True Precocious Puberty Complicating Congenital Adrenal Hyperplasia: Treatment with a Luteinizing Hormone-Releasing Hormone Analog*

Abstract

Congenital adrenal hyperplasia (CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen four such children (three boys and one girl) who had the diagnosis of CAH made between the ages of 3 and 6 yr. These patients were treated with standard doses of hydrocortisone and fludrocortisone. A diagnosis of true precocious puberty was made because of testicular enlargement in the boys, breast development in the girl, progressive pubic hair development, rapid growth, and rapid bone age maturation. Plasma steroid levels were elevated for age, and gonadotropin levels were within the normal pubertal range, both basally and in response to LHRH stimulation. We treated these children with daily sc injections of a LHRH analog (LHRHa) for 6-18 months in addition to the standard hydrocortisone and fludrocortisone therapy for CAH. LHRHa significantly decreased basal plasma LH and FSH, peak LH and FSH responses to native LHRH, and testosterone levels. Testis size decreased in the males, and breast development regressed in the female. LHRHa therapy led to significant decreases in linear growth rate, ulnar growth rate, and rate of bone age advancement. These results suggest that LHRHa is an effective adjunct to hydrocortisone and fludrocortisone in the treatment of true precocious puberty complicating CAH.

Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency

“…True CPP has been described previously in classical 21-OHD (29), NC21-OHD (22), and virilizing adrenal tumors (30), either at presentation or following institution of therapy when the hyperandrogenism resolved. The presentation of CPP associated with hyperandrogenism usually correlates with advanced BA to the range of the pubertal years (29,30). Our group B patients did tend to have more advanced BA SDS at diagnosis than group A (Table 2), but only three out of six had a BA of > 8 years at gonadarche, which appeared before initiation of therapy, i.e.…”

Premature adrenarche: novel lessons from early onset androgen excess

“…The condition is rare and most of the identified cases in boys are due to simple virilising and non-classic CAH variants. In CAH, transition from precocious pseudo-puberty to secondary central precocious puberty has been observed and is thought to be due to the induction of the GNRH pulse generator by persistently increased sex steroids (66). Pubertal progression in central precocious puberty is efficiently halted by GNRH analogues blocking GNRH action (67,68).…”

The Use of Gonadotropin-Releasing Hormone Analogs beyond Precocious Puberty

“…. Several small studies have demonstrated a significant improvement in adult height in children with CAH and secondary CPP who were treated with a GnRHa (37)(38)(39)(40). However, none have been randomized prospective trials, which likely explains why routine use of GnRHas to treat secondary CPP in children with CAH is not recommended by consensus guidelines (41).…”