Hypothyroid Myopathy 

Updated: May 28, 2020
Author: Divakara Kedlaya, MBBS; Chief Editor: Stephen Kishner, MD, MHA 

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] 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.[3, 4] However, it sometimes manifests as muscle enlargement (pseudohypertrophy) and stiffness; in adults, this condition is called Hoffman syndrome.[5, 6, 7] In children with hypothyroid disease (cretinism), a pattern of proximal weakness and diffuse muscle enlargement is known as Kocher-Debré-Sémélaigne syndrome.[8, 9, 10]

Several case reports describe rhabdomyolysis associated with hypothyroidism.[11] 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.[4] . The level returns to normal with adequate treatment.[12]

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 CenterHypothyroidism

Resource CenterThyroid Disease

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.[13]

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.[14, 15]

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%.[16] 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.[17]

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.[18]

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.[19]

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.[20]

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.[21]

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.

 

Presentation

History

Neuromuscular symptoms present in 30-80% of patients with hypothyroidism. These symptoms improve or disappear with correction of the hypothyroid state.

Patients may complain of muscle cramping, proximal symmetrical muscle weakness, muscle stiffness, and exercise intolerance. These manifestations can occur at any time during the presentation of hypothyroidism.[14, 22, 23]

Rarely, myopathy may be the sole presenting manifestation of hypothyroidism.[24]

Slowness of muscle relaxation and of muscle contraction are noted in hypothyroid myopathy.

Physical

Deep tendon reflexes are delayed in approximately 85% of patients with hypothyroidism.

Mounding of the muscle after light percussion (ie, myoedema) occurs in about one third of patients with hypothyroidism. It is much more common in primary hypothyroidism compared with secondary hypothyroidism. However, it is not specific to hypothyroidism; in rare cases, such mounding can be seen in hypoalbuminemia, hyponatremia, renal failure, rabies, and cachexia.[25]

Muscle enlargement, stiffness, and cramping are a constellation of findings seen in individuals with hypothyroidism. In adults, these findings are known as Hoffman syndrome.[5, 6, 7] In children, they are called Kocher-Debré-Sémélaigne syndrome.[26, 27]

Myokymia, which may be related to a low sodium level, may be seen.

A study by Spira et al indicated that even the subclinical form of hypothyroidism or hyperthyroidism can reduce muscle function. The report found that handgrip strength was significantly lower in persons with high or low thyroid-stimulating hormone (TSH) serum levels compared with individuals with TSH in the reference range.[28]

Causes

See Pathophysiology.

Hypothyroidism can impair mitochondrial metabolism, resulting in decreased muscle energy production. A low thyroid hormone level is the main causative factor.[29]

Certain drugs, such as lipid-lowering medications, may exacerbate myopathy in patients with hypothyroidism. There are reports of an increased risk for statin-induced myopathy in patients with hypothyroidism. Lipid-lowering drugs include beta-hydroxy-beta-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors; also commonly called statins, they include following:

  • Atorvastatin (Lipitor)

  • Fluvastatin (Lescol)

  • Simvastatin (Zocor)

  • Pravastatin (Pravachol)

  • Lovastatin (Mevacor)

Statin-induced myopathy caused by induced hypothyroidism has been reported.[30]

Interferon-alfa therapy for hepatitis, as well as hepatitis infection itself, has been reported to cause a number of adverse immunologic and/or autoimmune effects.[31, 32] Thyroiditis, seen in 10% of patients, may induce hypothyroidism.

Occasionally, hypothyroidism with myopathy may be misdiagnosed as statin intolerance in a patient with dyslipidemia. One must be aware that hypothyroidism can cause both dyslipidemia and myopathy.[33, 34]

Rarely, acute myopathy has been reported to occur with acute hypothyroidism following treatment of Graves disease with radioiodine in adults and adolescents.[35, 36]

 

DDx

Diagnostic Considerations

Myasthenia gravis

Myasthenia gravis has been associated with Graves disease and hypothyroidism.[37] Patients present with proximal muscle weakness that may be fatigable. Eventually, they can have dysphagia and respiratory distress.

Other metabolic, mitochondrial, and inflammatory myopathies

Glycogen metabolism deficiencies: These conditions are divided into dynamic and static deficiencies.

Dynamic myopathies: Manifestations of these disorders include exercise intolerance, pain, muscle cramps, and myoglobinuria.

  • Type V - Phosphorylase (McArdle disease)

  • Type VII - Phosphofructokinase (Tarui disease)

  • Type VIII - Phosphorylase B kinase

  • Type IX - Phosphoglycerate kinase

  • Type X - Phosphoglycerate mutase

  • Type XI - Lactate dehydrogenas

Static deficiencies: These disorders are associated with fixed weakness, but not with exercise intolerance or myoglobinuria.

  • Type II - Alpha-1,4 glucosidase (acid maltase)

  • Type III - Debranching

  • Type IV - Branching

Lipid metabolism deficiencies: These disorders can be accompanied by the following dynamic or static manifestations:

  • Carnitine palmitoyl transferase

  • Primary systemic/muscle carnitine deficiency

  • Secondary carnitine deficiency (eg, beta-oxidation defects, medications [such as valproic acid])

  • Purine metabolism deficiencies (eg, myoadenylate deaminase deficiency)

Mitochondrial myopathies

  • Pyruvate dehydrogenase complex deficiencies (eg, Leigh syndrome)

  • Progressive external ophthalmoplegia

  • Kearns-Sayre syndrome

  • Mitochondrial encephalopathy with lactic acidosis and strokelike episodes

  • Myoclonic epilepsy and ragged red fibers

  • Mitochondrial neurogastrointestinal encephalomyopathy

  • Mitochondrial depletion syndrome

  • Leigh syndrome and neuropathy, ataxia, or retinitis pigmentosa

  • Succinate dehydrogenase deficiency

Channelopathies are also differential diagnoses for myopathy.

Inflammatory myopathies are important differentials as well and may be difficult to differentiate from pure endocrine causes, including a heterogenous group of acquired, nonhereditary disorders characterized by muscle weakness and inflammation indicated by muscle biopsy.

Idiopathic inflammatory myopathies

  • Polymyositis

  • Dermatomyositis

  • Inclusion body myositis

  • Overlap syndromes with other connective tissue disease

  • Sarcoidosis and other granulomatous myositis conditions

  • Beh ç et syndrome

  • Inflammatory myopathies and eosinophilia

  • Focal myositis

  • Myositis ossificans

Bacterial infections

  • Staphylococcus aureus

  • Escherichia coli

  • Yersinia species

  • Legionella

  • Gas gangrene (Clostridium welchii)

  • Leprous myositis

  • Lyme disease

Viral infections

  • Acute influenza or other viral infections

  • Retrovirus-related myopathies (human immunodeficiency virus [HIV], human T-cell leukemia virus type 1)

  • Hepatitis B and C

  • Postpolio syndrome

Parasitic infections

  • Trichinosis

  • Toxoplasmosis

  • Cysticercosis

Fungal infections

  • Candida species

  • Cryptococcus species

  • Sporotrichosis species

Differential Diagnoses

 

Workup

Laboratory Studies

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.

Needle electromyography is usually normal or may be mildly myopathic. Myotonia may be present in rare cases.[38]

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.[4] . The level returns to normal with adequate treatment.[12]

Histologic Findings

Histologic findings on muscle biopsy are nonspecific. Pale central regions on nicotinamide adenine dinucleotide with accumulation of periodic acid-Schiff – positive material are seen. Decreased numbers of beta-adrenergic receptors are observed and are accompanied by glycogenolysis. Some muscle fiber atrophy is noted, and increased numbers of internal nuclei, glycogen aggregates, and (occasionally) deposition of mucopolysaccharides in the connective tissue are characteristic of hypothyroid myopathy.[39]

 

Treatment

Rehabilitation Program

Physical Therapy

Skeletal muscle weakness is the ultimate cause of most clinical problems in myopathy. In a study of patients with slowly progressive myopathies, a 12-week, moderate-resistance (30% of maximum isometric force) exercise program resulted in strength gains ranging from 4-20% without any notable deleterious effects. In the same population, a 12-week, high-resistance (training at the maximum weight that a subject could lift 12 times) exercise program showed no further added benefits when compared with the moderate-resistance program, and there was evidence of overwork weakness in some subjects.

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

Occupational therapy may be needed for training in the performance of ADL to enable the patient to compensate for proximal muscle weakness. Occupational therapists are able to provide adaptive equipment to assist the patient when he/she is performing ADL.

Recreational Therapy

Maintaining the ability to do avocational activities that promote physical fitness and mental health is important.

Medical Issues/Complications

Because there are multiple causes of muscle weakness, patients may not respond well to initial therapy because they have an undiagnosed secondary cause of myopathy. A thorough investigation for all causes is essential.

Consultations

See the list below:

  • Physical medicine and rehabilitation specialist

  • Endocrinologist

  • Neurologist

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Thyroid products

Class Summary

For replacement or supplementation of thyroid levels.

Levothyroxine (Eltroxin, Levo-T, Levothroid, Levoxyl, Synthroid, Thyrox)

Tablets contain synthetic crystalline L-3,L-3',L-5,L-5' tetraiodothyronine sodium salt (levothyroxine [T4] sodium).

Synthetic T4 is identical to that produced in the human thyroid gland.

Levothyroxine has a 7-day half-life, is absorbed relatively slowly, and equilibrates rapidly in its distribution volume, therefore avoiding significant postabsorptive perturbations in free thyroxine levels. Because of the 7-day half-life, it takes approximately 6 weeks before there is complete equilibration of the free thyroxine levels and the biologic effects of levothyroxine. Dosage is adjusted by following free thyroxine levels and thyrotropin levels, which should normalize in approximately 2 months.

The myopathy improves within 2-3 weeks, but months may be required for it to resolve completely.

 

Follow-up

Further Outpatient Care

See the list below:

  • Outpatient physical therapy is indicated.

Further Inpatient Care

See the list below:

  • Some patients with hypothyroid myopathy may need a short stay in acute rehabilitation.

Inpatient & Outpatient Medications

See the list below:

  • Continuation of thyroid supplementation is needed, with close monitoring of the levels. Once a normal value has been achieved (normal TSH), levels can be checked annually, unless the patient becomes pregnant or exacerbation of symptoms develops.

Deterrence

See the list below:

  • Patients with hypothyroid myopathy should be careful with regard to the use of cholesterol-reducing agents (ie, HMG CoA reductase inhibitors), such as statins.

Prognosis

With treatment, hypothyroidism has a good prognosis. An early diagnosis and the prompt introduction of thyroid supplemental treatment are needed. Complete resolution of weakness and other symptoms of hypothyroid myopathy may take several months to years of treatment.[21]

In a study of patients with endocrine disorder myopathies, Sharma et al found that out of 10 hypothyroid patients with apparent muscle dysfunction, 7 patients (70%) achieved resolution of muscle complaints after being treated for low T4 levels for an average period of 6.4 months.[40]