Endocrine Abstracts

Introduction: Alemtuzumab is a humanized anti-CD52 monoclonal antibody approved for the treatment of relapsing−remitting multiple sclerosis (RRMS). Through an immune reconstitution mechanism, it leads to thyroid autoimmunity in 35% of cases, with Graves’ disease (GD) being the most common presentation. Alemtuzumab-induced GD exhibits distinctive clinical and immunological features, with rarely reported cases of fluctuating thyroid status with documented both blocking (TBAb) and stimulating (TSAb) TRAb.

Case description: A 48-year-old woman, diagnosed with RRMS at the age of 33, underwent the first and second cycle of alemtuzumab in 2019 and 2020, respectively. Neither the patient nor her relatives had history of thyroid disease. Clinical and medication history were otherwise unremarkable. Almost 12 months after treatment, she complained about exacerbated fatigue, and was referred to the endocrinology appointment for altered function tests. Clinical examination revealed a non-pulsatile goiter, with no evident signs of orbitopathy (Clinical Activity Score 0). Laboratory workup showed TSH 0.004 mUI/ml (0.4-4), fT4 2.2 ng/dl (0.7-1.5), fT3 5.1 pg/ml (1.8-4.2), TRAb 110 U/l (<1.0) TSAb 40 U/l (<0.1) and anti-TPO 916 UI/ml (<5.6). Thyroid ultrasound excluded nodules. She started treatment with methimazole (MMI) 5 mg/day. Two months after, analytical follow-up revealed TSH 0.29 mUI/ml, fT3 2.1 pg/ml, fT4 0.60 ng/dl and was told to stop MMI. The patient was reevaluated in 2 months, under no therapy, with worsening of fatigue and palpebral oedema, with TSH 93 mUI/ml, fT4 <0.40 ng/dl, fT3 <1.0 pg/ml, TRAb 98 U/l, TSAb 7.3 U/l. At this point she started levothyroxine (LT4) with progressive doses up to 75 micrograms/day. Six months later, TSH was <0.004 mUI/ml, fT4 1.4 ng/ml, TRAbs 3.1 U/l, TSAb 2.7 U/l and LT4 was stopped. Thereafter, thyroid function kept switching unexpectedly between hyper and hypothyroidism, and was finally proposed to treatment with radioiodine (RAI). Six weeks after RAI, with no other therapy, TSH was 68 mUI/ml, fT4 <0.40 ng/dl, TRAbs 10 U/l, TSAb 7.3 U/l, and LT4 was re-started in progressive doses.

Conclusion: We present a case of alemtuzumab-induced GD with unexpected fluctuations from hyperthyroidism to hypothyroidism, not explained by omission or changes in therapy. There was evidence of periods were TRAb level were rising but TSAb levels were decreasing, which may be explained by the presence of TBAb in circulation. Our case report emphasizes the need for close monitoring of thyroid function in patients with alemtuzumab-induced GD, as maintaining euthyroidism in these patients may represent a challenge.