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 mug/kg, 74 tests, or 10 mug/m2, 36 tests). LH and FSH were determined by radioimmunoassay. Maximum concentration, maximum increment (deltamax), and response area were compared with degree of skeletal maturation to evaluate responses. Clinically, the most useful determination was the deltamax LH. All "normal" children with bone ages greater than 12 yr had LH responses in or slightly above the range of the values of the 6 normal men: deltamax LH, 39 +/- 8 (SE) mIU/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 less than 10 yr had significantly lower responses than "short normal" boys with similar skeletal maturation: deltamax LH, 4.8 +/- 0.9 vs 8 +/- 1.3 mIU/ml, P is less than .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 greater than 12 yr is presumptive evidence of gonadotropin deficiency.

Effect of insulin-like growth factor 1 on gonadotropin release from the hypothalamus-pituitary axis in vitro

“…Our result may have some correlation with a report of decreased LH and FSH responsiveness to GnRH in children with presumed isolated hGH deficiency (20). As their LH and FSH responsive¬ ness to GnRH was not improved by hGH treat¬ ment, the significance of IGF-I in gonadotropin release in puberty stays unsolved at present.…”

Estimation of GnRH Pulse Amplitude during Pubertal Development

“…Responsiveness to GnRH 2 hr. Patients with gonadal dysgenesis received one or two 0.0125 has been shown to depend on dosage, route, rate, and frequency &kg pulses in addition to the 0.025 &kg pulse because of of administration, age, sex, sexual maturity, stage of menstrual increased sensitivity to GnRH previously noted in this syndrome cycle, and time of day (7)(8)(9)(10)(11)(12)20,21,23). These studies have shown (7,9,21).…”

“…Four patients (patients 3 to 6) had bone ages of <I0 years, completk absence of secondary sexual development, and prepuSpeculation bertal responses to standard GnRH testing (2.5 &kg IV) (12). Five patients (patients 4 to 6, 13 and 14) were growth hormone Direct measurement of h~~o~h~s i a l portal plasma concentra-(GH) deficient based on failure to respond to two provocative tions of GnRH in human is impractical.…”

Relationship of each anterior pituitary hormone deficiency to the size of non-functioning pituitary adenoma in the hospitalized patients

“…In these patients, we evaluated the relative LH and FSH (peak LH or FSH/basal LH or FSH) [17]. We also analyzed ΔLH and ΔFSH (peak LH or FSH minus basal LH or FSH) and got the same conclusion as relative LH and FSH (data not shown) [22]. Blood samples were obtained before, and 15, 30, 45, 60, 90, 120 minutes after intravenous administration of insulin, 100 μg LHRH or 250 μg TRH.…”