130 Journal of the Royal Society of Medicine Volume 86 March 1993 Rheumatism and the thyroid D N Golding MA MD FRCPI The Old Forge, Woodside Green, Bishop's Stortford, Herts CM22 7UL Keywords: thyrotoxicosis; rheumatism; hypothyroidism; Hashimoto's disease Muscle weakness and myopathy are well-known Paradoxically the serum muscle enzymes (such as Presidential features of thyrotoxicosis. It is less well-known that creatine kinase) are more likely to be elevated in the Address muscle weakness, pain and even swelling of small mild myopathy associated with hypothyroidism than given to joints are not uncommon in hypothyroidism. Recently in the clinically more severe thyrotoxic myopathy6. Section of it has become apparent that a seronegative poly- Capsulitis of the shoulders is seen in some hypo- Rheumatology & arthritis of small joints may occur in patients with thyroid patients, though is commoner in thyrotoxicosis. Rehabilitation, Hashimoto's disease (even when euthyroid), and that A bilateral case has been described in a myxoedem- 13 May 1992 this condition may be responsible for other rheumatic atous patient with proximal myopathy and an acute features, such as neck and chest pain. phase response7. In hypothyroidism muscular pain is often associated with marked fatigue (the 'after tennis Historical note feeling') and prolonged morning stiffness (thought That rheumatic features can be associated with thyroid to be due to deficiency of alpha-glucosidase in this disorders has been known for some time: for example, condition), which may give a mistaken diagnosis in 1873 Sir William Gull described two cases of 'A of polymyalgia rheumatica. It must however be cretinoidal state supervening in Adult Women', remembered that polymyalgia rheumatica may coexist describing neck stiffness and joint pain; and early with hypothyroidism8- and indeed the prevalence of British reports were described in a recent paper by hypothyroidism in patients with polymyalgia is about in 5%, significantly greater than in controls. In practice Doyle this journal'. In 1883 Coxwell described it is myopathy in a case ofjuvenile myxoedema - a 13-year- worth screening polymyalgia patients, particularly old girl who 'previously could read a chapter out of those who have a normal, or only slightly raised the Bible, but then developed defective memory, her erythrocyte sedimentation rate (ESR), and those who head drooped forward unto her chest, her legs became are not doing so well on steroids, for hypothyroidism. weak and unsteady' 2. Retrospectively, this sounds Apart from muscle weakness, generalized pains and rather like stiffness may occur in hypothyroidism and this has myxoedematous cerebellar degeneration, been said to be a cause of 'fibrositis' (fibromyalgia). a rare complication of hypothyroidism. As recently in as 1966 the first full Impairment ofstage IV sleep occurs both conditions Ramsey gave description of and in a recent study of 15 patients fulfilling the thyrotoxic myopathy3. criteria of fibrositis all were found to have either hypothyroidism or psychiatric disturbance8. In a paper Rheumatic features of hypothyroidism presented at Budapest last year 22% cases offibrositis The spectrum ofrheumatic disorders which have been had a blunted thyroid-stimulating hormone (TSH) described in hypothyroidism is depicted in Figure 1. response and 7% had subclinical hypothyroidism9. These vary from muscle weakness to generalized pain Tricyclic antidepressants can be beneficial in treating and stiffness, synovitis of small or large joints and some patients with fibrositis associated with latent occasionally a destructive type of arthropathy4. depression, but this is not so in fibrositis associated Unlike thyrotoxicosis, severe myopathy and poly- with hypothyroidism, and indeed antidepressants myositis are rare in hypothyroidism. However, general often seem to aggravate pain in this condition. muscle weakness (often with some degree of pain or Coming to the synovial joints, a small-joint poly- discomfort) is not uncommon5. Histologically the arthritis is sometimes seen in patients with muscle may show deposits ofmucin in the perimysium hypothyroidism (and indeed in some euthyroid as well as the usual changes ofmyopathy, and electron patients having high titres of thyroid antibodies, as microscopy may show mitochondrial abnormalities. will be mentioned later). However, effusions into large joints, such as the knees, though reported are rarely seen in practice. Bland and Frymoyer first described effusions'0 and found the fluid to be Muceb hyphy synovial highly (re) viscous and to have other non-inflammatory features, suggesting that the effusions are related to hyaluron- tMtuacb,dmes_ - &(PclYm"eeW) (¶lbmdds_ andotffhe ate deposition in the synovium and ligaments. It Myophy has alternatively been proposed that activation of adenylate cyclase in synovial membranes by excess ( (use)~ ~ TSH produces effusions into joints". intfUdWorm Dedwecw Other possible causes ofjoint pain in myxoedema (rem) are secondary gout, hyperuricaemia being common fffob gc in this condition; and pyrophosphate pseudogout, calcium pyrophosphate dihydrate crystals having Figure 1. Spectrum ofrheumatic disorders in hypothyroidism been found in knee effusions, which in fact may be Journal of the Royal Society of Medicine Volume 86 March 1993 131 precipitated by the instigation of thyroid therapy or Rheumatic features of Hashimoto's disease sudden increase in dosage'2. It is ofconsiderable interest that rheumatic features Rarer musculoskeletal disorders in myxoedema may occur in euthyroid patients with auto-immune include a destructive arthropathy ofthe knees, possibly thyroiditis as well as in those with disturbed thyroid resulting from hyaluronate infiltration of bone13 and function. In recent years I have followed up 12 a destructive arthropathy of the small finger-joints such patients (see Table 2) who were euthyroid or has been described. marginally hypothyroid (eg T4 normal, TSH margin- Hypothyroid patients occasionally present at ally raised). These patients have high levels of rheumatology departments with neurological features, circulating thyroid antibodies, in particular thyroid particularly carpal tunnel syndromes. However, while microsomal antibodies - the titres of which may be in it is true that these occur in 7% of patients with the region of 1: 50 000 or higher. Some had a large, myxoedema, there is a mistaken belief that hypo- multinodular goitre, needle biopsy or excision showing thyroidism is a common cause of 'carpal tunnels'. lymphocytic infiltration (especially T-cells), lymphoid In a personal series, 50 patients presenting with follicles and variable destruction of thyroid cells. paraesthesiae ofthe fingers referred for median nerve Many had a raised ESR and altered gamma globulins. conduction tests were screened for hypothyroidism: In my series generalized pains and stiffness 25 had electrical evidence ofmedian nerve compression (especially neck pain) and a benign form of sero- in one or both wrists but only two of these were negative inflammatory polyarthritis resembling hypothyroid. A recent Japanese study confirmed early, mild rheumatoid disease were notable features that hypothyroidism was the cause of carpal tunnel of Hashimoto's syndrome (first described by Leriche syndromes in only 6% of 1215 patients. This contrasts in 198415). Many patients complained of significant with the high prevalence of slowing of median nerve morning stiffness, most had a mild small-joint poly- conduction (possibly 70%) in those with known arthritis, a few had more severe joint changes - these myxoedema, presumably due to an additional intrinsic had positive rheumatoid factor. It seems that these neuropathy'2. patients fall into one of two groups: (a) mild, seronegative, tend to have HLA-DR2 and the joint changes markedly improve with thyroid therapy; Rheumatic features of hyperthyroidism (Table 1) (b) there are more definite rheumatoid-like features Thyrotoxic myopathy is, of course, well-known. It with more severe synovitis, rheumatoid factor is may be due to an auto-antibody developing against present and they have HLA-DR4, the joints are TSH-receptors, so stimulating the thyroid cells to unaffected by thyroid therapy and usually require produce excessive thyroxine and breaking down second-line drug therapy for control. It appears that muscle fibres. As already mentioned, muscle biopsy the first, seronegative group represents a definite, often shows typical myopathic appearances but, non-rheumatoid syndrome ofseronegative polyarthritis unlike hypothyroid myopathy, paradoxically the associated with auto-immune thyroiditis. muscle enzymes are often normal. Occasionally Table 3 gives other possible associations ofrheumatic myasthenia gravis may coincide with severe pro- disorders with Hashimoto's disease, which must be gressive thyrotoxic myopathy. Frozen shoulders, considered as a generalized disorder often overlapping often bilateral, are not uncommon in patients with with systemic connective tissue disorders such as thyrotoxic myopathy and often antithyroid treatment systemic lupus and Sjogren's syndrome (thyroid improves the pain and stiffness14, though will not antibodies are found in 40% patients with Sjogren's afford complete resolution ofthe capsulitis. Sometimes syndrome16). In one series, abnormal thyroid function shoulder-hand syndromes occur in association with frozen shoulders - pain and swelling ofthe hands due to reflex sympathetic dystrophy, thought to be Table 2. Personal