Thyroid Myopathies (See also Chapters 557–562)

Thyrotoxicosis causes proximal weakness and wasting accompanied by myopathic electromyographic changes. Thyroxine binds to myofibrils and, if in excess, impairs contractile function. Hyperthyroidism can also induce myasthenia gravis and hypokalemic periodic paralysis.

Hypothyroidism, whether congenital or acquired, consistently produces hypotonia and a proximal distribution of weakness. Although muscle wasting is most characteristic, one form of cretinism, the Kocher-Debré-Sémélaigne syndrome, is characterized by generalized pseudohypertrophy of weak muscles. Infants can have a Herculean appearance reminiscent of myotonia congenita. The serum creatine kinase (CK) level is elevated in hypothyroid myopathy and returns to normal after thyroid replacement therapy.

Results of muscle biopsy in hypothyroidism reveal acute myopathic changes, including myofiber necrosis and sometimes central cores. In hyperthyroidism, the muscle biopsy specimen shows only mild, nonspecific myopathic changes without necrosis of myofibers.

The clinical and pathologic features of hyperthyroid myopathy and hypothyroid myopathy resolve after appropriate treatment of the thyroid disorder. Many of the systemic symptoms of hyperthyroidism, including myopathic weakness and ophthalmoparesis, improve with the administration of β-blockers.

Most patients with primary hyperparathyroidism (Chapter 567) develop weakness, fatigability, fasciculations, and muscle wasting that is reversible after removal of the parathyroid adenoma. The serum CK and muscle biopsy remain normal, but the electromyography can show nonspecific myopathic features. A minority of patients develop myotonia that could be confused with myotonic dystrophy.

Steroid-Induced Myopathy

Natural Cushing disease and iatrogenic Cushing syndrome due to exogenous corticosteroid administration can cause painless, symmetrical, progressive proximal weakness, increased serum CK levels, and a myopathic electromyogram and muscle biopsy specimen (Chapter 571). Myosin filaments may be selectively lost. The 9α-fluorinated steroids, such as dexamethasone, betamethasone, and triamcinolone, are the most likely to produce steroid myopathy. Dexamethasone alters the abundance of ceramides in myotubes in developing muscle. In patients with dermatomyositis or other myopathies treated with steroids, it is sometimes difficult to distinguish refractoriness of the disease from steroid-induced weakness, especially after long-term steroid administration. All patients who have been taking steroids for long periods develop reversible type II myofiber atrophy; this is a steroid effect but is not steroid myopathy unless it progresses to become a necrotizing myopathy. At greatest risk in the pediatric age group are children requiring long-term steroid therapy for asthma, rheumatoid arthritis, dermatomyositis, lupus, and other autoimmune or inflammatory diseases and in the treatment of leukemia and other hematologic diseases. In addition to steroids, acute or chronic toxic myopathies can occur from other drugs (Table 602-1).

Hyperaldosteronism (Conn syndrome) is accompanied by episodic and reversible weakness similar to that of periodic paralysis. The proximal myopathy can become irreversible in chronic cases. Elevated CK levels and even myoglobinuria sometimes occur during acute attacks.

Chronic growth hormone excess (sometimes illicitly acquired by adolescent athletes or seen in acromegaly) produces atrophy of some myofibers and hypertrophy of others, and scattered myofiber degeneration. Despite the augmented protein synthesis induced by growth hormone, it impairs myofibrillar adenosine triphosphatase (ATPase) activity and reduces sarcolemmal excitability, with resultant diminished, rather than increased, strength corresponding to the larger muscle mass.