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===Chloride phosphate ratio===
===Chloride phosphate ratio===
The serum chloride phosphate ratio is high (33 or more) in most patients with primary hyperparathyroidism. <ref name="pmid1155729">{{cite journal |author=Reeves CD, Palmer F, Bacchus H, Longerbeam JK |title=Differential diagnosis of hypercalcemia by the chloride/phosphate ratio |journal=Am. J. Surg. |volume=130 |issue=2 |pages=166-71 |year=1975 |pmid=1155729 |doi=}}<br><blockquote>This study found a ratio above 33 to have a [[sensitivity (tests)|sensitivity]] of 94% and a [[specificity (tests)|specificity]] of 96%.</blockquote></ref><ref name="pmid4405880">{{cite journal |author=Palmer FJ, Nelson JC, Bacchus H |title=The chloride-phosphate ratio in hypercalcemia |journal=Ann. Intern. Med. |volume=80 |issue=2 |pages=200-4 |year=1974 |pmid=4405880 |doi=}}</ref><ref name="pmid521012">{{cite journal |author=Broulík PD, Pacovský V |title=The chloride phosphate ratio as the screening test for primary hyperparathyroidism |journal=Horm. Metab. Res. |volume=11 |issue=10 |pages=577-9 |year=1979 |pmid=521012 |doi=}}<br><blockquote>This study found a ratio above 33 to have a [[sensitivity (tests)|sensitivity]] of 95% and a [[specificity (tests)|specificity]] of 100%.</blockquote></ref> However, [[thiazide]] medications have been reported to causes ratios above 33.<ref name="pmid6848626">{{cite journal |author=Lawler FH, Janssen HP |title=Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration |journal=The Journal of family practice |volume=16 |issue=1 |pages=153-4 |year=1983 |pmid=6848626 |doi=}}</ref>
The serum chloride phosphate ratio is high (33 or more) in most patients with primary hyperparathyroidism. <ref name="pmid1155729">{{cite journal |author=Reeves CD, Palmer F, Bacchus H, Longerbeam JK |title=Differential diagnosis of hypercalcemia by the chloride/phosphate ratio |journal=Am. J. Surg. |volume=130 |issue=2 |pages=166-71 |year=1975 |pmid=1155729 |doi=}}<br><blockquote>This study found a ratio above 33 to have a [[sensitivity (tests)|sensitivity]] of 94% and a [[specificity (tests)|specificity]] of 96%.</blockquote></ref><ref name="pmid4405880">{{cite journal |author=Palmer FJ, Nelson JC, Bacchus H |title=The chloride-phosphate ratio in hypercalcemia |journal=Ann. Intern. Med. |volume=80 |issue=2 |pages=200-4 |year=1974 |pmid=4405880 |doi=}}</ref><ref name="pmid521012">{{cite journal |author=Broulík PD, Pacovský V |title=The chloride phosphate ratio as the screening test for primary hyperparathyroidism |journal=Horm. Metab. Res. |volume=11 |issue=10 |pages=577-9 |year=1979 |pmid=521012 |doi=}}<br><blockquote>This study found a ratio above 33 to have a [[sensitivity (tests)|sensitivity]] of 95% and a [[specificity (tests)|specificity]] of 100%.</blockquote></ref> However, [[thiazide]] medications have been reported to causes ratios above 33.<ref name="pmid6848626">{{cite journal |author=Lawler FH, Janssen HP |title=Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration |journal=The Journal of family practice |volume=16 |issue=1 |pages=153-4 |year=1983 |pmid=6848626 |doi=}}</ref>.


===Serum Parathyroid hormone===
===Serum Parathyroid hormone===

Revision as of 17:44, 18 May 2020

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

Overview

An elevated serum calcium on routine biochemical screening in a asymptomatic patient should raise the suspicion of primary hyperparathyroidism. An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyoidism. Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium. An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism. Measurement of total serum calcium with automatic techniques has similar or even more reliability than serum ionized calcium measurement. Method of choice for measuring intact parathyroid hormone include Immunoradiometric assay (IMRA) or Immunochemiluminescent assay (ICMA). 24-Hour urinary calcium excretion is used to seperate the patients with familial hypocalciuric hypercalcemia and typical primary hyperparathyroidism. Serum 1,25-dihydroxy vitamin D (calcitriol) concentration are significantly lower in familial hypocalciuric hypercalcemia than primary hyperparathyroidism.

Laboratory Findings

Primary hyperparathyroidism

  • An elevated serum calcium on routine biochemical screening in a asymptomatic patient should raise the suspicion of primary hyperparathyroidism.[1]
  • An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism.
  • 25-Hydroxy vitamin D is usually normal among patients with primary hyperparathyroidism.
  • Laboratory findings consistent with the diagnosis of primary hyperparathyroidism include:

Secondary hyperparathyroidism

Tertiary hyperparathyroidism

Laboratory findings Hyperparathyroisidm
Primary hyperparathyroidism Secondary hyperparathyroidism Tertiary hyperparathyroidism
Parathyroid hormone
Serum calcium /Normal
Serum phosphate /Normal

Biochemical Tests

Serum Calcium

  • An elevated serum calcium on routine biochemical screening in a asymptomatic patient should raise the suspicion of primary hyperparathyroidism.[1]
  • Measurement of total serum calcium with automatic techniques has similar or even more reliability than serum ionized calcium measurement.
  • An elevated serum calcium should be confirmed by repeat measurement.
  • 20% of patients with proven primary hyperparathyroidism have normal total calcium and elevated parathyroid hormone. Serum ionized concentration measurement is helpful in such cases.[2]
  • Some patients with primary hyperparathyroidism may have elevated concentration of serum parathyroid hormone with normal serum calcium, which is usually suggestive of normocalcemic primary hyperparathyroidism.[3] Causes of secondary hyperparathyroidism should be rules out for making the diagnosis of normocalcemic primary hyperparathyroidism. Normocalcemic primary hyperparathyroidism might represent the first symptomatic stage of primary hyperparathyroidism.[4]

Chloride phosphate ratio

The serum chloride phosphate ratio is high (33 or more) in most patients with primary hyperparathyroidism. [5][6][7] However, thiazide medications have been reported to causes ratios above 33.[8].

Serum Parathyroid hormone

  • Method of choice for measuring intact parathyroid hormone include Immunoradiometric assay (IMRA) or Immunochemiluminescent assay (ICMA).[9]

24-Hour urinary calcium

Serum 1,25-dihydroxy vitamin D

  • May be used to differentiate between Familial hypercalciuric hypercalcemia (FHH) with primary hyperparathyroidism.[12][13]
  • Serum 1,25-dihydroxy vitamin D (calcitriol) concentration are significantly lower in FHH than primary hyperparathyroidism.

References

  1. 1.0 1.1 Silverberg SJ, Bilezikian JP (1996). "Evaluation and management of primary hyperparathyroidism". J. Clin. Endocrinol. Metab. 81 (6): 2036–40. doi:10.1210/jcem.81.6.8964825. PMID 8964825.
  2. Glendenning P, Gutteridge DH, Retallack RW, Stuckey BG, Kermode DG, Kent GN (1998). "High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria". Aust N Z J Med. 28 (2): 173–8. PMID 9612524.
  3. Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR (2009). "Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop". J. Clin. Endocrinol. Metab. 94 (2): 351–65. doi:10.1210/jc.2008-1760. PMC 5393372. PMID 19193910.
  4. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ (2007). "Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype". J. Clin. Endocrinol. Metab. 92 (8): 3001–5. doi:10.1210/jc.2006-2802. PMID 17536001.
  5. Reeves CD, Palmer F, Bacchus H, Longerbeam JK (1975). "Differential diagnosis of hypercalcemia by the chloride/phosphate ratio". Am. J. Surg. 130 (2): 166–71. PMID 1155729.

    This study found a ratio above 33 to have a sensitivity of 94% and a specificity of 96%.

  6. Palmer FJ, Nelson JC, Bacchus H (1974). "The chloride-phosphate ratio in hypercalcemia". Ann. Intern. Med. 80 (2): 200–4. PMID 4405880.
  7. Broulík PD, Pacovský V (1979). "The chloride phosphate ratio as the screening test for primary hyperparathyroidism". Horm. Metab. Res. 11 (10): 577–9. PMID 521012.

    This study found a ratio above 33 to have a sensitivity of 95% and a specificity of 100%.

  8. Lawler FH, Janssen HP (1983). "Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration". The Journal of family practice. 16 (1): 153–4. PMID 6848626.
  9. Endres DB, Villanueva R, Sharp CF, Singer FR (1991). "Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism" (PDF). Clin. Chem. 37 (2): 162–8. PMID 1993319.
  10. Marx SJ, Stock JL, Attie MF, Downs RW, Gardner DG, Brown EM, Spiegel AM, Doppman JL, Brennan MF (1980). "Familial hypocalciuric hypercalcemia: recognition among patients referred after unsuccessful parathyroid exploration". Ann. Intern. Med. 92 (3): 351–6. PMID 7356229.
  11. Marx SJ, Spiegel AM, Brown EM, Koehler JO, Gardner DG, Brennan MF, Aurbach GD (1978). "Divalent cation metabolism. Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism". Am. J. Med. 6http://www.sciencedirect.com/science/article/pii/0002934378908148?via%3Dihub5 (2): 235–42. doi:10.1016/0002-9343(78)90814-8. PMID 686009.
  12. Law WM, Bollman S, Kumar R, Heath H (1984). "Vitamin D metabolism in familial benign hypercalcemia (hypocalciuric hypercalcemia) differs from that in primary hyperparathyroidism". J. Clin. Endocrinol. Metab. 58 (4): 744–7. doi:10.1210/jcem-58-4-744. PMID 6699136.
  13. Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Rejnmark L, Brixen K, Mosekilde L (2008). "Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism" (PDF). Eur. J. Endocrinol. 159 (6): 719–27. doi:10.1530/EJE-08-0440. PMID 18787045.

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