SUN-321 - Lenalidomide Induced Thyroiditis

Introduction
Thyroiditis causes inflammation and damage of thyroid follicular cells, releasing thyroid hormones resulting in possible thyrotoxicosis. We present a case of a patient admitted with new onset atrial fibrillation with rapid ventricular response (A-fib with RVR) caused by lenalidomide induced thyroiditis leading to thyrotoxicosis.

Clinical Case
A 83-year-old male with a history of myelodysplastic syndrome (MDS), cutaneous squamous cell carcinoma on monthly cryotherapy, prior laryngeal carcinoma, CKD-3, BPH, and GERD presented to the emergency department for a 1-month history of generalized weakness, 4-day history of hoarseness, and 2-day history of exertional dyspnea. Vital signs were notable for tachycardia at 106 BPM and then developed new-onset A-fib with RVR. A multinodular thyroid gland with a dominant 5.9 cm left lobe nodule was found on a soft tissue neck CT with IV contrast. A thyroid function test showed suppressed TSH < 0.02 mIU/L (normal 0.465-4.680 mIU/L) with markedly elevated FT4 at > 6.99 ng/dL (normal 0.58 - 1.90 ng/dL) and FT3 at >22.80 pg/mL (normal 2.30-4.80 pg/mL) indicating severe thyrotoxicosis. MDS was managed with lenalidomide 5 mg daily and luspatercept injections every 3 weeks.

Endocrinology evaluation showed mildly elevated TPO antibodies at 18 IU/mL (normal < 9 IU/mL) with negative TSI and TRAb. A neck and thyroid ultrasound confirmed an enlarged thyroid with multiple sub-centimeter nodules and a dominant 7.5 cm, TI-RADS 0, cystic left lower pole nodule that was aspirated for compressive symptoms. Although not fully ruled out, the cystic nature of the dominant nodule and multiple sub-centimeter nodules typically do not produce enough hormones, making a toxic adenoma and toxic multinodular goiter unlikely. His thyrotoxicosis was attributed to lenalidomide induced thyroiditis. A direct dialysis FT4 was markedly elevated at >12.8 ng/dL (normal 0.9-2.2 ng/dL). Methimazole was briefly started and discontinued once autoimmunity was ruled out. He was discharged on metoprolol succinate 100 mg daily, prednisone 20 mg daily, and cholestyramine 4 g packets with outpatient endocrinology and oncology follow up.

Discussion
While lenalidomide rarely causes thyroid dysfunction, hypothyroidism predominates when it occurs. Thyrotoxicosis is even rarer, with only one prior case of transient thyroiditis. As an immunomodulator, it enhances T-cell and natural killer cell activity and increases tumor necrosis factor-alpha levels, potentially inducing destructive thyroiditis. A triphasic course is typically seen: thyrotoxicosis, hypothyroidism, and permanent hypothyroidism in 10-20% of those cases. This case adds to limited literature by demonstrating severe thyrotoxicosis and emphasizes the need for serial thyroid monitoring every 4-6 weeks to monitor for hypothyroidism. Our case also promotes future education and raises awareness of a rare but serious adverse effect.

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