Background: Van Wyk–Grumbach syndrome (VWGS) is a rare endocrine complication of severe, longstanding, untreated or inadequately treated primary hypothyroidism. It is characterized by gonadotropin-independent precocious puberty, typically with thelarche, recurrent vaginal bleeding, and ovarian cysts, in association with severe linear growth deceleration and delayed skeletal maturation.

Case Presentation: We report a 10-year-old girl with Down syndrome (trisomy 21), a history of surgical closure of an atrial septal defect, and primary hypothyroidism diagnosed at 5 years of age, followed by poor treatment adherence and loss to follow-up. She presented with recurrent, painless vaginal bleeding that had been present since the age of 7 years. Examination showed severe short stature (height 118 cm, −3.0 SD on WHO growth charts), clinical features of severe hypothyroidism, and isolated breast development without pubic or axillary hair (Tanner stage B2P1A1). Bone age was markedly delayed (6.5 years at a chronological age of 10 years). Laboratory evaluation showed severe primary autoimmune hypothyroidism (TSH >1000 µIU/mL, free T4 0.4 ng/dL, anti-thyroperoxidase antibodies 240.8 IU/mL), marked hyperestrogenism (estradiol 802.78 pg/mL), elevated FSH (17.14 mIU/mL), suppressed basal LH (0.06 mIU/mL), and mild hyperprolactinemia (27.89 ng/mL). Pelvic ultrasonography showed a pubertal-sized uterus with endometrial thickening and bilateral ovarian cysts (right: 32 × 17 mm; left multilocular cyst: 43 × 25 mm). Brain and pituitary magnetic resonance imaging was normal. Levothyroxine replacement resulted in cessation of vaginal bleeding, normalization of thyroid function and estrogen/prolactin levels, marked regression of the ovarian cysts and uterine enlargement, and improved linear growth over 12 months.

Conclusion: VWGS should be considered in girls with precocious pubertal signs, ovarian cysts, growth failure, and delayed bone age. Recognition of this reversible endocrine disorder can help avoid unnecessary invasive investigations and ovarian surgery. In children with Down syndrome, regular thyroid surveillance is particularly important because clinical manifestations of hypothyroidism may be subtle or attributed to the underlying condition.

Keywords: Van Wyk–Grumbach Syndrome; Primary Hypothyroidism; Gonadotropin-Independent Precocious Puberty; Down Syndrome; Trisomy 21; Ovarian Cysts; Vaginal Bleeding

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