Hypercalcemia causes

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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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