Postgrad. med. J. (May 1968) 44, 385-397. Postgrad Med J: first published as 10.1136/pgmj.44.511.385 on 1 May 1968. Downloaded from Thyrotoxic muscle disease IAN RAMSAY M.D., M.R.C.P., M.R.C.P.E. Lecturer in Medicine, King's College Hospital Medical School, Denmark Hill, London, S.E.5 Summary myasthenia gravis and periodic paralysis may be Evidence suggests that most hyperthyroid added. patients have a proximal myopathy. The more severe this is the more frequently are distal Chronic thyrotoxic myopathy muscles, and ultimately, bulbar muscles involved. Seventy-three cases of marked muscular Probably acute thyrotoxic myopathy or encepha- atrophy and weakness associated with hyperthy- lopathy supervenes on a previous chronic back- roidism which were reported in the literature be- ground or occurs concurrently with skeletal muscle tween 1895 and 1962 have been analysed (Ram- involvement. Using careful electromyographic say, 1964). techniques evidence of myopathy may be found Clinical features in most it with The mean of of cases of thyrotoxics; disappears adequate age presentation Protected by copyright. treatment of the primary disease. chronic thyrotoxic myopathy was 47-7 years Myasthenia gravis and periodic paralysis are with no significant sex difference. The age range also associated with thyrotoxicosis and their was 20-69 years for males and 11-70 for females. differentiation is discussed. Infiltrative ophthalmo- The women had longer histories of thyrotoxi- pathy is not related to the effects of excess thyroid cosis than the men, an average of 25-3 months hormone, but is possibly due to EPS working compared with 11-3 months, and they had also in conjunction with LATS. noticed myopathic symptoms for a longer period of time (22-5 months and 11 1 months). The Introduction mean weight loss was rather similar, being 16-6 Although muscular weakness was recognized kg for males and 15-1 kg for females. by both Graves (1835) and Basedow (1840) as a Proximal muscles alone were affected by weak- symptom of hyperthyroidism and the first case ness and/or wasting in 49-3% of the cases. In of muscular was described in 34-3% and distal muscles were in- thyrotoxic atrophy proximal http://pmj.bmj.com/ 1885 by Du Cazal (Sattler, 1952), the syndrome volved, and in the remaining 16-4% there was of thyrotoxic myopathy was thought to be ex- generalized muscle disease involving also bulbar tremely rare (Waldenstrom, 1945; Whitfield & muscles. There was no significant difference be- Hudson, 1961). Only seventy-three cases could tween the sexes as to the groups of muscles be found in the literature between 1895 and picked out by the myopathic process. 1962 (Ramsay, 1964). Recent work, however, In 23% of the patients the muscle lesion was suggests that muscular involvement may be pre- the presenting complaint. In most of the rest, sent in the majority of thyrotoxic patients (Havard however, the onset of muscle symptoms was on September 26, 2021 by guest. et al., 1963; Satoyoshi et al., 1963a; Ramsay, concurrent with those of hyperthyroidism. Char- 1966). acteristically, patients had noticed difficulty in In 1945 Waldenstrom reviewed a group of climbing stairs or trying to rise out of a chair. patients who had presented with acute muscular Some could not hold their arms up long enough weakness involving particularly the bulbar mus- to comb their hair, some experienced great fati- cles. Since then there has been argument as to gue even while walking along the level, while a whether these patients had acute thyrotoxic myo- few just experienced generalized weakness. pathy or encephalopathy or whether they had Two patients (Sanderson & Adey, 1952; Milli- myasthenia gravis (Millikan & Haines, 1953). An kan & Haines, 1953) had had cramps in their attempt will be made in this review to show that legs, while Hoffenburg & Eales (1956) des- there is probably one primary muscle disorder cribed a man with pain and stiffness in his of hyperthyroidism, of varying severity, to which muscles and contractures, and muscular aching occasionally the effects of other diseases such as was a feature noted by Whitfield & Hudson 386 Ian Ramsay Postgrad Med J: first published as 10.1136/pgmj.44.511.385 on 1 May 1968. Downloaded from (1961) in one patient. In the patients with bul- portion of men in the reported cases is higher bar involvement difficulty in speaking was the than would normally be expected in an unselected most common symptom and consisted of dys- group of thyrotoxics, but this can probably be phonia, hoarseness and weakness of speech or explained by the importance of normal muscle- an alteration in the quality of the voice. Dys- power in enabling a man to perform his job. phagia was the second commonest source of Half of the patients in the author's series (Ram- trouble and the nasal regurgitation of fluids say, 1966) had a history of some muscle weak- occurred in one patient. 41-7% of the men ness. The majority complained of difficulty in were noted to have spontaneous muscle move- walking upstairs, while the remainder had noti- ments, compared with only 3-2% of the women. ced principally arm weakness. The women among Although the movements were variously des- them had noticed great fatigue in trying to comb cribed by the authors as fasciculation or fibril- their hair. The men who were engaged in lation, the latter were unlikely to have been seen manual labour had noticed a decline in their since fibrillation consists of the contraction of ability to lift heavy objects and often required individual muscle fibres and cannot be seen assistance for tasks they had previously been through the skin (Thomas, 1963). McEachern & able to manage alone. There were no symptoms Ross (1942) and Kite, McLintock & Graves suggestive of bulbar muscle weakness. (1954) postulated that the 'fasciculations' in the The onset of typical thyrotoxic symptoms was thyrotoxics were due to an undue sensitivity of the presenting feature in 79.6% of the author's the motor end-plate in a state of abnormal meta- patients. In 3-7% weakness was the first symp- bolism. Harman & Richardson (1954) considered tom noted and in 16-7% this was concurrent that in many of these patients the phenomenon with thyrotoxic symptoms. No sex differences observed was, in fact, a of were discernible in of the three and myokymia, type any groups Protected by copyright. movement which may occur in normal people, in the patients with weakness, the duration of especially under conditions of fatigue. It is seen this symptom was much the same as that of the as coarse muscular twitchings, easily visible general features of thyrotoxicosis. through the skin. The spontaneous activity con- As can be seen in Table 1, 63% had proximal tinues after spinal or high nerve block, but is muscle involvement, usually weakness and wast- stopped by curare and is not increased by pros- ing, occasionally weakness without atrophy, tigmine. Electromyographic studies show that rarely atrophy without weakness (two patients). nerve excitability is increased, but that there is Distal muscles in addition to the proximal ones no evidence of a lower motor neurone lesion. were affected in 18-5%. No bulbar weakness However, if these findings in cases recorded was detected and in 18-5% the skeletal were as 'chronic thyrotoxic myopathy' are compared judged to be clinically normal. There was no (Table 1) with the findings in unselected thyro- variation in the findings between the two sexes, nor was there difference between those TABLE 1 any age http://pmj.bmj.com/ who had and those who had not A comparison between seventy-three patients with chronic muscle involve- thyrotoxic myopathy and fifty-four unselected thyrotoxics ment. An analysis of the muscles involved (Ramsay, 1964) showed that muscles of the shoulder girdle were more often affected than those of the pelvic Seventy-three Fifty-four and that 'chronic thyrotoxic unselected girdle extensors were involved twice as myopathy' patients thyrotoxics commonly as flexors. Havard et al. (1963) noted in their that the muscles Mean age (years) 47-7 47.9 fifty thyrotoxic patients most involved were on September 26, 2021 by guest. Male/female ratio 38 : 35 14: 40 commonly the deltoid, the Mean duration of thyro- supraspinatus and the quadriceps. toxic symptoms (months) 18-5 6-6 Table 2 compares the incidence of weakness Mean duration of weakness in the seventy-three patients reported as 'chronic (months) 16-4 5-0 with Mean weight loss (kg) 15-9 8-0 myopathy' six series of hyperthyroid patients. Ophthalmoplegia (%) 62 7.4 It can be seen that even in unselected thyro- Muscles affected: toxic patients weakness may be the presenting Proximal alone (%) 49 3 63 feature, that it is a symptom in about a third to Proximal and distal (%) 34-3 18-5 a half of cases and that it may be detected clini- Generalized and bulbar(%) 16-4 0 cally in 60-80%. The figures are remarkably uni- form in the unselected groups considering that toxics (Ramsay, 1966) it can be seen that the dif- the patients are drawn from Switzerland, Britain ferences are ones of degree only. The mean age and Japan. at presentation is virtually the same. The pro- Tendon reflexes were unremarkable in the Thyrotoxic muscle disease 387 Postgrad Med J: first published as 10.1136/pgmj.44.511.385 on 1 May 1968. Downloaded from TABLE 2 A comparison of the symptoms and signs of weakness in seventy-three patients with chronic thyroxtoxic myopathy and in several series of unselected thyrotoxic patients Weakness as Series No. of the presenting Weakness as Weakness patients complaint (%) a symptom (%) clinically (%) Recorded cases of myopathy (see above) 73 23 100 100 Pipberger, Kailin & Wegmann (1955) 13 61*5 69-2 Gimlette (1959) 40 32-5 60 Havard et al.