Endocrine Myopathies Clinical Presentation

Updated: Jul 02, 2021
  • Author: Shireen R Chacko, MBBS; Chief Editor: Nicholas Lorenzo, MD, CPE, MHCM, FAAPL  more...
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When approaching a patient with a suspected myopathy, the age of onset, rapidity of progression, distribution of muscle involvement, and whether the symptoms are intermittent, stable, or progressive can help guide the diagnosis. [2]  In endocrine myopathies, multiple organ systems are usually involved and myopathy is only one part of the history, although exceptions do occur where myopathy may be the presenting feature. For systemic manifestations of endocrine diseases, please refer to respective Medscape Reference articles for more details. This article will focus on muscular manifestations of endocrine diseases. Endocrine myopathies may have an acute or chronic presentation, depending on the etiology, and they are typically characterized by 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


Acute adrenal crisis is associated with severe generalized weakness. [3]  Addison disease may be associated with chronic weakness, myalgias, and lower extremity flexion contractures. [5, 6, 7]  Some cases are also associated with hyperkalemic periodic paralysis that presents with intermittent muscle weakness. [7]


Cushing’s syndrome may present with the usual cushingoid features plus myalgias and proximal muscle weakness. [44] Corticosteroid-induced myopathy is the most common endocrine-related muscle disease and may be acute, as in the intensive care unit setting, or may be a more chronic process. [45]  While hyperaldosteronism may be associated with subjective muscle weakness, objective weakness is rare. [13, 12, 11]  

Thyroid dysfunction

The muscular manifestations of hypothyroidism are myriad and are summarized below:

  • Kocher-Debre-Semelaigne syndrome is a condition characterized by hypothyroidism in childhood with muscular pseudohypertrophy and proximal muscle weakness. [46]
  • Hypothyroid myopathy in adults may present with muscle weakness, cramps, muscle stiffness, and myalgias. These may be the main or only presenting symptoms of hypothyroidism. [47] Rodolico et al described 10 patients with primary autoimmune hypothyroidism presenting solely with myopathy. [48]
  • Hypothyroid myopathy may present acutely with rhabdomyolysis. [40, 41]
  • Hoffman syndrome is a rare syndrome of hypothyroid myopathy, described as hypothyroidism associated with muscle weakness and pseudohypertrophy in adults. [49]

General symptoms of thyrotoxicosis include weight loss, sweating, tremor, muscle wasting, and painless weakness. Occasionally, patients have myalgia, cramps, and bulbar and ocular muscle weakness. Ocular symptoms (diplopia, reduced blinking, lid lag) and skin disease may be present, especially in the case of Graves disease.

Onset of symptoms may be gradual in mild hyperthyroidism and more rapid in severe hyperthyroidism. [7]  

Thyrotoxic periodic paralysis is a condition characterized by transient attacks of proximal muscle weakness lasting minutes to days, with sparing of bulbar and respiratory muscles. [7]

Parathyroid dysfunction

Hypoparathyroidism results in hypocalcemia manifesting as perioral and distal parasthesias and numbness, tetany, carpopedal spasm, and muscle cramps. Muscle weakness, if present, is usually mild.

In primary hyperparathyroidism, muscle wasting, proximal muscle weakness, and painful muscle stiffness are common. [7]  Patients may also have muscle cramps and paresthesias. [50]  Although there is usually sparing of bulbar and sphincter muscles, there have been reports of respiratory muscle weakness. [51, 52]

Patients with secondary hyperparathyroidism have similar muscle symptoms to those with primary hyperparathyroidism but usually have a concomitant neuropathy. [7]

Patients with osteomalacia typically have proximal muscle weakness, pain, and wasting. [7]  

Pituitary dysfunction

In patients with hypopituitarism, the myopathy often results from secondary adrenal and thyroid dysfunction. Patients have severe muscle weakness with relatively preserved muscle mass. [7]

As with hypopituitarism, secondary adrenal effects may be responsible for the myopathy in hyperpituitarism. In acromegaly, patients typically have gradually progressive muscle weakness, often with increased muscle mass.

Pancreatic islets of Langerhans dysfunction

Diabetic muscle infarction is a rare condition that tends to occur in patients with poorly controlled diabetes and typically presents acutely with muscle swelling and pain, most commonly affecting the lower extremities. [25]  


Physical Examination

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.

A detailed neurologic examination is required, including a complete assessment of power, tone, muscle bulk, and deep tendon reflexes. Early recognition of bulbar muscle weakness and respiratory muscle weakness is essential, as these can lead to life-threatening complications.

In general, there is predominant proximal rather than distal muscle involvement. Muscle atrophy may or may not be present. Muscle stretch reflexes are usually present (may be depressed) even in weak muscles.

The following patterns may be observed in specific endocrine myopathies.

Adrenal dysfunction


Hypoadrenalism may be associated with subjective muscle weakness, myalgias, and lower extremity flexion contractures. [5, 6, 7]


Glucocorticoid excess is typically associated with proximal muscle weakness and atrophy, with the lower extremities more affected than the upper extremities. [7]  Striated muscles of sphincters and those innervated by cranial nerves are spared. [7]  Although hyperaldosteronism may be associated with subjective muscle weakness, objective weakness is rare. [11, 13, 12]  

Thyroid dysfunction

Thyroid disorders may result in orbital myositis, a disorder that may impair ocular movement and therefore may clinically appear as eye muscle weakness. [53]


Patients typically have symmetric proximal muscle weakness with reduced velocity of motor movements and delayed relaxation of deep tendon reflexes. Median neuropathy at the wrist commonly accompanies this diagnosis. Myxedema is a classic, yet often forgotten sign of hypothyroid myopathy characterized by a typical localized mounding of muscle tissue induced by a light pressure or tactile stimulus, elicited by flicking the bulk of the biceps muscle with the thumb and index finger. [54]


In addition to the findings of Graves disease, muscle weakness with atrophy of proximal muscles may be present. Distal muscle involvement has also been described. [26]  In rare cases, bulbar and respiratory muscles may be involved and it is important to exclude this involvement on examination. Deep tendon reflexes are typically normal, or in some cases, are brisk. [7, 26]  

Parathyroid dysfunction


Tetany is a common finding. If the tetany is latent, it may be elicited on examination by hyperventilation or by specific maneuvers, including the Chvostek sign, where twitching of the facial muscles is caused by tapping the facial nerve, and the Trousseau sign, where carpopedal spasm is provoked by inflating a blood pressure cuff to block venous return. [7]  


Hyperparathyroid myopathy typically manifests with symmetric proximal muscle weakness and wasting with brisk deep tendon reflexes. [7] Respiratory muscle weakness may be present. [51, 52]


Patients may have proximal muscle weakness and wasting. [7]  

Pituitary dysfunction


Multiple endocrinopathies may result from pituitary dysfunction. The myopathy from pituitary disease may be a result of secondary adrenal or thyroid dysfunction or other endocrine disturbance. Patients have severe muscle weakness with relatively preserved muscle mass. A pituitary tumor may have focal mass effects.


Multiple endocrinopathies may result from pituitary dysfunction. Patients with acromegaly may have muscle weakness with increased muscle mass. Concomitant neuropathy, particularly of the median nerve is often present. [7]  Mass lesions may have local effects.

Pancreatic islets of Langerhans dysfunction

Diabetic muscle infarction

Typically presents acutely with muscle swelling and pain, most commonly affecting the lower extremities. Tenderness of the affected muscle group may be appreciated on examination. [25]  A few patients may have a mild fever. [24, 55]  Rarely, there may be associated erythema, warmth and induration. [55]  


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.
  • Respiratory muscle weakness has been reported to occur in various endocrine diseases. [42]
  • Physicians must also be alert to the possibility of malignancy as the underlying etiology for any endocrinopathy.