Thyroid : official journal of the American Thyroid Association | 2021
Identification of two different phenotypes of patients with amiodarone-induced thyrotoxicosis and positive thyrotropin receptor antibody tests.
Abstract
INTRODUCTION\nSerum TSH receptor antibodies (TRAbs) are occasionally found in patients with AIT, and usually orient toward a diagnosis of type 1 AIT (AIT1) due to Graves disease (GD). However, TRAb role and function in AIT are unsettled.\n\n\nMETHODS\nRetrospective cohort study of 309 AIT patients followed at a single Academic center over a 30-year period. AIT TRAb-positive patients (n=21, 7% of the whole series) constituted the study group; control groups were type 2 AIT (AIT2) TRAb-negative patients (n=233), and 100 non-AIT patients with GD. Clinical and biochemical data at diagnosis and during the course of disease were compared. Histological samples of patients submitted to total thyroidectomy were retrieved. Stored serum samples were used for a functional assay of TRAb immunoglobulins (IgGs) on Chinese hamster ovary (CHO) cells stably transfected with cDNA encoding for the TSH receptor.\n\n\nRESULTS\nTRAb-positive patients were grouped according to color flow Doppler sonography, thyroidal RAIU, duration of amiodarone therapy before thyrotoxicosis in type 1 (n=9, 43%; TRAb1) or type 2 (n=12, 57%; TRAb2) AIT. TRAb1 patients had clinical and biochemical features indistinguishable from GD controls, and were responsive to methimazole; conversely, TRAb2 patients had clinical features similar to AIT2 controls, and were responsive to glucocorticoids but not to methimazole. The CHO cells functional assay demonstrated that TRAb1 IgGs had a stimulatory effect on cyclic AMP production, which was absent in TRAb2 IgGs. Pathology in TRAb1 showed hyperplastic thyroid follicles and mild lymphocyte infiltration, reflecting thyroid stimulation, whereas TRAb2 samples revealed follicle destruction, macrophage infiltration and sometimes fibrosis, all expression of a destructive process.\n\n\nCONCLUSIONS\nAlmost 60% of TRAb-positive AIT patients had a destructive thyroiditis. Thus finding TRAb positive tests in AIT patients does not necessarily imply a diagnosis of Graves disease and type 1 AIT. Rather, it should be evaluated in the clinical and biochemical setting of each AIT patient.