A 6-year-old girl presents with breast development (Tanner stage III), vaginal bleeding, and accelerated growth. Bone age is 10 years. TSH is markedly elevated at 85 mIU/L, and free T4 is very low. Prolactin is mildly elevated. GnRH stimulation test shows a pubertal LH response. MRI brain is normal. What is the most likely mechanism of precocious puberty in this patient?

• A Premature activation of the hypothalamic-pituitary-gonadal axis
• B Exogenous estrogen ingestion
• C Autonomous ovarian estrogen secretion
• D TSH cross-reacting with FSH receptors on the ovary ✓

Explanation

Severe primary hypothyroidism can cause precocious puberty (Van Wyk-Grumbach syndrome) through elevated TSH cross-reacting with ovarian FSH receptors, stimulating estrogen production. This results in a pubertal LH response to GnRH stimulation but with delayed bone age (not seen here, though the mechanism still applies). The hallmark is markedly elevated TSH with low free T4. True central precocious puberty would not have abnormal thyroid function. Autonomous ovarian secretion shows suppressed gonadotropins.

Reference: Nelson Textbook of Pediatrics, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.