Muscle comprises a large proportion of all tissues in the body and the energy required for its function renders it susceptible to metabolic abnormalities from endocrine dysfunction and toxic effects of medications and environmental exposures. Muscle tissue is affected by the metabolic and trophic effects of various components of the endocrine system and by direct and indirect effects of toxins. This chapter highlights features of the most common endocrinopathies and toxins affecting muscle, concisely reviews the many others, and emphasizes the fundamental principles in diagnosis and treatment of these disorders.
ENDOCRINE MYOPATHIES
EPIDEMIOLOGY
Myopathy in endocrine disorders is rather common, but the earlier diagnosis and treatment of endocrinopathies has reduced the severity of myopathic symptoms. Thyroid disorders and corticosteroid abnormalities (most often from exogenous sources) are the most common endocrinopathies encountered and thus discussed in most detail. Exogenous corticosteroid administration at doses of 30 mg or more per day of prednisone confers the highest risk.
Historical studies suggest that up to 75% of patients with hyperthyroidism will experience myopathy, but current data regarding incidence of true myopathy in endocrinopathies is not available, likely a result of earlier diagnosis and treatment. Myopathy is also found in association with acromegaly, hypopituitarism, hyperparathyroidism, and hypoparathyroidism.
PATHOBIOLOGY
The exact basis of myopathy in endocrinopathy is unknown and may be multifactorial. Often, weakness and fatigue are out of proportion to muscle wasting, suggesting energy failure as a mechanism. Thyroxine has catabolic effects on muscle, may reduce efficiency of muscle contraction, alter membrane excitability, and lead to reduced potassium in muscle and serum, leading to weakness in hyperthyroidism. Hypothyroidism reduces glycogenolysis (animal studies indicate this occurs via reduced expression of β-adrenergic receptors on muscle cells), which may be responsible for cramps and fatigue. Hypothyroidism can also reduce mitochondrial oxidation, and studies in rats demonstrate changes in myosin from fast-twitch to slow-twitch muscle types. Thyroid-associated ophthalmopathy leads to edema in the extraocular muscles from both glycoprotein accumulation and inflammation. Corticosteroids cause muscle catabolism and stimulate protein degradation.
CLINICAL FEATURES
Myopathy from endocrine disorders causes nonspecific symptoms of myopathy. Proximal limb weakness, fatigue, and cramps are common. In some cases, myalgias are present. In steroid myopathy, symptoms may occur as early as after a few weeks of treatment. See Table 92.1 for clinical features of thyroid-associated myopathies and Table 92.2 for other endocrine-associated myopathies, including that due to exogenous steroid administration.
DIAGNOSIS
Other features related to specific endocrine disorders are usually apparent and suggest the diagnosis. However, if corticosteroids are being used for the treatment of a disease that also causes weakness (such as polymyositis or myasthenia gravis), it can be challenging to determine whether progression of the underlying disorder or the corticosteroid treatment is the cause of weakness. Laboratory testing for serum levels of thyroid function, adrenocorticotrophic hormone, cortisol, metabolic panel, parathormone, and growth hormone can be diagnostic. Serum creatine kinase (CK) levels are helpful in many cases.
TABLE 92.1 Myopathies Associated with Thyroid Disorders
Disorder
Clinical
Diagnostics
Treatment
Hypothyroidism
Muscle stiffness, pain, and cramps, especially with cold and exercise
May involve respiratory, bulbar, or distal muscles
CK is normal (except in thyroid storm)
EMG: myopathic in proximal muscles
Biopsy: nonspecific, type 1 and 2 fiber atrophy
Correction of thyroxine levels to normal (antithyroid medications, radioactive iodine, thyroidectomy)
Weakness may take months to resolve.
Propranolol (start 10 mg t.i.d. to q.i.d., may increase to 40 mg q.i.d.) may hasten recovery.
Thyrotoxic periodic paralysis
Severe weakness lasting hours to days, precipitated by cold, exercise, or highcarbohydrate intake
More common in men from Japan and China
Potassium levels low during attacks
+/− low magnesium or phosphorus
Associated HLA haplotypes
Correction of thyroid abnormality
Propranolol (start 10 mg t.i.d. to q.i.d., may increase to 40 mg q.i.d.) may prevent attacks.
Thyroid ophthalmopathy
Exophthalmos, pain, diplopia
May have compressive optic neuropathy
Mostly occurs with hyperthyroidism (sometimes with hypothyroidism, euthyroidism)
Edema of extraocular muscles on MRI
Correction of thyroid abnormality
Guanethidine eye drops (β-adrenergic)
Local steroid injection
Systemic steroids (prednisone 30-100 mg PO daily for at least 4 wks followed by taper or methylprednisolone 500 mg IV for one dose followed by 250 mg IV weekly)
Selenium 100 mg b.i.d. for 6 mo
CK, creatine kinase; EMG, electromyography; TSH, thyroid-stimulating hormone; HLA, human leukocyte antigen; MRI, magnetic resonance imaging; PO, by mouth; IV, intravenous.
TABLE 92.2 Myopathies Associated with Other Endocrinopathies
