eMedicine Specialties > Neurology > Neuromuscular Diseases

Endocrine Myopathies

Author: Wayne E Anderson, DO, Assistant Professor of Internal Medicine/Neurology, Western University of Health Sciences; Assistant Professor of Family Medicine, Touro University College of Osteopathic Medicine; Consulting Staff in Pain Management, Department of Neurology, California Pacific Medical Center
Coauthor(s): Ling Xu, MD, Director, Assistant Professor of Neurology, Neuromuscular Clinic and Pathology Lab, Saint Louis University Health Science Center
Contributor Information and Disclosures

Updated: Mar 13, 2007

Introduction

Background

A myopathy, simply, is any abnormal state of striated muscle. Clinically, the patient generally experiences muscle weakness, pain, cramps, muscle tenderness, and spasms in various degrees.

Disease of the endocrine system, including the thyroid, parathyroid, suprarenal, and pituitary glands, the ovaries, the testes, and the islands of Langerhans of the pancreas, usually results in multisystem signs and symptoms. A myopathy very often is present, and it rarely may be the presenting symptom.

Major categories of endocrine myopathy include those associated with (1) adrenal dysfunction (as in Cushing disease or steroid myopathy); (2) thyroid dysfunction (as in myxedema coma or thyrotoxic myopathy); (3) parathyroid dysfunction (as in multiple endocrine neoplasia); (4) pituitary dysfunction; and (5) islands of Langerhans dysfunction (as in diabetic myopathy from ischemic infarction of the femoral muscles). Steroid myopathy is the most common endocrine myopathy.

Articles on the specific endocrine diseases that may result in myopathy may be found in detail in this and the Medicine journals of eMedicine.

Pathophysiology

Although abnormal endocrine states usually present with muscle weakness—most often proximal weakness—the exact pathophysiology remains incompletely understood. Even histologic analysis and electromyographic testing may not show consistent, reproducible abnormalities in all cases, although some patterns are recognized and are discussed in the sections below.

Adrenal dysfunction

• The etiologies of hypoadrenalism are many, including infection, inflammatory disease, and tumor. Notably, adrenal failure may follow pituitary failure.
• In hypoadrenalism, neurological manifestations such as disturbances of behavior and mentation are prominent; myopathy is not likely to be a presenting finding.
• Factors contributing to muscle weakness in adrenal insufficiency include circulatory insufficiency, fluid and electrolyte imbalance, impaired carbohydrate metabolism, and starvation.
• The etiologies of hyperadrenalism include pituitary or ectopic overproduction of adrenocorticotropic hormone (ACTH), adrenal tumors, or exogenous corticosteroid administration. Pituitary ACTH hypersecretion (ie, Cushing disease) is caused by a corticotroph microadenoma in 90% of patients and by a macroadenoma in most of the rest.

Thyroid dysfunction

• Thyroid hormone deficiency states result in neurological syndromes that vary depending on the age of onset of the deficiency. Muscle weakness occurs most prominently in the adult forms of myxedema.
• Thyroid hormone excess also results in myopathy. Thyrotoxic myopathy is believed to be secondary to a disturbance in the function of the muscle fibers from increased mitochondrial respiration, accelerated protein degradation and lipid oxidation, and enhanced beta-adrenergic sensitivity due to excessive amounts of thyroid hormone.
• The heterogeneity of the endocrine myopathies is illustrated nicely by Rodolico and colleagues, who described 10 patients with primary autoimmune hypothyroidism presenting solely with myopathy.

Parathyroid dysfunction

• Hypoparathyroidism causes tetany, with or without carpopedal spasm. The pathophysiology may involve either deficiency of parathyroid hormone or inability of the hormone to have an effect at end-receptors because of dysfunction of the hormone receptors.
• Hyperparathyroidism does not cause tetany but results in muscle wasting and myopathy (ie, proximal muscle weakness). The pathophysiology is oversecretion of hormone, frequently from a parathyroid adenoma.
• Myopathy related to parathyroid dysfunction appears to result from altered parathyroid hormone (PTH) level and impaired action of vitamin D.

Pituitary dysfunction

• The myopathy from pituitary disease may be a result of secondary adrenal dysfunction and/or other endocrine disturbance such as thyroid dysfunction.
• Hypopituitarism as well as hyperpituitarism may result from multiple causes, from simple trauma, or from infection or tumor.

Polymyalgia rheumatica (PMR) and temporal arteritis (TA): Although research is just beginning, Imrich and colleagues note that age-related changes in the neuroendocrine system could represent a pathogenic factor for PMR and/or TA in genetically disposed.

Frequency

United States

In general, endocrine myopathies are recognized increasingly. However, the exact incidence and prevalence are unknown. Patients with endocrine dysfunction frequently complain of fatigue and weakness. These symptoms are referred to as a "myopathy" despite lack of defined histologic or electrophysiologic criteria fulfilling such a diagnosis. In fact, many of these patients show only muscle atrophy without muscle degeneration. Corticosteroid myopathy is the most common endocrine-related myopathy. Patients who have myopathy as the sole manifestation of endocrine dysfunction may sometimes have a delayed diagnosis.

International

As in the United States, the exact frequency is not known as the myopathies are heterogeneous.

Mortality/Morbidity

• Myopathy may result in weakness and/or pain. Either may significantly influence the quality of life and impair daily function. Myopathy also may result in muscle atrophy.
• Mortality is related to the underlying cause of myopathy. For example, myxedema coma may have a mortality rate between 50% (if treated aggressively) and 100%.

Sex

• Hyperparathyroid myopathy - Female-to-male ratio 2:1
• Hyperthyroid myopathy - Female-to-male ratio 1:1
• Iatrogenic steroid myopathy - Female-to-male ratio 2:1
• Hypothyroid myopathy - Female-to-male ratio 5:1
• Cushing myopathy - Depends on the etiology of Cushing syndrome

Age

• Hyperparathyroid myopathy - Peak incidence 40-60 years
• Hyperthyroid myopathy - Peak incidence 20-60 years
• Hypothyroid myopathy - Incidence increases after 40 years
• Cushing myopathy - Peak incidence 20-40 years

Clinical

History

Usually, multiple organ systems are involved and myopathy is only one part of the history, although exceptions do occur and are noted in Pathophysiology.

The history of myopathy in general is that of proximal more than distal muscle weakness, with or without associated muscle pain, cramps, and/or spasms. The weakness is typically symmetric or rapidly becomes symmetric. Muscle atrophy may or may not be present.

• Adrenal dysfunction
  • Hypoadrenalism: In hypoadrenalism, the neurological manifestations of behavioral disturbance and mentation are prominent; myopathy is not a frequent presenting finding.
  • Hyperadrenalism: Cushing syndrome may present with the usual cushingoid features plus pain and weakness. Corticosteroid myopathy is the most common endocrine-related muscle disease. Please refer to the article Cushing Syndrome for details.
• Thyroid dysfunction: Disorders of thyroid function may result in muscle weakness, and determination of thyroid function remains an integral part of the evaluation for muscle weakness.
  • Hypothyroidism: Muscle weakness occurs most prominently in the adult forms of myxedema. General symptoms include weight gain, neuropathy, fatigue, cold intolerance, sleepiness, and emotional disturbances in addition to muscle stiffness, weakness, and pain. Notably, psychiatric disease may be prominent. Cerebellar ataxia may be seen in adults, less often in children, in whom cerebellar involvement is more midline.
  • Hyperthyroidism: General symptoms include weight loss, sweating, tremor, muscle wasting, and painless weakness. Occasional patients have myalgia, cramps, and bulbar and ocular muscle weakness. Ocular symptoms (diplopia, reduced blinking, lid droop) and skin disease may be present, especially in the case of Graves disease.
• Parathyroid dysfunction
  • Hypoparathyroidism: Tetany with or without carpopedal spasm is seen. Muscle pain, cramps, and spasms are present in up to one half of patients. Muscle weakness is usually mild. General symptoms include short stature with rounded face, thickened calvarium and other bony abnormalities, and neurological symptoms (eg, seizures, mentation defects).
  • Hyperparathyroidism: Muscle wasting and myopathy (ie, proximal muscle weakness) are common. Other symptoms may include the findings denoted by the well-known phrase "(painful) bones, (renal) stones, (gastrointestinal) groans, and (psychiatric) moans." Notably, depression, mentation defects, memory loss, and mood changes may be present. Also, renal stones are an almost constant feature of this disease syndrome.
• Pituitary dysfunction: The myopathy from pituitary disease may be a result of secondary adrenal dysfunction or other endocrine disturbance.
  • Hypopituitarism: Often, the myopathy results from secondary adrenal dysfunction. General symptoms include amenorrhea, loss of libido, "alabaster skin," lethargy, constipation, and cold intolerance.
  • Hyperpituitarism: As with hypopituitarism, secondary adrenal effects may be responsible for the myopathy. General symptoms include infertility, impotence, headaches, and mass effects of the pituitary tumor.
• Polymyalgia rheumatica (PMR) and temporal arteritis (TA): Although research is just beginning, Imrich and colleagues note that age-related changes in the neuroendocrine system could represent a pathogenic factor for PMR and/or TA in genetically disposed.

Physical

Physical examination should focus on the entire body, as the endocrine diseases usually present with multiple system findings. An endocrine tumor is in the differential diagnosis, and signs of a hormone-secreting tumor may be seen on examination.

• Neck flexor weakness reflects proximal muscle weakness and may be noted in myopathies; dysphagia from bulbar weakness also can occur.
• Respiratory muscle weakness may occur in endocrine disease (Siafakas et al, 1999).
• Physical examination findings should correlate with the underlying endocrine disease. However, the following patterns may be observed:
  • In thyrotoxicosis, muscle weakness and atrophy may affect muscles of proximal arms more than those of the legs.
  • Muscle stretch reflexes are usually present (may be depressed) even in weak muscles.
• Adrenal dysfunction
  • Hypoadrenalism: Examination may show an ataxic gait. Cognition may be poor.
  • Hyperadrenalism: Papilledema and other signs and symptoms of increased intracranial pressure may be present.
• Thyroid dysfunction
  • Hypothyroidism: Motor movements can have a reduced velocity with delayed relaxation of muscle stretch reflexes. Median neuropathy at the wrist commonly accompanies this diagnosis.
  • Hyperthyroidism: In addition to the findings of Graves disease, muscle weakness with atrophy of the pelvic girdle musculature may be present.
• Parathyroid dysfunction
  • Hypoparathyroidism: Tetany is a common finding; cataracts may be present. Increased intracranial pressure is not a constant finding, but may be present.
  • Hyperparathyroidism: Myopathy is a prominent finding. Both symmetric weakness of the proximal limbs and atrophy are present.
• Pituitary dysfunction: The myopathy from pituitary disease may be a result of secondary adrenal dysfunction or other endocrine disturbance.
  • Hypopituitarism: Multiple endocrinopathies may result from pituitary dysfunction. Pituitary tumor may have focal mass effects.
  • Hyperpituitarism: Multiple endocrinopathies may result from pituitary dysfunction. Mass lesions may have local effects.

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