The maintenance dose of levothyroxine does not differ in patients with hypothyroidism with vs without heart failure, according to study results published in Endocrine Research.

Previous studies have investigated the relationship between thyroid replacement treatment and heart failure. The American Thyroid Association recommends starting levothyroxine at a lower dose (25-50 mcg) and titrating up slowly in patients with cardiovascular disease. The goal of the current study was to assess differences in levothyroxine maintenance dose in patients with and without heart failure.

The retrospective single-center cohort study included ambulatory patients treated at Houston Methodist Hospital clinics between December 2016 and July 2017. All patients had a diagnosis of hypothyroidism and received levothyroxine at a stable dose for at least 6 weeks before measurement of recorded thyroid-stimulating hormone (TSH) level. Patients with heart failure were divided into 2 groups: those with reduced ejection fraction (<40%) and those with other types of heart failure, including heart failure with preserved ejection fraction.

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The researchers also screened for known severe drug-drug interactions that may decrease absorption of levothyroxine, including aluminum hydroxide, bile acid sequestrants, calcium salts, lanthanum, iron salts, magnesium salts, orlistat, patiromer, polaprezinc, raloxifene, sevelamer, sodium polystyrene sulfonate, and sucroferric oxyhydroxide.

The primary outcome was the average levothyroxine dose (µg/kg) in patients without heart failure, those with heart failure with reduced ejection fraction, and those with other types of heart failure. Subgroup analyses were also completed to assess average levothyroxine dose in patients with normal TSH levels, in elderly patients (aged ≥65 years), and in all patients with heart failure.

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The study cohort included 300 patients, with 100 patients in each study group. Average levothyroxine dose was 1.6±0.9 µg/kg in the group of patients with heart failure with reduced ejection fraction, 1.6±0.8 µg/kg in those with other types of heart failure, and 1.5±0.7 µg/kg in those without heart failure (P =.9).

The multivariable linear regression analysis revealed higher levothyroxine doses in female patients, patients with drug-drug interactions, and patients who had a clinic visit prior to TSH level measurement. There were no differences between groups in laboratory values of thyroid function tests. Results were similar when data from all patients with heart failure were combined and compared with those of patients without heart failure.

The researchers acknowledged several limitations of the study, including the retrospective design, missing data regarding adherence or titration schedule of levothyroxine, and the possibility that in some cases, TSH was measured before the patients reached steady state.

“To our knowledge, this was the first study to explore levothyroxine doses in [patients with heart failure]. We found no difference in dosing between [patients with heart failure] and the general medical population. Future studies are needed to address the appropriate initiation dose and titration, so [patients with heart failure] may reach a euthyroid state in a timely manner,” concluded the researchers.


Yang T, Ruegger M, Colavecchia AC, Sadhu A, Patham B, Tatara A. Comparison of levothyroxine dosing in patients with and without heart failure [published online July 26, 2019]. Endocr Res. doi:10.1080/07435800.2019.1645165

This article originally appeared on Endocrinology Advisor