Evaluation of hypocalcemia
Summary
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]
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 poorly sensitive and specific of hypocalcemia, and Trousseau sign).[2][3][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. Neuropsychiatric manifestations include dementia in adults, anxiety, depression, lethargy, and extrapyramidal symptoms (parkinsonism). 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.
Differentials
Common
- Iatrogenic postsurgical hypoparathyroidism
- Vitamin D deficiency
- Hypomagnesemia
- Hyperventilation
Uncommon
- Isolated hypoparathyroidism
- Pseudohypoparathyroidism
- Autoimmune hypoparathyroidism
- HIV-related hypoparathyroidism
- Hypermagnesemia
- Hyperphosphatemia
- Hypercalciuria
- Sepsis
- Burns
- Renal failure
- Acute pancreatitis
- Extensive osteoblastic skeletal metastasis
- Hungry bone syndrome
- Drug-induced hypocalcemia
- Multiple transfusions
- Hypoalbuminemia
- Drug interference with assay
- Infiltrative hypoparathyroidism
- DiGeorge syndrome and other developmental complexes
- Rhabdomyolysis
- Tumor lysis syndrome
- Constitutively activating calcium sensing receptor (CaSR) abnormalities (mutations or autoimmune activation)
- Vitamin D resistance or receptor mutations
Contributors
Authors
John Ayuk, MD, FRCP
Consultant Endocrinologist/Service Lead for Endocrinology
Department of Endocrinology
Queen Elizabeth Medical Centre
Queen Elizabeth Hospital
Birmingham
UK
Disclosures
JA declares that he has no competing interests.
Neil Gittoes, BSc, MB ChB, PhD, FRCP
Consultant Endocrinologist and Honorary Professor of Endocrinology
Department of Endocrinology
Centre for Endocrinology, Diabetes and Metabolism
Queen Elizabeth Medical Centre
Queen Elizabeth Hospital
Birmingham
UK
Disclosures
NG has received payment for consultancy work and attendance to a European meeting for Takeda on hypoparathyroidism. NG is a Global Scientific Co-Chair of the PARADIGM disease registry in hypoparathyroidism. NG is an author of references cited in this topic.
Acknowledgements
Dr John Ayuk and Prof Neil Gittoes would like to gratefully acknowledge Dr Berhane Seyoum, a previous contributor to this topic. BS declares that he has no competing interests.
Peer reviewers
Shehzad Basaria, MD
Assistant Professor
Johns Hopkins University School of Medicine
Baltimore
MD
Disclosures
SB declares that he has no competing interests.
Lawrence Kirschner, MD, PhD
Associate Professor of Medicine
The Ohio State University
Columbus
OH
Disclosures
LK declares that he has no competing interests.
Richard Quinton, MD
Consultant and Senior Lecturer
Endocrine Unit
Newcastle University and Royal Victoria Infirmary
Newcastle-upon-Tyne
UK
Disclosures
RQ has been reimbursed by Amgen, the manufacturer of cinacalcet, for attending a conference and for giving an educational seminar (total under £1,200 over past 3 years).
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