deficient 813 Postgrad Med J: first published as 10.1136/pgmj.73.866.813 on 1 December 1997. Downloaded from Treatment of vitamin D deficient osteomalacia may unmask autonomous hyperparathyroidism

AVG Taylor, PH Wise

Summary of generalised aches and pains and limping due Two cases of vitamin D deficient osteo- to left hip pain. There was no history of joint malacia with secondary hyperparathy- swelling or fractures and investigations per- roidism are presented. In both cases formed by the general practitioner suggested treatment with vitamin D replacement the possibility of osteomalacia, with a raised therapy resulted in elevated levels of 988 U/l (reference and a failture of parathormone levels to values 90-250), a low serum phosphate of normalise, indicating autonomous para- 0.1 mmolIl (0.6-1.4) and a normal corrected activity. Subsequent surgery in calcium of 2.4 mmolIl (2.15-2.55). She was one case resulted in removal of a para- not a vegetarian but her only dairy product was thyroid adenoma. The importance of yoghurt. There was no history of liver or renal osteomalacia and its complications are disease but recurrent iron deficiency anaemia discussed. had been treated with ferrous sulphate, although not further investigated. She de- Keywords: osteomalacia, vitamin D, hyperparathy- scribed no abdominal symptoms and her roidism, Asians periods were regular but heavy. Examination was unremarkable. A diagnosis of osteomalacia with secondary hyperparathyroidism was con- The prevalence of osteomalacia in the British firmed by a raised level of Asian community, its associated morbidity and 560 ng/l (10-50) and a low 25-OH vitamin D the availability of simple treatment indicate level of 5 nmol/l (15-100). A bone scan that there is a continued need to identify and showed multiple areas of increased uptake. eliminate the disorder within this community. X-Rays were normal, as was serum electro- However, vitamin D replacement therapy may phoresis. was excluded by sub- unmask autonomous hyperparathyroidism and sequent investigations and the cause ofher iron monitoring of serum clacium levels is therefore deficiency was found to be dietary in nature. mandatory. Two cases are presented. Treatment was commenced with 0.25 jug twice daily resulting in a fall in

Case reports parathyroid hormone levels: however levels http://pmj.bmj.com/ remained elevated above the normal range. Case 1 Concurrently, serum calcium levels rose, in- A 43-year-old Kenyan Asian woman who had dicating the unmasking of autonomous hyper- been living in the UK for 21 years was referred parathyroidism; this is illustrated in figure 1. to the endocrine out-patients department by She was referred for surgery which resulted in her general practitioner, with a two-year history excision of a left . on September 25, 2021 by guest. Protected copyright.

Surgery Surgery 3.0 700 2.960 2.8 0 2.750 Department of E , E 2.6 Charing Cross Hospital, London W6 8RF, UK AVG Taylor PH Wise M Norma Correspondence to . Dr AVG Taylor, Consultant Physician & Endocrinologist, Horton General Hospital NHS id-in2.0 0 Trust, Oxford Road, Banbury, Oxon OX16 9AL, UK Accepted 1 May 1997 Figure 1 Corrected calcium and parathyroid hormone (PTH) levels following vitamin D replacement therapy 814 Taylor, Wise

Therapy stopped Therapy stopped 3.0 60 Postgrad Med J: first published as 10.1136/pgmj.73.866.813 on 1 December 1997. Downloaded from

50 2.8 0 2.7 E 40

I20 o 2.3 - 1111 2.2 10 2.1 2.0 Io Fgr corec ci and leves f n v i D rl m h?erpt Figure 2 Corrected calcium and parathyroid hormone (PTH) levels following vitamin D replacement therapy

Following surgery, serum calcium and para- results in secondary hyperparathyroidism and thyroid hormone levels returned to the normal the clinical syndrome of osteomalacia, which range. The patient remains well on vitamin D was present in both these patients. Correction supplements but has made no attempt to alter of usually results in her diet. normalisation of raised parathyroid hormone levels. The development of tertiary hyperpar- Case 2 athyroidism, although well recognised in A 54-year-old Asian man with insulin-depen- chronic renal failure, has only rarely been dent diabetes mellitus complained of lower described in solar/nutritional vitamin D defi- limb pains during a consultation for review of ciency.5'6 It is indicated by persistently raised his diabetes in 1989. There was no evidence of parathyroid hormone levels in association with peripheral neuropathy or peripheral vascular following vitamin D replace- disease. In view of his vegetarian habits 25-OH ment. The predominant histological findings vitamin D levels were checked and found to be are usually those of parathyroid hyperplasia,7 less than 5.0 nmolIl. but adenomata have been described as in case Renal function and repeated serum calcium 1L8 The finding of an adenoma also raised the levels were normal. He was commenced on possibility of primary hyperparathyroidism alfacalcidol 0.5 ,ug daily with symptomatic associated with vitamin D deficiency.9 It is for http://pmj.bmj.com/ improvement, although medication was only this reason that the term autonomous para- taken intermittently over the next five years. In thyroid activity is preferred. 1994, hypercalcaemia was first noted in asso- Efficient methods of preventing vitamin D ciation with raised parathyroid hormone levels, deficiency are now being implemented, parti- as illustrated in figure 2, and this prompted cularly involving the annual or bi-annual discontinuation of alfacalcidol. Unsuppressed administration of high-dose oral or intramus- serum parathyroid hormone in association with cular calciferol to major at-risk populations of on September 25, 2021 by guest. Protected copyright. raised calcium levels indicated autonomous Asians and elderly institutionalised patients. parathyroid activity. Management is currently Whether primary or tertiary hyperparathy- conservative in view of the only mildly elevated roidism, it is likely that the phenomenon calcium levels. represented by these two patients is occurring more frequently that is currently recognised, Discussion with potentially serious consequences. Vita- min D repletion may prevent the develop- Osteomalacia is still a common problem in the British Asian community, affecting up to 20% of adult Asians.' It is also common in the institutionalised elderly.2 The pathogenesis is Summary points multifactorial and involves reduced UV radia- * osteomalacia is still a common problem in tion exposure and dietary factors.3 The diag- the British Asian community, affecting up to nosis can be made biochemically by the finding 20% adult Asians of low 25-OH vitamin D levels associated with * prolonged osteomalacia is associated with elevated parathyroid hormone levels, but is autonomous hyperparathyroidism. This may often only become apparent following vitamin D delayed because of non-specific symp- replacement therapy toms and a lack of awareness. In case 1, two * monitoring of serum calcium levels is years elapsed from the onset of symptoms to mandatory in the treatment of osteomalacia presentation and others have reported similar for early detection of autonomous findings.4 parathyroid activity Prolonged or severe vitamin D deficiency Vitamin D deficient osteomalacia 815

ment of autonomous parathyroid activity. present in at least 1: 1000 of the population. However, it may also reveal it in those with Regular screening for hypercalcaemia in either prolonged vitamin D deficiency or populations receiving such vitamin D reple- Postgrad Med J: first published as 10.1136/pgmj.73.866.813 on 1 December 1997. Downloaded from previously unrecognised primary hyperpara- dion regimens is therefore considered to be thyroidism, a condition now known to be mandatory.

1 Finch PJ, Ang L, Eastwood JB, Maxwell JD. Clinical and 6 Seshadri MS, Qurttom MAF, Sivanandan R, Samiaman histological spectrum of osteomalacia among Asians in SAM. Tertiary hyperparathyroidism in nutritional osteoma- South London. Q J Med 1992; 83: 439 - 48. lacia (letter). Postgrad MedJ7 1994; 70: 595 - 6. 2 Corless D, Beer M, Boucher BJ, Gupta SP, Cohen RD. 7 Krause MW, Hedinger CE. Pathologic study of parathyroid Vitamin D status in long stay geriatric patients. Lancet 1975; glands in tertiary hyperparathyroidism. Hum Pathol 1984; ii: 1404-6. 16: 772-84. 3 Henderson JB, Dunnigan MG, McIntosh WB, Motaal AA, 8 Davies DR, Dent CE, Watson L. Tertiary hyperparathy- Hole D. Asian osteomalacia is determined by dietary factors roidism. BMJ 1968; 2: 395-8. when exposure to ultraviolet radiation is restricted: a risk 9 Clements MR, Davies M, Fraser DR, Lumb GA, Mawer factor model. QJ Med 1990; 76: 923-33. EB, Adams PH. Metabolic inactivation of vitamin D is 4 Nellen JFJB, Smulders YM, Jos Frissen PH, Slaats EH, enhanced in primary hyperparathyroidism. Clin Sci 1987; Silberbusch J. Hypovitaminosis D in immigrant women: 73: 659-64. slow to be diagnosed. BMJ 1996; 312: 570-2. 5 Sultan AH, Bruckner FE, Eastwood JB. Association between prolonged vitamin D deficiency and autonomous hyperparathyroidism. BMJ 1989; 299: 236-7.

Meningismus, fever and macular rash as presenting features ofthe primary antiphospholipid syndrome?

Tim Houghton, Aeron G Davies

Summary macular rash and who was found to have We report here, we believe for the first positive serology for antiphospholipid antibo- time, the primary antiphospholipid syn- dies. drome, presenting with fever, meningis- mus and skin rash. Serology was positive Case report for antiphospholipid antibodies but nega- tive for antinuclear factor. Such presen- A 21-year-old woman was admitted as an http://pmj.bmj.com/ tations, once meningitis has been emergency with a 24-hour history of severe excluded, should be screened for antipho- generalised headache and photophobia, neck- spholipid antibodies. If serology proves to stiffness and rigors. She had a history of three be positive, anticoagulation for life should miscarriages and a previous admission two be considered to avoid thrombotic epi- years previously with headache and meningis- sodes and death due to pulmonary embo- mus, with a normal computed tomography

lism. scan of brain. on September 25, 2021 by guest. Protected copyright. Examination revealed an ill-looking woman Keywords: antiphospholipid syndrome, meningis- with a pyrexia of 39.2°C, neck-stiffness, mus, thrombosis Kemig's sign and a generalised macular erythematous rash. There were no other neurological signs. Initial investigations re- The antiphospholipid syndrome is a rare but vealed a polymorphonuclear leukocytosis of increasingly recognised clinical entity. It was 12.1 x 109/1 (82% polys). C-Reactive protein first described by Hughes in 19831 as a clinical (CRP) was > 150 mg/I (normal range 1 - 15). condition presenting with widespread venous Lumbar puncture and other haematological and arterial thrombosis in the presence of parameters were normal. antiphospholipid antibodies. Features of this Initially a working diagnosis of possible Department of syndrome are widespread and varied, and meningococcal meningitis was made and the General Medicine, Bronglais General include stroke, chorea, migraine, transient patient was commenced on high-dose intrave- Hospital, Aberyst- cerebral ischaemic attack,' livedo-reticularis,3 nous benzylpenicillin. The following day she wyth, Wales, UK pulmonary ,4 recurrent abortion,5 was much better and apyrexial, but she still had T Houghton epilepsy, transverse myelopathy, valvular heart the headache and macular rash. In view of the AG Davies disease and ocular ischaemia.6 This list will normal lumbar puncture and clinical improve- the intravenous antibiotics were Correspondence to Dr probably be added to, as serological testing for ment, Tim Houghton, Royal antiphospholipid antibodies is now more gen- stopped. She continued to improve and on Hull Infirmary, Anlaby eral. the day of discharge was well except for a low- Road, Hull HU3 2JZ, UK We describe the case of a young woman grade pyrexia. Haematological parameters Accepted 6 May 1997 who presented with meningismus, fever and such as white cell count had returned to