Hyperparathyroidism laboratory findings: Difference between revisions
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**Low normal serum [[phosphate]] concentration | **Low normal serum [[phosphate]] concentration | ||
**Elevated [[1,25-dihydroxy vitamin D]] ([[calcitriol]]) may be found in around half of patients. | **Elevated [[1,25-dihydroxy vitamin D]] ([[calcitriol]]) may be found in around half of patients. | ||
**There is a mild elevation in bone turnover indices including serum [[alkaline phosphatase]] activity, [[osteocalcin]], and urinary hydroxypiridinium collagen crosslinks. | **There is a mild elevation in bone turnover indices including serum [[alkaline phosphatase]] activity, [[osteocalcin]], and urinary hydroxypiridinium [[collagen]] crosslinks. | ||
===Secondary hyperparathyroidism=== | ===Secondary hyperparathyroidism=== | ||
| Line 58: | Line 58: | ||
*An elevated serum [[calcium]] should be confirmed by repeat 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.<ref name="pmid9612524">{{cite journal |vauthors=Glendenning P, Gutteridge DH, Retallack RW, Stuckey BG, Kermode DG, Kent GN |title=High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria |journal=Aust N Z J Med |volume=28 |issue=2 |pages=173–8 |year=1998 |pmid=9612524 |doi= |url=}}</ref> | *20% of patients with proven primary hyperparathyroidism have normal total [[calcium]] and elevated [[parathyroid hormone]]. Serum ionized concentration measurement is helpful in such cases.<ref name="pmid9612524">{{cite journal |vauthors=Glendenning P, Gutteridge DH, Retallack RW, Stuckey BG, Kermode DG, Kent GN |title=High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism: a challenge to current diagnostic criteria |journal=Aust N Z J Med |volume=28 |issue=2 |pages=173–8 |year=1998 |pmid=9612524 |doi= |url=}}</ref> | ||
*Some patients with primary hyperparathyroidism may have elevated concentration of serum [[parathyroid hormone]] with normal serum [[calcium]], which is usually suggestive of normocalcemic | *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.<ref name="pmid19193910">{{cite journal |vauthors=Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR |title=Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop |journal=J. Clin. Endocrinol. Metab. |volume=94 |issue=2 |pages=351–65 |year=2009 |pmid=19193910 |pmc=5393372 |doi=10.1210/jc.2008-1760 |url=}}</ref> 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.<ref name="pmid17536001">{{cite journal |vauthors=Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ |title=Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype |journal=J. Clin. Endocrinol. Metab. |volume=92 |issue=8 |pages=3001–5 |year=2007 |pmid=17536001 |doi=10.1210/jc.2006-2802 |url=}}</ref> | ||
===Serum Parathyroid hormone=== | ===Serum Parathyroid hormone=== | ||
| Line 64: | Line 64: | ||
===24-Hour urinary calcium=== | ===24-Hour urinary calcium=== | ||
*24-Hour urinary calcium excretion is indicated by the urinary calcium:creatinine clearance ratio.<ref name="pmid7356229">{{cite journal |vauthors=Marx SJ, Stock JL, Attie MF, Downs RW, Gardner DG, Brown EM, Spiegel AM, Doppman JL, Brennan MF |title=Familial hypocalciuric hypercalcemia: recognition among patients referred after unsuccessful parathyroid exploration |journal=Ann. Intern. Med. |volume=92 |issue=3 |pages=351–6 |year=1980 |pmid=7356229 |doi= |url=}}</ref><ref name="pmid686009">{{cite journal |vauthors=Marx SJ, Spiegel AM, Brown EM, Koehler JO, Gardner DG, Brennan MF, Aurbach GD |title=Divalent cation metabolism. Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism |journal=Am. J. Med. |volume=6http://www.sciencedirect.com/science/article/pii/0002934378908148?via%3Dihub5 |issue=2 |pages=235–42 |year=1978 |pmid=686009 |doi=10.1016/0002-9343(78)90814-8 |url=}}</ref> | *24-Hour urinary [[calcium]] excretion is indicated by the urinary calcium:creatinine clearance ratio.<ref name="pmid7356229">{{cite journal |vauthors=Marx SJ, Stock JL, Attie MF, Downs RW, Gardner DG, Brown EM, Spiegel AM, Doppman JL, Brennan MF |title=Familial hypocalciuric hypercalcemia: recognition among patients referred after unsuccessful parathyroid exploration |journal=Ann. Intern. Med. |volume=92 |issue=3 |pages=351–6 |year=1980 |pmid=7356229 |doi= |url=}}</ref><ref name="pmid686009">{{cite journal |vauthors=Marx SJ, Spiegel AM, Brown EM, Koehler JO, Gardner DG, Brennan MF, Aurbach GD |title=Divalent cation metabolism. Familial hypocalciuric hypercalcemia versus typical primary hyperparathyroidism |journal=Am. J. Med. |volume=6http://www.sciencedirect.com/science/article/pii/0002934378908148?via%3Dihub5 |issue=2 |pages=235–42 |year=1978 |pmid=686009 |doi=10.1016/0002-9343(78)90814-8 |url=}}</ref> | ||
*It is used to seperate the patients with familial hypocalciuric hypercalcemia and typical primary hyperparathyroidism. | *It is used to seperate the patients with [[familial hypocalciuric hypercalcemia]] and typical primary hyperparathyroidism. | ||
===Serum 1,25-dihydroxy vitamin D=== | ===Serum 1,25-dihydroxy vitamin D=== | ||
*May be used to differentiate between Familial | *May be used to differentiate between Familial hypercalciuric hypercalcemia (FHH) with primary hyperparathyroidism.<ref name="pmid6699136">{{cite journal |vauthors=Law WM, Bollman S, Kumar R, Heath H |title=Vitamin D metabolism in familial benign hypercalcemia (hypocalciuric hypercalcemia) differs from that in primary hyperparathyroidism |journal=J. Clin. Endocrinol. Metab. |volume=58 |issue=4 |pages=744–7 |year=1984 |pmid=6699136 |doi=10.1210/jcem-58-4-744 |url=}}</ref><ref name="pmid18787045">{{cite journal |vauthors=Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Rejnmark L, Brixen K, Mosekilde L |title=Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism |journal=Eur. J. Endocrinol. |volume=159 |issue=6 |pages=719–27 |year=2008 |pmid=18787045 |doi=10.1530/EJE-08-0440 |url=http://www.eje-online.org/content/159/6/719.full.pdf}}</ref> | ||
*Serum [[1,25-dihydroxy vitamin D]] ([[calcitriol]]) concentration are significantly lower in FHH than primary hyperparathyroidism. | *Serum [[1,25-dihydroxy vitamin D]] ([[calcitriol]]) concentration are significantly lower in FHH than primary hyperparathyroidism. | ||
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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:
- Elevated concentration of serum calcium
- Elevated serum parathyroid hormone level
- Low normal serum phosphate concentration
- Elevated 1,25-dihydroxy vitamin D (calcitriol) may be found in around half of patients.
- There is a mild elevation in bone turnover indices including serum alkaline phosphatase activity, osteocalcin, and urinary hydroxypiridinium collagen crosslinks.
Secondary hyperparathyroidism
- Laboratory findings consistent with the diagnosis of secondary hyperparathyroidism include:
- Elevated serum parathyroid hormone level
- Low to normal serum calcium
- Low serum vitamin D (25-hydroxy vitamin D) may be found if vitamin D deficiency is the cause of secondary hyperparathyroidism.
- Elevated serum phosphate
Tertiary hyperparathyroidism
- An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.
- Elevated serum phosphate is also present.
| 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]
Serum Parathyroid hormone
- Method of choice for measuring intact parathyroid hormone include Immunoradiometric assay (IMRA) or Immunochemiluminescent assay (ICMA).[5]
24-Hour urinary calcium
- 24-Hour urinary calcium excretion is indicated by the urinary calcium:creatinine clearance ratio.[6][7]
- It is used to seperate the patients with familial hypocalciuric hypercalcemia and typical primary hyperparathyroidism.
Serum 1,25-dihydroxy vitamin D
- May be used to differentiate between Familial hypercalciuric hypercalcemia (FHH) with primary hyperparathyroidism.[8][9]
- Serum 1,25-dihydroxy vitamin D (calcitriol) concentration are significantly lower in FHH than primary hyperparathyroidism.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.