG and/or free or bioavailable testosterone measurement. Our objective was to identify a TT range for which subsequent SHBG measurement/calculation adds no additional clinical information. DESIGN AND METHODS: Study data were composed of 3955 sets of TT, SHBG and calculated bioavailable testosterone (cBAT) results from unscreened ambulatory male subjects, aged 18-99. RESULTS: 90% of mismatches between TT and cBAT were observed with TT levels between 6.5 and 13.0 nmol/L, with only slight age variation and no important change with albumin level. SHBG measurement restricted to male patients with TT between 6.5 and 13.0 nmol/L should enable reagent cost savings of over 55%. CONCLUSION: We suggest that a TT level below 6.5 nmol/L or above 13.0 nmol/L provides sufficient useful information for ruling out hypogonadism in ambulatory adult males. This strategy of BAT testing should lead to significant time and cost savings.