SAT-385 Ruxolitinib Induced Thyroiditis

Abstract Disclosure: A. Kang: None. H. Akbari: None. R. Devbhandari: None. R.M. Jhingan: None. Drug-induced thyroiditis is characterized by inflammation of the thyroid gland which requires discontinuation of the offending agent and close clinical monitoring. Ruxolitinib is an antineoplastic agent that is used to treat myelofibrosis and works by inhibiting janus kinase (JAK) receptors. To our knowledge, this is the first case of ruxolitinib associated thyroid dysfunction in myelofibrosis. Our patient was a woman in her 70s with a history of JAK2 myelofibrosis, portal hypertension and no prior history of thyroid disease who was admitted to the hospital for an upper gastrointestinal bleed secondary to esophageal varices. Her clinical course was complicated by hypotension, bradycardia, hypothermia which prompted evaluation of the thyroid. Labs were significant for thyroid stimulating hormone 11.03, free T4 < 0.42. She had been experiencing fatigue and cold intolerance for the past week and had been taking a new medication ruxolitinib for the past 6 weeks for myelofibrosis. Her family confirmed that she did not have any personal or family history of thyroid disorders. Previous imaging studies were unremarkable for thyroid pathology. She also did not have any recent medication changes apart from the addition of ruxolitinib. Ruxolitinib was discontinued and the patient was treated with intravenous levothyroxine and hydrocortisone with appropriate improvement of labs and clinical features. Thyroiditis is not a known adverse effect of ruxolitinib, but other tyrosine kinase inhibitors such as sunitinib have been reported to induce either hypothyroidism or hyperthyroidism. Among reported cases, thyroid dysfunction typically developed in the time frame of 1-2 months which is consistent with our patient’s timeline of symptoms. Ruxolitinib is currently being evaluated for its role in anaplastic thyroid cancer. In a recent study, JAK1/2-STAT3 receptors were observed to be upregulated in anaplastic thyroid carcinoma compared to normal thyroid and papillary thyroid cancer tissues. Ruxolitinib suppresses the phosphorylation of STAT3 which ultimately results in mitochondrial deficiency and impaired cell division. In vitro and vivo administration of ruxolitinib resulted in significant apoptosis of the tumor cells. Regarding our patient, it is plausible that inhibition of the JAK1 and JAK2 pathway in thyroid hormone metabolism could have contributed to her presentation. Much remains to be elucidated on the long-term implications of JAK inhibitors such as ruxolitinib, and ongoing research is imperative to substantiate the safety and efficacy of their use in thyroid disease. Presentation: Saturday, July 12, 2025