The Musculo-Skeletal Features of Hypothyroidism DOUGLAS N. GOLDING M.D., F.R.C.P.I

Home , Thyroiditis

Postgraduate Medical Journal (September 1971) 47, 611-614. Postgrad Med J: first published as 10.1136/pgmj.47.551.611 on 1 September 1971. Downloaded from

CLINICAL REVIEW The musculo-skeletal features of hypothyroidism DOUGLAS N. GOLDING M.D., F.R.C.P.I. Consultant in Rheumatology, Princess Alexandra Hospital and Harlow Group Summary TABLE 1. Hypothyroid-rheumatic syndromes Patients with hypothyroidism may present in rheu- (1) Muscle pain and stiffness matism departments with muscle pain and weakness, (Golding, 1970) acroparaesthesiae or less commonly definite myo- (3) Arthralgia, synovial thickening with lesions are rare and further effusion (Bland & Frymoyer, 1970) pathy. Osteolytic require (3) Osteolytic lesions study. (Bland & Frymoyer, 1970) (4) Hypothyroid myopathy DURING recent years it has become accepted that (5) Acroparaesthesiae patients with hypothyroidism may present with a of rheumatic sometimes well Doniach Becker variety syndromes, upon by (personal communication). Protected by copyright. before the more obvious features of myxoedema et al. (1963), in a retrospective study of 506 patients have appeared, and these 'hypothyroid-rheumatic with Hashimoto's thyroiditis, found that forty had syndromes' will be described. This term is used in 'secondary fibrositis' not associated with myxoedema preference to 'myxoedematous arthropathy', because -joint or muscle stiffness and aching, often maximal the patients in question are not frankly myxoedema- on rising in the morning-and sixty had thoracic tous, myalgia is more frequent than arthralgia, and pain. Although it is difficult to exclude osteo- joint destruction is only an occasional feature. arthritis in such a retrospective series of patients, The various musculo-skeletal syndromes associ- these figures are suggestive of an association between ated with hypothyroidism are of clinical interest auto-immune thyroiditis and rheumatism, and the because of the vast number of rheumatic conditions symptoms described are very reminiscent of those in that may be simulated. For example, either osteo- hypothyroid patients presenting with muscle pain arthritis ofperipheraljoints or the spine, rheumatoid and stiffness. arthritis, atypical gout, or non-articular rheumatism may be initially suspected. However, since the above Hypothyroidism presenting with muscle pain and conditions occur much more frequently than the stiffness hypothyroid-rheumatic syndromes, every effort must Golding (1970) described nine hypothyroid http://pmj.bmj.com/ be made to exclude them by clinical, radiological and patients presenting with muscle and joint pains and laboratory investigations. Also, it must be remem- stiffness: the various clinical features and their bered that osteoarthritis is very common in this age frequency is given in Table 2. Hypothyroidism was group, and that clinical gout may occur as a result of suspected on account of lethargy, cold-sensitivity, hyperuricaemia which may be associated with weight-gain or mental dullness, but only one patient myxoedema, and consequently these conditions looked typically myxoedematous. Notable features can themselves give rise to symptoms in addition to were: aggravation of pain and stiffness by cold on October 1, 2021 by guest. those features due to hypothyroidism. weather (as might be expected in hypothyroid The 'hypothyroid-rheumatic syndromes' which patients, who often complain of cold-sensitivity); have been documented are listed in Table 1. Mention aggravation by phenylbutazone (which has an anti- must also be made of auto-immune thyroiditis thyroid action); and stiffness most pronounced in (Hashimoto's disease) as a possible cause of rheu- the early morning, sometimes lasting for 30 min or matic pain. It seems possible that aching and more and initially raising suspicion of rheumatoid stiffness, particularly affecting the neck muscles, arthritis or polymyalgia rheumatica. Muscle cramps trapezii and upper dorsal muscles may be a feature (usually affecting the calves) occurred in most of active auto-immune thyroiditis in the pre- patients. Five had acroparaesthesiae, and carpal myxoedematous stage. This has been commented tunnel syndromes were established by median nerve 612 Clinical review Postgrad Med J: first published as 10.1136/pgmj.47.551.611 on 1 September 1971. Downloaded from TABLE 2. Features in nine hypo- years of growth. There may be a characteristic X-ray thyroid patients presenting with muscle pain and stiffness (from appearance, sometimes termed epiphyseal dys- Golding, 1970) genesis, due to defective epiphyseal ossification (Wilkins, 1941). High levels of serum calcium and No. of alkaline phosphatase, corrected by thyroid therapy, patients may occur in cretinism (Talbot, 1939). Wilkins (1957) Muscle pain 9 described a 7-year-old girl with hypothyroidism who Muscle stiffness 8 developed a painful epiphyseal lesion in one hip, Cramps 6 with flattening and fragmentation of the femoral Acroparaesthesiae 5 head. Weissbein et al. (1959) reported a young man with adult myxoedema who presented with hip-pain conduction tests in three. There was a universally due to an osteolytic lesion in the femoral head, which good response to thyroid, with parallel improvement improved clinically and radiologically with thyroid in the electrocardiogram voltage and T-wave dis- therapy. Bywaters (1969) described cystic lesions in position. the ends of the phalanges in myxoedema, considered Pain and stiffness also occurred in the majority of to be due to defective development of bone from patients in Bland & Frymoyer's series (1970) cartilage. (Table 3), and here also there was a complete An interesting osteolytic lesion of perhaps similar symptomatic response to thyroid administration. nature occurred in three of Bland & Frymoyer's patients (Fig. 1). There was compression and Hypothyroidism with arthralgia, synovial thickening crumbling of the tibial plateau with marked loss of and effusion bone density, resembling the bone necrosis occasion- In a series of thirty-eight patients with proven ally seen in severe cases of rheumatoid arthritis, hypothyroidism, thirteen hadjoint pain and synovial especially after frequent intra-articular steroid injec- Protected by copyright. thickening affecting principally knees and small tions. It would seem possible that this represents joints of the hands and feet, often with synovial actual infiltration of bone with hyaluronic acid-like effusions (Bland & Frymoyer, 1970; Table 3). substance, and in future instances it would be of Although in the past these features have been sporadically noted in myxoedematous patients, this is the first report of a definite arthropathy occurring in association with hypothyroidism. The synovial thickening was not due to inflammatory synovitis, and the appearance and composition of the synovial fluid was normal. It is postulated that the condition is due to hyaluronic acid deposition in the connective tissue, ligaments and other joint structures leading to laxity of ligaments, joint in- stability, and consequent synovial effusion. Hyper- uricaemia can occur in et

myxoedema (Leeper al., http://pmj.bmj.com/ 1960), and in this series four patients had a serum uric acid over 7 mg/100 ml, so it is possible that in this group the symptoms may have been at least partially due to secondary gout. However, if this were the case one would expect to have found low- viscosity synovial fluid with a high leucocyte count and, in particular, a high concentration of intra- and extia-cellular urate crystals in the fluid. Synovial on October 1, 2021 by guest. thickening was not observed in any of Golding's series, and this would seem to be a distinct entity occurring in a proportion of patients with hypothroidism. As already mentioned, all Bland & Frymoyer's patients recovered on thyroid replace- ment therapy. Osteolytic lesions in hypothyroidism result in characteristic Thyroxine deficiency may FIG. 1. Bone lesion (right knee-joint) in a case of hypo- bone changes if the deficiency occurs during the thyroidism. (By kind permission of Dr J. H. Bland.) Clinical review 613 Postgrad Med J: first published as 10.1136/pgmj.47.551.611 on 1 September 1971. Downloaded from

* vr00o - 0 in in -4 , _ _ I I 0 1 W7 I 0 (%) wia I l Go o a, 'o %Oo \ 00 WI O (lm 001/Sw) loJasaoloqD in N a Sn N o\ c,o I o\ a N I IIN' 00 (jq tZ) 81 N c nt cm N a .0 'I I I (Jq tZ) IVL _ so _\ I 0' N4 O N\ Xt m Snv ^- c I OI I 0 I I? C - (IU 001/srI) Ial C:j : t N n 6 C1 * e

o 0t0 A1ISOOSTA I .s_

Cd 00 eunu/sliao I > I I I I I oo ^ O i' § i ( I I I (CIU 001T/) uOojda N.

uopT.uItUIBEu I I I I I

'I + I I + I + I C) sduIBmo Olsn[ a + I I I . aelsaqisa.sd + + ++ I + + + + .Y

uo!snjga + + ++ + rA I i Protected by copyright. 10 a0 9S uuo1)oTq IjuouAs *o'0 o a BOTBlMS + l.S!itmllXV + o +++++ *S ssau.pS + (sjea) uo!pnmaC C 0oo S o S .4. o\ CU m Cf

.0 ssauasJloH + I I I I I + + I lauunl I.Bdji I + I I I I + + + + + 3 I uolUlsuam MolIS I + I I I I + BTSSO1lSoJOB I + I I I + + http://pmj.bmj.com/ saoBj umoapaoxAj I + + + I I I + + + 'a + uloqdTda + I I I + I I + 0 + + + + 1 + I I I + c21I uotBdp!suoJ + + I I I ++ + I I + + I + + o SupiaMs pasaJoaaQ + I + I + JeIq aslsoD3 + + + I +I + + .up[s £oc[ + I + + ++

10 on October 1, 2021 by guest. aoutualoIuI Pio° + + + ++ +I + I + UIIS + + + + C: sagureqo ++ + + 4- -4 + tuapao llqlio.uajd + I I I ++ + + a I suoapao le!qpaloJ + 4- + I +I 4- ++ + + + uop!tXtlj xsaal Jo a01o paSuoloiJ + + I + ++ + + SSaUto,M,--A, 1VBp0' + I I + ++ + + 00o- t-00 t %O N 0% (sloaX) uop.ein q- 4- N + t- co xas inw ...o 14- c,I 00 oav n. Co 4 $i on 8 C- 3r s4 n P_ oj 4- V t-; s3 .i 614 Clinical review Postgrad Med J: first published as 10.1136/pgmj.47.551.611 on 1 September 1971. Downloaded from great interest to carry out bone biopsies, which as feature of median or medial popliteal nerve com- yet have never been attempted in these cases. pression in the carpal or tarsal tunnels, but it should be borne in mind that in some very advanced cases of Hypothyroid myopathy myxoedema deposition of pseudo-mucinous sub- The majority of patients with myxoedema are stance (presumably hyaluronate) has been observed weak, and it is possible that they have a minor degree in tendon and nerve sheaths; and also that an of myopathy. Thefact that the serum creatine-kinase intrinsic hypothyroid neuropathy, in which there is and (less frequently) the SGOT and aldolase are (predominantly sensory) nerve conduction slowing, raised in most cases of hypothyroidism (Griffiths, diminished deep reflexes, paraesthesiae and slight 1965) lends weight to this possibility. Only a small distal impairment of sensation, has been demon- proportion of hypothyroid patients are affected with strated in some cases (Fincham & Cape, 1968). severe muscle weakness as the predominant feature. The weakness principally affects the proximal muscle groups, and in the absence of treatment spreads References distally. BECKER, K. L., FERGUSON, R.H. & MCCONAHEY, W.M. Hypotonic weakness with or without muscle (1963) The connective-tissue diseases and symptoms associated with Hashimoto's thyroiditis. New England atrophy is usually the case in severe hypothyroid Journal of Medicine, 268, 277. myopathy, but myotonic, myasthenic and pseudo- BLAND, J.H. & FRYMOYER, J.W. (1970) Rheumatic syndromes hypertrophic forms very rarely occur. The pseudo- of myxedema. New England Journal ofMedicine, 282, 1171. hypertrophic type has been described in acquired BYWATERS, E.G.L. (1969) Textbook of Rheumatic Diseases (Ed. by W. S. C. Copeman), 4th edn. E & S. Livingstone, myxoedema (Hoffman's syndrome) and in con- Edinburgh. genital hypothyroidism (the Debre-Semelaigne syn- DEBRE, R. & SEMELAIGNE, G. (1935) Syndrome of diffuse drome). The more usual form, hypotonic myopathy muscular hypertrophy in infants causing athletic appearance: its connection with congenital American without hypertrophy, is exemplified by three cases myxedema. Protected by copyright. Journal of Diseases of Children, 50, 1351. described by Fessel (1968). The symptoms closely DONIACH, D. (1962) Personal communication. resembled polymyositis-marked weakness associ- FESSEL, W.J. (1968) Myopathy of hypothyroidism. Annals of ated with muscle pain and increase in serum muscle the Rheumatic Diseases, 27, 590. enzymes. In two patientsthemuscular symptomswere FINCHAM, R.W. & CAPE, C.A. (1968) Neuropathy in myxe- not abolished after several months of dema. A study of sensory nerve conduction in the upper thyroid extremities. Archives of Neurology, 19, 464. therapy, illustrating an Important difference be- GOLDING, D.N. (1970) Hypothyroidism presenting with tween hypothyroid myopathy and the 'hypothyroid- musculoskeletal symptoms. Annals of the Rheumatic rheumatic syndromes' already described, where Diseases, 29, 10. there is a to This GRIFFITHS, P.D. (1965) Serum enzymes in diseases of the always good response thyroid. thyroid gland. Journal of Clinical Pathology, 18, 660. probably reflects a different pathology underlying HOFFMAN, J. (1897) Weiterer Beitrag zur Lehre von der the two conditions-hyaluronic acid accumulation Tetanie. Deutsche Zeitschrift fur Nervenheilkunde, 9, 278. in the hypothyroid-rheumatic syndromes, intrinsic LEEPER, R.D., BENUA, R.S. & BRENER, J.L. (1960) Hyper- muscle lesions with fibre and interstitial uricemia in myxedema. Journal of Clinical Endocrinology atrophy and Metabolism, 20, 1457. histiocyte infiltration in hypothyroid myopathy. NORRIS, F.H. Jr & PANNER, B.J. (1966) Hypothyroid myo- The latter, in effect, may be considered as a form of pathy. Clinical electromyographical and ultrastructural polymyositis secondary to hypothyroidism. Electron observations. Archives of Neurology, 14, 574. http://pmj.bmj.com/ showed in muscle SALICK, A.I., COLACHIS, S.C. Jr & PEARSON, C.M. (1968) microscopy significant changes Myxedema myopathy: clinical, electrodiagnostic and mitochondria by electron microscopy in a case of pathologic findings in advanced case. Archives of Physical hypothyroid myopathy described by Norris & Medicine and Rehabilitation, 49, 230. Panner (1966). It is possible that thyroid deficiency TALBOT, N.B. (1939) Influence of thyroid hormone on serum can cause direct to muscle membranes and phosphatase. Endocrinology, 24, 230. damage WEISSBEIN, A.S., DARBY, J.P. & LAWSON, J.D. (1959) An fibres. Electromyography has also shown changes unusual bone lesion in an adult with Archives of in with this myxedema. suggestive polymyositis patients of Internal Medicine, 104, 643. on October 1, 2021 by guest. condition (Salick et al., 1968). WILKINS, L. (1941) Epiphysical dysgenesis associated with hypothroidism. American Journal of Diseases of Children, 61, 13. Acroparaesthesiae WILKINS, L. (1957) The Diagnosis and Treatment ofEndocrine Finally, hypothyroid patients may present with Disorders in Childhood and Adolescence, 2nd edn. Charles paraesthesiae of the hands and feet. This is usually a C. Thomas, Springfield, Illinois.