Precocious and delayed puberty
文摘
The critical event in pubertal development, which is dependent on the maturation of gonadal function (gonadarche), is the establishment of the pulsatile secretion of GnRH, and hence of pituitary gonadotropins (Gn), which in turn activate sex steroid secretions estradiol (E2) in girls and testosterone (T) in boys. Adrenarche, characterized by increases in adrenal androgens, dehydroepiandrosterone (DHA), and its sulfate (DHAS), begins about 2 years before gonadarche. Precocious puberty is defined by the isosexual development of secondary sex characteristics before age 8 in girls and age 9 in boys. In girls, E2 is in the pubertal range, and pelvic ultrasound shows bilateral ovarian and uterine enlargement. In boys, T is in the pubertal range, and testes are enlarged bilaterally. It is important to distinguish central precocious puberty (CPP), in which the hypothalamo-pituitary control axis is intact, from peripheral precocious puberty (PPP), in which it is not. In PPP, urinary LH/FSH and/or the Gn response to Gn-RH stimulation are prepubertal or suppressed, whereas in CPP, it is pubertal. PPP is secondary to either McCune-Albright syndrome (due to constitutive activation of the LH receptor) or familial male-linked precocious puberty (due to inactivating mutations in the LH receptor). In both CPP and PPP, adrenarche is dissociated from gonadarche, occurring at a normal (bone) age. Other forms of Gn-independent puberty are (pseudo-precocious puberty) due to either adrenal or gonadal tumors, congenital adrenal hyperplasias (each with a specific steroid profile), or Gn-producing tumors such as hepatoblastoma or choriocarcinoma. Partial forms of pubertal development include premature thelarche in girls (low E2 levels) or premature adrenarche (high DHAS levels for age, but appropriate for Tanner stage of pubic hair); in both conditions, the response to Gn-RH is prepubertal. Delayed puberty is considered when there is no sign of puberty at 13 years in girls and 14 years in boys, occurring more often in boys. In most instances, delayed pubertal development and growth are constitutional; sex steroids and Gn are prepubertal, DHAS levels are somewhat low for age but adequate for bone age. In a small percentage, there is an endocrine abnormality due to gonadal failure (low sex steroids, high Gn levels) or central failure (low sex steroids and low Gn). Diagnosis of the latter is often difficult, requiring repeated testing.