Hypercalcemia differential diagnosis: Difference between revisions
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[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Hypercalcemia]] | |||
{{CMG}}; {{AE}} {{Anmol}} | {{CMG}}; {{AE}} {{Anmol}} | ||
==Overview== | ==Overview== | ||
Various common causes of hypercalcemia should be differentiated from each other.Causes of [[hypercalcemia]] to be differentiated include [[hyperparathyroidism]], [[familial hypocalciuric hypercalcemia]], [[hypercalcemia]] related to [[malignancy]], [[medication-induced]] [[hypercalcemia]], [[hypercalcemia]] due to [[nutritional]] disorders, and [[hypercalcemia]] related to [[Granulomatous|granulomatous diseases]]. | Various common causes of hypercalcemia should be differentiated from each other. Causes of [[hypercalcemia]] to be differentiated include [[hyperparathyroidism]], [[familial hypocalciuric hypercalcemia]], [[hypercalcemia]] related to [[malignancy]], [[medication-induced]] [[hypercalcemia]], [[hypercalcemia]] due to [[nutritional]] disorders, and [[hypercalcemia]] related to [[Granulomatous|granulomatous diseases]]. | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
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* [[Biopsy]] | * [[Biopsy]] | ||
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==References== | ==References== | ||
Latest revision as of 21:37, 13 February 2019
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
Various common causes of hypercalcemia should be differentiated from each other. Causes of hypercalcemia to be differentiated include hyperparathyroidism, familial hypocalciuric hypercalcemia, hypercalcemia related to malignancy, medication-induced hypercalcemia, hypercalcemia due to nutritional disorders, and hypercalcemia related to granulomatous diseases.
Differential Diagnosis
Different causes of hypecalcemia should be differentiated from each other. Common causes of hypercalcemia to be differentiaetd include:
- Parathyroid related
- Hyperparathyroidism
- Primary hyperparathyroidism
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- Hyperparathyroidism
- Non-parathyroid related
- Malignancy
- Humoral hypercalcemia of malignancy
- Osteolytic tumors
- Production of calcitriol by tumors
- Ectopic parathyroid hormone production
- Medication-induced
- Nutritional
- Granulomatous disease
- Surgical
- Immobization
- Malignancy
| Differential diagnosis of hypercalcemia | ||||||||
|---|---|---|---|---|---|---|---|---|
| Disorder | Mechanism of hypercalcemia | Clinical features | Laboratory findings | Imaging & diagnostic modalities | ||||
| PTH | Calcium | Phosphate | Other findings | |||||
| Hyperparathyroidism | Primary hyperparathyroidism | Increase in secretion of parathyroid hormone (PTH) from a primary process in parathyroid gland. Parathyroid hormone causes increase in serum calcium. |
|
↑ | ↑ | ↓/Normal | Normal/↑ calcitriol | Findings of bone resorption:
Preoperative localization of hyperfunctioning parathyroid gland:
Predicting post-operative success:
|
| Secondary hyperparathyroidism | Increase in secretion of parathyroid hormone (PTH) from a secondary process. Parathyroid hormone causes increase in serum calcium after long periods. |
|
↑ | ↓/Normal | ↑ | -- | ||
| Tertiary hyperparathyroidism | Continuous elevation of parathyroid hormone (PTH) even after successful treatment of the secondary cause of elevated parathyroid hormone. Parathyroid hormone causes increase in serum calcium. |
|
↑ | ↑ | ↑ | -- | ||
| Familial hypocalciuric hypercalcemia | This is a genetic disorder caused my mutation in calcium-sensing receptor gene. |
|
Normal/↑ | Normal/↑ | -- | -- |
| |
| Malignancy[1][2] | Humoral hypercalcemia of malignancy[3][4][5][6] | Tumor cells secretes parathyroid hormone-related protein (PTHrP) which has similar action as parathyroid hormone. |
|
-- | ↑ | ↓/Normal | ↑ PTHrP
Normal/↑ calcitriol |
|
| Osteolytic tumors[7][8] | Multiple myeloma produces osteolysis of bones causing hypercalcemia. Osteolytic metasteses can cause bone resorption causing hypercalcemia. |
|
↓ | ↑ | -- | -- | ||
| Production of calcitirol[9] | 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. |
|
-- | ↑ | -- | ↑ Calcitriol | ||
| Ectopic parathyroid hormone[10] | Some tumors leads to ectopic production of parathyroid hormone. |
|
↑ | ↑ | ↓/Normal | Normal/↑ calcitriol | ||
| Medication induced | Lithium[11] | Lithium lowers urinary calcium and causes hypercalcemia. Lithium has been reported to cause an increase in parathyroid hormone and enlargement if parathyroid gland after weeks to months of therapy. |
|
↑ | ↑ | -- | -- |
|
| Thiazide diuretics[12] | Thiazide diuretics lowers urinary calcium excretion and causes hypercalcemia. |
|
-- | ↑ | -- | -- | -- | |
| Nutritional | Milk-alkali syndrome | Hypercalcemia is be caused by high intake of calcium carbonate. |
|
-- | ↑ | -- | ↓ calcitriol | |
| Vitamin D toxicity[13][14][15] | Excess vitamin D causes increased absorption of calcium from intestine causing hypercalcemia. |
|
-- | ↑ | -- | ↑ Vitamin D (calcidiol and/or calcitriol) | -- | |
| Granulomatous disease | Sarcoidosis[18] | Hypercalcemia is causes by endogeous production of calcitriol by disease-activated macrophages. |
|
-- | ↑ | -- | ↑ Calcitriol
↑ ACE levels |
|
References
- ↑ 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.
- ↑ Mallette LE, Khouri K, Zengotita H, Hollis BW, Malini S (1989). "Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume". J. Clin. Endocrinol. Metab. 68 (3): 654–60. doi:10.1210/jcem-68-3-654. PMID 2918061.
- ↑ Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ; et al. (2016). "Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades". J Clin Endocrinol Metab. 101 (3): 1166–73. doi:10.1210/jc.2015-3964. PMC 4803175. PMID 26751196.
- ↑ Hoeck HC, Laurberg G, Laurberg P (1994). "Hypercalcaemic crisis after excessive topical use of a vitamin D derivative". J. Intern. Med. 235 (3): 281–2. PMID 8120527.
- ↑ Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW (1992). "Hypervitaminosis D associated with drinking milk". N. Engl. J. Med. 326 (18): 1173–7. doi:10.1056/NEJM199204303261801. PMID 1313547.
- ↑ Sharma OP (1996). "Vitamin D, calcium, and sarcoidosis". Chest. 109 (2): 535–9. PMID 8620732.
- ↑ Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW (1992). "Hypervitaminosis D associated with drinking milk". N. Engl. J. Med. 326 (18): 1173–7. doi:10.1056/NEJM199204303261801. PMID 1313547.
- ↑ Hoeck HC, Laurberg G, Laurberg P (1994). "Hypercalcaemic crisis after excessive topical use of a vitamin D derivative". J. Intern. Med. 235 (3): 281–2. PMID 8120527.
- ↑ Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E (1997). "gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses". J. Clin. Endocrinol. Metab. 82 (7): 2222–32. doi:10.1210/jcem.82.7.4074. PMID 9215298.