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{{Hypocalcemia}}
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==Overview==
==Overview==
Measurement of the serum [[albumin]] concentration is essential to distinguish pseudohypocalcemia from true hypocalcemia.  Laboratory investigations that detect alterations in [[parathyroid hormone]], [[vitamin D]], and [[phosphate]] in the serum or urine aid in the differential diagnosis of the underlying etiologies. Other laboratory tests include serum [[alkaline phosphatase]], [[liver function test]]s, [[coagulation|coagulation profile]], [[blood urea nitrogen]], [[creatinine]], and urinary [[cAMP]] levels at baseline or after PTH challenge.
Measurement of the serum [[albumin]] concentration is essential to distinguish pseudohypocalcemia from true hypocalcemia.  Laboratory investigations that detect alterations in [[parathyroid hormone]], [[vitamin D]], and [[phosphate]] in the [[serum]] or urine aid in the differential diagnosis of the underlying etiologies. Other laboratory tests include [[serum]] [[alkaline phosphatase]], [[liver function test]]s, [[coagulation|coagulation profile]], [[blood urea nitrogen]], [[creatinine]], and urinary [[cAMP]] levels at baseline or after PTH challenge.


==Laboratory Findings==
==Laboratory Findings==
==== CONFIRM HYPOCALCEMIA====
==== CONFIRM HYPOCALCEMIA====
*The first step in diagnostic approach to hypocalcemia includes repeat measurement of calcium levels and confirming the levels.
*The first step in diagnostic approach to [[hypocalcemia]] includes '''"Repeat"''' measurement of [[calcium]] levels and confirming the levels.
*Patient previous levels for serum calcium should also be reviewed, if possible or available.
*Patient previous levels for [[serum]] calcium should also be reviewed, if possible or available.


==== Hypoalbuminemia ====
==== Hypoalbuminemia ====
* Calcium in blood is bound to albumin and measurement of the serum albumin is essential to distinguish true hypocalcemia.
* [[Calcium]] in [[blood]] is bound to albumin and calculation of the serum albumin is essential to distinguish true hypocalcemia.
* 1 g/dL decrease in the serum albumin levels will lower the total calcium levels by approximately 0.8 mg/dL (0.2 mmol/L).
* 1 g/dL decrease in the [[serum albumin]] levels will lower the total [[calcium]] levels by approximately 0.8 mg/dL (0.2 mmol/L).
* But these reduction in serum albumin levels does not affect serum ionized calcium levels and therefore no signs of hypocalcemia.
* But these reduction in [[serum albumin]] levels does not affect serum ionized calcium levels and therefore no signs of hypocalcemia.
* So, a patient who has a serum albumin level that is 2 g/dL (20 g/L) below normal will have a fall in serum total calcium level of 1.6 mg/dL (0.4 mmol/L).
* So, a patient who has a [[serum albumin]] level that is 2 g/dL (20 g/L) below normal will have a fall in serum total calcium level of 1.6 mg/dL (0.4 mmol/L).
 
Laboratory findings consistent with the diagnosis of hypocalcemia include
===Factors Interfere with Calcium Concentration Measurement===
* [[Parathyroid hormone|Serum PTH]] concentrations
* In [[alkalosis]], free calcium decreases due to enhanced binding of Ca<sup>++</sup> to [[albumin]].  A rise in pH of 0.1 unit will cause an approximately 0.05 mmol/L (0.1 mEq/L) fall in ionized Ca<sup>++</sup> concentration.  Direct measurement of ionized calcium concentration may be required in critically ill patients with [[acid-base disturbances|acid-base disorders]].
* [[Magnesium]] concentrations
* [[Hypoproteinemia]] may contribute to reduced total calcium levels.
* [[Phosphate]] concentrations
* Excessive use of [[laxatives]] may lower blood calcium levels by increasing intestinal calcium loss.
* Vitamin D metabolites
* Hypocalcemia may be masked by calcium supplements taken shortly before specimen collection or the use of calcium-ion exchange resin in [[hemodialysis]] for [[hyperkalemia]].<ref>{{cite book | last = Fischbach | first = Frances | title = A manual of laboratory and diagnostic tests | publisher = Wolters Kluwer Health | location = Philadelphia | year = 2015 | isbn = 978-1451190892 }}</ref>


==Adjustment for Hypoalbuminemia==
==Adjustment for Hypoalbuminemia==
* Adjustment of total serum calcium concentration for changes in plasma albumin level:<ref>{{Cite journal| issn = 0007-1447| volume = 1| issue = 6061| pages = 598| title = Correcting the calcium| journal = British Medical Journal| date = 1977-03-05| pmid = 843828| pmc = PMC1605322}}</ref>
* Adjustment of total [[Calcium|serum calcium]] concentration for changes in plasma albumin level:<ref>{{Cite journal| issn = 0007-1447| volume = 1| issue = 6061| pages = 598| title = Correcting the calcium| journal = British Medical Journal| date = 1977-03-05| pmid = 843828| pmc = PMC1605322}}</ref>
: ''Adjusted total calcium in mg/dL = Total calcium in mg/dL + 0.8 * (4 - Albumin in g/dL)''
: ''Adjusted total calcium in mg/dL = Total calcium in mg/dL + 0.8 * (4 - Albumin in g/dL)''
: ''Adjusted total calcium in mmol/L = Total calcium in mmol/L + 0.02 * (40 - Albumin in g/L)''
: ''Adjusted total calcium in mmol/L = Total calcium in mmol/L + 0.02 * (40 - Albumin in g/L)''

Latest revision as of 12:01, 13 August 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

Measurement of the serum albumin concentration is essential to distinguish pseudohypocalcemia from true hypocalcemia. Laboratory investigations that detect alterations in parathyroid hormone, vitamin D, and phosphate in the serum or urine aid in the differential diagnosis of the underlying etiologies. Other laboratory tests include serum alkaline phosphatase, liver function tests, coagulation profile, blood urea nitrogen, creatinine, and urinary cAMP levels at baseline or after PTH challenge.

Laboratory Findings

 CONFIRM HYPOCALCEMIA

  • The first step in diagnostic approach to hypocalcemia includes "Repeat" measurement of calcium levels and confirming the levels.
  • Patient previous levels for serum calcium should also be reviewed, if possible or available.

Hypoalbuminemia

  • Calcium in blood is bound to albumin and calculation of the serum albumin is essential to distinguish true hypocalcemia.
  • 1 g/dL decrease in the serum albumin levels will lower the total calcium levels by approximately 0.8 mg/dL (0.2 mmol/L).
  • But these reduction in serum albumin levels does not affect serum ionized calcium levels and therefore no signs of hypocalcemia.
  • So, a patient who has a serum albumin level that is 2 g/dL (20 g/L) below normal will have a fall in serum total calcium level of 1.6 mg/dL (0.4 mmol/L).

Laboratory findings consistent with the diagnosis of hypocalcemia include

Adjustment for Hypoalbuminemia

  • Adjustment of total serum calcium concentration for changes in plasma albumin level:[1]
Adjusted total calcium in mg/dL = Total calcium in mg/dL + 0.8 * (4 - Albumin in g/dL)
Adjusted total calcium in mmol/L = Total calcium in mmol/L + 0.02 * (40 - Albumin in g/L)

Laboratory Differential Diagnosis of Hypocalcemia

Abbreviations: ADHP, autosomal dominant hypoparathyroidism; CKD, chronic kidney disease; Cr, creatinine; Def, deficiency; HP, hyperphosphatemia; HPTH, hypoparathyroidism; PHP, pseudohypoparathyroidism; VDDR, vitamin D-dependent rickets.[2]

 
 
 
 
 
 
 
 
 
 
 
 
 
↓Ca
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑PTH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↔↓PTH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑PO4
 
 
 
 
 
 
 
↔↓PO4
 
 
 
 
 
 
↔Mg
 
 
 
↓Mg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑Cr
 
 
 
↔Cr
 
↓25(OH)D
 
 
 
↔↑25(OH)D
 
 
 
HPTH
 
 
 
ADHP or Mg def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CKD
 
 
 
PHP or HP
 
Vitamin D def↓1,25(OH)2D
 
 
 
↑1,25(OH)2D
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type I VDDR
 
 
 
Type II VDDR
 
 
 
 
 
 
 
 
 

References

  1. ↑ "Correcting the calcium". British Medical Journal. 1 (6061): 598. 1977-03-05. ISSN 0007-1447. PMC 1605322. PMID 843828.
  2. ↑ Ferri, Fred (2015). Ferri's clinical advisor 2015 : 5 books in 1. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323083751.

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