Van Wyk-Grumbach syndrome in a female pediatric patient with trisomy 21: a case report

Background Children with hypothyroidism typically present with delayed growth and development, but on rare occasions can present with signs of precocious puberty. This presentation is called Van Wyk-Grumbach syndrome. Van Wyk-Grumbach syndrome has seldom been described in patients with trisomy 21. Case presentation We present the case of a 4-year-old girl with trisomy 21, who recently moved to the United States from Guyana, and presented to the emergency room with recurrent vaginal bleeding. She was eventually diagnosed with hypothyroidism and Van Wyk-Grumbach syndrome. She was noted to have Tanner I breasts and pubic hair. A pelvic ultrasound was performed, which showed a simple cyst in the right adnexa. Subsequent laboratory evaluation revealed a thyroid stimulating hormone (TSH) of > 150 mIU/ml along with low free thyroxine of 0.3 ng/dl, suggesting longstanding untreated hypothyroidism. Estradiol and alpha-fetoprotein (AFP) levels were elevated. Bone age was delayed. The patient was diagnosed with Van Wyk-Grumbach syndrome and was started on levothyroxine therapy with subsequent resolution of vaginal bleeding. Estradiol and AFP both normalized after initiating levothyroxine therapy. Conclusion This case emphasizes the importance of recognizing the presence of precocious puberty, delayed bone age and ovarian cyst as a manifestation of primary hypothyroidism. In addition, it highlights the need for thyroid function screening in patients with Trisomy 21. Tumor markers may be elevated in Van Wyk-Grumbach syndrome with subsequent normalization after treatment.