Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypercalcemia Testing Algorithm
Clinical Background
Hypercalcemia is a common metabolic abnormality which is frequently related to primary hyperparathyroidism.
Epidemiology
- Incidence - 8/100,000
- Age - average is 55 years; range is 40-60 years
- Sex - F>M for primary hyperparathyroidism
Etiology
- Primary hyperparathyroidism
- Malignancy
- Usually metastatic disease; 1/3 related to squamous cell carcinoma
- Humoral mediated parathyroid related peptide cancer
- Excess vitamin D or rarely vitamin A
- Milk-alkali syndrome
- Elevated vitamin D, 1, 25-dihydroxy (granulomatous disease and B- and T-cell lymphomas)
Risk Factors
- Genetic
- Multiple Endocrine Neoplasia (MEN)
- MEN 1 (Werner Syndrome)
- Hyperparathyroidism, tumors of the anterior pituitary and enterohepatic tumors such as Zollinger-Ellison
- MEN 2A
- Medullary carcinoma of the thyroid, pheochromocytoma and mild hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- Hypercalcemia with subnormal urine calcium excretion
- Removal of parathyroids does not correct hypocalcemia
- Neonatal severe primary hyperparathyroidism
- Rare, potentially lethal
- Enlargement of all 4 parathyroids with very high parathyroid hormone (PTH)
- Hyperparathyroidism - jaw tumor syndrome
- Hyperparathyroidism with cementoossifying tumors of the jaw, Wilms tumor and renal cysts
Pathophysiology
- Hyperparathyroidism
- Four parathyroid glands found within the thyroid gland secrete PTH
- PTH acts directly on bone and induces calcium resorption with a tight negative feedback loop
- Pathology
- Adenoma
- Hyperplasia
- Carcinoma (rare)
- Most patients are asymptomatic when hypercalcemia is discovered due to frequent use of screening chemistries
Clinical Presentation
- Clinical symptoms progress slowly
- Renal - nephrolithiasis
- Cancer - usually fatigue, weakness as a result of very high calcium levels
- Bone - classic finding is osteitis fibrosa which is rare
- Central nervous system - easy fatigability, proximal muscle weakness, muscle atrophy
- Gastrointestinal - vague symptoms of nausea, bloating, constipation
Treatment
- Based on etiology of hypercalcemia
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypercalcemia Testing Algorithm
Diagnosis
Diagnosis
- Laboratory testing
- Indicated when hypercalcemia detected; measure ionized serum calcium
- Intact PTH
Differential Diagnosis
- Metastatic cancer
- Medication induced (eg, thiazide diuretics)
- Immobilization
- Granulomatous disease (sarcoidosis, TB)
- Vitamin D intoxication
- Paget disease
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Hypercalcemia Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Parathyroid Hormone, Intact with Calcium
|
| ARUP #: 0070172 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use:
Monitor hyperparathyroidism
|
| Limitations: |
| Follow-up:
|
| Test name: Parathyroid Hormone-Related Peptide (PTHrP)
|
| ARUP #: 0093014 |
| Methodology: Immunoradiometric Assay
|
| Use:
Differential diagnosis of hyperparathyroidism
|
| Limitations: |
| Follow-up:
|
| Test name: Calcium, Ionized, Serum
|
| ARUP #: 0020135 |
| Methodology: Ion-Selective Electrode/pH-Electrode
|
| Use:
Diagnose hyperparathyroidism
|
| Limitations: |
| Follow-up:
|
Additional Tests Available
| Test name: Vitamin D, 25-Hydroxy
|
| ARUP #: 0080379 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
| Test name: Vitamin D, 1, 25-Dihydroxy
|
| ARUP #: 0080385 |
| Methodology: Radioimmunoassay
|
| Comments: Differentiate type of cancer |
| Test name: Calcium, Serum or Plasma
|
| ARUP #: 0020027 |
| Methodology: Spectrophotometry
|
| Comments: |
| Test name: Calcium, Ionized, Whole Blood
|
| ARUP #: 0020140 |
| Methodology: Ion-Selective Electrode/pH-Electrode
|
| Comments: |
| Test name: Parathyroid Hormone, Intact
|
| ARUP #: 0070346 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Comments: |
| Test name: Parathyroid Hormone, CAP
|
| ARUP #: 0095611 |
| Methodology: Immunoradiometric Assay
|
| Comments: |
References
General References
Arnold A, Shattuck TM, Mallya SM, Krebs LJ, Costa J, Gallagher J, Wild Y, Saucier K. Molecular pathogenesis of primary hyperparathyroidism. J Bone Miner Res.
2002;
17 Suppl 2:
N30-N36.
Clement B. Parathyroid pathophysiology. Semin Perioper Nurs.
1998;
7(
3):
186-192.
D'Amour P. Circulating PTH molecular forms: what we know and what we don't. Kidney Int Suppl.
2006;
(
102):
S29-S33.
Locatelli F, Limardo M, Pontoriero G. New perspectives in the management of secondary hyperparathyroidism. Mini Rev Med Chem.
2007;
7(
6):
591-598.
Lynn J, Patel T. Blood testing diagnostic for parathyroid disease. Practitioner.
2007;
251(
1692):
69-3.
Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med.
2000;
343(
25):
1863-1875.
Shepard MM, Smith JW III. Hypercalcemia. Am J Med Sci.
2007;
334(
5):
381-385.
Silverberg SJ, Bilezikian JP. The diagnosis and management of asymptomatic primary hyperparathyroidism. Nat Clin Pract Endocrinol Metab.
2006;
2(
9):
494-503.
Sitges-Serra A, Bergenfelz A. Clinical update: sporadic primary hyperparathyroidism. Lancet.
2007;
370(
9586):
468-470.
Suliburk JW, Perrier ND. Primary hyperparathyroidism. Oncologist.
2007;
12(
6):
644-653.
Younes NA, Shafagoj Y, Khatib F, Ababneh M. Laboratory screening for hyperparathyroidism. Clin Chim Acta.
2005;
353(
1-2):
1-12.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Abraham D, Sharma PK, Bentz J, Gault PM, Neumayer L, McClain DA. Utility of ultrasound-guided fine-needle aspiration of parathyroid adenomas for localization before minimally invasive parathyroidectomy. Endocr Pract.
2007;
13(
4):
333-337.
Medical Reviewers
Lehman, Christopher M., M.D. Co-Medical Director, University Hospital Clinical Laboratory; Associate Professor, Clinical Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Comprehensive Review: March 2008
Last Update: March 2008
