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

Diagnose disorders of calcium metabolism

Calcium, Serum or Plasma 0020027

Method: Quantitative Spectrophotometry

Order concurrent with calcium to assess for hypoalbuminemia

Albumin, Serum or Plasma by Spectrophotometry 0020030

Method: Quantitative Spectrophotometry

Diagnose disorders of calcium metabolism

Abnormal pH will alter results

No correction necessary for hypoalbuminemia

Calcium, Ionized, Serum 0020135

Method: Ion-Selective Electrode/pH Electrode

Evaluate renal function

Phosphorus, Inorganic, Plasma or Serum 0020028

Method: Quantitative Spectrophotometry

Diagnose disorders of the parathyroid glands

Parathyroid Hormone, Intact 0070346

Method: Quantitative Electrochemiluminescent Immunoassay

May help to determine etiology of hypocalcemia

Magnesium, Plasma or Serum 0020039

Method: 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

Vitamin D, 25-Hydroxy 0080379

Method: Quantitative Chemiluminescent Immunoassay

Related Tests

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

Creatinine, Serum or Plasma 0020025

Method: Quantitative Enzymatic

Use to evaluate calcium dysregulation

Parathyroid Hormone, Intact with Calcium 0070172

Method: Quantitative Electrochemiluminescent Immunoassay

Investigate potential autoimmune disorders involving the parathyroid gland

Parathyroid Hormone (PTH) Antibody 3000003

Method: Qualitative Radiobinding Assay

Assess calcium status

Available only to University of Utah patients

Calcium, Ionized, Whole Blood 0020140

Method: Ion-Selective Electrode/pH Electrode

Medical Experts

Genzen, Jonathan R., MD, PhD, Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical 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

Content Review:

May 2018

Last Update: November 2019

Hypocalcemia

Diagnosis

Indications for Testing

Laboratory Testing

Differential Diagnosis

Monitoring

Background

Epidemiology

Etiology

Pathophysiology

Clinical Presentation

ARUP Lab Tests

Medical Experts

References

General References

Hypocalcemia Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult


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	Hypocalcemia. ARUP Consult^©. Retrieved December 4, 2019, 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 Experts

References

General References

Hypocalcemia Testing Algorithm

ARUP Laboratories

ARUP Websites

ARUP Consult