- Marc L Miller, MD
Marc L Miller, MD
- Clinical Assistant Professor of Medicine
- Tufts University School of Medicine
- Devon I Rubin, MD
Devon I Rubin, MD
- Professor of Neurology
- Mayo Clinic College of Medicine
- Section Editors
- Michael J Aminoff, MD, DSc
Michael J Aminoff, MD, DSc
- Editor-in-Chief — Neurology
- Section Editor — Medical Neurology
- Professor of Neurology
- University of California, San Francisco School of Medicine
- Jeremy M Shefner, MD, PhD
Jeremy M Shefner, MD, PhD
- Section Editor — Neuromuscular Disease
- Professor and Chair of Neurology, Barrow Neurological Institute
- Professor of Neurology, University of Arizona, Phoenix
- Clinical Professor of Neurology, Creighton University
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
Muscle involvement in a variety of forms is a frequent problem in both congenital and adult-onset hypothyroidism . This topic will discuss the clinical manifestations, pathogenesis, and treatment of hypothyroid myopathy. Other neurologic manifestations of hypothyroidism are discussed separately. (See "Neurologic manifestations of hypothyroidism" and "Clinical manifestations of hypothyroidism".)
The Kocher-Debre-Semelaigne syndrome describes infants with typical features of cretinism associated with diffuse muscular hypertrophy and muscle weakness that is predominantly proximal. These infants have motor and cognitive developmental delay, constipation, myxedema, enlarged tongue, and coarse hair and skin typical of cretinism. Despite a very muscular, almost muscle-bound appearance, they are in fact weak and often have difficulty with sitting and head control . (See "Iodine deficiency disorders", section on 'Cretinism'.)
Serum creatine kinase (CK) and other muscle enzymes are often elevated in these infants. The electromyogram may be normal or show scattered low amplitude motor unit potentials in involved muscles. Muscle biopsy shows variable muscle fiber size with predominantly type I fiber atrophy. There is also increased interstitial connective tissue related to the duration of the hypothyroidism and abnormal glycogen accumulation. Muscle fiber necrosis and inflammation are not prominent features of this disorder .
Treatment with thyroid hormone results in prompt improvement in muscle strength and normalization of serum CK concentrations, even in infants with longstanding congenital hypothyroidism .
Muscle involvement in adults with hypothyroidism is common; in one series, 79 percent of patients with hypothyroidism had muscle complaints (weakness, cramps, myalgias) . Patients with more severe or longstanding untreated hypothyroidism are more likely to develop clinically significant muscle disease.
- Sindoni A, Rodolico C, Pappalardo MA, et al. Hypothyroid myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature. Rev Endocr Metab Disord 2016; 17:499.
- NAJJAR SS, NACHMAN HS. THE KOCHER-DEBR'E-S'EM'ELAIGNE SYNDROME; HYPOTHYROIDISM WITH MUSCULAR "HYPERTROPHY". J Pediatr 1965; 66:901.
- Spiro AJ, Hirano A, Beilin RL, Finkelstein JW. Cretinism with muscular hypertrophy (Kocher-Debré-Sémélaigne syndrome). Histochemical and ultrastructural study of skeletal muscle. Arch Neurol 1970; 23:340.
- Mastaglia FL, Ojeda VJ, Sarnat HB, Kakulas BA. Myopathies associated with hypothyroidism: a review based upon 13 cases. Aust N Z J Med 1988; 18:799.
- Duyff RF, Van den Bosch J, Laman DM, et al. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry 2000; 68:750.
- Kaminski, HJ, Ruff, RL. Endocrine myopathies. In: Myology, 2d ed, Engel, AG, Franzini-Armstrong, C (Eds), McGraw-Hill, New York 1994. p.1741.
- Monzani F, Caraccio N, Siciliano G, et al. Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab 1997; 82:3315.
- Argov Z, Arnold DL. MR spectroscopy and imaging in metabolic myopathies. Neurol Clin 2000; 18:35.
- Riggs JE. Acute exertional rhabdomyolysis in hypothyroidism: the result of a reversible defect in glycogenolysis? Mil Med 1990; 155:171.
- Sekine N, Yamamoto M, Michikawa M, et al. Rhabdomyolysis and acute renal failure in a patient with hypothyroidism. Intern Med 1993; 32:269.
- Klein I, Parker M, Shebert R, et al. Hypothyroidism presenting as muscle stiffness and pseudohypertrophy: Hoffmann's syndrome. Am J Med 1981; 70:891.
- Doran GR. Serum enzyme disturbances in thyrotoxicosis and myxoedema. J R Soc Med 1978; 71:189.
- Biron R, Burger A, Chinet A, et al. Thyroid hormones and the energetics of active sodium-potassium transport in mammalian skeletal muscles. J Physiol 1979; 297:47.
- Simonides WS, van Hardeveld C. The postnatal development of sarcoplasmic reticulum Ca2+ transport activity in skeletal muscle of the rat is critically dependent on thyroid hormone. Endocrinology 1989; 124:1145.
- Winder WW, Hardie DG, Mustard KJ, et al. Long-term regulation of AMP-activated protein kinase and acetyl-CoA carboxylase in skeletal muscle. Biochem Soc Trans 2003; 31:182.
- Madariaga MG. Polymyositis-like syndrome in hypothyroidism: review of cases reported over the past twenty-five years. Thyroid 2002; 12:331.
- McKeran RO, Slavin G, Ward P, et al. Hypothyroid myopathy. A clinical and pathologaical study. J Pathol 1980; 132:35.
- Giampietro O, Clerico A, Buzzigoli G, et al. Detection of hypothyroid myopathy by measurement of various serum muscle markers--myoglobin, creatine kinase, lactate dehydrogenase and their isoenzymes. Correlations with thyroid hormone levels (free and total) and clinical usefulness. Horm Res 1984; 19:232.
- Hekimsoy Z, Oktem IK. Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res 2005; 31:171.
- Hochberg MC, Koppes GM, Edwards CQ, et al. Hypothyroidism presenting as a polymyositis-like syndrome. Report of two cases. Arthritis Rheum 1976; 19:1363.
- Cabili S, Pines A, Kaplinsky N, Frankl O. Hypothyroidism masquerading as polymyositis. Postgrad Med J 1982; 58:545.
- Salvarani C, Marcello N, Macchioni P, et al. Hypothyroidism simulating polymyositis. Report of two cases. Scand J Rheumatol 1988; 17:147.
- Ciompi ML, Zuccotti M, Bazzichi L, Puccetti L. Polymyositis-like syndrome in hypothyroidism: report of two cases. Thyroidology 1994; 6:33.
- Kim JM, Song EJ, Seo JS, et al. Polymyositis-like syndrome caused by hypothyroidism, presenting as camptocormia. Rheumatol Int 2009; 29:339.
- Halverson PB, Kozin F, Ryan LM, Sulaiman AR. Rhabdomyolysis and renal failure in hypothyroidism. Ann Intern Med 1979; 91:57.
- Scott KR, Simmons Z, Boyer PJ. Hypothyroid myopathy with a strikingly elevated serum creatine kinase level. Muscle Nerve 2002; 26:141.
- Finsterer J, Stöllberger C, Grossegger C, Kroiss A. Hypothyroid myopathy with unusually high serum creatine kinase values. Horm Res 1999; 52:205.
- Kiernan TJ, Rochford M, McDermott JH. Simvastatin induced rhabdomyolysis and an important clinical link with hypothyroidism. Int J Cardiol 2007; 119:374.
- Yeter, E, Keles, T, Durmaz, T, Bozkurt, E. Rhabdomyolysis due to the additive effect of statin therapy: a case report. J Med Case Reports 2007; 10:130.
- Antons KA, Williams CD, Baker SK, Phillips PS. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med 2006; 119:400.
- Mizusawa H, Takagi A, Sugita H, Toyokura Y. Mounding phenomenon: an experimental study in vitro. Neurology 1983; 33:90.
- Mizusawa H, Takagi A, Nonaka I, et al. Muscular abnormalities in experimental hypothyroidism of rats with special reference to the mounding phenomenon. Exp Neurol 1984; 85:480.
- Vignesh G, Balachandran K, Kamalanathan S, Hamide A. Myoedema: A clinical pointer to hypothyroid myopathy. Indian J Endocrinol Metab 2013; 17:352.
- Horak HA, Pourmand R. Endocrine myopathies. Neurol Clin 2000; 18:203.
- Eslamian F, Bahrami A, Aghamohammadzadeh N, et al. Electrophysiologic changes in patients with untreated primary hypothyroidism. J Clin Neurophysiol 2011; 28:323.
- Khaleeli AA, Griffith DG, Edwards RH. The clinical presentation of hypothyroid myopathy and its relationship to abnormalities in structure and function of skeletal muscle. Clin Endocrinol (Oxf) 1983; 19:365.
- Evans RM, Watanabe I, Singer PA. Central changes in hypothyroid myopathy: a case report. Muscle Nerve 1990; 13:952.
- Klein I, Mantell P, Parker M, Levey GS. Resolution of abnormal muscle enzyme studies in hypothyroidism. Am J Med Sci 1980; 279:159.
- Khaleeli AA, Edwards RH. Effect of treatment on skeletal muscle dysfunction in hypothyroidism. Clin Sci (Lond) 1984; 66:63.
- Torres CF, Moxley RT. Hypothyroid neuropathy and myopathy: clinical and electrodiagnostic longitudinal findings. J Neurol 1990; 237:271.