Sex Steroids, Precursors, and Metabolite Deficiencies in Men With Isolated Hypogonadotropic Hypogonadism and Panhypopituitarism: A GCMS-Based Comparative Study

Context: Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism or Kallmann syndrome. Objective: The objective of the study was to compare the serum levels of sex steroids, precursors, and metabolites between men with complete IHH and those with Hypo-Pit. Patients: We studied 42 healthy men, 16 untreated men with IHH (normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxine, and GH replacement therapy but not T. Methods: Gas chromatography/mass spectrometry (GCMS) was used to measure the serum levels of sex steroids [T, dihydrotestosterone (DHT), and estradiol (E2)], their precursors (pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17-hydroxyprogesterone, and androstenedione), and their metabolites (androsterone, estrone, and estrone sulfate) as well as pregnenolone and dehydroepiandrosterone sulfate esters. Results: All the above-mentioned steroids, and notably T, DHT, and E2, were significantly lower in IHH patients than in controls but remained well above the detection limit of the relevant assays. In Hypo-Pit men, all these steroids were dramatically and significantly lower than in IHH. Interestingly, T, DHT, and E2, as well as pregnenolone and dehydroepiandrosterone sulfate esters, were undetectable or barely detectable in the Hypo-Pit men. Conclusions: Steroid deficiencies are marked but partial in men with complete IHH. In contrast, men with Hypo-Pit have a very severe overall steroid deficiency. These deficiencies could affect health and quality of life.