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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., (© 2022 John Wiley & Sons Ltd.)

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.

Purpose: Masked hypertension (MH) is the association of normal office blood pressure (BP) with high ambulatory or home BP. This condition is associated with increased cardiovascular target organ damage, as true hypertension. Because the relation with hypothyroidism is controversial, we investigated it in a pilot longitudinal and controlled study., Methods: We consecutively enrolled 64 newly diagnosed hypothyroid patients, 38 subclinical (s-HYPO), and 26 overt (o-HYPO). The control group consisted of 50 euthyroid subjects seen at outpatient clinics. All participants underwent office and 24-h ambulatory BP measurement., Results: BP monitoring revealed a higher prevalence of MH both in s-HYPO (26.3 %) and in o-HYPO (15.4 %) than in euthyroid subjects (10 %, p = 0.05); true hypertension also was more frequent in o-HYPO (11.5 %) and s-HYPO (10.5 %) than in controls (8 %, p = 0.03). The odds ratio for hypertension versus normotension confirmed a significantly increased risk of MH in hypothyroid patients versus euthyroid subjects (3.29, 1.08-10.08; p = 0.02). In a subgroup of patients reevaluated after restoration of euthyroidism, an improvement of BP profile was observed, especially in s-HYPO subgroup, with a decreased prevalence of MH (from 25 to 10.7 %) and true hypertension (from 10.7 to 3.4 %)., Conclusions: Hypothyroidism may be an important predictor of higher BP values, with an increased risk of MH. Because MH is a cardiovascular risk and can be reversed by thyroid hormone replacement, its presence should represent an indication for thyroid hormone replacement therapy also in patients with s-HYPO.

Background: The prevalence and natural history of Graves' orbitopathy (GO) are poorly documented., Methods: A large series of 346 patients with newly diagnosed and recent onset Graves' hyperthyroidism seen at a single (nontertiary referral) center over an 8-year period were enrolled in an observational prospective study and evaluated for GO activity and severity according to the EUGOGO (European Group on Graves' Orbitopathy) criteria. After excluding patients immediately treated for moderate-to-severe GO, patients undergoing total thyroidectomy or radioactive iodine treatment, and patients lost to follow-up, 237 patients were submitted to antithyroid drug (ATD) treatment, with ocular evaluation at 6, 12, and 18 months., Results: Among the whole cohort, at presentation 255 (73.7%) had no ocular involvement, 70 (20.2%) had mild and inactive GO, 20 (5.8%) had moderate-to-severe and active GO, and 1 (0.3%) had sight-threatening GO with dysthyroid optic neuropathy. Of the 237 patients who completed the 18-month follow-up during or after ATD treatment, 194 (81.9%) had no GO at baseline. Progression to moderate-to-severe GO occurred in 5 (2.6%) of these patients. Of the 43 (18.1%) patients with mild and inactive GO at baseline, 1 (2.4%) progressed to moderate-to-severe GO, and 25 (58.1%) experienced complete remission., Conclusions: Most patients with newly diagnosed Graves' disease have no ocular involvement. Moderate-to-severe and active GO or sight-threatening GO are rare at presentation and rarely develop during ATD treatment. Most patients (>80%) with no GO at baseline do not develop GO after an 18-month follow-up period. Remission of mild GO occurs in the majority of cases.

Autoimmune thyroid disorders (AITDs) are the result of a complex interplay between genetic and environmental factors, the former account for about 70-80% of liability to develop AITDs. However, at least 20-30% is contributed by environmental factors, which include certainly smoking (at least for Graves' disease and orbitopathy), probably stress, iodine and selenium intake, several drugs, irradiation, pollutants, viral and bacterial infections, allergy, pregnancy, and post-partum. Evidence for the intervention of these factors is often limited, and the mechanisms whereby environmental factors may concur to the onset of AITDs are in many instances unclear. Nevertheless, gene-environment interaction seems a fundamental process for the occurrence of AITDs.