Laboratory approaches for the diagnosis and assessment of hypercalcemia

Abstract

Calcium, the fifth most common element in the body, plays major physiological functions. Measurement of blood calcium is one of the most commonly ordered laboratory tests in assessments of calcium homeostasis and disease diagnosis. Hypercalcemia is an increased level of calcium in the blood. This disorder is most commonly caused by primary hyperparathyroidism and malignancy. However, other less common causes of elevated calcium levels need to be considered when making a differential diagnosis. This review is intended to provide readers with a better understanding of calcium homeostasis and the causes and pathophysiology of hypercalcemia. Most importantly, this review describes useful approaches for laboratory scientists and clinicians to appropriately diagnose and assess hypercalcemia.

Predictive accuracy of serum total calcium for both critically high and critically low ionized calcium in critical illness

“…For serum or plasma calcium tests, critical value reporting is more complex than other laboratory tests. In plasma or serum, calcium exists in three physiochemical states: protein‐bound calcium (approximately 40%), free (ionized) calcium (approximately 50%), and calcium complexes with small anions (approximately 10%) . The actual percentage of calcium in each state is strongly affected by many factors, such as serum total protein, albumin, and pH .…”

“…In plasma or serum, calcium exists in three physiochemical states: protein‐bound calcium (approximately 40%), free (ionized) calcium (approximately 50%), and calcium complexes with small anions (approximately 10%) . The actual percentage of calcium in each state is strongly affected by many factors, such as serum total protein, albumin, and pH . Among these three states, only ionized calcium is physiologically relevant, and critically high or low ionized calcium is life‐threatening .…”

“…The actual percentage of calcium in each state is strongly affected by many factors, such as serum total protein, albumin, and pH . Among these three states, only ionized calcium is physiologically relevant, and critically high or low ionized calcium is life‐threatening . Indeed, previous studies concluded that extremely low or high ionized calcium is independently associated with hospital mortality in adult patients admitted to the intensive care unit (ICU) …”

“…Therefore, to detect hypercalcemia or hypocalcemia, direct measurement of ionized calcium is recommended . However, the International Federation of Clinical Chemistry and Laboratory Medicine's (IFCC)‐recommended assay for ionized calcium is ion‐selective electrodes (ISE), which is usually performed on blood gas analyzers and the majority of commercial vendors do not offer an ionized calcium assay based on large chemistry analyzers . By contrast, total calcium is usually measured on large chemistry analyzers along with other blood chemistry tests.…”

“…Medicine's (IFCC)-recommended assay for ionized calcium is ionselective electrodes (ISE), 8 which is usually performed on blood gas analyzers 2,3 and the majority of commercial vendors do not offer an ionized calcium assay based on large chemistry analyzers. 3,9 By contrast, total calcium is usually measured on large chemistry analyzers along with other blood chemistry tests.…”