Sex steroids, precursors, and metabolite deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism: a GCMS-based comparative study.
BACKGROUND
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.


METHODS
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.
Assistance Publique-Hôpitaux de Paris (F.G., S.T., J.S., Y.L.B., S.B.-T., J.Y.); Centre d'Investigations Biologiques (F.G.), Hôpital Henri Mondor, F-94010 Créteil, France; INSERM Unité 955 Eq07 (F.G., J.F.), Centre de Recherches Chirurgicales, Faculté de Médecine Paris Est, Université Paris Est, F-77454 Marne-la-Vallée; Faculté de Médecine Paris-Sud (S.T., J.S., S.B.-T., J.Y.), Université Paris-Sud, Laboratoire de Génétique Moléculaire, Pharmacogénétique, et Hormonologie (S.T., S.B.-T.) and Service d'Endocrinologie et des Maladies de la Reproduction (L.M., J.S., J.Y.), Hopital Bicêtre, and INSERM Unité 693 (S.T., S.B.-T., J.Y.), F-94275 Le Kremlin Bicêtre, France; and Laboratoire d'Explorations Fonctionnelles (Y.L.B.), Hôpital Trousseau, F-75571 Paris, France; Université Pierre et Marie Curie (Y.L.B.), F-75005 Paris, France; and INSERM Unité Mixte de Recherche en Santé 938 (Y.L.B.), F-75020 Paris, France.
Frank
F
Giton
Séverine
S
Trabado
Luigi
L
Maione
Julie
J
Sarfati
Yves
Y
Le Bouc
Sylvie
S
Brailly-Tabard
Jean
J
Fiet
Jacques
J
Young
D000328:Adult; D000735:Androstenedione / Q000097:blood; D002849:Chromatography, Gas; D003687:Dehydroepiandrosterone / Q000097:blood; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood; D006801:Humans; D007006:Hypogonadism / Q000097:blood* / Q000188:drug therapy; D007018:Hypopituitarism / Q000097:blood* / Q000188:drug therapy; D008297:Male; D013058:Mass Spectrometry; D011374:Progesterone / Q000097:blood; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
D013196:Dihydrotestosterone; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D004958:Estradiol