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. 2018 Aug 1;103(8):3010-3018.
doi: 10.1210/jc.2018-00359.

Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features

Nadia Pariani  1 , Mark Willis  2 , Ilaria Muller  3 , Sarah Healy  2 , Taha Nasser  2 , Anne McGowan  1 , Greta Lyons  1 , Joanne Jones  4 , Krishna Chatterjee  1 , Colin Dayan  3 , Neil Robertson  2 , Alasdair Coles  4 , Carla Moran  1
Affiliations

Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features

Nadia Pariani et al. J Clin Endocrinol Metab. .

Abstract

Context: Alemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves disease (GD), with a reportedly indolent course.

Objective: To determine the type, frequency, and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated patients with MS in the United Kingdom.

Design: Case records of alemtuzumab-treated patients who developed TD were reviewed.

Results: A total of 41.1% (102 out of 248; 80 female and 22 male) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2 to 107) following the last dose, with the majority (89%) within 3 years. Follow-up data (range 6 to 251 months) were available in 71 case subjects, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 patients with GD commenced antithyroid drugs (ATDs): 3 required radioiodine (RAI) due to ATD side effects, and drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI, n = 17; thyroidectomy, n = 5; and long-term ATDs, n = 8). Three cases of thyroiditis and 16 cases of hypothyroidism were documented: 5 with antithyroid peroxidase antibody positivity only, 10 with positive TSH receptor antibody (TRAb), and 1 of uncertain etiology. Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases.

Conclusions: Contrary to published literature, we recorded frequent occurrence of GD that required definitive or prolonged ATD treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

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Figures

Figure 1.
Figure 1.
Overview of patients (pts) included in the study.
Figure 2.
Figure 2.
Course of TD in a patient (patient 6 in Table 3) with fluctuating GD.
Figure 3.
Figure 3.
(a) Initial treatment modality in 52 patients with GD and follow-up data. Three patients underwent RAI treatment due to intolerance of ATDs. (b) Longer-term management in 47 patients with GD following completion of initial course of ATD therapy.
See this image and copyright information in PMC

Comment in

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