Myopathies associated with thyroid disease

Douglas J Lanska MD FAAN MS MSPH (

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.

Originally released July 17, 1995; last updated November 21, 2019; expires November 21, 2022

This article includes discussion of myopathies associated with thyroid disease and thyroid myopathy. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Abnormal thyroid function, either too much or too little, can cause a myopathy. Thyroid disorders can lead to neuromuscular manifestations, including thyrotoxic myopathy, hypothyroid myopathy, thyrotoxic periodic paralysis, and thyroid-associated ophthalmopathy. In this article, the author provides a review of myopathies associated with thyroid disease. He discusses the clinical manifestations, current concepts of pathophysiology, and latest advances in diagnostic work-up and management.

Key points


• Dyspnea may be the presenting symptom in hyperthyroid myopathy, in contrast to most other endocrine myopathies.


• The clinical features of hypothyroid myopathy are proximal weakness, fatigue, slowed contraction and relaxation, stiffness, myalgia, and myoedema.


• There are three main subtypes of thyroid-associated ophthalmopathy: congestive ophthalmopathy, ocular myopathy, and a mixed form.


• Although antibodies directed against the thyrotropin receptor may be the initiating event that leads to orbital inflammation, collagen XIII is a good candidate antigen in the congestive subtype of thyroid-associated ophthalmopathy, and calsequestrin antibodies may be the primary culprits for the ocular myopathy subtype.


• Mutations in a potassium channel gene cause susceptibility to thyrotoxic hypokalemic periodic paralysis.

Historical note and terminology

English physician Caleb Hillier Parry's (1755-1822) account of eight cases of exophthalmic goiter was included in a posthumously published collection of his previously unpublished writings in 1825, based on observations he made originally in 1786 (Parry 1825; Hull 1998; Loriaux 2016).

English physician Caleb Hillier Parry Image: Caleb Hillier Parry (1755-1822)
The first reports of muscle weakness and atrophy in the setting of thyrotoxicosis were published during the first half of the 19th century by Irish surgeon Robert James Graves FRCS (1796-1853) in 1835, and by German physician Carl Adolph von Basedow (1799-1854) in 1840 (Graves 1835; von Basedow 1840; Medvei 1982; Loriaux 2016).
Irish surgeon Robert James Graves Image: Robert James Graves (1796-1853)
German physician Carl Adolph von Basedow Image: Carl Adolph von Basedow (1799-1854)
Fifty years later, du Cazal in 1885 and Bathurst in 1895 observed that muscular atrophy, weakness, and orbitopathy may be the presenting signs of thyrotoxicosis (Sattler 1952; Ramsay 1968; Ramsay 1974; Durairaj 2006). In 1886, German neurologist Paul Julius Moebius (1853-1907) proposed that Graves disease was a primary disease of the thyroid gland.
A 55-year-old woman with myxedema before and after treatment Image: Paul Julius Möbius (1853-1907)

Successful treatment of myxedema was first reported by English physician George Redmayne Murray (1865-1939) in 1891 using sheep thyroid extract (Murray 1891).

55-year-old woman with Myxedema Image: Myxedema in 55-year-old woman
Improvement of cretinism with thyroid extract was also reported around this time. British surgeon William Miller Ord MRCS (1834-1902) coined the term "myxedema" to describe the nonpitting edema and gelatinous appearance of the skin in hypothyroid patients (Ord 1878; Anonymous 1902).
British surgeon William Miller Ord Image: William Miller Ord (1834-1902)
In 1879, Ord also described an autoimmune thyroiditis (Ord thyroiditis) associated with atrophy of the thyroid gland (in contrast to the more common Hashimoto thyroiditis, a goitrous form of autoimmune thyroiditis). In 1912, Japanese physician Hakaru Hashimoto (1881-1934) published “Report on lymphomatous goiter” (in translation), which was later labeled Hashimoto disease (Hashimoto 1912; Amino et al 2002; Sawin 2002; Weetman 2013).
Japanese physician Hakaru Hashimoto Image: Hakaru Hashimoto (1881-1934)
Histology of struma lymphomatosa Image: Struma lymphomatosa histology

Reports of weakness, muscle enlargement, and slow movements from hypothyroidism date back more than a century (Kocher 1892). German neurologist Johann Hoffmann (1857-1919) first reported reversal of these symptoms with thyroid extract shortly thereafter (Hoffmann 1897).

German neurologist Johann Hoffmann Image: Johann Hoffmann (1857-1919)
Hoffmann syndrome (sometimes misspelled “Hoffman”) is a specific, rare form of hypothyroid myopathy, with proximal weakness and pseudohypertrophy of muscles. Johann Hoffmann first described it in 1897 in an adult who developed muscle stiffness and difficulty in relaxation of muscles after thyroidectomy (Hoffmann 1897). A similar presentation in children (often with cretinism) is referred as Kocher-Debré-Sémélaigne syndrome – named after Swiss physician and Nobel laureate Emil Theodor Kocher (1841-1917), French pediatrician Robert Debré (1882-1978), and Georges Sémelaigne.
Swiss physician and Nobel laureate Emil Theodor Kocher Image: Emil Theodor Kocher (1841-1917)
The syndrome was initially described by Kocher in 1892, and more than 40 years later the association of hypothyroidism with muscle pseudohypertrophy was emphasized by Debré and Sé;melaigne in 1935 when they demonstrated its responsiveness to treatment with thyroid extract (Kocher 1892; Debré and Sé;melaigne 1935). Kocher received the 1909 Nobel Prize in Physiology or Medicine for his work concerning the physiology, pathology, and surgery of the thyroid. He promoted aseptic surgery and scientific methods in surgery, and reduced the mortality of thyroidectomies below 1%. He was the first surgeon to ever receive a Nobel Prize.

Thyroxine was first isolated in pure form in 1914 at the Mayo Clinic in Rochester, Minnesota, by American chemist and Nobel laureate Edward Calvin Kendall (1886-1972) from extracts of hog thyroid glands (Note: Kendall's Nobel Prize in Physiology or Medicine in 1950 was not for his work with thyroxine, but rather for work in developing cortisone as a therapeutic agent) (Ingle 1974; Nusynowitz 1983). This crystallized hormone was later named “thyroxin,” but when it was discovered to be an amino acid with an amine group, the name was changed to “thyroxine” (Ingle 1974). Thyroxine was synthesized in 1927 by British chemists Sir Charles Robert Harington FRS (1897-1972) and George Barger FRS FRSE (1878-1939) (Harington and Barger 1927).

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