Endocrine Abstracts

Background: Secondary hypogonadism (SH) is a common comorbidity of Cushing’s syndrome (CS) in men. There is a large overlap in associated symptoms and comorbidities between hypogonadism and hypercortisolism. To date, the influence of coexistent SH on clinical and biochemical parameters in CS is largely unknown and longitudinal data investigating its recovery during the remission phase are scarce.

Hypothesis: We hypothesized that SH is a frequent and important risk factor for adverse outcomes of myopathy and osteoporosis.

Participants and Methods: We included 30 treatment-naïve adult men with overt CS diagnosed since 2012 with available baseline testosterone data. Hypogonadism was diagnosed based on age-specific cut-offs of total testosterone (TT). Outcomes were compared to 30 age- and BMI-matched male controls. In a subgroup of 20 men with CS, a longitudinal analysis after remission was conducted at 6, 12, and 24 months.

Results: Men with CS had significantly lower levels of TT, bioavailable T, and free T compared to controls (P<0.0001) with lowest levels in ectopic CS. At baseline, 16 (53%) men with CS had SH: 9/21 (42%) with pituitary, 5/6 (83%) with adrenal, and 2/3 (67%) with ectopic CS. Glucocorticoid excess measured by late night salivary cortisol was weakly but significantly inversely correlated with bioavailable T (r=-0.396, P=0.0499) and other reproductive hormones and there was a similar trend for serum cortisol (r=-0.373, P=0.0605). As expected, muscle function, both self-reported and confirmed by hand-grip strength, was significantly lower in men with CS (P<0.0001 and P=0.0482), whereas osteoporosis was more frequent in men with CS vs controls (50% vs 7%, P<0.0001). However, when stratified according to presence or absence of SH there was no significant difference in signs and symptoms of CS. SHBG correlated negatively and significantly with red blood cell (RBC) parameters (Haemoglobin, haematocrit, erythrocytes, and MCH, r=-0.42 to -0,47, P<0.05), with a similar trend for related reproductive hormones. Following successful surgery, testosterone levels increased significantly (P=0.0010), reaching normal levels six months after remission. Despite normalisation of SHBG levels, RBC parameters remained lower in men with CS even two years after remission.

Conclusion: SH is a common comorbidity in men with all types of endogenous CS and is reversible in most patients after six months of successful therapy. Despite being related to glucocorticoid excess, SH was not directly associated with myopathy. However, there seems to be a correlation with RBC parameters, some of which do not normalise even two years after remission.