Identification of Two Different Phenotypes of Patients with Amiodarone-Induced Thyrotoxicosis and Positive Thyrotropin Receptor Antibody Tests

Thyroid autoantibodies

“…While TRAb positivity points to type-1 AIT, in several reports, a significant proportion of these patients was found to have type-2 AIT (table 1). 50–52 This limits the usefulness of TRAb as a solitary tool in making this differentiation and its use alongside colour-flow Doppler study is a better option.…”

Short review: novel concepts in the approach to patients with amiodarone-induced thyrotoxicosis

“…A longer follow-up showed that for AIT patients affected by moderate-to-severe left-ventricular systolic dysfunction (i.e., LVEF < 40%, as defined by the Framingham Heart Study [ 55 ]), surgery presented a significant survival advantage compared to optimal medical therapies, both when considering cardiovascular mortality at 5 years and overall mortality at 10 years [ 17 ]. The same survival advantage was not confirmed for patients affected by less severe cardiac dysfunction [ 18 ]. The favorable result obtained when surgery was performed in this high-risk setting was ascribed to its capability to promptly restore euthyroidism with a consequent improvement in systolic function (mean LVEF 45% pre-surgery vs 50% post-surgery, p < 0.0001) [ 17 ].…”

“…Thyroid hormones concentrations are not useful to differentiate type 1 and type 2 AIT, although they tend to be higher in type 2 AIT [ 15 , 17 ]. In the past, an increased T4/T3 ratio (> 4) was considered to be a feature of type 2 AIT, as derived from populations studies [ 17 , 18 ], but this parameter is not useful in the individual patient due to the large overlap in the ratios between the two AIT types [ 15 , 17 ]. However, when present, it might be considered.…”

“…More recently, the role of thyrotropin receptor autoantibodies (TSHR-Ab) in the differential diagnosis between the two AIT types has been questioned: as a matter of fact, the presence of TSHR-Ab was found in patients classified as either AIT1 or AIT2 on the basis of clinical and histopathological features [ 21 ]. A functional assay demonstrated that only TSHR-Ab obtained from patients displaying AIT1 and Graves’ disease features stimulated the TSH receptor, whereas TSHR-Ab obtained from AIT2 patients displayed a neutral or inhibiting activity [ 21 ]. The presence of TSHR-Ab is reported in the most recent guidelines as a distinctive marker of AIT1 in the form of amiodarone-induced Graves’ disease [ 10 ], but this point probably needs to be revised in future guidelines.…”

“…At variance, assays measuring the stimulatory activity of the TSHR-Ab on the TSH receptor (so-called TSI assays, i.e., thyroid stimulating immunoglobulin assays) [ 23 , 24 ] do not measure TSHR-Ab with a neutral or inhibitory effect. Even though the use of TSI assays has not been reported to date in the setting of AIT, it may be anticipated that the use of TSI in the clinical practice may help to reduce misclassification of TSHR-Ab-positive AIT patients [ 18 ].…”