Hypothyroid Myopathy

Updated: May 09, 2022
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Stephen Kishner, MD, MHA  more...
  • Print
Overview

Practice Essentials

Deficiency of thyroid hormone leads to a state called hypothyroidism. Common causes of hypothyroidism include the following:

  • Treatment with radioactive iodine (I 131) for Graves disease
  • Hashimoto disease - An autoimmune process in which lymphocytic infiltration and fibrous tissue accumulation cause replacement of normal thyroid tissue
  • Drug-induced hypothyroidism - Known to occur with amiodarone and iodine (ie, Wolff-Chaikoff effect)
  • Hereditary disorders of the iodothyronine synthesis pathway (thyroxine [T4] and triiodothyronine [T3])
  • Pituitary tumors and related surgical resections

Hypothyroidism can cause several symptoms, ranging from mild (eg, fatigue, weight gain, cold intolerance, mental slowing, muscle cramping) to severe (eg, heart enlargement, myxedema coma [rare]).

Without regard to the cause of hypothyroidism, neuromuscular and musculoskeletal manifestations can be observed in many patients with the condition. [1, 2, 3] These manifestations can occur at any time in the hypothyroidism disease process. Usually mild, they include weakness, pain, aching, and stiffness.

Signs and symptoms of hypothyroid myopathy

Hypothyroid myopathy typically manifests as polymyositis-like myopathy with proximal muscle weakness and an increased creatine kinase level. [4, 5] However, it sometimes manifests as muscle enlargement (pseudohypertrophy) and stiffness; in adults, this condition is called Hoffman syndrome. [6, 7, 8] In children with hypothyroid disease (cretinism), a pattern of proximal weakness and diffuse muscle enlargement is known as Kocher-Debré-Sémélaigne syndrome. [9, 10, 11]

Several case reports describe rhabdomyolysis associated with hypothyroidism. [12] In these cases, the hypothyroidism is thought to have predisposed individuals to rhabdomyolysis.

Workup in hypothyroid myopathy

Nerve conduction studies may show decremental response to low-rate nerve stimulation and incremental response to high-rate nerve stimulation, suggesting some neuromuscular junction abnormality.

Increased thyroid-stimulating hormone (TSH) is seen in primary hypothyroidism, and decreased TSH is seen in pituitary-hypothalamic disease with secondary hypothyroidism.

Low free T4 and T3 levels, as well as a low total T4 level and a decreased free T4 index, are seen. The degree of myopathy is not necessarily correlated to the degree of hypothyroidism.

The creatine kinase level can be very high (10-100 times greater than the normal level) in some patients, but it has no correlation with weakness. [5] . The level returns to normal with adequate treatment. [13]

Management of hypothyroid myopathy

Early intervention with gentle, low-impact aerobic exercises may increase muscle efficiency and cardiovascular performance, may fight fatigue and depression, may maintain body weight, and may improve pain tolerance. Activities include walking, swimming, and stationary bicycling.

Occupational therapy may be needed for training in the performance of activities of daily living (ADL) to enable the patient to compensate for proximal muscle weakness.

Related Medscape Reference topics:

Endocrine Myopathies

Hypothyroidism [Endocrinology]

Pediatric Hypothyroidism

Myopathies

Neurological Manifestations of Thyroid Disease

Related Medscape resources:

Resource Center Hypothyroidism

Resource Center Thyroid Disease

Next:

Pathophysiology

Hypothyroidism causes a constellation of changes in the body. The lack of thyroid hormone results in slowed or reduced metabolic function, such as decreased protein turnover and impaired carbohydrate metabolism. These metabolic changes occur in many organ systems, including the muscles. Pain with muscle exertion is characteristic of defective carbohydrate metabolism.

Slowed muscle contraction and relaxation, known as hypothyroid myopathy, may be caused by a shift in the distribution of muscle fiber types from fast-twitch fibers to slow-twitch fibers. A reduction in muscle mitochondrial oxidative capacity and beta-adrenergic receptors, as well as the induction of an insulin-resistant state, may result in these changes.

Evidence from a study by Sinclair and colleagues suggests that a decrease in muscle carnitine in patients with either hypothyroidism or hyperthyroidism may contribute to thyroid myopathy. [14]

The global inhibition of the main oxidative pathways (substrate incorporation, substrate oxidation) and of the respiratory chain within cells also may cause myopathic symptoms. A diminished energetic consumption is related partially to a transition in the myosin isoforms, which express a slower adenosine triphosphatase, and to an impairment of the transsarcolemmal transports. All of these factors may contribute to muscle weakness, fatigue, and exertional pain.

Exercise intolerance could be due to an abnormal recruitment of several metabolic pathways, such as glycolysis, related to the mitochondrial metabolism impairment. An abnormal accumulation of protons and monovalent phosphate ions (which are involved in the actin-myosin interaction), as well as abnormal Ca++ metabolism, also may cause reduced exercise tolerance. [15, 16]

Hyponatremia often is seen in patients with hypothyroidism. The decreased number of Na+/K+ adenosine triphosphatase–dependent pumps could imply an abnormal intracellular Na+ level and explain frequent disorders of membrane excitability.

Myoedema is a phenomenon in which mounding up of muscle tissue occurs after light percussion. Myoedema occurs in approximately one third of patients with hypothyroidism, but it is not entirely specific for hypothyroidism. In one study, myoedema was elicited in 40% of overt hypothyroid patients, while historical clinical features of myopathy were present in 73%. [17] Myoedema is thought to be caused by delayed Ca++ reuptake by the sarcoplasmic reticulum, which also prolongs muscle contraction. Although not proven, this type of prolongation of muscle contraction is also thought to cause muscle hypertrophy.

A study by Ruchala et al reported a negative correlation between the myokine irisin and thyroid-stimulating hormone (TSH) levels and a positive correlation between irisin and free thyroxine levels. The report suggested that irisin levels change in association with the thyrometabolic state and that a relationship may exist between this phenomenon and the degree of muscle damage present. [18]

A study by Zybek-Kocik et al reported finding a lower concentration of irisin in association with prolonged hypothyroidism, with the investigators stating that the decrease may primarily result from prolonged myopathy. [19]

A study by Stratigou et al, on the other hand, found that in patients with subclinical hypothyroidism, serum levels of irisin were increased. The report suggested that the rise counterbalances reductions in lipid metabolism and insulin sensitivity and compensates for oxidative muscle and thyroid cell stress. [20]

Previous
Next:

Epidemiology

Frequency

United States

In North America, acquired impairment of thyroid function affects about 2% of adult women and about 0.1-0.2% of adult men.

Neonatal hypothyroidism occurs with a frequency of 0.02% in the white population. In the black population, the frequency falls to 0.003%.

Of individuals with hypothyroidism, 30-80% manifest neuromuscular symptoms, depending on the severity of hypothyroidism. Weakness is observed in one third of patients with hypothyroidism. Carpal tunnel syndrome, although not part of the myopathy, is a peripheral nerve dysfunction found in 15-30% of patients with hypothyroidism. [21]

International

In a prospective cohort study done in The Netherlands, in newly diagnosed patients with hypothyroidism, 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. [22]

Neonatal screening programs for congenital hypothyroidism in many areas of the world show that hypothyroidism is present in 1 out of every 4000 newborns. In iodine-deficient areas of the world, the incidence of hypothyroidism is 10- to 20-fold higher.

Mortality/Morbidity

Mortality has not been shown to be increased in patients with hypothyroid myopathy. Morbidity is significantly increased, reflected in the performance of activities of daily living (ADL) and in patients' quality of life.

Race

No race predilection has been established.

Sex

The incidence of hypothyroidism is much greater in women than in men. Myxedema coma is extremely rare, but its incidence is higher in elderly women, especially those older than 60 years.

Age

Hypothyroidism is seen more commonly in women aged 40-60 years; however, it can be seen in persons of all ages.

Previous