All about hypercalcemia (increased blood calcium)

In health serum total calcium concentration is maintained within the approximate reference range of 2.15-2.60 mmol/L largely by the synergistic action of two hormones: parathyroid hormone (PTH) and the vitamin-D-derived hormone, calcitriol. These two hormones control absorption of dietary calcium from the gut, renal excretion of calcium, and resorption of calcium from bone to blood. 

As the authors of a recently published review article observe, increased serum calcium (hypercalcemia) is a common finding in both a primary care and hospital setting. The article, which is based on a thorough and clearly defined search of the literature for the period of 1990-2015, provides a comprehensive and up-to-date account of the causes, clinical presentation and treatment of hypercalcemia. 

The article begins by defining hypercalcemia. The important distinction between total and ionized serum calcium and significance of change in serum albumin and blood pH for this distinction is also discussed in this introductory section. There follows extended discussion of the causes of hypercalcemia under two broad headings: parathyroid-hormone mediated, and non-parathyroid-hormone mediated. 

This way of classifying the causes of hypercalcemia reflects the central role of serum parathyroid hormone (PTH) measurement in helping to elucidate the cause of hypercalcemia in particular patients. PTH is raised or at the high end of the normal range in all parathyroid-mediated causes but appropriately suppressed (i.e. reduced) in all non-parathyroid-mediated causes. 

Primary hyperparathyroidism is the principal parathyroid-mediated cause of hypercalcemia and malignancy is the principal non-parathyroid-mediated cause. Primary hyperthyroidism and malignancy together account for 90 % of all cases of hypercalcemia but the authors provide some detail of other causes that account for the remaining 10 %. 

Current understanding of the several mechanisms involved in hypercalcemia due to malignancy is discussed. Effective treatment depends on establishing cause of hypercalcemia and to this end the authors helpfully provide an algorithm for establishing cause, which involves the use of supplementary laboratory tests such as serum PTH, calcitriol and creatinine measurement. 

Treatment options are discussed by reference to the most recent clinical trials and expert guidelines under two headings: mild hypercalcemia (serum calcium in the range of 2.60-3.0 mmol/L) and severe hypercalcemia (serum calcium >3.5 mmol/L), the latter being a medical emergency requiring admission to hospital. This is a concise, comprehensive and, above all, up-to-date review of hypercalcemia for the non-specialist.