Hypercalcemia classification
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Hypercalcemia may be classified according to severity into 3 groups including mild, moderate, and severe hypercalcemia
Classification
Common Terminology Criteria for Adverse Events (CTCAE) grade:
Common Terminology Criteria for Adverse Events (CTCAE) grade classifies hypercalcemia into 4 grades on the basis of corrected serum calcium (CSC):[1]
| Grade | Corrected serum calcium (CSC) |
|---|---|
| Grade 1 | Corrected serum calcium of >ULN - 11.5 mg/dL; >ULN - 2.9 mmol/L; Ionized calcium >ULN - 1.5 mmol/L |
| Grade 2 | Corrected serum calcium of >11.5 - 12.5 mg/dL; >2.9 - 3.1 mmol/L; Ionized calcium >1.5 - 1.6 mmol/L; symptomatic |
| Grade 3 | Corrected serum calcium of >12.5 - 13.5 mg/dL; >3.1 - 3.4 mmol/L; Ionized calcium >1.6 - 1.8 mmol/L; hospitalization indicated |
| Grade 4 | Corrected serum calcium of >13.5 mg/dL; >3.4 mmol/L; Ionized calcium >1.8 mmol/L; life-threatening consequences |
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Based on severity
Hypercalcemia may be classified according to severity into 3 groups:[3]
| Severity | Calcium concentration | Key Points |
|---|---|---|
| Mild hypercalcemia | <3.0 mmol/L |
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| Moderate hypercalcemia | 3.0–3.5 mmol/L |
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| Severe hypercalcemia | >3.5 mmol/L |
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Classification of hypercalcemia associated with malignancy
Hypercalcemia associated with malignancy may be classified according to mechanism of increased production of calcium into four types:[4][5]
| Disorder | Mechanism of hypercalcemia | Clinical features | Laboratory findings | |||
|---|---|---|---|---|---|---|
| PTH | Calcium | Phosphate | Other findings | |||
| Humoral hypercalcemia of malignancy[6][7][8][9] | Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. |
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-- | ↑ | ↓/Normal | ↑ PTHrP Normal/↑ calcitriol |
| Osteolytic tumors[10][11] | Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. |
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↓ | ↑ | -- | -- |
| Production of calcitirol[12] | Some tumors has ectopic activity of 1-alpha-hydroxylase leading to increased production of calcitriol. Calcitriol is active form of vitamin D and causes hypercalcemia. |
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-- | ↑ | -- | ↑ Calcitriol |
| Ectopic parathyroid hormone[13] | Some tumors leads to ectopic production of parathyroid hormone. |
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↑ | ↑ | ↓/Normal | Normal/↑ calcitriol |
References
- ↑ US Department of Health and Human Services . National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. Published: November 27, 2017.
- ↑ 2.0 2.1 Fraser, William D. (2018). "63. Bone and Mineral Metabolism". In Rifai, Nader. Tietz textbook of clinical chemistry and molecular diagnostics. St. Louis, Missouri: Elsevier. ISBN 0323359213.
- ↑ Walsh J, Gittoes N, Selby P, Society for Endocrinology Clinical Committee (2016). "SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients". Endocr Connect. 5 (5): G9–G11. doi:10.1530/EC-16-0055. PMC 5314807. PMID 27935816.
- ↑ Mirrakhimov AE (2015). "Hypercalcemia of Malignancy: An Update on Pathogenesis and Management". N Am J Med Sci. 7 (11): 483–93. doi:10.4103/1947-2714.170600. PMC 4683803. PMID 26713296.
- ↑ Stewart AF (2005). "Clinical practice. Hypercalcemia associated with cancer". N Engl J Med. 352 (4): 373–9. doi:10.1056/NEJMcp042806. PMID 15673803.
- ↑ Ratcliffe WA, Hutchesson AC, Bundred NJ, Ratcliffe JG (1992). "Role of assays for parathyroid-hormone-related protein in investigation of hypercalcaemia". Lancet. 339 (8786): 164–7. doi:10.1016/0140-6736(92)90220-W. PMID 1346019.
- ↑ Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T (1994). "Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma". J. Clin. Endocrinol. Metab. 79 (5): 1322–7. doi:10.1210/jcem.79.5.7962324. PMID 7962324.
- ↑ Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña A, Stewart AF (2003). "Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)] versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers". J. Clin. Endocrinol. Metab. 88 (4): 1603–9. doi:10.1210/jc.2002-020773. PMID 12679445.
- ↑ Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE; et al. (1982). "Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity". J Clin Endocrinol Metab. 55 (2): 219–27. doi:10.1210/jcem-55-2-219. PMID 7085851.
- ↑ Roodman GD (2004). "Mechanisms of bone metastasis". N Engl J Med. 350 (16): 1655–64. doi:10.1056/NEJMra030831. PMID 15084698.
- ↑ Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF; et al. (1996). "Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis". J Clin Invest. 98 (7): 1544–9. doi:10.1172/JCI118947. PMC 507586. PMID 8833902.
- ↑ Seymour JF, Gagel RF, Hagemeister FB, Dimopoulos MA, Cabanillas F (1994). "Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma". Ann Intern Med. 121 (9): 633–40. PMID 7944070.
- ↑ VanHouten JN, Yu N, Rimm D, Dotto J, Arnold A, Wysolmerski JJ, Udelsman R (2006). "Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene". J. Clin. Endocrinol. Metab. 91 (2): 580–3. doi:10.1210/jc.2005-2095. PMID 16263810.