Abstract
CONTEXT: The treatment of resistance to thyroid hormone β (RTHβ) is challenging because features of hyperthyroidism in some tissues coexist with a hormone-resistant, hypothyroid state in other organs. OBJECTIVE: To determine whether triiodothyroacetic acid (TRIAC) therapy alleviates hyperthyroid symptoms and changes circulating thyroid hormones, resting energy expenditure and metabolic parameters in RTHβ. DESIGN: Retrospective cohort study. SETTING: Referral center. PARTICIPANTS: Eight adult patients with RTHβ (mean age 41 years; 4 males, 4 females). MAIN OUTCOME MEASURES: Hyperthyroid Symptom Scale (HSS) score, serum free T4 and total T3, resting energy expenditure, sleeping heart rate, fasting lipids, and glucose and systemic insulin resistance. RESULTS: From abnormally elevated levels prior to treatment, TRIAC therapy lowered HSS scores (baseline 17.5 vs posttreatment 6; P = .0014), showed a reduced resting energy expenditure trend (baseline Z-score +1.3 vs posttreatment +0.89; P = .38) and normalized circulating free T4 (baseline free T4 30 pmol/L vs posttreatment 17 pmol/L; P = .007) and total T3 (baseline 2.5 nmol/L vs posttreatment 1.4 nmol/L; P = .001) concentrations in 7 out of 8 patients, without any rise in their serum TSH (baseline 2.1 mU/L vs posttreatment 1.7 mU/L; P = .65), total cholesterol (baseline 4.9 mmol/L vs posttreatment 4.8 mmol/L; P = .81), and triglyceride (baseline 1.3 mmol/L vs post-treatment 1.3 mmol/L; P = .44). Their mean sleeping heart rate (baseline 60 bpm vs posttreatment 58 bpm; P = .56) and plasma N-terminal pro-brain natriuretic peptide (baseline 55 ng/L vs posttreatment 54 ng/L) were unchanged. TRIAC treatment was well tolerated, with no side effects. CONCLUSION: TRIAC therapy in RTHβ relieves hyperthyroid symptoms and lowers resting energy expenditure and circulating thyroid hormones without worsening hepatic hormone resistance or exacerbating cardiac thyromimetic activity. Future clinical trials to determine whether TRIAC treatment alters adverse cardiovascular outcomes in this disorder are warranted.