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An Increase in Plasma Cholesterol Independent of Thyroid Function during Long-Term Amiodarone Therapy: A Dose-Dependent Relationship

Wilmar M. Wiersinga, MD, PhD; Mieke D. Trip, MD; Mieke H. van Beeren, PhD; Theo A. Plomp, PhD; and Hans Oosting, PhD
[+] Article and Author Information

Grant Support: By the Dutch Heart Foundation (grant no. 82. 052).

Requests for Reprints: Wilmar M. Wiersinga, MD, Department of Endocrinology, Academisch Medisch Centrum F5-258, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands.

Current Author Addresses: Drs. Wiersinga and van Beeren: Department of Endocrinology, Academisch Medisch Centrum F5-258, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands.

Dr. Trip: Department of Cardiology, Academisch Medisch Centrum F4-140, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. Dr. Plomp: The Netherlands Institute for Drugs and Doping Research, State University of Utrecht, Vondellaan 14, Utrecht 3521 GE, The Netherlands.

Dr. Oosting: Department of Medical Physics and Informatics, Academisch Medisch Centrum, L0-57, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands.


©1991 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1991;114(2):128-132. doi:10.7326/0003-4819-114-2-128
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Objective: To determine whether long-term amiodarone treatment is associated with a rise in plasma cholesterol, and, if so, to analyze its relation with thyroid function.

Design: Consecutive entry trial, including cardiac patients who initiated amiodarone medication but excluding those with abnormal thyroid function (defined as peak thyroid-stimulating hormone [TSH] response to thyrotropin-releasing hormone [TRH] < 2.8 or > 22.0 mU/L) either before or during amiodarone treatment.

Patients: Twenty-three patients who remained euthyroid were studied.

Intervention: Oral administration of amiodarone (mean duration of treatment, 17 months; range, 6 to 30 months).

Measurements: Fasting plasma lipids, thyroid hormones, and peak TSH to TRH values were recorded before and every 6 months during amiodarone treatment.

Results: Plasma cholesterol gradually increased from 5.1 ± 0.2 mmol/L before treatment to 6.9 ± 0.8 mmol/L after 30 months of amiodarone medication (P < 0.001); the peak TSH response to TRH did not change. When age- and sex-specific reference values were applied, 30% of the patients had cholesterol values above the 75th percentile before treatment; this number rose to 69% after 2 years of treatment. The rise in plasma cholesterol was associated with an equal increase in apoprotein B. Plasma cholesterol was not related to the daily dose of amiodarone or to plasma concentrations of amiodarone, desethylamiodarone, thyroxine (T4), triiodothyronine (T3), or reverse triiodothyronine (rT3). Linear regression analysis indicated a positive relation between plasma cholesterol and the cumulative dose of amiodarone (r = 0.25, P < 0.05).

Conclusion: Long-term amiodarone treatment is associated with a dose-dependent increase in plasma cholesterol that is independent of thyroid function.

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