Evaluation of hypocalcemia

Hypocalcemia is a state of electrolyte imbalance in which the circulating serum calcium level is low. During hypocalcemia, the total calcium level and the ionized calcium level fall below the laboratory reference range.

Hypocalcemia may occur subsequent to failure of any of the mechanisms by which serum calcium concentration is maintained. But it is usually the result of failure of parathyroid hormone secretion or an inability to release calcium from bone.

The clinical features of hypocalcemia largely manifest through neuromuscular excitability. Hypocalaemia can present acutely and be life threatening; early recognition and correction is critical. Quantitatively severe hypocalcemia can sometimes present with few symptoms, if onset has been protracted and chronic.

Pathophysiology

Calcium is one of the most abundant electrolytes in the body, and levels are tightly controlled by parathyroid hormone and vitamin D. Calcium is essential for cell function, cell membrane stability, neuronal transmission, bone physiology, blood homeostasis, and cell signaling.

Circulating calcium levels are impaired by several factors, but hypocalcemia is mainly secondary to the imbalance of calcium absorption, excretion, and distribution.

As 40% of circulating calcium is bound to albumin, in a ratio of 1 mg albumin to 0.8 mg calcium, measuring albumin is essential in interpreting total serum calcium levels. However, if ionized calcium is determined, there is no need to measure albumin or adjust the value of calcium concentration. Approximately 15% of circulating calcium is bound to sulfates, phosphates, lactate, and citrate, and the remaining 45% circulates as biologically active calcium in an ionized form.[1]Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335 http://www.ncbi.nlm.nih.gov/pubmed/18535072?tool=bestpractice.com

Signs and symptoms

Hypocalcemia varies from a mild asymptomatic biochemical abnormality to a life-threatening disorder. Acute hypocalcemia can lead to paresthesia, tetany, and seizures (characteristic physical signs may be observed, including Chvostek sign, which is neither sensitive nor specific for hypocalcemia, and Trousseau sign).[2]Turner J, Gittoes N, Selby P, et al. Society for endocrinology endocrine emergency guidance: emergency management of acute hypocalcaemia in adult patients. Endocr Connect. 2016 Sep;5(5):G7-8. https://ec.bioscientifica.com/view/journals/ec/5/5/G7.xml http://www.ncbi.nlm.nih.gov/pubmed/27935815?tool=bestpractice.com [3]Jesus JE, Landry A. Images in clinical medicine. Chvostek's and Trousseau's signs. N Engl J Med. 2012 Sep 13;367(11):e15. https://www.doi.org/10.1056/NEJMicm1110569 http://www.ncbi.nlm.nih.gov/pubmed/22970971?tool=bestpractice.com [Figure caption and citation for the preceding image starts]: Carpopedal spasm (Trousseau sign) occurred a few minutes after inflation of a sphygmomanometer cuff above systolic blood pressurePedrazzini B et al. BMJ Case Reports 2010;2010:bcr.08.2009.2188 [Citation ends].

Papilledema, cataracts, basal ganglia calcifications, and skin, hair, and dental changes may occur with chronic hypocalcemia.[4]Pepe J, Colangelo L, Biamonte F, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020 Sep;69(3):485-95. http://www.ncbi.nlm.nih.gov/pubmed/32367335?tool=bestpractice.com ​ Neuropsychiatric manifestations include dementia in adults, anxiety, depression, lethargy, and extrapyramidal symptoms (parkinsonism).[4]Pepe J, Colangelo L, Biamonte F, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020 Sep;69(3):485-95. http://www.ncbi.nlm.nih.gov/pubmed/32367335?tool=bestpractice.com [5]Maiti A, Chatterjee S. Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia. J Indian Med Assoc. 2013 Mar;111(3):174-7. http://www.ncbi.nlm.nih.gov/pubmed/24592758?tool=bestpractice.com ​​​​ Skin exam may show dermatitis, eczema, hyperpigmentation, psoriasis, brittle hair with patchy alopecia, and brittle nails with characteristic transverse grooves.[Figure caption and citation for the preceding image starts]: Nail dystrophy due to hypocalcemiaNijjer S et al. BMJ Case Reports 2010;2010:bcr.08.2009.2216 [Citation ends]. Patients rarely may have congestive heart failure, angina, and hypotension.