SAT-518 Progression of Graves Disease to Hashimoto’s Thyroiditis Following Alemtuzumab Therapy for Multiple Sclerosis

Abstract

Introduction: Alemtuzumab, an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis is most commonly associated with Graves disease, but autoimmune hypothyroidism may also be seen. We present an unusual case where both were present in the same patient and progression from hyperthyroidism to hypothyroidism was seen within only a few months. Clinical Case: A 33-year-old female referred to Endocrinology clinic for evaluation of hyperthyroidism. She was complaining of palpitations, tremors, increased sweating, heat intolerance, and unintentional weight loss for 3 months. She received 2 cycles of alemtuzumab treatments over the last 21 months for her multiple sclerosis. Last treatment was 8 months before she developed hyperthyroid symptoms. Patient had no prior history of thyroid disorder. Thyroid stimulating hormone (TSH) level was within normal range before alemtuzumab was administered. TSH was monitored periodically and was normal till 8 months after receiving alemtuzumab therapy. Physical exam was remarkable for diffuse enlarged thyroid, not tender, without palpated thyroid nodules but with thyroid bruit. No proptosis was present.Thyroid function tests obtained by her primary care physician were consistent with hyperthyroidism. Patient found to have suppressed TSH <0.015 IU/mL [0.465 - 4.680IU/mL], elevated total T3 372ng/dL [97-169ng/dL], and elevated total T4 >24.9 ug/dL [5.5 - 11.0 ug/dL].Further workup revealed elevated Free T3, 10.90 [2.77 - 5.27 pg/mL] and elevated free T4 > 6.99 ng/dL [0.78 - 2.19 ng/dL]. Thyrotropin receptor antibody (TR Ab) was elevated as well at 3.43 IU/L [<1.75 IU/L]. Pregnancy test was negative. Thyroid ultrasound demonstrated goiter with no focal thyroid nodules seen. She was started on methimazole 10 mg daily.One month later, TSH was elevated at 31.58 though she only took methimazole for one week and then discontinued due to rash and pruritus. At that time, she reported severe fatigue and 25 lbs weight gain. Repeated labs one month later showed elevated TSH, 60.978 IU/ML, low free T4 0.08 pg/mL and low free T3 0.72 ng/dL. Thyroid peroxidase Antibody (TPO Ab) was obtained and was 5308.8 IU/mL [0.0 - 5.5 IU/mL]. She was started on levothyroxine 100 mcg daily. Two months later, levothyroxine dose was increased to 112 mcg daily due persistent TSH elevated. At subsequent visit, patient was euthyroid with normal TSH 3.191IU/mL and normal free T4 1.48 ug/dL. Conclusion: This case was unique in that the patient developed both TR Ab and TPO Ab after alemtuzumab therapy which resulted in Grave’s disease followed by Hashimoto’s thyroiditis. The case highlights the importance of continuous monitoring of thyroid function in patients treated with alemtuzumab given the unpredictable autoimmune phenomena which may occur.