Differential Diagnosis Of Delayed Puberty

The cutoff age for boys who need an evaluation for delayed puberty may vary in different ethnic groups, but in most populations, early signs of secondary sexual development should be present by age 14 yr.

A thorough medical history should note the symptoms and signs of anorexia nervosa, the intensity of athletic training, and the timing of puberty of both parents (see Fig. 5). In boys with constitutional delay of puberty, one parent often developed late as well. A history of chronic illness, such as celiac disease or inflammatory bowel disease, suggests a temporary or secondary delay of puberty. Stature and height velocity should be evaluated using appropriate growth charts. Height velocity is usually reduced in patients with constitutional delay but is normal in patients with isolated hypogo-

LH/FSH levels

Low values 4-GnRH analog testing -► High values-

nadotropic hypogonadism, but acquired hypogonadotropic hypogonadism is often associated with GH deficiency, short stature, and a slow growth rate. Likewise, bone age (X-ray film of left hand and wrist read according to standards such as Greulich and Pyle) delay provides useful information in the growth analysis but contributes little to the differential diagnosis.

Gonadotropin levels are generally increased in primary testicular failure or in Kline-felter syndrome, but single basal serum LH and FSH determinations are not useful in the differential diagnosis of constitutional delay vs hypogonadotropic hypogonadism. Dynamic testing, such as synthetic GnRH administration, may provide information for the differential diagnosis (54,55). Boys with constitutional delay who are destined to undergo spontaneous pubertal development within 6 to 12 mo may have a pubertal pattern of response to GnRH (post-GnRH maximum LH levels higher than maximum FSH levels), but a low prepubertal LH response to GnRH is usually found in boys with constitutional delay who will develop later than that, as well as in boys with hypogo-nadotropic hypogonadism. The LH response to a superactive GnRH agonist may be higher in a boy who will undergo spontaneous puberty than in one with permanent hypogonadotropic hypogonadism (65,66). Accurate differential diagnosis between constitutional delay and hypogonadotropic hypogonadism has been reported, using multiple overnight samples for LH analysis by a highly sensitive assay (67). Ultimately, third-generation supersensitive assays for LH and FSH may improve distinction between the two conditions (68). but patient follow-up is often necessary for definitive diagnosis.

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