Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.
BACKGROUND
Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty.


OBJECTIVE
To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation.


METHODS
We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men.


METHODS
Serum INSL3 was immunoassayed with a validated RIA.


RESULTS
Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS.


CONCLUSIONS
INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.
Université de Paris-Sud (S.T., L.M., S.S., P.C., J.S., C.B., S.B.T., J.Y.), Faculté de Médecine Paris-Sud, Unité Mixte de Recherche-S693, Le Kremlin-Bicêtre, F-94276, France; Assistance Publique-Hôpitaux de Paris (S.T., S.B.T.), Hôpital de Bicêtre, Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin-Bicêtre, F-94275, France; Service d'Endocrinologie et des Maladies de la Reproduction (L.M., H.B.G., H.A., S.S., J.S., P.C., J.Y.), Département de Pédiatrie Endocrinienne (C.B.), Hôpital de Bicêtre, F-94275, France; Service d'Endocrinologie (B.D.), Centre Hospitalier Robert Debré, Reims F-51092, France; Inserm U693 (S.T., L.M., P.C., S.B.T., J.Y.), IFR93, Le Kremlin-Bicêtre, F94275, France; and Laboratoire d'Explorations Fonctionnelles Hôpital Trousseau (Y.L.B.), Assistance Publique-Hôpitaux de Paris and Université Pierre et Marie Curie and Inserm UMRS-938, Paris F-75012, France.
Séverine
S
Trabado
Luigi
L
Maione
Hélène
H
Bry-Gauillard
Hélène
H
Affres
Sylvie
S
Salenave
Julie
J
Sarfati
Claire
C
Bouvattier
Brigitte
B
Delemer
Philippe
P
Chanson
Yves
Y
Le Bouc
Sylvie
S
Brailly-Tabard
Jacques
J
Young
D000328:Adult; D006063:Chorionic Gonadotropin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy; D007328:Insulin / Q000097:blood*; D017436:Kallmann Syndrome / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011506:Proteins; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
D006063:Chorionic Gonadotropin; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone