eMedicine Specialties > Physical Medicine and Rehabilitation > Myopathy

Hypothyroid Myopathy

Divakara Kedlaya, MBBS, Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine
Diana M Echeverry, MD, MPH, Assistant Professor, Department of Endocrinology, Charles R Drew University of Medicine and Science

Updated: Aug 21, 2008

Introduction

Background

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

Treatment with radioactive iodine (I¹³¹ ) 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 These manifestations can occur at any time in the hypothyroidism disease process. Usually mild, they include weakness, pain, aching, and stiffness.

Hypothyroid myopathy typically manifests as polymyositis-like myopathy with proximal muscle weakness and an increased creatine kinase level.^2,3 However, it sometimes manifests as muscle enlargement (pseudohypertrophy); in adults, this condition is called Hoffman syndrome.^4,5,6 In children with hypothyroid disease (cretinism), a pattern of proximal weakness and diffuse muscle enlargement is known as Kocher-Debr é -S é m é laigne syndrome.

Several case reports describe rhabdomyolysis associated with hypothyroidism.⁷ In these cases, the hypothyroidism is thought to have predisposed individuals to rhabdomyolysis.

Related eMedicine topics:
Endocrine Myopathies
Hypothyroidism [Endocrinology]
Hypothyroidism [Pediatrics: General Medicine]
Myopathies
Thyroid Disease

Related Medscape topics:
Resource Center Hypothyroidism
Resource Center Thyroid 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.⁸

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.^9,10

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. 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.

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.¹¹

International

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.

Clinical

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.^9,12,13
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 one third of patients with hypothyroidism, but it is not necessarily specific to hypothyroidism.
Muscle enlargement, stiffness, and cramping are a constellation of findings seen in individuals with hypothyroidism. In adults, these findings are known as Hoffman syndrome. In children, they are called Kocher-Debré-Sémélaigne syndrome.
Myokymia, which may be related to a low sodium level, may be seen.

Causes

See Pathophysiology.

Hypothyroidism can impair mitochondrial metabolism, resulting in decreased muscle energy production. A low thyroid hormone level is the main causative factor.¹⁴
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)
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.^15,16 Thyroiditis, seen in 10% of patients, may induce hypothyroidism.

Differential Diagnoses

Acid Maltase Deficiency Myopathy
Acute Poliomyelitis
Amyotrophic Lateral Sclerosis
Becker Muscular Dystrophy
Limb-Girdle Muscular Dystrophy

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.
Increased thyrotropin is seen in primary hypothyroidism, and decreased thyrotropin 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 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.³

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.¹⁸

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

Physical medicine and rehabilitation specialist
Endocrinologist
Neurologist

Medication

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

Thyroid products

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.

Dosing

Adult

1.4-1.6 mcg/kg or 75-200 mcg/d PO in adult patients with no evidence of CAD; in patients with suggestion or evidence of CAD, start at 25 mcg/d and increase q2-4 wk based on CAD symptomatology to goal dose as above

Pediatric

Neonate to 6 months: 25-50 mcg/d PO
6-12 months: 50-75 mcg/d PO
1-5 years: 75-100 mcg/d PO
5-12 years: 100-150 mcg/d PO
>12 years: 150 mcg/d PO

Interactions

Cholestyramine may decrease absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in elderly with CAD and in patients with angina pectoris or cardiovascular disease; periodically monitor thyroid status

Follow-up

Further Inpatient Care

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

Further Outpatient Care

Outpatient physical therapy is indicated.

Inpatient & Outpatient Medications

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

Deterrence

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 takes several months of treatment.

Miscellaneous

Medicolegal Pitfalls

Failure to identify the cause of myopathy can lead to potential medical or legal problems. See Medical Issues/Complications.

References

Barohn R. Metabolic myopathies. In: Cecil RL, Goldman L, eds. Textbook of Medicine. 21 ed. Orlando, Fla: Harcourt Health Sciences; 2000.
Miyake I, Hiromatsu Y. [Hypothyroid myopathy]. Ryoikibetsu Shokogun Shirizu. 2001;(36):294-7. [Medline].
Scott KR, Simmons Z, Boyer PJ. Hypothyroid myopathy with a strikingly elevated serum creatine kinase level. Muscle Nerve. Jul 2002;26(1):141-4. [Medline].
Deepak S, Harikrishnan, Jayakumar B. Hypothyroidism presenting as Hoffman's syndrome. J Indian Med Assoc. Jan 2004;102(1):41-2. [Medline].
Turker H, Bayrak O, Gungor L, et al. Hypothyroid myopathy with manifestations of Hoffman's syndrome and myasthenia gravis. Thyroid. Feb 2008;18(2):259-62. [Medline].
Tuncel D, Cetinkaya A, Kaya B, et al. Hoffmann's syndrome: a case report. Med Princ Pract. 2008;17(4):346-8. [Medline].
Kisakol G, Tunc R, Kaya A. Rhabdomyolysis in a patient with hypothyroidism. Endocr J. Apr 2003;50(2):221-3. [Medline]. [Full Text].
Sinclair C, Gilchrist JM, Hennessey JV, et al. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve. Sep 2005;32(3):357-9. [Medline].
Lochmuller H, Reimers CD. Exercise induced myalgia in hypothyroidism. In: Year Book of Sports Medicine. St Louis, Mo: Mosby; 1994:999-1001.
Casimiro-Lopes G, Alves SB, Salerno VP, et al. Maximum acute exercise tolerance in hyperthyroid and hypothyroid rats subjected to forced swimming. Horm Metab Res. Apr 2008;40(4):276-80. [Medline].
Cakir M, Samanci N, Balci N, et al. Musculoskeletal manifestations in patients with thyroid disease. Clin Endocrinol (Oxf). Aug 2003;59(2):162-7. [Medline].
Horak HA, Pourmand R. Endocrine myopathies. Neurol Clin. Feb 2000;18(1):203-13. [Medline].
Pourmand R. Metabolic myopathies. A diagnostic evaluation. Neurol Clin. Feb 2000;18(1):1-13. [Medline].
Monzani F, Caraccio N, Siciliano G, et al. Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab. Oct 1997;82(10):3315-8. [Medline]. [Full Text].
Ghilardi G, Gonvers JJ, So A. Hypothyroid myopathy as a complication of interferon alpha therapy for chronic hepatitis C virus infection. Br J Rheumatol. Dec 1998;37(12):1349-51. [Medline]. [Full Text].
Obolonczyk L, Obolonczyk L, Siekierska-Hellmann M, et al. Side effects during interferon-alpha therapy of hepatitis C with special consideration of thyroid dysfunction. Postepy Hig Med Dosw (Online). Jun 26 2007;62:309-21. [Medline].
Takanami I, Imamuma T, Yamamoto Y, et al. The rapid transformation of hyperthyroidism to hypothyroidism complicated by myasthenia gravis. J Thorac Cardiovasc Surg. Sep 1995;110(3):852. [Medline].
Modi G. Cores in hypothyroid myopathy: a clinical, histological and immunofluorescence study. J Neurol Sci. Apr 1 2000;175(1):28-32. [Medline].

Keywords

hypothyroid myopathy, polymyositis-like syndrome, polymyositislike syndrome, Hoffmann's syndrome, Hoffmann syndrome, Hoffman's syndrome, Hoffman syndrome, Kocher-Debre-Semelaigne syndrome, Kocher-Debré-Sémélaigne syndrome

Contributor Information and Disclosures

Author

Divakara Kedlaya, MBBS, Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine
Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, and Colorado Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Diana M Echeverry, MD, MPH, Assistant Professor, Department of Endocrinology, Charles R Drew University of Medicine and Science
Disclosure: Nothing to disclose.

Medical Editor

Elizabeth A Moberg-Wolff, MD, Associate Professor and Pediatric PM&R Fellowship Director, Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin; Program Director, Tone Management and Mobility, Department of Physical Medicine and Rehabilitation, Children's Hospital of Wisconsin
Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Medtronic Neurological Grant/research funds Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kat Kolaski, MD, Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine
Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center
Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix
Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers
Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching

Further Reading

eMedicine Specialties > Physical Medicine and Rehabilitation > Myopathy

Hypothyroid Myopathy

Introduction

Background

Pathophysiology

Frequency

United States

International

Mortality/Morbidity

Race

Sex

Age

Clinical

History

Physical

Causes

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Histologic Findings

Treatment

Rehabilitation Program

Physical Therapy

Occupational Therapy

Recreational Therapy

Medical Issues/Complications

Consultations

Medication

Thyroid products

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

Dosing

Adult

Pediatric

Interactions

Contraindications

Precautions

Pregnancy

Precautions

Follow-up

Further Inpatient Care

Further Outpatient Care

Inpatient & Outpatient Medications

Deterrence

Prognosis

Miscellaneous

Medicolegal Pitfalls

References

Keywords

Contributor Information and Disclosures

Author

Coauthor(s)

Medical Editor

Pharmacy Editor

Managing Editor

CME Editor

Chief Editor