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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.

AbstractCONTEXT:
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.
PATIENTS:
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.
AuthorsSéverine Trabado, Luigi Maione, Hélène Bry-Gauillard, Hélène Affres, Sylvie Salenave, Julie Sarfati, Claire Bouvattier, Brigitte Delemer, Philippe Chanson, Yves Le Bouc, Sylvie Brailly-Tabard, Jacques Young
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 2 Pg. E268-75 (Feb 2014) ISSN: 1945-7197 [Electronic] United States
PMID24243640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chorionic Gonadotropin
  • Insulin
  • Leydig insulin-like protein
  • Proteins
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
Topics
  • Adult
  • Chorionic Gonadotropin (therapeutic use)
  • Drug Therapy, Combination
  • Follicle Stimulating Hormone (therapeutic use)
  • Hormone Replacement Therapy
  • Humans
  • Hypogonadism (blood, congenital, diagnosis, drug therapy)
  • Insulin (blood)
  • Kallmann Syndrome (blood, diagnosis, drug therapy)
  • Luteinizing Hormone (blood)
  • Male
  • Proteins
  • Testosterone (blood, therapeutic use)
  • Treatment Outcome

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