Q J Med 2002; 95: 255-257
© 2002 Association of Physicians
Correspondence |
Severe osteoporosis and autonomous hyperparathyroidism: making the numbers add up
Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth
Sir,
We present an unusual case of severe osteoporosis caused by hyperparathyroidism in which diagnostic confusion arose because of concomitant Vitamin D deficiency attributable to coeliac disease.
A 65-year-old woman presented following a nontraumatic fracture of her distal ulna. The radiograph of the forearm showed a distal fracture of the left ulna, and suggested significant reduction in bone mineral density. The fracture failed to heal. Bone densitometry (dual X-ray absorptiometry) confirmed severe osteoporosis, with measurements of the lumbar spine and femur greater than 5 and 3 SD below that of a young adult (T-score), respectively. Her baseline investigations revealed normal ESR, full blood count and renal function, protein electrophoresis, a mildly elevated corrected calcium of 2.66 mmol/l, a low phosphate of 0.55 mmol/l and a raised alkaline phosphatase of 262 IU/l (30–95 IU/l), which was bony in origin. Her intact parathyroid hormone (PTH) level was elevated at 53.5 pmol/l (<7.3 pmol/l).
She was otherwise symptom-free apart from loss of 5 cm of height over the preceding 5 years. Her past medical history was unremarkable other than an early menopause at the age of 40. She had never taken oestrogen replacement, nor been on any regular medication. She was a non-smoker and her alcohol intake was moderate.
Based upon these findings, her osteoporosis was initially ascribed to primary hyperparathyroidism. However, we considered that the magnitude of reduction in mineral density was too severe to be explained by hyperparathyroidism alone, so other causes of osteoporosis were sought.
At this stage, more detailed questioning elicited a vague history of loose bowel motions, which had been difficult to flush away. Many years previously, she had been on a short course of folic acid and iron supplements. Subsequent investigations revealed a vitamin 25-OH-D level of 5.1 µg/l, at the lower range of normal (4–40 µg/l), and moderately positive anti endomysium IgA and IgA anti reticulin antibodies. An upper GI endoscopy and duodenal biopsy confirmed coeliac disease. A gluten-free diet was initiated, and subsequent investigations showed improved vitamin 25-OH D (14.1 µg/l) concentration. Her alkaline phosphatase normalizedm and PTH concentrations dropped from 51 pmol/l to 31 pmol/l, but remained inappropriately high. Despite the fall in PTH concentrations, there was a rise in serum calcium to 3.14 mmol/l.
Combined pertechnate–sestamibi isotope scan of the neck confirmed one single hyperfunctioning left parathyroid nodule. This single enlarged gland was successfully resected; the other three glands appeared macroscopically normal. Histology confirmed typical appearances of a parathyroid adenoma. Subsequently, her calcium and alkaline phosphatase levels have been remained in the normal range. She has gained 5 kg in weight and is asymptomatic. Six months after parathyroidectomy, her vertebral and femur bone densitometries have improved by 24% and 21%, respectively.
Our report serves to highlight that ‘mild’ hyperparathyroidism (typically defined as corrected serum calcium <2.7 mmol/l) as was the initial impression in this case, is not usually associated with severe reduction of bone density.1 The estimated bone loss with this condition was 0.9% per year in one series.2 In a further study examining the clinical course of untreated mild primary hyperparathyroidism over a period of 10 years, there were no changes in bone density in the lumbar spine and radius, nor were any fractures reported.3 Only severe hyperparathyroidism (associated with a serum calcium >3 mmol/l) is usually associated with profound (>2.5 SD) reduction in bone density.1 Successful management of this patient's coeliac disease unmasked the magnitude of her hyperparathyroidism as evidenced by a rise in calcium level above 3 mmol/l. It is difficult in retrospect therefore to be certain of the relative contribution of parathyroid overactivity and vitamin D deficiency to the development of her reduction in bone density, although a bone biopsy may have helped to determine the predominant aetiological factor.
In cases of severe osteoporosis, it is important to consider whether single or multiple factors may be involved in the causative process. Conditions such as hyperparathyroidism, vitamin D deficiency (especially in the Asian population), hypo-oestrogenism, immobility, smoking and excess alcohol intake frequently co-exist, with a heterogeneous effect on the bone mineral density (Table 1
). Normal calcium levels do not exclude, therefore, the presence of hyperparathyroidism or osteomalacia.
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