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Rheumatology 2001; 40: 1417-1418
© 2001 British Society for Rheumatology
Letters to the Editor |
Hypoparathyroidism presenting as myopathy with raised creatine kinase
Departments of Rheumatology,
1Metabolic Medicine and
2Histopathology, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK
SIR, We report a case of severe hypocalcaemia associated with myopathy and raised serum creatine kinase (CK). In September 1998 a 71-yr-old retired farmer developed anorexia, lethargy and generalized stiffness with weakness of the shoulder and hip girdle muscles. His erythrocyte sedimentation rate was 39 mm in the first hour and his general practitioner (GP) considered the diagnosis of polymyalgia rheumatica and gave him a trial of prednisolone. This had little effect and it was soon discontinued. In December 1998 he was seen again by his GP in a distressed state with anxiety and tremor. Depression was suspected and he was started on paroxetine but developed urinary retention and was admitted to the local cottage hospital. At this stage it was noted that he had a pruritic erythematous rash on his face, including the eyelids, and on the front and back of his torso. He had a chest infection with obstructive airways disease and was started on prednisolone 7.5 mg daily as well as antibiotics. Investigations revealed alanine transaminase 639 U/l (normal range 5–60 U/l) and CK 1600 U/l (normally<175 U/l).
In March 1999 he still complained of lethargy, tremor, depression, irritability and pruritic rash and was referred to the rheumatology unit. There was a history of bilateral cataract surgery but no other illness, in particular no tetany or carpopedal spasm. On examination, the rash on his face and eyelids bore some resemblance to dermatomyositis but power was normal in all muscle groups. There was a mild, coarse tremor but no focal neurological signs; reflexes were present and Chvostek's sign was negative. The joints and skeleton were unremarkable but the nails were brittle and cracked; there was no significant abnormality on general examination. The serum calcium concentration had not been measured previously but investigations revealed severe hypocalcaemia: serum calcium concentration 1.13 mmol/l with albumin 40 g/l and phosphate 2.33 mmol/l. Twenty-four-hour calcium excretion was 1.5 mmol (normal range 2.5–7.5), the calcium/creatinine ratio 0.13 mmol/mmol and tubular reabsorption of phosphate 94%. The serum parathyroid hormone (PTH) level was<0.1 pmol/l (normal range 1.3–7.6), 25-hydroxyvitamin D 49.7 nmol/l (25–100) and 1,25-dihydroxyvitamin D 76.9 pmol/l (40–120). In his four sons, all of whom had normal serum calcium values, 1,25-dihydroxyvitamin D concentrations were between 95 and 104 pmol/l. Serum magnesium concentration was 0.58 mmol/l (normal range 0.7–1.0), alkaline phosphatase 54 U/l (45–125), sodium 141 mmol/l, potassium 4.0 mmol/l, creatinine 118 µmol/l and CK 615 U/l, and there was normal liver and thyroid function. Thyroid peroxidase and adrenal antibodies were negative. ECG showed a corrected QT interval at the upper limit of normal at 0.44 s. Quadriceps muscle biopsy showed a little variation in fibre size (30–100 µm), type II fibres tending to be smaller. There were some internal nuclei but no inflammatory cell infiltrate, excess connective tissue or evidence of regeneration. HLA class I antigens were confined to blood vessels. The changes were those of a mild, non-specific myopathy. Chest X-ray, barium swallow, abdominal ultrasound and computed tomography were unremarkable. A skull X-ray showed osteosclerosis, particularly in the frontal regions, but no calcification of the basal ganglia.
He was treated with calcitriol 500 ng daily and calcium carbonate 1 g daily with rapid resolution of his tremor, anxiety and lethargy. His CK had returned to normal (97 U/l) 6 weeks later, when his serum calcium level was 1.99 mmol/l, phosphate 1.49 mmol/l, albumin 43 g/l and 24-h urinary calcium 4 mmol. He continued to feel very well on the same treatment 2 yr later, when his investigations showed similar results.
The clinical features were remarkably modest for the very severe degree of hypocalcaemia, which suggests that the hypocalcaemia had developed gradually over some years. It is possible that the prednisolone started for his chest disease aggravated his hypocalcaemia by reducing calcium absorption and increasing calciuria, although the latter remained subnormal. The negative Chvostek's sign and QT interval within the normal range indicate that both cardiac and skeletal muscle can adapt remarkably well to a severe reduction in the serum calcium concentration, although psychological symptoms were prominent. The cataracts might perhaps have been a complication of longstanding hypocalcaemia. The fact that his children did not have evidence of hypoparathyroidism makes familial disease less likely than organ-specific autoimmune disease. Hypocalcaemia with inappropriately low serum PTH levels may be a feature of gain-of-function mutations of the calcium-sensing receptor. In favour of hypoparthyroidism in this case were the late age at onset and very low PTH, serum calcium and urinary calcium:creatinine ratio; gain of function mutations rarely have such a low serum calcium concentration and calcium:creatinine ratios are substantially higher [1]. 1,25-Dihydroxyvitamin D levels may be only moderately reduced in hypoparathyroidism [2], as was the case in this patient.
Myopathy is well recognized in hypocalcaemia associated with osteomalacia [3], but the serum CK is normal. The association between hypocalcaemia and a raised serum CK concentration has been reported previously in hypoparathyroidism [4–6] but is not widely recognized. In some reports the CK level varies inversely with the serum calcium concentration [7–9]. The raised CK has been attributed to tetany but can be seen in its absence [8], as in the present case. It seems likely that increased permeability of the muscle membrane induced by hypocalcaemia leads to leakage of CK [10]. Non-specific muscle biopsy findings of the type seen in this case have been reported previously [11]. The combination of rash and raised CK had raised the possibility of dermatomyositis, but this was excluded by biopsy and resolution of these features with treatment of the hypocalcaemia. This case illustrates the importance of checking the serum calcium in patients with muscular symptoms and the clinical value of effective treatment of hypocalcaemia.
Notes
Correspondence to: R. C. Butler. 
References
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