Premature Adrenarche Premature adrenarche or pubarche may be caused by increased sensitivity to low levels of androgens and must be distinguished from late-onset (nonclassic) CAH. If there is no evidence of breast development or of progression, these conditions are virtually always benign.
Girls with premature adrenarche are at increased risk of developing polycystic ovary syndrome (PCOS), hyperinsulinemia, acanthosis nigricans, and dyslipidemia in adolescence and adult life, especially if fetal growth was reduced and birth weight was low (71). Although mean androgen levels are within the normal range, a significant minority have an exaggerated response to corticotropin stimulation. The magnitude of this response is inversely related to insulin sensitivity. Thus, premature adrenarche may be the first sign of insulin resistance or PCOS in some individuals. Treatment of coexisting obesity and long-term follow-up are indicated to address potential complications of PCOS and insulin resistance.
Isolated premature menarche is vaginal bleeding at age 1 to 9 years in the absence of other signs of puberty. The bleeding is usually limited to a few days. It can recur for 1 to 6 years and then cease. The etiology is uncertain. Most cases are associated with subsequent normal pubertal development and fertility. The differential diagnosis includes vaginal foreign bodies, trauma, sexual abuse, vaginal infection, or neoplasms such as rhabdomyosarcoma, McCune-Albright syndrome (in which menarche may occur before other manifestations of sexual precocity), and primary hypothyroidism.
In central precocious puberty, GnRH prematurely stimulates increased gonadotropin secretion. Central precocious puberty may occur in children in whom there is no structural abnormality, in which case it is termed constitutional or idiopathic. Constitutional (idiopathic) sexual precocity is the most common cause of precocious puberty. It is often familial and represents the so-called tail of the Gaussian curve (i.e., the early 2.5% for the age distribution for the onset of puberty). In many of these girls, puberty is slowly progressive, but in a few, development progresses rapidly. The major complication of sexual precocity is limitation of height. Thus, therapy may be warranted to prevent this consequence.
Figure 29.17 Five-year-old girl with development of pubic hair (A) as shown more closely in (B) (precocious adrenarche). Gonadotropin levels were prepubertal, and bone age was appropriate for age. No further development occurred until breast budding at approximately age 9.
Figure 29.18 Left: A71/2-year-old girl with Tanner stage 4 pubertal development who began menstruating 1 month earlier. She was 57 inches tall (above the 95th percentile). Luteinizing hormone and follicle-stimulating hormone levels were consistent with her development. A large neoplasm that proved to be a hypothalamic hamartoma was present on computed tomography scan. Pubertal development began at about 5 years of age.
Figure 29.19 Right: A: A101/2-year-old girl with 21-hydroxylase deficiency before treatment. 17-Ketosteroid (KS) excretion was 34 mg per day. B: The same patient after 9 months of therapy with cortisone (17-KS excretion: 4.6 mg per day). (From Wilkins L. The diagnosis and treatment of endocrine disorders in childhood and adolescence. 3rd ed. Springfield, IL: Charles C Thomas, 1965:439, with permission.)