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Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism
P W Ladenson1, S I Sherman, K L Baughman
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Insights
Severe hypothyroidism in humans can cause dilated cardiomyopathy. Thyroxine replacement therapy improved cardiac function and reversed abnormal gene expression in heart muscle, suggesting a treatable cause for this heart condition.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone's impact on heart gene expression is known in animals, but its role in human cardiac dysfunction due to hypothyroidism was unclear.
- Hypothyroidism can lead to significant cardiovascular issues, including impaired heart muscle function.
Observation:
- A case study of a young man with profound hypothyroidism and dilated cardiomyopathy was examined.
- Cardiac performance metrics, including ejection fraction and cardiac index, were monitored over 9 months of thyroxine therapy.
Findings:
- Before treatment, the patient exhibited low alpha-myosin heavy-chain mRNA and high atrial natriuretic factor mRNA levels, alongside decreased phospholamban mRNA.
- Thyroxine replacement normalized these mRNA levels and significantly improved cardiac function, indicated by increased ejection fraction and cardiac index.
- The study observed a direct correlation between improved myocardial function and normalized gene expression after euthyroidism was restored.
Implications:
- This case suggests that cardiac dysfunction in hypothyroidism, specifically dilated cardiomyopathy, is linked to reversible alterations in myocardial gene expression.
- Identifying and treating the underlying cause, such as hypothyroidism, can lead to recovery of heart function.
- These findings highlight the critical role of thyroid hormone in maintaining normal cardiac gene expression and function in humans.
Abstract:
Thyroid hormone effects on myocardial gene expression have been well defined in animal models, but their relationship to the pathogenesis of cardiac dysfunction in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid young man with dilated cardiomyopathy. Before and during 9 months of thyroxine therapy, serial assessment of myocardial performance documented substantial improvements in the left ventricular ejection fraction (16-37%), left ventricular end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters.min-1.m-2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured in biopsy samples obtained before and after thyroxine replacement. In comparison with myocardium from nonfailing control hearts, this patient's pretreatment alpha-myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic factor mRNA level was markedly elevated, and the phospholamban mRNA level was decreased. All of these derangements were reversed 9 months after restoration of euthyroidism. These observations in an unusual patient with profound myxedema and cardiac dilatation permit correlation between the reversible changes in myocardial function and steady-state mRNA levels in a cardiomyopathy. They suggest that alterations in gene expression in the dilated myopathic heart may be correctable when a treatable cause is identified.