Endocrine Abstracts

23-year-old woman presented with rapid cycling bipolar disorder (RCBPD) with alternating episodes of mixed affective states, hypomania & severe depression. Quetiapine was initiated & discontinued due to side effects. Levothyroxine was started & gradually increased to 500mcg daily. This was coupled with 6 weeks of low frequency (LF) rTMS. She was clinically euthyroid. TSH <0.01 miu/l (0.27–4.2), fT4 37.1 pmol/l (12–22), fT3 8.4 pmol/l (3.1–6.8), rT3 30 ng/dL (10–24). Genetics: heterozygote polymorphism DIO2 (rs225014; T92A). A 53-year-old woman presented with refractory RCBPD. Quetiapine was started, increased to 700 mg with no response. Levothyroxine was added and increased to 750 mcgs daily & rTMS was commenced. She was clinically euthyroid. TSH <0.01 miu/l, fT4 77.3 pmol/l, fT3 11.7 pmol/l, rT3 79 ng/dl. Genetics: heterozygote polymorphism DIO2 (rs225014; T92A). Both cases achieved sustained remission for 7 months and 9 months respectively. We describe 2 cases of RCBPD with SNPs of DIO2, resistant to standard treatments who achieved sustained remission using HDL. This combination, we believe, has not been described before. Previous data highlights safety and effectiveness of supra-physiological doses of Levothyroxine in promoting remission. Heterozygote polymorphism DIO2 gene is associated 1.6-fold risk of bipolar disorder. Both patients had this and elevated fT4:fT3 ratio. Low circulating T4 weakens effectiveness of DIO2’s ability to generate T3 in the brain. We speculate high dose Levothyroxine helps to overcome this relative deficiency while robust inactivating deiodinases in the periphery help to protect from systemic thyrotoxicosis. RCBPD is a dangerous condition and has a 1: 6.5 mortality rate. Standard treatments are ineffective. We venture that HDL overcomes relative thyroid deficiency in patients with RCBPD while robust inactivating deiodinases in the periphery protect from systemic thyrotoxicosis. DIO2 is found in the brain. We speculate that RCBPD is a predominantly thyroid condition.