SUN-419 Quetiapine-Induced Central Hypothyroidism

Background: Thyroid dysfunction has been associated with the use of quetiapine, but the underlying mechanism is not well understood. The scant data published on quetiapine-induced hypothyroidism suggests that the hypothyroidism is primary. We present a pediatric patient who developed symptomatic central hypothyroidism while on quetiapine. Case: A 12-year-old girl with pervasive developmental disorder and multiple psychiatric issues presented with a 2-week history of extreme sleepiness and a 3 kg weight gain over 2 months. She denied constipation, skin or hair changes, irregular menses and temperature intolerance, and was otherwise in her usual state of health. Her medications included fluoxetine 75 mg/day and quetiapine 100 mg AM/125 mg PM. She had been on quetiapine for 1 year and her dose was increased 3 months prior to onset of symptoms. She had normal TFTs prior to initiation of quetiapine and no history of head trauma. Family history was significant for a maternal grandmother with hypothyroidism. Initial TFTs revealed Free T4 (FT4) 0.8 ng/dL (0.9-1.4), Free T3 (FT3) 3.2 pg/mL (3.3-4.8) and TSH 1.53 mIU/mL (0.5-4.3). Two weeks later, repeat TFTs showed FT4 (equilibrium dialysis) 0.8 ng/dL (1.0-2.4), FT3 3.1 pg/mL (3.3-4.8) and TSH 1.18 mIU/mL (0.5-4.3). She was started on levothyroxine (LT4) 25 mcg daily, and 1 month later she was evaluated by Pediatric Endocrinology. Her fatigue had improved, and her interim history and physical examination were unremarkable. Her weight was 50.6 kg and BMI was 21. TFTs showed FT4 (equilibrium dialysis) 1.1 ng/dL (1.0-2.4), FT3 3.5 pg/mL (3.3-4.8) and TSH 1.06 mIU/mL (0.50-4.30). Additional testing revealed IGF-1 595 ng/mL (178-636), FSH 7.8 U/L, LH 4.9 U/L, prolactin 6.6 mcg/L (2-25) and random cortisol 8.9 mcg/dL (5.0-25.0). LT4 was increased to 50 mcg daily, and 6 weeks later, TFTs showed FT4 0.9 ng/dL (0.9-1.4), FT3 3.4 pg/mL (3.3-4.8) and TSH 0.46 mIU/mL (0.5-4.30). Conclusion: This is the first report of quetiapine-induced central hypothyroidism. The drug manufacturer reports low T4 without change in TSH in up to 50% of patients treated with quetiapine in clinical trials, which is suggestive of central hypothyroidism. However, central hypothyroidism is not mentioned as the etiology of low T4 by the drug manufacturer or in any publications to date. The scant published literature describing quetiapine-associated thyroid dysfunction reports that the drug causes low T4 with either normal or elevated TSH, and that typically, only those with elevated TSH are treated with LT4. This suggests that the medical community presumes that quetiapine-induced hypothyroidism is primary. Our case suggests that quetiapine-associated hypothyroidism is central rather than primary in some, if not all, cases. We propose consideration of LT4 treatment for patients on quetiapine with low T4 and low, normal or elevated TSH.