Impact of Cushing's syndrome on the hypothalamus-pituitary-gonad axis in women

BackgroundThe reproductive and sexual disorders commonly occur in patient with Cushings syndrome (CS), but only few clinical studies focused on the hypothalamus-pituitary-gonad (HPG) axis status in women with CS. A comprehensive spectrum of the impairment on HPG axis in women with CS of different tensity and causes is needed. MethodThis retrospective study analyzed the status of HPG axis in 137 women with different CS causes diagnosed between 2007 and May 2024, and the correlation between reproductive hormones and the tensity of hypercortisolism. Receiver operating characteristic (ROC) analysis was performed in 45 women with available data of plasma steroids by tandem mass spectrometry (LC-MS/MS) as well. ResultsWomen with ectopic adrenocorticotropin (ACTH) secretion (EAS) had significantly higher levels of serum cortisol, 24h urinary-free cortisol (UFC), ACTH, with marked increase in testosterone and decrease in Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) (P<0.001).The serum cortisol and ACTH were positively associated with testosterone, while negatively associated with LH and FSH, especially in postmenopausal women. Further investigation of steroid profiles found plasma androgen including testosterone, Androstenedione (A2), dehydrospiandrostenedione (DHEA) and dehydrospiandrostenedione sulfate (DHEAS) had high sensitivity and specificity in discriminating CD from adrenal CS. Additional analysis of thyroid axis found hypercortisolism had less influence on TSH compared with LH and FSH. ConclusionExcessive cortisol caused by CS can impair the HPG axis in women, which were especially intense in EAS. The degrees of impairment were associated with the intensity and the underlying causes of hypercortisolism.