Van Wyk–Grumbach syndrome: a case report and review of the literature

Van Wyk-Grumbach syndrome (VWGS) is a rare manifestation of acquired hypothyroidism that was first described in 1960. It is characterized by precocious puberty, delayed bone age, and, in some cases, galactorrhea. We report the case of a 9-yr-old girl with growth retardation, delayed bone age, and vaginal bleeding without pubic hair development. Laboratory tests showed severe hypothyroidism (TSH level: 1,805 µIU/mL; free T4: 0.1 ng/dL), suppressed LH level, elevated estradiol (53 pg/mL) level, and hyperprolactinemia (59.79 ng/mL). Bilateral ovarian cysts were observed. Levothyroxine normalized thyroid function and reduced the number of cysts; however, central puberty progressed within 5 mo, requiring GnRH analog therapy. A review of 44 previously reported female patients revealed consistent findings including delayed bone age, elevated TSH level, suppressed gonadotropin levels, and frequent vaginal bleeding despite the absence of pubic hair. This atypical sequence likely resulted from TSH-induced estradiol secretion without concurrent adrenal androgen activity. This atypical pubertal development sequence may serve as a useful clinical indicator of VWGS. Assessment of thyroid function is warranted in young girls presenting with isolated vaginal bleeding in the absence of pubic hair, not only to avoid misdiagnosis, but more importantly, to ensure the timely initiation of appropriate treatment for underlying hypothyroidism.