FREE ALPHA SUBUNIT SECRETION--DISTINGUISH DELAY OF PUBERTY &GNRH DEF

Massachusetts General Hospital, Boston MA

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Abstract

Delayed puberty may be defined as a failure to achieve pubertal change at an age greater than 2.5 S.D. above the mean for the population. When the initial evaluation defines a hypogonadotropic state without any disernable underlying pathology, the differential diagnosis centers on distinguishing patients with constitutional delay of puberty (CD) (who will eventually u ndergo puberty spontaneously) from patients with GnRH deficiency or idiopathic hypogonadotropic hypogonadism (IHH) (who will require permanent reproductive hormone replacement). In both groups, the accompanying short stature and absence of muscular development and virilizing changes are often of particular concern to the adolescent patients and may be associated with significant phychosocial problems. Treatment with testosterone accelerates height velocity and the appearance of sexual characteristics with associated emotional benefits while not comprising adult height as long as the doses employed are chosen judiciously. For instance, in one study (n = 15 boys with CD) low dose depot testosterone (50mg IM monthly x 6 months) did not alter final adult height, a conclusion based on comparing adult heights after testosterone therapy to predicted heights prior to treatment. While a brief course of low dosetestosterone therapy may thus be indicated in some patients with CD, the concerns of many patients and their families may be completely relieved by the simple knowledge that puberty will be achieved in the future and that the condition is not permanent. However, the distinction between adolescents with constitutional delayed puberty (CD) and those with complete GnRH deficiency or IHH remains a diagnostic dilemma. Endocrine evaluations of the hypothalamic-pituitary-gonadal and adrenal axes have been undertaken, but no previous studies successfully distinguished between these two groups with any single test. TRH-stimulated prolactin levels were found to be higher on average in CD compared to IHH, but considerable overlap existed between the two groups. DHEAS levels were reported to be higher on average in IHH than in CD, but again there was considerable overlap in values in the two groups.