Surgery for primary hyperparathyroidism

A decade ago, Broadus reviewed the historical data on the clinical manifestations of primary hyperparathyroidism.¹ Previously renal stone disease was recognised to be a far more frequent complication than bone disease—about half the patients with primary hyperparathyroidism in clinical series published through the 1970s presented with renal stones.¹ Modern diagnostic tools for recognising hypercalcaemia and serum concentrations of parathyroid hormone have had a dramatic impact on the frequency with which primary hyperparathyroidism is diagnosed, especially in older people with non-specific symptoms of the disease. Renal stone disease is considered a less frequent complication by some investigators,²,³ although others have reported that up to 75% of patients undergoing surgical treatment for primary hyperparathyroidism present with nephrolithiasis.⁴ Now, a study by Mollerup et al in this issue shows that patients with primary hyperparathyroidism not only have a greater risk of renal stone disease but that this risk persists for 10 years after surgery.⁵

In 1990 the US National Institutes of Health presented a consensus statement on indications for parathyroidectomy. Patients with markedly elevated excretion of urinary calcium and patients with renal stones would be considered candidates for surgery, whereas asymptomatic patients qualified for medical monitoring without surgery.⁶ In view of the variability of reported renal complications in patients undergoing parathyroidectomy it seems reasonable to question the consensus on indications for surgery and what constitutes “successful” surgery.⁷ The consensus statement by the National Institutes of Health called for research to clarify the effect of operative versus non-operative management of primary hyperparathyroidism. So far no Cochrane reviews or meta-analyses have addressed this issue, and controversies therefore persist.⁸

The renal manifestations of primary hyperparathyroidism include recurrent calcium nephrolithiasis, nephrocalcinosis, and impaired renal function. After successful parathyroidectomy, urinary calcium excretion, serum concentrations of calcium, and intestinal calcium absorption are believed to be restored to normal.⁹ It is, however, unclear to what extent parathyroid surgery reduces the risk of further stone formation.

Mollerup et al report the results of a register based controlled historical follow up study of 674 consecutive patients with surgically verified primary hyperparathyroidism.⁵ Compared with age matched controls the patients undergoing surgery had a 40 times increased risk of renal stone disease. An increased risk could be traced up to 10 years before diagnosis and parathyroidectomy. The authors suggest that the disease starts several years before diagnosis and stress the importance of early diagnosis and treatment. A study of the natural history of primary hyperparathyroidism shows a biphasic course of the disease with an initial period of progression followed by long period of stability.¹⁰ The natural time course for mutation in a single parathyroid cell and subsequent monoclonal parathyroid growth to a clinical adenoma may take years and supports the findings by Mollerup et al. The present study confirms that patients with primary hyperparathyroidism have an increased risk of renal stone events and that this risk can be reduced by surgery. This study, however, elucidates not only the preoperative period of increased risk of renal stone disease but also a postoperative span of 10 years. Most scientific papers in the past reported duration of follow up to a limited degree compared with the study by Mollerup et al and might reflect just a point on the time curve describing the decrease in risk profile.

The present study does not offer a causal relation between primary hyperparathyroidism and the development of renal stone disease. Though we do not have all the necessary information we have gathered further information to help us make a clinical decision about surgical versus non-surgical treatment. A recent study using SF-36, an instrument to measure wellness, indicated improved function after parathyroidectomy compared with patients who did not undergo operation.¹¹ But we still need a large multicentred randomised controlled trial of sufficient size and duration to decide on the operative versus non-operative management of primary hyperparathyroidism, as proposed by National Institutes of Health in 1990.

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