eMedicine Specialties > Physical Medicine and Rehabilitation > Myopathy

Hypothyroid Myopathy: Differential Diagnoses & Workup

Author: Divakara Kedlaya, MBBS, Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine
Coauthor(s): Diana M Echeverry, MD, MPH, Assistant Professor, Department of Endocrinology, Charles R Drew University of Medicine and Science
Contributor Information and Disclosures

Updated: Aug 21, 2008

Differential Diagnoses

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

Other Problems to Be Considered

Myasthenia gravis

Myasthenia gravis has been associated with Graves disease and hypothyroidism.17 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 dehydrogenase
    • 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 also are 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
    • Parasitic infections
      • Trichinosis
      • Toxoplasmosis
      • Cysticercosis
    • Fungal infections
      • Candida species
      • Cryptococcus species
      • Sporotrichosis species

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

More on Hypothyroid Myopathy

Overview: Hypothyroid Myopathy
Differential Diagnoses & Workup: Hypothyroid Myopathy
Treatment & Medication: Hypothyroid Myopathy
Follow-up: Hypothyroid Myopathy
References
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References

  1. Barohn R. Metabolic myopathies. In: Cecil RL, Goldman L, eds. Textbook of Medicine. 21 ed. Orlando, Fla: Harcourt Health Sciences; 2000.

  2. Miyake I, Hiromatsu Y. [Hypothyroid myopathy]. Ryoikibetsu Shokogun Shirizu. 2001;(36):294-7. [Medline].

  3. 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].

  4. Deepak S, Harikrishnan, Jayakumar B. Hypothyroidism presenting as Hoffman's syndrome. J Indian Med Assoc. Jan 2004;102(1):41-2. [Medline].

  5. 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].

  6. Tuncel D, Cetinkaya A, Kaya B, et al. Hoffmann's syndrome: a case report. Med Princ Pract. 2008;17(4):346-8. [Medline].

  7. Kisakol G, Tunc R, Kaya A. Rhabdomyolysis in a patient with hypothyroidism. Endocr J. Apr 2003;50(2):221-3. [Medline]. [Full Text].

  8. Sinclair C, Gilchrist JM, Hennessey JV, et al. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve. Sep 2005;32(3):357-9. [Medline].

  9. Lochmuller H, Reimers CD. Exercise induced myalgia in hypothyroidism. In: Year Book of Sports Medicine. St Louis, Mo: Mosby; 1994:999-1001.

  10. 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].

  11. 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].

  12. Horak HA, Pourmand R. Endocrine myopathies. Neurol Clin. Feb 2000;18(1):203-13. [Medline].

  13. Pourmand R. Metabolic myopathies. A diagnostic evaluation. Neurol Clin. Feb 2000;18(1):1-13. [Medline].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. Modi G. Cores in hypothyroid myopathy: a clinical, histological and immunofluorescence study. J Neurol Sci. Apr 1 2000;175(1):28-32. [Medline].

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Further Reading

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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

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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

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