Role of Thyroid Disease in the Development of Statin-Induced Myopathy

Abstract

Hypothyroidism is a common endocrine disease, which, in addition to its classic signs and symptoms, can present with primary complaints of myopathy. Myopathy can cause skeletal muscle weakness, tenderness, and pain and is often associated with elevated creatine kinase levels. There are many neuromuscular causes of myopathy, including inflammatory and infectious myopathies, metabolic and hereditary myopathies, and those caused by drugs or toxins. Hypothyroid patients with musculoskeletal symptoms can have elevated serum creatine kinase levels, which clinically resemble polymyositis. However, hypothyroid myopathies can be distinguished from polymyositis by coexisting signs and symptoms of hypothyroidism such as delayed relaxation phase of the deep tendon reflexes and the absence of inflammatory changes on muscle biopsy. The treatment of hypothyroidism with thyroid hormone replacement will alleviate symptoms of myopathy as well as lower the characteristic hyperlipidemia associated with hypothyroidism. Hypercholesterolemia, which can arise from different etiologies, is frequently treated with a class of HMG-CoA reductase inhibitors called statins. One of the most significant risks associated with the use of statins is the development of myopathy, a risk that may be compounded by the coexistence of hypothyroidism. The underlying metabolic mechanisms that account for muscle disease in these 2 settings show some common etiologies. The overlap of symptoms associated with hypothyroidism and statin-induced myopathy should prompt the physician to screen all patients presenting with myopathic symptoms with or without elevated creatine kinase levels and all hyperlipidemic patients before initiating statin therapy for hypothyroidism using a measurement of thyroid-stimulating hormone. (The Endocrinologist 2006;16: 279 -285) Learning Objectives• Describe the characteristics of the myopathy sometimes associated with hypothyroidism as well as the relationship between the hypothyroid state and hyperlipidemia. • Identify the key features of statin-induced myopathy.• Outline the ways in which hypothyroidism, statin treatment, and myopathy relate to one another, and the clinical implications of these associations.

Thyroid Disease and the Heart

“…The reported mechanisms for the development of hypercholesterolemia in hypothyroidism include decreased fractional clearance of LDL by a reduced number of LDL receptors in the liver in addition to decreased receptor activity. 64,69,70 The catabolism of cholesterol into bile is mediated by the enzyme cholesterol 7␣-hydroxylase. 71 This liver-specific enzyme is negatively regulated by T 3 and may contribute to the decreased catabolism and increased levels of serum cholesterol associated with hypothyroidism.…”

“…71 This liver-specific enzyme is negatively regulated by T 3 and may contribute to the decreased catabolism and increased levels of serum cholesterol associated with hypothyroidism. 70 The increased serum lipid levels in subclinical hypothyroidism as well as in overt disease are potentially associated with increased cardiovascular risk. 72 Treatment with thyroid hormone replacement to restore euthyroidism reverses the risk ratio.…”

“…72 Treatment with thyroid hormone replacement to restore euthyroidism reverses the risk ratio. 70 If untreated, the dyslipidemia together with the diastolic hypertension associated with hypothyroidism may further predispose the patient to atherosclerosis. 3,5,6 …”

Cardiovascular Changes in Hypothyroidism, a Tertiary Centre Study

“…This reduced number of receptors is further complemented by a diminished receptor-activity. [23][24][25] The metabolism of cholesterol into bile, mediated by an enzymecholesterol 7α-hydroxylase, is negatively regulated by T3. This mechanism may be one of the principal reasons of increased serum cholesterol levels seen in hypothyroidism.…”

“…This mechanism may be one of the principal reasons of increased serum cholesterol levels seen in hypothyroidism. [25,26] Subclinical hypothyroidism is a condition typically characterised by very low or decreased levels of TSH and normal levels of both T3 and T4. [27] This subgroup of patients often remains asymptomatic.…”