LH and FSH Responsiveness to Intravenous Gonadotropin-Releasing Hormone (GnRH) in Children with Hypothalamic or Pituitary Disorders: Lack of Effect of Replacement Therapy with Human Growth Hormone

Abstract

To evaluate the diagnostic and prognostic usefulness of the GnRH test, gonadotropin responses to iv GnRH (Parke-Davis) were determined in 82 young patients (2.5 mo.-21 yr.) and 6 normal men. After extensive evaluation, 40 patients (31 boys and 9 girls) were considered “endocrinologically normal.” Repeat tests were performed in 17 patients at 6–12 mo. intervals. Nine patients with presumed isolated hGH deficiency and 3 patients with multiple pituitary deficiencies were studied before and at the end of 12 mo. of hGH therapy. Serial blood samples were obtained before and after an iv bolus injection of GnRH (2.5 μg/kg, 74 tests, or 10 μg/m², 36 tests). LH and FSH were determined by radioimmunoassay. Maximum concentration, maximum increment (Δmax), and response area were compared with degree of skeletal maturation to evaluate responses. Clinically, the most useful determination was the Δmax LH. All “normal” children with bone ages >12 yr had LH responses in or slightly above the range of the values of the 6 normal men: Δmax LH, 39 ± 8 (SE) mlU/ml; range 13–57. Severely blunted or absent responses were seen in 14/15 patients (bone ages 3 mo.-14 yr.) with multiple pituitary deficiencies. Boys with isolated hGH deficiency and bone ages of vs 8 ± 1.3 mlU/ml, P < .05. Although the mean growth velocity of hGH-treated children increased from 3.2 to 8.9 cm/yr, LH and FSH responses were unchanged. These studies indicate that 1) children with idiopathic hypopituitarism (including those with presumed isolated hGH deficiency) have significantly decreased responsiveness to GnRH which does not respond to 6 to 12 months of hGH treatment; and 2) decreased responsiveness to GnRH in patients with bone ages of >12 yr is presumptive evidence of gonadotropin deficiency.