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Primary hyperparathyroidism

Key Points

  • Primary hyperparathyroidism (PHPT), a common endocrine disorder characterized by hypercalcaemia and elevated or inappropriately normal levels of parathyroid hormone, is diagnosed based upon biochemical evaluation

  • Over the past 50 years, the clinical profile of PHPT has evolved from a highly symptomatic disease to one that is most often asymptomatic, albeit with evidence of subclinical target organ involvement

  • Even 'asymptomatic' patients can have skeletal deterioration (evident upon imaging; for example, dual-energy X-ray absorptiometry), and subclinical manifestations can include osteoporosis and hypercalciuria as well as clinically silent vertebral fractures and nephrolithiasis

  • The diagnosis of normocalcaemic PHPT can be made after eliminating secondary causes of hyperparathyroidism; however, data are limited on its natural history and appropriate criteria for and response to surgery

  • Parathyroidectomy by an experienced parathyroid surgeon is recommended for patients with symptomatic disease or subclinical end-organ involvement, as no single medical therapy addresses hypercalcaemia and the skeletal and renal consequences of PHPT

Abstract

In this Review, we describe the pathogenesis, diagnosis and management of primary hyperparathyroidism (PHPT), with a focus on recent advances in the field. PHPT is a common endocrine disorder that is characterized by hypercalcaemia and elevated or inappropriately normal serum levels of parathyroid hormone. Most often, the presentation of PHPT is asymptomatic in regions of the world where serum levels of calcium are routinely measured. In addition to mild hypercalcaemia, PHPT can manifest with osteoporosis and hypercalciuria as well as with vertebral fractures and nephrolithiasis, both of which can be asymptomatic. Other clinical forms of PHPT, such as classical disease and normocalcaemic PHPT, are less common. Parathyroidectomy, the only curative treatment for PHPT, is recommended in patients with symptoms and those with asymptomatic disease who are at risk of progression or have subclinical evidence of end-organ sequelae. Parathyroidectomy results in an increase in BMD and a reduction in nephrolithiasis. Various medical therapies can increase BMD or reduce serum levels of calcium, but no single drug can do both. More data are needed regarding the neuropsychological manifestations of PHPT and the pathogenetic mechanisms leading to sporadic PHPT, as well as on risk factors for complications of the disorder. Future work that advances our knowledge in these areas will improve the management of the disorder.

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Figure 1: Relationship between serum levels of calcium and PTH.
Figure 2: Trabecular deterioration in PHPT.

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Acknowledgements

The authors acknowledge the National Institiutes of Health (NIH; Grants DK074457 and DK084986 to S.J.S. and DK104105 to M.D.W.).

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M.D.W. and S.J.S. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Shonni J. Silverberg.

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Walker, M., Silverberg, S. Primary hyperparathyroidism. Nat Rev Endocrinol 14, 115–125 (2018). https://doi.org/10.1038/nrendo.2017.104

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