The natural history of autonomous gonadal function, adrenarche, and central puberty in gonadotropin-independent precocious puberty.
Gonadotropin-independent precocity (GIP) is a syndrome marked by precocious pubertal development in the absence of pubertal levels of gonadotropins. To investigate the discrete patterns of central nervous system, gonadal, adrenal, and skeletal maturation in this syndrome, we conducted longitudinal studies spanning up to 10 yr in two such affected individuals. A cross-sectional analysis of adrenal androgen secretion was performed in nine additional patients to assess further the time course of adrenarche in GIP. Serial evaluations revealed progression of secondary sexual characteristics, statural growth, and skeletal maturation, all consistent with ongoing exposure to pubertal gonadal steroid levels. On the other hand, adrenarche (n = 11) and spontaneous and GnRH-stimulated gonadotropin secretion (n = 2) progressed in chronological age-appropriate manners despite long term pubertal levels of gonadal sex steroid secretion. After the development of central puberty, as documented by the appearance of pulsatile gonadotropin secretion, we sought to determine whether the potential for gonadal autonomy persisted. Despite complete pituitary desensitization induced by administration of a GnRH agonist, both patients studied demonstrated an ongoing capacity to secrete pubertal levels of gonadal steroids. Our study suggests that the timing of adrenarche and central puberty in these subjects with GIP was apparently unaltered by prolonged exposure to gonadal steroids. Subsequent to the development of central puberty, pulsatile gonadotropin secretion may override and, thus, mask the underlying defect(s) in adolescents and adults with histories of GIP.
Boepple
P A
PA
Pediatric Unit, Massachusetts General Hospital, Boston 02114.
Frisch
L S
LS
Wierman
M E
ME
Hoffman
W H
WH
Crowley
W F
WF
D000311:Adrenal Glands / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006062:Gonadotropins / Q000502:physiology; D006066:Gonads / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011627:Puberty; D011629:Puberty, Precocious / Q000503:physiopathology*
D000728:Androgens; D006062:Gonadotropins