A 6-year-old girl is brought to the office for evaluation of breast and pubic hair development. Her parents noticed that she started developing breasts several months ago, and she recently started growing coarse axillary and pubic hair. The patient has had no changes in her behavior or school performance. She has no headaches, visual changes, vomiting, or vaginal bleeding. The patient has no chronic medical conditions and no previous surgery. She takes no daily medications and has no known allergies. BMI is at the 50th percentile for age. Physical examination reveals axillary hair; pubic hair is Tanner stage 3, and breasts are Tanner stage 3. The remainder of the examination is unremarkable. Bone age is consistent with age 8. Basal LH level is high. Which of the following is the best next step in evaluation of this patient?
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Central (gonadotropin-dependent) precocious puberty (PP) results from the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls age <8 and boys age <9. Early exposure to increased gonadal hormones results in breast development or testicular enlargement and axillary/pubic hair growth at a young age. High levels of androgens and estrogens also promote increased bone formation and cartilage growth, which leads to early pubertal growth spurts (increased height velocity) and advanced bone age. However, estrogen stimulates growth plate closure, so patients will often have shorter than expected adult height.
Central PP is distinguished from peripheral PP by an elevated LH level at baseline (due to hypothalamic secretion of GnRH) or following stimulation with a GnRH agonist. In contrast, elevated sex hormones in patients with peripheral PP suppress LH levels via negative feedback.
Although central PP is typically idiopathic, it can be the first manifestation of an intracranial process even in asymptomatic patients, as in this child. Central nervous system (CNS) lesions can cause PP through endogenous hormone production (eg, GnRH-secreting hypothalamic hamartoma, FSH- and LH-secreting pituitary adenomas) or by indirectly affecting the HPG axis due to mass effect or increased intracranial pressure (eg, craniopharyngioma). Patients with central PP require an MRI of the brain to evaluate for hypothalamic or pituitary tumor.
Medical and psychosocial consequences exist for PP as affected children appear different than their peers, and physical changes precede emotional maturity. Once a CNS tumor is excluded, the primary treatment for idiopathic central PP is GnRH agonist therapy, which prevents premature epiphyseal plate fusion and maximizes adult height potential.
(Choices A and E) Adrenal CT scan or pelvic ultrasound evaluates for adrenal or gonadal tumors, respectively, which may cause peripheral PP. Patients with peripheral PP have low LH and FSH levels.
(Choice B) Dexamethasone suppression test is used to diagnose Cushing syndrome. Patients may have signs of isolated adrenal androgen overproduction (eg, acne, hirsutism); there is no associated premature breast development.
(Choice C) Karyotype analysis is not indicated in PP but is used for delayed puberty to detect chromosomal abnormalities such as Klinefelter syndrome (XXY) and Turner syndrome (XO).
(Choice F) Reassurance can be provided in cases of isolated premature thelarche or adrenarche when bone age is normal.
Educational objective:
Central (gonadotropin-dependent) precocious puberty (PP) is characterized by premature breast and pubic/axillary hair development, advanced bone age, and an elevated LH level. Patients with central PP require an MRI of the brain to evaluate for a tumor prior to starting GnRH agonist therapy.