Unusual Endocrinopathies in 18q Deletion Syndrome: Pseudoparathyroidism and Hyper-/Hypo-Thyroidism

Abstract

Objective: To describe new and unusual endocrinopathies in children with de novo 18q deletion (18q-) syndrome. Methods: We describe 2 patients who have atypical thyroid conditions and 1 who also developed symptomatic hypocalcemia. Results: The first patient developed hyperthyroidism at the age of 3 years, with a free thyroxine level of 3.9 (range, 0.8-1.8) ng/dL. Thyroid peroxidase antibodies were 262 (range, 0-32) IU/mL, and thyroidstimulating immunoglobulin antibodies were 384% (range, 0-139%). On low-dose methimazole treatment, she developed hypothyroidism. Thyroid-stimulating hormone (TSH) level was 163 (range, 0.4-4.5) mIU/mL. Moreover, she later developed growth hormone deficiency. The second patient developed hypothyroidism at the age of 4 years, with a TSH level of 46 mIU/mL. However, TSH remained elevated at levels of 10 to 24 mIU/mL for 3 years, despite appropriate treatment, suggesting TSH resistance. She then developed hypocalcemic seizures and was diagnosed with pseudohypoparathyroidism. Her total calcium level was 6.6 (range, 8.5-10.5) mg/dL and parathyroid hormone level was 432 (range, 15-65) pg/dL. Conclusion:The first patient had a mixed picture of autoimmune hypothyroidism and hyperthyroidism, requiring a combination of methimazole and levothyroxine to achieve a euthyroid state. For the second patient, the mild TSH resistance was possibly the early suggestion of a parathyroid hormone resistant state. Although growth hormone deficiency and hypothyroidism are common in patients with 18qsyndrome, the occurrence of hyperthyroidism due to Graves' disease with the coexistence of Hashimoto's hypothyroidism is rare. Pseudohypoparathyroidism has not yet been reported in patients with 18qsyndrome.