Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function.

Abstract

CONTEXT:

Hypothyroidism is a common endocrine disorder frequently accompanied by alterations in lipid metabolism, such as hypercholesterolemia and high circulating triglycerides, both risk factors for nonischemic cardiomyopathy. Rodent studies suggest that the hypothyroid state promotes cardiac lipid retention by increasing lipid uptake into cardiomyocytes while reducing fatty acid oxidation. Furthermore, increased cardiac lipid load has been linked to cardiac dysfunction.

OBJECTIVE:

Dyslipidemia and hypothyroidism frequently coexist; thus, we hypothesized that overt hypothyroidism causes cardiac lipid deposition and ultimately cardiac dysfunction.

DESIGN:

An interventional prospective study with balanced within-subject comparison. PARTICIPANTS/SETTING/INTERVENTION: Ten patients recruited at an academic center, who underwent a thyroidectomy due to differentiated thyroid carcinoma, were examined 4 weeks postoperatively in the overtly hypothyroid state, right before radioiodine therapy, and 6-8 weeks after initiation of levothyroxine replacement.

MAIN OUTCOME PARAMETERS:

We measured cardiac lipid content and function in vivo before and after levothyroxine treatment using electrocardiogram-gated (1)H-magnetic resonance spectroscopy and imaging.

RESULTS:

Levothyroxine therapy reduced cardiac lipid content in nine of the 10 patients (0.35 ± 0.09 vs 0.22 ± 0.06 % water signal; P = .008; n = 10) and improved cardiac index (2 ± 0.2 vs 2.4 ± 0.1 L/min/m(2); P = .047) when comparing the hypothyroid with the euthyroid state, independent of changes in liver fat content (7.5 ± 3.2 vs 7.1 ± 2.6% magnetic resonance spectroscopy signal; P = .60) or body weight.

CONCLUSION:

Here we show that levothyroxine treatment reduces lipid accumulation in the heart and increases cardiac output in overtly hypothyroid patients. These results could in part explain the increased risk of death and heart failure in hypothyroid patients.

• Authors: Thomas Scherer, Peter Wolf, Yvonne Winhofer, Heying Duan, Elisa Einwallner, Alois Gessl, Anton Luger, Siegfried Trattnig, Martha Hoffmann, Alexander Niessner, Sabina Baumgartner-Parzer, Martin Krššák, Michael Krebs
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 11 Pg. E2341-6 (Nov 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 25105733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Thyroxine

Topics

• Adenocarcinoma, Follicular (metabolism, surgery)
• Adult
• Carcinoma, Papillary (metabolism, surgery)
• Electrocardiography
• Female
• Heart (drug effects, physiopathology)
• Hormone Replacement Therapy
• Humans
• Hypothyroidism (drug therapy, metabolism, physiopathology)
• Lipids (analysis)
• Male
• Middle Aged
• Myocardium (chemistry)
• Prospective Studies
• Thyroid Neoplasms (metabolism, surgery)
• Thyroxine (pharmacology, therapeutic use)
• Treatment Outcome