Hypocalcemia can occur either acutely or chronically in hospitalized patients and outpatients. Testing includes calcium, albumin, phosphate, magnesium, creatinine, 25-hydroxy vitamin D, and parathyroid hormone (PTH).
Diagnosis
Indications for Testing
- Neurologic signs
- Perioral numbness or other paresthesias
- Muscle spasms/cramps
- Neuromuscular irritability
- Thyroid or parathyroid resection or other neck surgery, irradiation to neck
- Chronic kidney disease
- Prolongation of QT interval on electrocardiogram (ECG)
- Malnutrition or malabsorption
Laboratory Testing
- Initial testing
- Serum calcium and albumin
- Corrected calcium = measured total calcium + 0.8 (4.0 - serum albumin)
- Phosphate
- Magnesium
- Creatinine
- Serum calcium and albumin
- If calcium is low, consider repeat testing with ionized calcium
- Ionized calcium needs no correction for hypoalbuminemia but should be corrected for pH
- If hypocalcemia is confirmed, order intact PTH
- Elevated PTH, normal or high phosphate, normal magnesium, high creatinine – consider renal failure/pseudohypoparathyroidism
- Elevated PTH, normal or low phosphate, normal magnesium, normal creatinine – consider vitamin D testing
- Low vitamin D 25(OH) – vitamin D deficiency confirmed
- Low PTH, normal or high phosphate, normal creatinine, low or normal magnesium – consider hypoparathyroidism or hypomagnesemia
- Normal PTH, normal or low phosphate, normal creatinine, normal magnesium, low albumin – consider hypoalbuminemia (pseudohypocalcemia)
Differential Diagnosis
Refer to Etiology in Background
Monitoring
- Serum calcium, phosphate, and creatinine – measure weekly during initial therapy, then monthly
- Once stabilized on therapy, measure values one to two times/year
Background
Epidemiology
Prevalence – occurs in 12-80% of critically ill patients
Etiology
- Acute severe illness – patients in intensive care unit (acute pancreatitis, sepsis, burns)
- Hypoparathyroidism
- Acquired
- Surgical removal of parathyroid glands (eg, head and neck surgery)
- Radiation-induced parathyroid destruction
- Metastatic infiltration of glands (rare)
- Other infiltrative disorders (eg, hemochromatosis)
- Autoimmune
- Associated with autoimmune polyglandular syndrome 1
- Autosomal recessive inheritance
- Symptoms – chronic mucocutaneous candidiasis, alopecia, vitiligo
- Associated with autoimmune polyglandular syndrome 1
- Pseudohypoparathyroidism
- Resistance to PTH (eg, chronic renal failure)
- Genetic syndromes
- DiGeorge (22q11.2 deletion) syndrome and velocardiofacial syndrome
- Rare congenital disorder
- Symptoms – cardiac, facial, thymic, thyroid abnormalities
- Learning disorders
- Genetics – rearrangements on chromosome 22 (TBX1 gene)
- Familial hypocalcemias (eg, Bartter syndrome subtype V and Gitelman syndrome)
- X-linked hypoparathyroidism
- Mitochondrial disorders with hypoparathyroidism (eg, Kearns-Sayre syndrome)
- Hypoparathyroidism, sensorineural deafness, and renal disease (HDR) syndrome
- Sanjad-Sakati and Kenny-Caffey type 1 syndromes
- DiGeorge (22q11.2 deletion) syndrome and velocardiofacial syndrome
- Acquired
- Chronic kidney disease
- Vitamin D deficiency
- Malabsorption
- Inadequate diet/sunlight
- Magnesium deficiency
- Malabsorption
- Inadequate diet
- Alcohol misuse
- Medications
- Chemotherapy drugs
- Anticonvulsants
- Foscarnet
- Histamine 2 (H2) receptor blockers
- Proton pump inhibitors
- Bisphosphonates
Pathophysiology
- Serum calcium concentration is normally maintained within a narrow physiologic range
- Calcium is controlled by PTH, vitamin D (1,25), calcium, and phosphate
- Calcium is bound to albumin
- Low levels may reflect hypoalbuminemia, not level of ionized calcium
Clinical Presentation
- Symptom severity is related to the rate of change and absolute calcium levels
- Most patients with mild hypocalcemia are asymptomatic
- Acute
- Neuromuscular – tetany, paresthesias, muscle spasms (Chvostek and Trousseau signs), perioral numbness
- Neuropsychiatric – anxiety, hallucinations, confusion, irritability
- Cardiovascular – bradycardia, ventricular arrhythmias, congestive heart failure, cardiac collapse
- Pulmonary – laryngeal stridor, bronchospasm
- Chronic
- Neuropsychiatric – cognitive deficits, extrapyramidal symptoms
- Dermatologic – dermatitis, dry skin, brittle nails
- Dental – enamel hypoplasia
- Ophthalmologic – cataracts
ARUP Laboratory Tests
Diagnose disorders of calcium metabolism
Quantitative Spectrophotometry
Order concurrent with calcium to assess for hypoalbuminemia
Quantitative Spectrophotometry
Diagnose disorders of calcium metabolism
Abnormal pH will alter results
No correction necessary for hypoalbuminemia
Ion-Selective Electrode/pH Electrode
Evaluate renal function
Quantitative Spectrophotometry
Diagnose disorders of the parathyroid glands
Quantitative Electrochemiluminescent Immunoassay
May help to determine etiology of hypocalcemia
Quantitative Spectrophotometry
Preferred test to diagnose vitamin D insufficiency and monitor response to therapy
Testing is recommended only for patients at risk for vitamin D insufficiency
Quantitative Chemiluminescent Immunoassay
Screening test to evaluate kidney function
Assay interference (negative) may be observed when high concentrations of N-acetylcysteine (NAC) are present
Negative interference has also been reported with NAPQI (an acetaminophen metabolite) but only with concentrations at or above those expected during acetaminophen overdose
Quantitative Enzymatic Assay
Use to evaluate calcium dysregulation
Quantitative Electrochemiluminescent Immunoassay
Investigate potential autoimmune disorders involving the parathyroid gland
Qualitative Radiobinding Assay
References
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