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.
In a retrospective analysis of alemtuzumab-induced thyroid dysfunction, Graves disease with fluctuating status that was relatively refractory to treatment and anti-TSH receptor antibody–positive hypothyroidism was recorded.
Objective
Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post‐RI and ...compare effectiveness of common management strategies.
Design
Retrospective, multicentre and observational study.
Patients
Adult patients with Graves' disease treated with RI with 12 months' follow‐up.
Measurements
Euthyroidism was defined as both serum thyrotropin (thyroid‐stimulating hormone TSH) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo‐ and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4.
Results
Of 812 patients studied post‐RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post‐RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%–28.7%). No negative outcomes (new‐onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres.
Conclusions
Dysthyroidism in the 12 months post‐RI was common. Differences between post‐RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.
Luigi Bartalena (luigi.bartalena@uninsubria.it) Endocrine Unit, University of Insubria, Varese, Italy Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. When fully ...expressed, it is characterized by inflammatory soft tissue changes, exophthalmos, ocular dysmotility causing diplopia, and, rarely, sight-threatening dysthyroid optic neuropathy (DON). The prevalence of GO among Graves' patients seems lately declining, probably due to early diagnosis, early intervention on risk factors associated with its occurrence or progression (smoking, uncontrolled thyroid dysfunction), early correction of hyper and hypothyroidism. Only about 25-30% of newly diagnosed Graves' hyperthyroids are affected with GO, which is usually mild and rarely progressive. Assessment of activity and severity of GO according to standardized criteria is fundamental to plan management. The European Thyroid Association and the European Group on Graves' Orbitopathy (EUGOGO) have recently published the first guideline on management of GO. Mild GO usually requires only a watchful strategy, in addition to local measures (eye drops, ointments) and removal of risk factors. Intravenous glucocorticoids (ivGCs) are the first-line treatment for moderate-to-severe and active GO, as demonstrated by randomized clinical trials. When ivGCs fail or GO recurs after treatment withdrawal, options include a second course of ivGCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab. Evidence that the any of the above treatment be effective in the context of a poor response to a first course of ivGCs is limited and should be investigated in larger studies. In addition to rituximab, ongoing investigations are exploring the role of other biologics targeting, e.g., the IGF-1 receptor or the IL-6 receptor, and results will probably available in 1-2 years. When GO has been treated medically and is inactive, rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) is often needed.
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