SUN-057 Mifepristone as a Potential Risk Factor for Hypothyroidism: A Case Report of a Puerto Rican Woman with Cushing Disease

Abstract Disclosure: A.C. Cotto-Vazquez: None. L. Rodriguez-Franco: None. O. Mora-Osoria: None. G. Rosario-Guzman: None. A. Fret-Cruz: None. C. Rosario-Martinez: None. J.M. Garcia-Mateo: None. Background: Mifepristone, a glucocrticoid receptor antagonist, has been used for hyperglycemia secondary to persistent Cushing syndrome in patients with type 2 diabetes mellitus (DM). Although hypothyroidism is not a known side effect of mifepristone, several case reports have noted an association between altered thyroid function tests and the use of mifepristone in patients with a predisposition to or established hypothyroidism.Case: We present a 53-year-old Hispanic female with a history of type 2 DM, obstructive sleep apnea, hypertension, dyslipidemia and osteopenia who has been evaluated at an endocrinology clinic for diabetes management. Physical examination revealed signs of cortisol excess. Laboratory workup established ACTH dependent Cushing. Pituitary MRI suggested a right sided microadenoma and diagnosis was confirmed after bilateral inferior petrosal sinus sampling. Initial treatment with transsphenoidal surgery was unsuccessful, with postoperative 1-mg overnight dexamethasone suppression test levels remaining elevated. Considering her chronic conditions of diabetes and obesity, the patient was started on mifepristone 300mg daily, gradually titrated to 900mg daily over eight months. Follow up laboratory assessment demonstrated normal levels of cortisol as well as improvement in comorbid conditions. Over the course of the 8-month long treatment, thyroid function tests (TFTs) demonstrated an elevated TSH and normal free T4 in comparison to baseline TFTs. Further work up revealed elevated anti-thyroid peroxidase (TPO) antibody. There is limited evidence about the effect of mifepristone on thyroid function, however some studies have suggested it can influence thyroid receptor sensitivity, the signaling pathways of thyroid hormones or their deiodination. Moreover, some studies have discussed it can reduce the expression of proteins essential to thyroid hormone synthesis. In patients with anti-TPO antibodies, the immune system attacks the thyroid gland impairing its ability to produce adequate amounts of thyroid hormones. This gradual destruction of thyroid tissue renders the thyroid less capable of synthesizing and secreting thyroid hormones. Thus, our patient remains at an elevated risk for developing hypothyroidism, further compounded by the use of mifepristone, which may exacerbate thyroid dysfunction.Conclusion: Although our patient remained clinically euthyroid, these findings suggest mifepristone can propel a subclinical patient into a more symptomatic state. In addition, this case presents the importance of baseline TFTs and repeat monitoring of patients with autoimmune predisposition to hypothyroidism. Furthermore, this raises important considerations regarding patients with pre-existing hypothyroidism, who may exhibit increased levothyroxine requirements while receiving mifepristone. Presentation: Sunday, July 13, 2025