Investigative algorithms for disorders causing hypercalcaemia and hypocalcaemia: a narrative review

Abstract

Background and Objective: The following article is part of a special series to aid the reader in diagnosing the cause of various electrolyte imbalances. By the end of the article, the reader should be able to order and interpret appropriate laboratory investigations when faced with a patient with hypercalcaemia or hypocalcaemia. Methods: A narrative, focused literature review was performed using Medline, PubMed, Google Scholar and OMIM during August 2023 to November 2023 to identify references published from database inception. Reference lists from these articles, as well as expert opinion from the authors, were also used. Language was restricted to English. Key Content and Findings: Calcium is an essential electrolyte and its blood concentration is tightly controlled by multiple homeostatic hormones, including parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D. However, calcium imbalance can occur in many disease states and can lead to significant morbidity and mortality. PTH analysis is of primary importance in identifying the cause of a calcium disturbance. It should be noted that calcium results are particularly susceptible to being falsely low or high depending on whether ionised or total calcium is analysed, therefore the validity of calcium results should always be questioned if the results are not consistent with the clinical presentation. Hypercalcaemia is most commonly associated with primary hyperparathyroidism (PHPT) or malignancy. Hypocalcaemia is much rarer than hypercalcaemia, and if no obvious cause is found—e.g., post total thyroidectomy—consider hypomagnesaemia. Conclusions: Diagnostic flow charts are presented, and the limitations of the laboratory tests discussed. These algorithms, by focusing on the approach to the investigation of hypercalcaemia and hypocalcaemia, should support healthcare professionals to efficiently and rapidly diagnose the majority of causes of abnormal calcium states.