MON-237 - A Thyroid Rollercoaster in A Trisomy 21 Toddler: Congenitalhypothyroidism to Graves Disease, Challenged Withagranulocytosis

Background: Children with Down syndrome (DS) have markedly increased risk of thyroid diseases. Congenital Hypothyroidism is well known risk and Graves disease occurring in 6.6 per 1000 compared to 1 per 10,000 in the general pediatric population. However, transition from congenital hypothyroidism (CH) to Graves disease in early childhood is rare and presents with unique challenges.

Case Presentation: We present a 3-year-11-month-old female with trisomy 21 who had an unusual thyroid clinical course. Initially diagnosed with CH at 2 weeks (TSH 124.48 mIU/L, FT4 0.4 ng/dL), she started taking Levothyroxine 15 mcg/kg/day. She continued the same dose, and by 19 months she had "grown out" of her dose to 2.3 mcg/kg/day while maintaining euthyroidism. At 22 months of age, she developed biochemical hyperthyroidism (TSH 0.01 mIU/L, FT4 2.2 ng/dL) despite unchanged Levothyroxine dosing, and she underwent gradual weaning of Levothyroxine. She continued with hyperthyroidism off medication. At 24 months of age thyroid antibody testing revealed positive TRAb (17.45 IU/L) and TSI (351%), confirming Graves disease. Methimazole therapy (0.25 mg/kg/day) was initiated at 27 months. Following COVID-19 infection at 30 months, Absolute Neutrophil Count(ANC) decreased to 729µ/L, and due to concern for Methimazole related agranulocytosis medication stopped. Hematology consultation suggested that baseline neutropenia is common in healthy DS children. Studies established DS-specific reference ranges with lower ANC values than general pediatric populations. Due to patient size at that time (Height 71th%, Weight 21th % Down Girls Growth Chart) surgical option was not pursued. With continuous hyperthyroidism and ANC levels improved to 980µ/L, Methimazole was cautiously restarted at 38 months. The patient achieved euthyroidism (TSH 1.4 mIU/L, FT4 1.5 ng/dL) with normalized ANC (1403µ/L) at 40 months and remains to be stable up to date.

Discussion: Our case illustrates the rare occurrence of conversion of CH to Graves in a toddler with DS, highlighting the complex autoimmune dysregulation in trisomy 21, the diagnostic challenge of distinguishing Methimazole-induced agranulocytosis from syndrome associated neutropenia in DS patients and the limited treatment options for Graves disease in children under 5 years. Radioactive iodine is not an option and thyroidectomy carries amplified risks in DS patients due to anatomical considerations and anesthetic challenges and surgical challenges.

Conclusion: This case emphasizes the importance of understanding DS-specific physiologic variations when managing autoimmune thyroid disease and interpreting potential medication adverse effects in this population compared to unique surgical and operational challenges.

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