Endocrine Abstracts

Case History: Case 1: A 37-year-old lady with relapsing-remitting multiple sclerosis was initiated on Alemtuzumab and symptoms of sweats and heat intolerance arose. Hyperthyroidism was confirmed with free T4 30.1 pmol/l (12–22) and suppressed TSH. Symptoms settled without antithyroid medication and within 2 months T4 had fallen to 10.2 pmol/l with TSH 6.95 mIU/L. After a further 6 weeks T4 was 9.8 with TSH 20.35 and levothyroxine was initiated. Anti-TPO was raised at 442 U/mL, with TSH receptor antibodies (TRAb) of <0.3I U/L. The patient did not complain of any swelling in the neck and the thyroid examined normally throughout. Case 2: A 27-year-old female with relapsing-remitting multiple sclerosis had two periods of alemtuzumab treatment through 2016 and 2017. In 2018, she developed symptoms of sweating, feeling faint and palpitations. T4 rose to 65.5 pmol/L with suppressed TSH, improving at 6 weeks to a T4 of 11.4 pmol/L, but TSH remained suppressed without treatment. Within another 8 weeks TSH was measurable at 6.04 mIU/L with T4 falling to 7.4 pmol/L and levothyroxine 50micrograms was started. TRAb were markedly raised at 85.4 IU/L.

Results and treatment: Neither case received antithyroid medication and both cases eventually became hypothyroid and were started on Levothyroxine. Given that alemtuzumab is strongly associated with autoimmune thyroiditis (40%), watchful-waiting is the way forward in cases like this. Treatment should be initiated early in those with ophthalmoplegia, those with acutely enlarging goitre and those with prolonged symptoms. TSH receptor antibodies are an important test as graves thyroid disease is less likely to self-resolve.

Conclusions and points for discussion: These cases highlight firstly the need for awareness of the impact of alemtuzamab on thyroid function, given its frequent use and its reported 40% incidence of associated thyroid dysfunction. Secondly, there is a need for awareness of the variable clinical and immunological presentation induced by alemtuzamab. Both our cases had a symptomatic hyperthyroid phase, of short duration and self-limiting progressing rapidly to a hypothyroid phase. In Case 1, anti TPO antibodies were strongly positive with unmeasurable TRAb, whereas Case 2 had significantly raised TRAb with a much smaller anti TPO rise. Additionally, variation in TRAb bioactivity both between patients and over time in individual patients treated with alemtuzamab has been recently described. In summary, our cases demonstrate a need for careful thyroid monitoring in alemtuzamab treated patients. The significance of thyroid antibody results in predicting clinical course or guiding treatment decisions needs to be more clearly determined.