8208 Unexpected and significant rise in TSH in the setting of Relugolix use

Abstract Disclosure: A.Y. Groysman: None. A. Poloju: None. P. Majety: None. T. Abraham: None. Background: Relugolix is a gonadotropin-releasing hormone antagonist used as androgen deprivation therapy for metastatic and nonmetastatic castration-resistant prostate cancer that was FDA-approved in December 2020. Common side effects include hot flashes, increased glucose and triglycerides, and decreased hemoglobin. We report a case of Relugolix interference with the absorption of levothyroxine, which has not been reported in the literature. Case: A 79-year-old white man with high-risk, Gleason 9 prostate cancer and Hashimoto’s hypothyroidism presented for evaluation of elevated thyroid stimulating hormone (TSH) level- 52.87 mIU/L (0.28-4.10 mIU/L). He did not have cold intolerance, constipation, fatigue, or weight gain. He was diagnosed with hypothyroidism in 1998 and was on a stable dose of levothyroxine 88mcg daily from 2016 until the time of this presentation. He is adherent and reports following a routine of having breakfast with coffee soon after taking levothyroxine for many years. In June 2022, his TSH was 4.48 mIU/L. In July 2022, he started taking Relugolix along with levothyroxine. Following this, his TSH levels increased to 30.08 mIU/L (FT4: 0.67 ng/dL), 35.43 mIU/L (FT4: 0.57 ng/dL), 52.87 mIU/L (FT4: 0.48 ng/dL) on 2/24/23, 3/3/23, and 3/14/23, respectively. No new medications were reported. His other medications were atorvastatin, tamsulosin, and vitamin D, which he took at night. He did not take calcium or biotin supplements. He had gradual weight gain (8 lbs) over the last 9 months. Levothyroxine dose was increased from 88 to 125 mcg daily and he was instructed to separate Relugolix from levothyroxine so he started taking Relugolix at bedtime. Repeat TSH was low at 0.12 mIU/L. The levothyroxine dose was eventually titrated back to 88 mcg daily and TSH was 5.2 (appropriate for age). Conclusion: Several medications are known to interfere with the absorption of levothyroxine. Our case suggests that Relugolix may be one of them. The significant rise in TSH and levothyroxine requirements months after starting Relugolix and the ability to return to the previous dose of levothyroxine only by separating Relugolix from levothyroxine strongly suggests that there is an interference between these medications that has not been reported. Presentation: 6/2/2024