Hypocalcemia

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).

Tabs Content

Clinical Overview

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
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
- 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
      - Severe early childhood infections
    - 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
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 Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Calcium, Serum or Plasma 0020027
Method: Quantitative Spectrophotometry

Recommended Use

Diagnose disorders of calcium metabolism

Albumin, Serum or Plasma by Spectrophotometry 0020030
Method: Quantitative Spectrophotometry

Recommended Use

Order concurrent with calcium to assess for hypoalbuminemia

Calcium, Ionized, Serum 0020135
Method: Ion-Selective Electrode/pH Electrode

Recommended Use

Diagnose disorders of calcium metabolism

Abnormal pH will alter results

No correction necessary for hypoalbuminemia

Phosphorus, Inorganic, Plasma or Serum 0020028
Method: Quantitative Spectrophotometry

Recommended Use

Evaluate renal function

Parathyroid Hormone, Intact 0070346
Method: Quantitative Electrochemiluminescent Immunoassay

Recommended Use

Diagnose disorders of the parathyroid glands

Magnesium, Plasma or Serum 0020039
Method: Quantitative Spectrophotometry

Recommended Use

May help to determine etiology of hypocalcemia

Vitamin D, 25-Hydroxy 0080379
Method: Quantitative Chemiluminescent Immunoassay

Recommended Use

Preferred test to diagnose vitamin D insufficiency and monitor response to therapy

Testing is recommended only for patients at risk for vitamin D insufficiency

Medical Reviewers

Genzen, Jonathan R., MD, PhD, Laboratory Section Chief, Clinical Chemistry, and Medical Director, Automated Core Laboratory, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Pearson, Lauren N., DO, MPH, Medical Director, University of Utah Health Hospital Clinical Laboratory; Assistant Professor of Clinical Pathology, University of Utah

Straseski, Joely A., PhD, MS, MT(ASCP), DABCC, Medical Director, Endocrinology and Automated Core Laboratory at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

General References

Baird GS. Ionized calcium. Clin Chim Acta. 2011; 412(9-10): 696-701. PubMed

Bosworth M, Mouw D, Skolnik DC, Hoekzema G. Clinical inquiries: what is the best workup for hypocalcemia? J Fam Pract. 2008; 57(10): 677-9. PubMed

Chang WW, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014; 32(2): 349-66. PubMed

Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008; 336(7656): 1298-302. PubMed

De Sanctis V, Soliman A, Fiscina B. Hypoparathyroidism: from diagnosis to treatment. Curr Opin Endocrinol Diabetes Obes. 2012; 19(6): 435-42. PubMed

Fong J, Khan A. Hypocalcemia: updates in diagnosis and management for primary care. Can Fam Physician. 2012; 58(2): 158-62. PubMed

McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods, 23rd ed. St. Louis, MO: Elsevier, 2017.

Michels TC, Kelly KM. Parathyroid disorders. Am Fam Physician. 2013; 88(4): 249-57. PubMed

Testing Algorithms

Hypocalcemia Testing Algorithm

Read more about Hypocalcemia Testing Algorithm

Educational Videos

(50 min)

Content Review:

May 2018

Last Update: June 2018


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	Hypocalcemia. ARUP Consult^©. Retrieved June 17, 2018, from: https://arupconsult.com/content/hypocalcemia

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Hypocalcemia

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Monitoring

Background

Epidemiology

Etiology

Pathophysiology

Clinical Presentation

ARUP Lab Tests

Medical Reviewers

References

General References

Hypocalcemia Testing Algorithm