A 7-year-old girl is brought in to see you by her mother because the girl has developed breasts and a few pubic hairs. Evaluation demonstrates a pubertal response to a GnRH-stimulation test and a prominent increase in luteinizing hormone (LH) pulses during sleep.
These findings are characteristic of patients with which of the following?
A. Theca cell tumorsPrecocious puberty is diagnosed if a young girl develops pubertal changes before the age of 8 years. This patient is most likely to have true central precocious puberty. The GnRH results and LH pulses described in the question are seen in normal puberty. Normal signs of puberty involve breast budding (thelarche), pubic hair (pubarche or adrenarche), and menarche. Besides an increase in androgens and a moderate rise in FSH and LH levels, one of the first indications of puberty is an increase in the amplitude and frequency of nocturnal LH pulses. In patients with idiopathic central precocious puberty, the pituitary response to GnRH is identical to that in girls undergoing normal puberty. Iatrogenic sexual precocity (ie, the accidental ingestion of estrogens), premature thelarche, and ovarian tumors are examples of sexual precocity independent of GnRH, FSH, and LH function. Precocious puberty can be treated by agents that reduce gonadotropin levels by exerting negative feedback in the hypothalamic—pituitary axis or that directly inhibit gonadotropin secretion from the pituitary gland. Currently, the most effective treatment for central precocious puberty is the use of a long-acting GnRH agonist, such as leuprolide (Lupron) and others. These drugs act by downregulating pituitary gonadotropes, eventually decreasing the secretion of FSH and LH, which are inappropriately stimulating the ovaries of these patients. As a result of this induced hypogonadotropic state, ovarian steroids (estrogens, progestins, and androgens) are suppressed back to prepubertal levels and precocious pubertal development stops or regresses. During the first 1 or 2 weeks of therapy there is a flare-up effect of increased gonadotropins and sex steroids, a predicted side effect of these medications. At the time of expected puberty, the GnRH analogue is discontinued and the pubertal sequence resumes.