Endocrine Myopathies 

Updated: Jun 12, 2017
Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE 

Overview

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.[1]

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

See the list below:

  • 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

See the list below:

  • 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.[2]

  • Thyroid disorders may result in orbital myositis, a disorder than may impair ocular movement and therefore appear clinically as eye muscle weakness.[3]

  • 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.[4]

Parathyroid dysfunction

See the list below:

  • 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

See the list below:

  • 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.[5]

Epidemiology

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%.[6]

Sex

See the list below:

  • 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

See the list below:

  • 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

 

Presentation

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.[7] 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. Muscle fatigue, stiffness, myalgias, or cramps may be the main or only presenting symptoms of hypothyroidism.[8]

    • 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.[9]

  • 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.

Physicians must be especially alert in the following scenarios:

  • Physicians must be alert to the possibility of an endocrine etiology in cases of pure muscle weakness—even in the absence of systemic findings—as endocrine diseases may be associated with significant morbidity or mortality.

  • Siafakas et al reported evidence of respiratory muscle weakness in endocrine disease.

  • Physicians must be alert to the possibility of an endocrine etiology in cases of new-onset psychosis or behavior disturbance.

  • Physicians must be alert to the possibility of malignancy as the underlying etiology for any endocrinopathy.

 

DDx

 

Workup

Laboratory Studies

Because the diagnosis is made by elucidating the underlying endocrine abnormality, laboratory studies are considered in relation to the most likely etiologies.

Laboratory studies measuring hormone levels may help distinguish one endocrine myopathy from another. These tests are best ordered in consultation with an endocrinologist.

Creatine kinase levels may be normal or increased.

  • Hypothyroidism: Creatine kinase usually is elevated markedly.

  • Hyperthyroidism: Creatine kinase usually is normal.

Imaging Studies

Imaging studies neither confirm nor exclude the presence of muscle disease. They may be of benefit in the diagnosis of endocrine disorders.

Other Tests

Electromyography (EMG) may reveal the presence of a myopathy, although a normal examination does not rule out the diagnosis. Although commonly performed with nerve conduction study testing, needle EMG is direct, invasive testing of muscle and therefore differs from nerve conduction study testing. Myopathy is a disorder of muscle, and the nerve conduction study portion of the electrophysiological examination should be normal; however, the endocrinopathies often also cause neuropathies or may be associated with other conditions (such as diabetes) in which neuropathies are common. This heterogeneity explains the great variability and lack of consensus regarding the electrophysiological findings in endocrine disease.

Needle EMG examination preferentially studies the type I units, as these units fire selectively during weak muscle contraction. Thus, a disease process selectively involving type II units, such as steroid myopathy, may reveal no abnormalities on EMG.

EMG findings consistent with a myopathic process include the following:

  • Polyphasic motor unit potentials

  • Shortened duration of motor unit potentials

  • Decreased amplitude of motor unit potentials

  • Adrenal dysfunction: In cases of adrenomyeloneuropathy, a distinct and different disorder not otherwise considered in this article, nerve conduction velocity may be normal or decreased.

  • Hypothyroidism: EMG helps differentiate delayed muscle relaxation from myotonia.

  • Hyperthyroidism: EMG abnormalities may be found more proximally and are of the typical myopathic type. Motor conduction studies typically are normal, although some find distal leg denervation.

  • Hyperparathyroidism: The usual finding is myopathic motor unit potentials and increased frequency of polyphasic potentials without spontaneous activity. However, patients with severe proximal weakness and bulbar involvement may have fasciculations and a reduced recruitment pattern with normal nerve conduction velocities.

Histologic Findings

Muscle biopsy is considered mainly to exclude other treatable or congenital muscle diseases, including myotonic dystrophy or congenital myopathies.[10, 11] Histologic changes associated with endocrine myopathies are variable and rarely are specific. There is a striated muscle protein that may prove to be a disease progression marker.[12]

  • Hyperthyroidism - Normal histology versus nonspecific findings

  • Hypothyroidism - Nonspecific type II muscle fiber atrophy, occasionally with glycogen storage

  • Steroid myopathy - Nonspecific type II muscle fiber loss, sometimes with lipid storage

  • Thyrotoxic periodic paralysis - Vacuolar dilation of the sarcoplasmic reticulum

  • Corticosteroid therapy - Rapid evolving myopathy with myosin-deficient muscle fibers. (This was reported by al-Lozi et al in 5 patients who received corticosteroid therapy.)[13]

 

Treatment

Medical Care

Treatment of endocrine myopathies involves correction of the underlying endocrine dysfunction, either surgically or medically. Care should be taken to avoid neurapraxic lesions. Beta-adrenergic–blocking agents may improve the strength of the muscles, especially respiratory muscles.

Surgical Care

Underlying cause of endocrine myopathies may be a hormone-secreting tumor or tumor of the endocrine glands, which may be surgically removable.

Consultations

Endocrinology consultation is recommended.

Neurology consultation may be appropriate if neurological findings such as specific muscle weakness require elucidation; neurologists also may perform EMG examination to determine the presence of myopathic findings.

Physical medicine consultation may be helpful if the patient has suffered weakness and has not recovered fully.

 

Medication

Medication Summary

No specific medication is recommended for endocrine myopathy. Refer to the appropriate Medscape Reference article(s) for the appropriate medical management of each endocrinopathy.

 

Follow-up

Complications

See the list below:

  • Hyperthyroidism, hypothyroidism, and other endocrine states may be fatal.

  • Myopathy may be painful, and the pain must be addressed either in the form of symptomatic therapies or curative treatment of the endocrine diseases.

Prognosis

See the list below:

  • Prognosis depends on the underlying endocrine process. Myopathy often abates with correction of underlying disease.

  • Prolonged weakness and partial recovery are common especially in severe cases and in patients with delayed or suboptimal treatment.

Patient Education

For excellent patient education resources, visit eMedicineHealth's Thyroid and Metabolism Center. Also, see eMedicineHealth's patient education article Anatomy of the Endocrine System.