A 6-year-old girl is brought to the office by her parents after they noticed the development of axillary and pubic hair. She has also had a significant growth spurt over the past year. There has been no change in her behavior or school performance. The patient has no headaches, vomiting, or visual disturbances. She has no chronic medical conditions and takes no medications. Family history is unremarkable. BMI is at the 97th percentile for age and sex. The abdomen is soft, nontender, and nondistended. Axillary hair is present and pubic hair is Tanner stage 3; external genitalia are normal. The breasts are Tanner stage 3. Neurologic examination is normal. Bone age is advanced. Serum FSH and LH levels are elevated. Which of the following is the most likely etiology of this patient's symptoms?
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This patient has breast and pubic/axillary hair development consistent with precocious puberty, the onset of secondary sexual characteristics in girls age <8 and boys age <9. The initial evaluation of patients with precocious puberty is a bone age radiograph, which helps differentiate true precocious puberty from other causes of early pubic/axillary hair development (eg, premature adrenarche). Patients with true precocious puberty have increased estrogen/testosterone levels that accelerate skeletal maturation, resulting in advanced bone age and increased growth velocity (as seen in this patient).
The etiology of precocious puberty is categorized as either central (gonadotropin-dependent) or peripheral (gonadotropin-independent).
Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. Pulsatile GnRH secretion stimulates elevated FSH and LH levels, as seen in this patient.
Peripheral precocious puberty (PPP) is caused by gonadal or adrenal release of excess sex hormones. Basal levels of FSH and LH are typically low due to negative feedback and remain low following GnRH agonist stimulation.
Patients with CPP require MRI of the brain to evaluate for a hypothalamic or pituitary tumor activating the HPG axis. If MRI is negative, the cause is most likely idiopathic precocious puberty, and GnRH therapy can be initiated. GnRH desensitizes the pituitary and suppresses FSH and LH secretion to slow pubertal progression and maximize height potential.
(Choices B and E) Estrogen-producing ovarian cysts and exogenous estrogen exposure result in PPP. Although girls may demonstrate premature development of secondary sexual characteristics and may also have advanced bone age, they have low FSH and LH levels.
(Choice C) Excess peripheral conversion of testosterone to estrogen, as seen with aromatase excess, results in precocious puberty in girls but low FSH and LH due to feedback inhibition.
(Choices D and F) Elevated 17-hydroxyprogesterone is found in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Significant increases in dehydroepiandrosterone sulfate occur in patients with an adrenal tumor. CAH and adrenal tumors can cause PPP; affected patients have low FSH and LH levels.
Educational objective:
Precocious puberty, the onset of secondary sexual characteristics in girls age <8 and boys age <9, has both central and peripheral causes. Central precocious puberty is due to early activation of the hypothalamic-pituitary-gonadal axis and presents with increased levels of FSH and LH.