Van Wyk Grumbach Syndrome and Ovarian Hyperstimulation in Juvenile Primary Hypothyroidism: Lessons From a 30-Case Cohort

CONTEXT: Prolonged hypothyroidism in children commonly causes short stature with delayed bone maturation, and delayed puberty. However, a paradoxical occurrence of peripheral precocious puberty and pituitary enlargement in chronically untreated juvenile hypothyroidism was first reported by Van Wyk and Grumbach in 1960. OBJECTIVE: To create increased awareness and a better understanding of this clinical entity among emergency room physicians, pediatricians, surgeons, gynecologists and oncologists. METHODS: Case records of children diagnosed with Van Wyk–Grumbach syndrome (VWGS) were analyzed retrospectively. RESULTS: Twenty-six girls and 4 boys were identified (2005-2020). All had profound primary hypothyroidism (total thyroxine [T4]: 2.5-33.5 nmol/L, thyrotropin: > 75-3744 μIU/mL). Hypothyroidism was not the referral diagnosis in any of the girls. Among them, 17 were referred for precocious puberty, 5 with a diagnosis of pituitary tumor on magnetic resonance imaging, and others for acute surgical abdomen in 7 girls (painful abdominal mass—2, ovarian tumor—2, ovarian torsion—2, ruptured ovarian cyst—1), acute myelopathy in 1, and menorrhagia with headache in another. All girls were successfully managed with levothyroxine replacement alone, except for the 2 with ovarian torsion, who required surgery. Menstruation ceased promptly with T4 therapy in all girls, occurring at an age-appropriate later date. All boys had testicular enlargement at presentation that regressed partially after T4 treatment. Catch-up growth was remarkable during the first treatment year, but the final height was compromised in all. CONCLUSION: Increased awareness of varied presentations of VWGS is vital among pediatricians to facilitate early diagnosis and targeted investigations, and to help in the initiation of the simple yet highly rewarding T4 replacement therapy to avoid all possible complications.