Treatment of amiodarone-induced thyrotoxicosis (AIT) type 2: a RCT
Silvia A Eskes & Wilmar M Wiersinga
Background: AIT type 2 is self-limiting in nature and therefore discontinuation of amiodarone may not be necessary; however, the feasibility of continuing amiodarone has never been tested formally. Potassium perchlorate (KClO4) may have advantage when prednisone is unsuccessful in AIT type 2, possibly due to mixed cases of types 1 and 2. KClO4 also mitigates the cytotoxic effect of desethylamiodarone on thyrocytes in vitro.
Objectives: i) To demonstrate the feasibility of continuation of amiodarone in AIT type 2.
ii) To evaluate if KClO4 is useful in AIT type 2, given either alone or in combination with prednisone (to shorten time to euthyroidism).
Patients: We included patients with AIT type 2 (TSH<0.1 mU/l+FT4>25 pmol/l, TPO-Ab<50 kU/l, TBII<2.0 kU/l, poor or no visualisation of thyroid gland on 99mTc-pertechnate scintigraphy, no nodular goiter on ultrasound) in whom amiodarone was continued. Exclusioncriteria: severe co-existent illness, no informed consent.
Research design and methods: Randomised multicenter study, central randomisation in 3 treatment arms: i) 30 mg prednisone/day+30 mg methimazole/day, ii) 500 mg perchlorate 2×/day+30 mg methimazole/day, iii) 30 mg prednisone/day+500 mg perchlorate 2×/day+30 mg methimazole/day. If thyrotoxicosis persisted after 12 weeks of treatment, perchlorate was added in group A and prednisone in group B. In all groups amiodarone was continued. Total follow up time was 24 months.
Results: Fifty-six patients were registered of whom 42 patients randomised. 9 had no inclusion criterion (5 FT4<25 pmol/l, 3 because the cardiologist preferred to stop amiodarone, 1 AIT type 1). Five were excluded (4 no informed consent, 1 severe co-existent illness). Six were excluded after randomisation (3 high TBII or TPO-Ab, 2 because amiodarone was inadvertently withdrawn, 1 emigration). Thirty-six patients completed the study (12 group A, 14 group B, 10 group C). Euthyroidism ensued in all patients. Mean time to euthyroidism was shortest in group A (11 weeks; group B 14.9 and group C 13.2). Secondary therapy was required in 4 patients (group B) and recurrent thyrotoxicosis occurred in 5 (1 group A, 1 group B, 3 group C). There were no severe side effects.
Conclusions: Continuation of amiodarone is feasible in AIT type 2. Continuation of amiodarone after successful treatment of AIT type 2 is associated with 14% recurrences in 2 years. Treatment with prednisone is preferable to perchlorate and adding perchlorate to prednisone does not shorten time to euthyroidism in AIT type 2.