Hypercalcemia causes: Difference between revisions

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{{Hypercalcemia}}
{{Hypercalcemia}}
{{CMG}}
{{CMG}}; {{AE}} {{Anmol}}, {{LRO}}


==Overview==
==Overview==
Hypercalcemia is most commonly caused by [[hyperparathyroidism]] and [[malignancy]]. Other causes of hypercalcemia include [[hyperthyroidism]], [[Hypervitaminosis D|vitamin D toxicity]], increased calcium intake, granulomatous diseases ( such [[sarcoidosis]]), and various renal disorders.
==Causes==
==Causes==
=== Life-Threatening Causes ===
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Severity of hypercalcemia is more related to life-threatening situations rather that particular cause.
===Common Causes===
===Common Causes===
Primary [[hyperparathyroidism]] is the most common cause of hypercalcemia. It is due to excess [[PTH]] release by the parathyroid glands. This excess occurs due to an enlargement of one or more of the parathyroid glands, or a growth (usually not cancer) on one of the glands.
Common causes of hypercalcemia include:<ref name="pmid23148166">{{cite journal| author=Carroll R, Matfin G| title=Endocrine and metabolic emergencies: hypercalcaemia. | journal=Ther Adv Endocrinol Metab | year= 2010 | volume= 1 | issue= 5 | pages= 225-34 | pmid=23148166 | doi=10.1177/2042018810390260 | pmc=3474617 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23148166  }} </ref>
*[[Hyperparathyroidism]]<ref name="pmid12412783">{{cite journal |vauthors=Peacock M |title=Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum |journal=J. Bone Miner. Res. |volume=17 Suppl 2 |issue= |pages=N87–94 |year=2002 |pmid=12412783 |doi= |url=}}</ref><ref name="pmid2763869">{{cite journal |vauthors=Silverberg SJ, Shane E, de la Cruz L, Dempster DW, Feldman F, Seldin D, Jacobs TP, Siris ES, Cafferty M, Parisien MV |title=Skeletal disease in primary hyperparathyroidism |journal=J. Bone Miner. Res. |volume=4 |issue=3 |pages=283–91 |year=1989 |pmid=2763869 |doi=10.1002/jbmr.5650040302 |url=}}</ref>
**Primary hyperparathyroidism
***Parathyroid adenoma<ref name="pmid20614300">{{cite journal |vauthors=Wieneke JA, Smith A |title=Parathyroid adenoma |journal=Head Neck Pathol |volume=2 |issue=4 |pages=305–8 |year=2008 |pmid=20614300 |pmc=2807581 |doi=10.1007/s12105-008-0088-8 |url=}}</ref>
***Parathyroid hyperplasia
***Parathyroid carcinoma
**Secondary hyperparathyroidism (long standing)<ref name="pmid15507543">{{cite journal| author=Rodriguez M, Nemeth E, Martin D| title=The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism. | journal=Am J Physiol Renal Physiol | year= 2005 | volume= 288 | issue= 2 | pages= F253-64 | pmid=15507543 | doi=10.1152/ajprenal.00302.2004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15507543  }} </ref>
**Tertiary hyperparathyroidism<ref name="pmid9780988">{{cite journal |vauthors=Kilgo MS, Pirsch JD, Warner TF, Starling JR |title=Tertiary hyperparathyroidism after renal transplantation: surgical strategy |journal=Surgery |volume=124 |issue=4 |pages=677–83; discussion 683–4 |year=1998 |pmid=9780988 |doi=10.1067/msy.1998.91483 |url=}}</ref>
**Neonatal severe hyperparathyroidism
*[[Hypercalcemia]] of [[malignancy]]<ref name="pmid26713296">{{cite journal |vauthors=Mirrakhimov AE |title=Hypercalcemia of Malignancy: An Update on Pathogenesis and Management |journal=N Am J Med Sci |volume=7 |issue=11 |pages=483–93 |year=2015 |pmid=26713296 |pmc=4683803 |doi=10.4103/1947-2714.170600 |url=}}</ref><ref name="pmid15673803">{{cite journal| author=Stewart AF| title=Clinical practice. Hypercalcemia associated with cancer. | journal=N Engl J Med | year= 2005 | volume= 352 | issue= 4 | pages= 373-9 | pmid=15673803 | doi=10.1056/NEJMcp042806 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15673803  }} </ref>
*[[Hyperthyroidism]]<ref name="pmid937877">{{cite journal| author=Burman KD, Monchik JM, Earll JM, Wartofsky L| title=Ionized and total serum calcium and parathyroid hormone in hyperthyroidism. | journal=Ann Intern Med | year= 1976 | volume= 84 | issue= 6 | pages= 668-71 | pmid=937877 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=937877  }} </ref><ref name="pmid14715479">{{cite journal| author=Iqbal AA, Burgess EH, Gallina DL, Nanes MS, Cook CB| title=Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis. | journal=Endocr Pract | year= 2003 | volume= 9 | issue= 6 | pages= 517-21 | pmid=14715479 | doi=10.4158/EP.9.6.517 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14715479  }} </ref>
*Hypervitaminosis D<ref name="pmid8120527">{{cite journal |vauthors=Hoeck HC, Laurberg G, Laurberg P |title=Hypercalcaemic crisis after excessive topical use of a vitamin D derivative |journal=J. Intern. Med. |volume=235 |issue=3 |pages=281–2 |year=1994 |pmid=8120527 |doi= |url=}}</ref><ref name="pmid1313547">{{cite journal |vauthors=Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GE, Seely EW |title=Hypervitaminosis D associated with drinking milk |journal=N. Engl. J. Med. |volume=326 |issue=18 |pages=1173–7 |year=1992 |pmid=1313547 |doi=10.1056/NEJM199204303261801 |url=}}</ref><ref name="pmid8620732">{{cite journal| author=Sharma OP| title=Vitamin D, calcium, and sarcoidosis. | journal=Chest | year= 1996 | volume= 109 | issue= 2 | pages= 535-9 | pmid=8620732 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8620732  }}</ref>
*Chronic kidney disease<ref name="pmid2239937">{{cite journal| author=Meric F, Yap P, Bia MJ| title=Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy. | journal=Am J Kidney Dis | year= 1990 | volume= 16 | issue= 5 | pages= 459-64 | pmid=2239937 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2239937  }} </ref>
*Milk-alkali syndrome
*[[Hypokalaemic distal renal tubular acidosis]]
*[[Sarcoidosis]]<ref name="pmid9215298">{{cite journal |vauthors=Dusso AS, Kamimura S, Gallieni M, Zhong M, Negrea L, Shapiro S, Slatopolsky E |title=gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=7 |pages=2222–32 |year=1997 |pmid=9215298 |doi=10.1210/jcem.82.7.4074 |url=}}</ref><ref name="pmid22412034">{{cite journal| author=Vanstone MB, Oberfield SE, Shader L, Ardeshirpour L, Carpenter TO| title=Hypercalcemia in children receiving pharmacologic doses of vitamin D. | journal=Pediatrics | year= 2012 | volume= 129 | issue= 4 | pages= e1060-3 | pmid=22412034 | doi=10.1542/peds.2011-1663 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22412034  }}</ref>
*Post renal transplantation


Other common causes include:
=== Less Common Cause ===
* [[Drugs]]
Less common causes of hypercalcemia include:<ref name="pmid23148166">{{cite journal| author=Carroll R, Matfin G| title=Endocrine and metabolic emergencies: hypercalcaemia. | journal=Ther Adv Endocrinol Metab | year= 2010 | volume= 1 | issue= 5 | pages= 225-34 | pmid=23148166 | doi=10.1177/2042018810390260 | pmc=3474617 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23148166  }} </ref>
* Exogenous [[vitamin D]]
* Humoral hypercalcemia of [[malignancy]]
* Immobilization
* Immobilization
* Primary [[hyperparathyroidism]]
* Pagets disease of bone
* [[Sarcoidosis]]
* Hypervitaminosis A
* Secondary [[hyperparathyroidism]]
* Pheochromocytoma
* Adrenal insufficiency
* Rhabdomyolysis
* Acute renal failure
* Familial hypocalciuric hypercalcemia<ref name="pmid26963950">{{cite journal| author=Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C et al.| title=Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 5 | pages= 2185-95 | pmid=26963950 | doi=10.1210/jc.2015-3442 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26963950  }}</ref>
* Methphysial chondrodysplasia
* Conenital lactase deficienccy
*Idiopathic infantile hypercalcemia (Williams syndrome)
*Mutations of the calcium-sensing receptor
*Subcutaneous fat necrosis
*Blue diaper syndrome
*[[Hypophosphataemia]]
*[[Hypophosphatasia ]]
*Dietary phosphate deficiency
*Medication-induced
**[[Lithium]]<ref name="pmid2918061">{{cite journal |vauthors=Mallette LE, Khouri K, Zengotita H, Hollis BW, Malini S |title=Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume |journal=J. Clin. Endocrinol. Metab. |volume=68 |issue=3 |pages=654–60 |year=1989 |pmid=2918061 |doi=10.1210/jcem-68-3-654 |url=}}</ref>
**[[Thiazide]]<ref name="pmid26751196">{{cite journal| author=Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ et al.| title=Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 3 | pages= 1166-73 | pmid=26751196 | doi=10.1210/jc.2015-3964 | pmc=4803175 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26751196  }}</ref>
**Theophylline toxicity
**[[Teriparatide]]
** Estrogen
** [[Cidofovir]]
**[[Danazol]]
**[[Dexlansoprazole]]
**[[Fluoxymesterone]]
**[[Gestrinone]]
**[[Nandrolone]]
**[[Paricalcitol]]
** [[Tamoxifen]]
** [[Toremifene]]


===Causes by Organ System===
===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
{| style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
| style="width:75%" bgcolor="Beige" ; border="1" | [[Beuren-Williams syndrome]], [[Vasoactive intestinal polypeptide-producing tumor]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Aluminum]] intoxication, [[Hypervitaminosis D]], [[Vitamin A]] intoxication, [[Vitamin D]] intoxication
| bgcolor="Beige" | Aluminium antacid overuse, Aluminum intoxication, [[Calcium acetate]], [[Caspofungin acetate]], [[Cefepime]], [[Chlortalidone]], [[Theophylline|Theophylline toxicity]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| '''Dermatologic'''
|bgcolor="Beige"| [[Leprosy]]
| bgcolor="Beige" | [[Leprosy]], Subcutaneous fat necrosis of newborn
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| '''Drug Side Effect'''
|bgcolor="Beige"| [[Calcium acetate]], [[caspofungin acetate]], [[Cefepime]], [[Cidofovir]], [[Dexlansoprazole]], [[Fluoxymesterone]],  
| bgcolor="Beige" | [[Cidofovir]], [[Danazol]], [[Dexlansoprazole]], [[Diuretics]], [[Fluoxymesterone]], [[Gestrinone]], [[Lithium]], [[Nandrolone]], [[Paricalcitol]], [[Tamoxifen]], [[Teriparatide]], [[Thiazide]], [[Toremifene]]
[[Lithium]], [[Nandrolone]], [[Tamoxifen]], [[Thiazide]] [[diuretic]]s, [[Toremifene]],
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| '''Ear Nose Throat'''
|bgcolor="Beige"| [[Oral candidiasis]]
| bgcolor="Beige" | [[Oral candidiasis]],  [[Sjogren's syndrome]]
|-  
|-  
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| '''Endocrine'''
|bgcolor="Beige"| Abnormal [[parathyroid gland]] function, [[Acromegaly]], [[Osteoporosis|Acute osteoporosis]], [[Addison's Disease]], [[Adrenal insufficiency]], Autonomous [[hyperparathyroidism]] (post long-term [[renal failure]]), [[Bartter's Syndrome]], [[Cushing's syndrome]], Familial isolated [[hyperparathyroidism]], [[Hyperparathyroidism]] (in the preceding oliguric-anuric phase), [[Hyperthyroidism]], Isolated or multinodal [[adenoma]], [[Multiple endocrine neoplasia]] (MEN), Parathyroid [[carcinoma]], [[Parathyroid]] hyperplasia, [[Pheochromocytoma]], [[Primary hyperparathyroidism]], Primary Parathyroid [[hyperplasia]], Secretion of [[prostaglandin]]s, Severe [[secondary hyperparathyroidism]], Solitary parathyroid [[adenoma]], [[Vasoactive intestinal polypeptide-producing tumor]] ([[VIPoma]])
| bgcolor="Beige" | Abnormal parathyroid gland function, [[Acromegaly]], [[Addison's disease]], [[Adenoma]], [[Adrenal cortex insufficiency]], [[Adrenal insufficiency]], [[Adult T-cell leukemia]], [[Bartter's syndrome]], [[Cushing's syndrome]], [[Familial hypocalciuric hypercalcemia]], [[Hyperparathyroidism|Familial isolated hyperparathyroidism]], [[Growth hormone secreting pituitary adenoma|Growth hormone-secreting pituitary adenoma]], Hypercalcemia of malignancy, [[Hyperparathyroidism]] , [[Hyperthyroidism]], [[Multiple endocrine neoplasia]], [[Hyperparathyroidism|Neonatal severe primary hyperparathyroidism]], [[Paget's disease of bone]], [[Parathyroid adenoma]], [[Parathyroid cancer|Parathyroid carcinoma]], Parathyroid hormone-related peptide, Parathyroid hyperplasia, [[Pituitary tumor|Pituitary tumour]], Tryptophan malabsorption syndrome
|-  
|-  
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| '''Environmental'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Hepatocellular carcinoma]], [[Hypervitaminosis D]], [[Oral candidiasis]], [[Total parenteral nutrition]]
| bgcolor="Beige" | [[Hepatocellular carcinoma]], [[Vipoma]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| '''Genetic'''
|bgcolor="Beige"| Familial hypocalcuric hypercalcemia, Familial isolated [[hyperparathyroidism]], [[Gitelman syndrome]], [[William's syndrome]]
| bgcolor="Beige" | Activation of extra-renal 1 alpha-hydroxylase, [[Beuren-Williams syndrome]], [[Familial isolated hyperparathyroidism]],  Metaphyseal chondrodysplasia, Phosphoethanolaminuria, Pseudophosphatasia, [[William's syndrome]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| '''Hematologic'''
|bgcolor="Beige"|[[Hodgkin's lymphoma]], [[Leukemia]], [[Lymphoma]], [[Multiple myeloma]], [[Plasma cell]] [[granuloma]], [[Polycythemia]]
| bgcolor="Beige" | [[Acute adult T-cell leukemia]], [[Adult T-cell leukemia]], [[Chronic adult T-cell leukemia]], Cuffed blood sample, [[Cushing's syndrome]], [[Familial hypocalciuric hypercalcemia]], [[Hematologic malignancy]], [[Hodgkin's lymphoma]], [[Hypervitaminosis A]], [[Hypervitaminosis D]], [[Hypokalaemic distal renal tubular acidosis]], [[Hypophosphataemia]], [[Hypophosphatasia]], [[Leukemia]], [[Lymphoma]], [[Multiple myeloma]], Plasma cell granuloma, [[Polycythemia]], Pseudophosphatasia, [[Adult T-cell leukemia|Smoldering adult T-cell leukemia]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Kidney transplant]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| '''Infectious Disease'''
|bgcolor="Beige"| [[Coccidioidomycosis]], [[Leprosy]], [[Oral candidiasis]]
| bgcolor="Beige" | [[Coccidioidomycosis]], [[Histoplasmosis]], [[Oral candidiasis]], [[Tuberculosis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[Osteoporosis|Acute osteoporosis]], Bone [[fracture]], [[Paget's Disease]], Rebound hypercalcemia after [[rhabdomyolysis]]
| bgcolor="Beige" | [[Bone cancer]], [[Bone fracture]], Immobilization, Osteolytic bone metastases and local cytokines, [[Osteomalacia]], [[Osteoporosis]], [[Paget's disease of bone]], [[Paraplegia]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Adrenal cortex insufficiency]], [[Brown-Sequard syndrome]] 
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Dehydration]], [[Milk-alkali syndrome]], [[Osteomalacia]], [[Total parenteral nutrition]], [[Vitamin A]] intoxication, [[Vitamin D]] intoxication, [[Vitamin D]] [[metabolic disorders]]
| bgcolor="Beige" | [[Milk-alkali syndrome]], [[Parenteral nutrition]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| [[Breast cancer]], [[Ovarian cancer]], [[Paget's Disease]]
| bgcolor="Beige" | [[Breast cancer]], [[Ovarian cancer]], Subcutaneous fat necrosis of newborn
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| '''Oncologic'''
|bgcolor="Beige"| [[Breast cancer]], [[Bronchial carcinoma]], [[Carcinoma]], [[Hematologic]] [[malignancy]] ([[multiple myeloma]], [[lymphoma]], [[leukemia]]), [[Hepatocellular carcinoma]], [[Hodgkin's lymphoma]], Isolated or multinodal [[adenoma]], [[Kidney cancer]], [[Leukemia]], [[Lymphoma]], [[Malignancy]], [[Multiple endocrine neoplasia]] (MEN), [[Multiple Myeloma]], [[Ovarian cancer]], [[Paget's Disease]], Parathyroid [[carcinoma]], [[Pheochromocytoma]], [[Plasma cell]] [[granuloma]], [[Silicone]]-Induced [[granuloma]], Solid tumor with humoral mediation of hypercalcemia (e.g. [[lung cancer|lung]] or [[renal cell carcinoma|kidney cancer]], [[pheochromocytoma]]), Solid tumor with metastasis (e.g. [[breast cancer]]), Solitary parathyroid [[adenoma]], [[Vasoactive intestinal polypeptide-producing tumor]] ([[VIPoma]])
| bgcolor="Beige" | [[Acute adult T-cell leukemia]], [[Adenoma]], [[Adult T-cell leukemia]], [[Adult T-cell leukemia|Adult T-cell lymphoma]], [[Bone cancer]], [[Breast cancer]], [[Bronchial carcinoma]], [[Chronic adult T-cell leukemia]], [[Growth hormone secreting pituitary adenoma]], [[Hematologic malignancy]], [[Hepatocellular carcinoma]], [[Hodgkin's lymphoma]], Hypercalcemia of malignancy, [[Renal cancer]], [[Lymphoma]], [[Metastatic neoplasm]], [[Multiple endocrine neoplasia]], [[Multiple myeloma]], Osteolytic bone metastases and local cytokines, [[Osteomalacia]], [[Ovarian cancer]], [[Paraneoplastic syndrome]], [[Parathyroid adenoma]], [[Parathyroid carcinoma]], Parathyroid hyperplasia,  [[Pheochromocytoma]], [[Pituitary tumor|Pituitary tumour]], Plasma cell granuloma, Silicone-induced granuloma, [[Adult T-cell leukemia|Smoldering adult T-cell leukemia]], [[Vasoactive intestinal polypeptide-producing tumor]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| '''Ophthalmologic'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
| '''Overdose / Toxicity'''
|bgcolor="Beige"| , [[Aluminum]] intoxication, [[Aspirin]] (in large amounts), [[Drugs]], [[Hypervitaminosis D]], [[Vitamin A]] intoxication, [[Vitamin D]] intoxication
| bgcolor="Beige" | [[Aluminum]] intoxication, [[Aspirin]] (in large amounts), [[Drugs]], [[Hypervitaminosis A]], [[Hypervitaminosis D]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| '''Pulmonary'''
|bgcolor="Beige"| [[Berylliosis]], [[Bronchial carcinoma]], Granulomatous diseases with [[tuberculosis]], [[Histoplasmosis]], [[Sarcoidosis]], [[Tuberculosis]], [[Tuberculosis]]
| bgcolor="Beige" | [[Berylliosis]], [[Bronchial carcinoma]], [[Coccidioidomycosis]], [[Histoplasmosis]], [[Sarcoidosis]], [[Tuberculosis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
| '''Renal / Electrolyte'''
|bgcolor="Beige"| [[Acute renal failure]], After [[kidney transplant]], [[Bartter's Syndrome]], [[Chronic renal failure]], Familial hypocalcuric hypercalcemia, [[Kidney cancer]], [[Medullary sponge kidney]], [[Milk-alkali syndrome]], Rebound hypercalcemia after [[rhabdomyolysis]], [[Renal failure]]
| bgcolor="Beige" | [[Acute renal failure]], [[Bartter's syndrome]], [[Gitelman syndrome]], [[Hypokalaemic distal renal tubular acidosis]], [[Hypophosphataemia]], [[Hypophosphatasia]], [[Renal cancer]], [[Kidney transplant]], [[Milk-alkali syndrome]], [[Renal failure]], [[Rhabdomyolysis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| [[Osteoporosis|Acute osteoporosis]], [[Sarcoidosis]], [[Sjogren's syndrome]]
| bgcolor="Beige" | Chronic granulomatous disorders, [[Sarcoidosis]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | No underlying causes
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
| bgcolor="Beige" | [[Bone fracture]], [[Dehydration]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| '''Urologic'''
|bgcolor="Beige"| [[Acute renal failure]], [[Chronic renal failure]], [[Milk-alkali syndrome]], [[Renal failure]]
| bgcolor="Beige" | [[Acute renal failure]], [[Chronic renal failure]], [[Milk-alkali syndrome]], [[Renal failure]]
|-
|-
|-bgcolor="LightSteelBlue"
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| '''Miscellaneous'''
|bgcolor="Beige"| [[Idiopathic]] hypercalcemia (in infants), Immobilization, [[Paraplegia]]
| bgcolor="Beige" | [[Idiopathic]] hypercalcemia (in infants), Immobilization, [[Paraplegia]]
|-
|-
|}
|}


[[Category:Needs content]]
===Causes in Alphabetical Order===
<div style="-moz-column-count:3; column-count:3;">
*Abnormal parathyroid gland function
*[[Acromegaly]]
*Activation of extra-renal 1 alpha-hydroxylase
*[[Acute adult T-cell leukemia]]
*[[Acute renal failure]]
*[[Addison's disease]]
*[[Adenoma]]
*[[Adrenal cortex insufficiency]]
*[[Adult T-cell leukemia]]
*Aluminium antacid overuse
*[[Aluminum]] intoxication
*[[Aspirin]] (in large amounts)
*[[Bartter's syndrome]]
*[[Berylliosis]]
*[[Beuren-Williams syndrome]]
*[[Blue diaper syndrome]]
*[[Bone cancer]]
*[[Bone fracture]]
*[[Breast cancer]]
*[[Bronchial carcinoma]]
*[[Brown-Sequard syndrome]] 
*[[Calcium acetate]]
*[[Caspofungin acetate]]
*[[Cefepime]]
*[[Chlortalidone]]
*[[Chronic adult T-cell leukemia]]
*Chronic granulomatous disorders
*[[Chronic kidney disease]]
*[[Chronic renal failure]]
*[[Cidofovir]]
*[[Coccidioidomycosis]]
*Conenital lactase deficiency
*Cuffed blood sample
*[[Cushing's syndrome]]
*[[Danazol]]
*[[Dehydration]]
*[[Dexlansoprazole]]
*Dietary phosphate deficiency
*[[Diuretics]]
*[[Estrogen]]
*[[Excessive vitamin a]]
*[[Familial hypocalciuric hypercalcemia]]
*Familial isolated hyperparathyroidism
*[[Fluoxymesterone]]
*[[Gestrinone]]
*[[Gitelman syndrome]]
*[[Growth hormone secreting pituitary adenoma]]
*[[Hematologic malignancy]]
*[[Hepatocellular carcinoma]]
*[[Histoplasmosis]]
*[[Hodgkin's lymphoma]]
*[[Hypercalcemia]] of [[malignancy]]
*[[Hyperparathyroidism ]]
*[[Hyperparathyroidism|Familial isolated hyperparathyroidism]]
*[[Hyperparathyroidism|Neonatal severe primary hyperparathyroidism]]
*[[Hyperthyroidism]]
*[[Hypervitaminosis A]]
*[[Hypervitaminosis D]]
*[[Hypokalaemic distal renal tubular acidosis]]
*[[Hypoparathyroidism]]
*[[Hypophosphataemia]]
*[[Hypophosphatasia]]
*Idiopathic infantile hypercalcemia (Williams syndrome)
*[[Idiopathic]] hypercalcemia (in infants)
*[[Immobilization]]
*[[Infantile hypophosphatasia ]]
*[[Inherited variants]]
*[[Jansen type metaphyseal chondrodysplasia ]]
*[[Kidney cancer]]
*[[Kidney transplant]]
*[[Leprosy]]
*[[Leukemia]]
*[[Lithium]]
*[[Lymphoma]]
*[[Metaphyseal chondrodysplasia]]
*[[Metastatic neoplasm]]
*[[Milk-alkali syndrome]]
*[[Multiple endocrine neoplasia]]
*[[Multiple myeloma]]
*Mutations of the calcium-sensing receptor
*[[Mycobacterium tuberculosis]]
*[[Nandrolone]]
*Neonatal severe hyperparathyroidism
*Neonatal severe primary hyperparathyroidism
*[[Oral candidiasis]]
*Osteolytic bone metastases and local cytokines
*[[Osteomalacia]]
*[[Osteoporosis]]
*[[Ovarian cancer]]
*[[Paget's disease of bone]]
*[[Paget's disease]]
*[[Paraneoplastic syndrome]]
*[[Paraplegia]]
*[[Parathyroid adenoma]]
*[[Parathyroid cancer|Parathyroid carcinoma]]
*Parathyroid hormone related peptide
*[[Parenteral nutrition]]
*[[Paricalcitol]]
*[[Pheochromocytoma]]
*Phosphoethanolaminuria
*[[Pituitary tumour ]]
*[[Plasma cell granuloma]]
*[[Polycythemia]]
*Post [[renal transplantation]]
*[[Primary hyperparathyroidism]]
*[[Pseudophosphatasia ]]
*[[Renal cancer]]
*[[Renal failure]]
*[[Rhabdomyolysis]]
*[[Sarcoidosis]]
*[[Secondary hyperparathyroidism]] (long standing)
*[[Silicone-induced granuloma]]
*[[Sjogren's syndrome]]
*[[Smoldering adult t-cell leukemia |Smoldering adult T-cell leukemia]]
*Subcutaneous fat necrosis of newborn
*Subcutaneous fat necrosis
*[[Tamoxifen]]
*[[Teriparatide]]
*Tertiary hyperparathyroidism
*[[Theophylline|Theophylline toxicity]]
*[[Thiazide]]
*[[Toremifene]]
*Tryptophan malabsorption syndrome
*[[Tuberculosis]]
*[[Vasoactive intestinal polypeptide-producing tumor]]
*[[Vipoma]]
*[[William's syndrome]]
</div>
 
==References==
{{reflist|2}}
 
[[Category:Endocrinology]]
 
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Latest revision as of 20:26, 5 July 2018

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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], Luke Rusowicz-Orazem, B.S.

Overview

Hypercalcemia is most commonly caused by hyperparathyroidism and malignancy. Other causes of hypercalcemia include hyperthyroidism, vitamin D toxicity, increased calcium intake, granulomatous diseases ( such sarcoidosis), and various renal disorders.

Causes

Life-Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Severity of hypercalcemia is more related to life-threatening situations rather that particular cause.

Common Causes

Common causes of hypercalcemia include:[1]

Less Common Cause

Less common causes of hypercalcemia include:[1]

Causes by Organ System

Cardiovascular Beuren-Williams syndrome, Vasoactive intestinal polypeptide-producing tumor
Chemical / poisoning Aluminium antacid overuse, Aluminum intoxication, Calcium acetate, Caspofungin acetate, Cefepime, Chlortalidone, Theophylline toxicity
Dermatologic Leprosy, Subcutaneous fat necrosis of newborn
Drug Side Effect Cidofovir, Danazol, Dexlansoprazole, Diuretics, Fluoxymesterone, Gestrinone, Lithium, Nandrolone, Paricalcitol, Tamoxifen, Teriparatide, Thiazide, Toremifene
Ear Nose Throat Oral candidiasis, Sjogren's syndrome
Endocrine Abnormal parathyroid gland function, Acromegaly, Addison's disease, Adenoma, Adrenal cortex insufficiency, Adrenal insufficiency, Adult T-cell leukemia, Bartter's syndrome, Cushing's syndrome, Familial hypocalciuric hypercalcemia, Familial isolated hyperparathyroidism, Growth hormone-secreting pituitary adenoma, Hypercalcemia of malignancy, Hyperparathyroidism , Hyperthyroidism, Multiple endocrine neoplasia, Neonatal severe primary hyperparathyroidism, Paget's disease of bone, Parathyroid adenoma, Parathyroid carcinoma, Parathyroid hormone-related peptide, Parathyroid hyperplasia, Pituitary tumour, Tryptophan malabsorption syndrome
Environmental No underlying causes
Gastroenterologic Hepatocellular carcinoma, Vipoma
Genetic Activation of extra-renal 1 alpha-hydroxylase, Beuren-Williams syndrome, Familial isolated hyperparathyroidism, Metaphyseal chondrodysplasia, Phosphoethanolaminuria, Pseudophosphatasia, William's syndrome
Hematologic Acute adult T-cell leukemia, Adult T-cell leukemia, Chronic adult T-cell leukemia, Cuffed blood sample, Cushing's syndrome, Familial hypocalciuric hypercalcemia, Hematologic malignancy, Hodgkin's lymphoma, Hypervitaminosis A, Hypervitaminosis D, Hypokalaemic distal renal tubular acidosis, Hypophosphataemia, Hypophosphatasia, Leukemia, Lymphoma, Multiple myeloma, Plasma cell granuloma, Polycythemia, Pseudophosphatasia, Smoldering adult T-cell leukemia
Iatrogenic Kidney transplant
Infectious Disease Coccidioidomycosis, Histoplasmosis, Oral candidiasis, Tuberculosis
Musculoskeletal / Ortho Bone cancer, Bone fracture, Immobilization, Osteolytic bone metastases and local cytokines, Osteomalacia, Osteoporosis, Paget's disease of bone, Paraplegia
Neurologic Adrenal cortex insufficiency, Brown-Sequard syndrome 
Nutritional / Metabolic Milk-alkali syndrome, Parenteral nutrition
Obstetric/Gynecologic Breast cancer, Ovarian cancer, Subcutaneous fat necrosis of newborn
Oncologic Acute adult T-cell leukemia, Adenoma, Adult T-cell leukemia, Adult T-cell lymphoma, Bone cancer, Breast cancer, Bronchial carcinoma, Chronic adult T-cell leukemia, Growth hormone secreting pituitary adenoma, Hematologic malignancy, Hepatocellular carcinoma, Hodgkin's lymphoma, Hypercalcemia of malignancy, Renal cancer, Lymphoma, Metastatic neoplasm, Multiple endocrine neoplasia, Multiple myeloma, Osteolytic bone metastases and local cytokines, Osteomalacia, Ovarian cancer, Paraneoplastic syndrome, Parathyroid adenoma, Parathyroid carcinoma, Parathyroid hyperplasia, Pheochromocytoma, Pituitary tumour, Plasma cell granuloma, Silicone-induced granuloma, Smoldering adult T-cell leukemia, Vasoactive intestinal polypeptide-producing tumor
Ophthalmologic No underlying causes
Overdose / Toxicity Aluminum intoxication, Aspirin (in large amounts), Drugs, Hypervitaminosis A, Hypervitaminosis D
Psychiatric No underlying causes
Pulmonary Berylliosis, Bronchial carcinoma, Coccidioidomycosis, Histoplasmosis, Sarcoidosis, Tuberculosis
Renal / Electrolyte Acute renal failure, Bartter's syndrome, Gitelman syndrome, Hypokalaemic distal renal tubular acidosis, Hypophosphataemia, Hypophosphatasia, Renal cancer, Kidney transplant, Milk-alkali syndrome, Renal failure, Rhabdomyolysis
Rheum / Immune / Allergy Chronic granulomatous disorders, Sarcoidosis
Sexual No underlying causes
Trauma Bone fracture, Dehydration
Urologic Acute renal failure, Chronic renal failure, Milk-alkali syndrome, Renal failure
Miscellaneous Idiopathic hypercalcemia (in infants), Immobilization, Paraplegia

Causes in Alphabetical Order

References

  1. ↑ 1.0 1.1 Carroll R, Matfin G (2010). "Endocrine and metabolic emergencies: hypercalcaemia". Ther Adv Endocrinol Metab. 1 (5): 225–34. doi:10.1177/2042018810390260. PMC 3474617. PMID 23148166.
  2. ↑ Peacock M (2002). "Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum". J. Bone Miner. Res. 17 Suppl 2: N87–94. PMID 12412783.
  3. ↑ Silverberg SJ, Shane E, de la Cruz L, Dempster DW, Feldman F, Seldin D, Jacobs TP, Siris ES, Cafferty M, Parisien MV (1989). "Skeletal disease in primary hyperparathyroidism". J. Bone Miner. Res. 4 (3): 283–91. doi:10.1002/jbmr.5650040302. PMID 2763869.
  4. ↑ Wieneke JA, Smith A (2008). "Parathyroid adenoma". Head Neck Pathol. 2 (4): 305–8. doi:10.1007/s12105-008-0088-8. PMC 2807581. PMID 20614300.
  5. ↑ Rodriguez M, Nemeth E, Martin D (2005). "The calcium-sensing receptor: a key factor in the pathogenesis of secondary hyperparathyroidism". Am J Physiol Renal Physiol. 288 (2): F253–64. doi:10.1152/ajprenal.00302.2004. PMID 15507543.
  6. ↑ Kilgo MS, Pirsch JD, Warner TF, Starling JR (1998). "Tertiary hyperparathyroidism after renal transplantation: surgical strategy". Surgery. 124 (4): 677–83, discussion 683–4. doi:10.1067/msy.1998.91483. PMID 9780988.
  7. ↑ 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.
  8. ↑ Stewart AF (2005). "Clinical practice. Hypercalcemia associated with cancer". N Engl J Med. 352 (4): 373–9. doi:10.1056/NEJMcp042806. PMID 15673803.
  9. ↑ Burman KD, Monchik JM, Earll JM, Wartofsky L (1976). "Ionized and total serum calcium and parathyroid hormone in hyperthyroidism". Ann Intern Med. 84 (6): 668–71. PMID 937877.
  10. ↑ Iqbal AA, Burgess EH, Gallina DL, Nanes MS, Cook CB (2003). "Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis". Endocr Pract. 9 (6): 517–21. doi:10.4158/EP.9.6.517. PMID 14715479.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Sharma OP (1996). "Vitamin D, calcium, and sarcoidosis". Chest. 109 (2): 535–9. PMID 8620732.
  14. ↑ Meric F, Yap P, Bia MJ (1990). "Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy". Am J Kidney Dis. 16 (5): 459–64. PMID 2239937.
  15. ↑ 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.
  16. ↑ Vanstone MB, Oberfield SE, Shader L, Ardeshirpour L, Carpenter TO (2012). "Hypercalcemia in children receiving pharmacologic doses of vitamin D." Pediatrics. 129 (4): e1060–3. doi:10.1542/peds.2011-1663. PMID 22412034.
  17. ↑ Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C; et al. (2016). "Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences". J Clin Endocrinol Metab. 101 (5): 2185–95. doi:10.1210/jc.2015-3442. PMID 26963950.
  18. ↑ 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.
  19. ↑ 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.

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