Subnormal Gonadotropin Responses to Gonadotropin-Releasing Hormone Persist into Puberty in Children with Isolated Growth Hormone Deficiency*

Abstract

To determine the value of a standard gonadotropin- releasing hormone (GnRH) test (2.5 µg/kg; iv bolus) in the diagnosis of gonadotropin deficiency, 38 children with presumed isolated GH deficiency (IGHD) were tested at 6- to 12-month intervals for 1–6 yr. For comparison, 102 normal children and 15 children with idiopathic multiple pituitary hormone deficiencies were tested 1-6 times during the same period. Basal LH concentrations in IGHD boys were subnormal after a skeletal age of 12 yr [basal LH, bone age (BA) ≥ 12 yr: normal boys, 6.0 ± 0.5 mlU/ml; IGHD boys, 4.4 ± 0.7 mlU/ml (mean ± SE); P < 0.05]. LH responses to synthetic GnRH were significantly lower than normal in boys with IGHD both before and after puberty [mean maximum change (A max) in LH, BA = 2-10 yr; BA > 12 yr: normal boys, 7.9 ± 1.0/36.6 ± 2.6 mlU/ml; IGHD boys, 4.3 ± 0.4/12.4 ± 1.2 mlU/ml; P < 0.001]. LH responses of prepubertal IGHD girls were subnormal (mean A max LH, BA < 8 yr: normal girls, 10.9 ± 2.2 mlU/ml; IGHD girls, 5.7 ± 1.1 mlU/ml; P < 0.05). FSH responses of IGHD and normal boys showed no age dependency and were considered nonsignificant approximately20% of the time. IGHD girls had blunted FSH responses to synthetic GnRH throughout maturation; although subnormal, FSH responses of IGHD girls decreased with advancing age in a manner similar to that found in normal girls. Ninety-one percent of the presumed IGHD children whose skeletal ages exceeded 12 yr had entered into puberty (6 of 7 boys and 4 of 4 girls). Nonetheless, LH responses of prepubertal children with IGHD were considered significant only 46% and 64% of the time in boys and girls, respectively. We conclude that blunted LH responses to a single GnRH test in prepubertal children with presumed IGHD are not useful in the diagnosis of gonadotropin deficiency. Similarly, the FSH responsiveness of IGHD boys is not diagnostically reliable. We speculate, however, that extremely low FSH responses in IGHD girls (BA < 5 yr) may be predictive of gonadotropin deficiency. In view of their subnormal basal LH concentrations and normal progression of sexual maturation, pubertal IGHD boys may secrete LH with a greater than normal biological to immunological potency ratio.