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  • Updated 05.20.2024
  • Released 07.17.1995
  • Expires For CME 05.20.2027

Myopathies associated with thyroid disease



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account of eight cases of exophthalmic goiter was included in a posthumously published collection of his previously unpublished writings in 1825, based on observations he made originally in 1786 (164; 95; 131).

Caleb Hillier Parry (1755-1822)

English physician Caleb Hillier Parry (1755-1822) gave one of the earliest accounts of exophthalmic goiter. (Source: Hull G. Caleb Hillier Parry 1755-1822: a notable provincial physician. J R Soc Med 1998;91(6):335-8. Courtesy ...

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 (71; 233; 143; 131).

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 (203; 180; 181; 55). In 1886, German neurologist Paul Julius Moebius (1853-1907) proposed that Graves disease was a primary disease of the thyroid gland.

Paul Julius Möbius (1853-1907)
German neurologist Paul Julius Möbius (1853-1907) around 1900. (Courtesy of Wikimedia Commons. Public domain.)

Successful treatment of myxedema was first reported by English physician George Redmayne Murray (1865-1939) in 1891 using sheep thyroid extract (155).

Myxedema in 55-year-old woman
A 55-year-old woman (A W) with myxedema, before and after treatment. Photographs taken at the German Hospital Dalston in 1895. Frederick Parkes Weber collection. Wellcome Images. (Courtesy of Wikimedia Commons. Images edited by Do...

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 (161; 11).

William Miller Ord (1834-1902)

British surgeon William Miller Ord MRCS (1834-1902). (Source: Anonymous. William Miller Ord, M.D., F.R.C.P. Lond. Br Med J 1902;1(2160):1315-7. Public domain.)

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 (82; 09; 204; 236).

Reports of weakness, muscle enlargement, and slow movements from hypothyroidism date back more than a century (116). German neurologist Johann Hoffmann (1857-1919) first reported reversal of these symptoms with thyroid extract shortly thereafter (90).

Johann Hoffmann (1857-1919)
German neurologist Johann Hoffmann (1857-1919). (Courtesy of Wikimedia Commons. Public domain.)

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 (90). 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.

Emil Theodor Kocher (1841-1917)
Swiss physician and Nobel laureate Emil Theodor Kocher (1841-1917). (Courtesy of the U.S. National Library of Medicine. Public domain.)

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 Sémelaigne in 1935 when they demonstrated its responsiveness to treatment with thyroid extract (116; 46). 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) (97; 158). 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” (97). Thyroxine was synthesized in 1927 by British chemists Sir Charles Robert Harington FRS (1897-1972) and George Barger FRS FRSE (1878-1939) (81).

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