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 hyperparathyroisism 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

Hyperparathyroidism^[1]^[2]
- Primary hyperparathyroidism
  - Parathyroid adenoma^[3]
  - Parathyroid hyperplasia
  - Parathyroid carcinoma
- Secondary hyperparathyroidism (long standing)^[4]
- Tertiary hyperparathyroidism^[5]
- Neonatal severe hyperparathyroidism
Hypercalcemia of malignancy^[6]^[7]
Hyperthyroidism
Hypervitaminosis D^[8]^[9]
Increased calcium intake
Chronic kidney disease
Milk-alkali syndrome
Hypokalaemic distal renal tubular acidosis
Sarcoidosis^[10]
Post renal transplantation

Less Common Cause

Immobilization
Pagets disease of bone
Hypervitaminosis A
Lithium^[11]
Pheochromocytoma
Adrenal insufficiency
Rhabdomyolysis
Acute renal failure
Theophylline toxicity
Familial hypocalciuric hypercalcemia
Methphysial chondrodysplasia
Conenital lactase deficienccy
Teriparatide
Thiazide
Estrogen
Idiopathic infantile hypercalcemia (Williams syndrome)
Mutations of the calcium-sensing receptor
Subcutaneous fat necrosis
Cidofovir
Danazol
Dexlansoprazole
Blue diaper syndrome
Fluoxymesterone
Gestrinone
Hypophosphataemia
Hypophosphatasia
Nandrolone
Paricalcitol
Tamoxifen
Toremifene
Dietary phosphate deficiency

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 lymphoma , Bartter's syndrome, Cushing's syndrome, Familial hypocalcuric hypercalcemia, Familial isolated hyperparathyroidism, Growth hormone secreting pituitary adenoma, Hypercalcemia of malignancy, Hyperparathyroidism , Hyperthyroidism, Hypoparathyroidism, Multiple endocrine neoplasia, Neonatal severe primary hyperparathyroidism, Non-parathyroid mediated, Paget's disease of bone, Parathyroid carcinoma, Parathyroid hormone related peptide, Parathyroid hyperplasia, Parathyroid mediated, Pituitary tumour , Pthrp, Tryptophan malabsorption syndrome
Environmental	No underlying causes
Gastroenterologic	Hepatocellular carcinoma, Vipoma
Genetic	Activation of extrarenal 1 alpha-hydroxylase , Beuren-williams syndrome, Familial isolated hyperparathyroidism, Inherited variants, 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 hypocalcuric 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 , Pthrp, Smoldering adult t-cell leukemia
Iatrogenic	Kidney transplant
Infectious Disease	Coccidioidomycosis, Histoplasmosis, Mycobacterium tuberculosis, 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, Kidney cancer, Lymphoma, Metastatic neoplasm, Multiple endocrine neoplasia, Multiple myeloma, Osteolytic bone metastases and local cytokines, Osteomalacia, Ovarian cancer, Paraneoplastic syndrome, 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 D, Vitamin A intoxication, Vitamin D intoxication
Psychiatric	No underlying causes
Pulmonary	Berylliosis, Bronchial carcinoma, Coccidioidomycosis, Histoplasmosis, Mycobacterium tuberculosis, Sarcoidosis, Tuberculosis
Renal / Electrolyte	Acute renal failure, Bartter's syndrome, Gitelman syndrome, Hypokalaemic distal renal tubular acidosis, Hypophosphataemia, Hypophosphatasia , Kidney cancer, Kidney transplant, Milk-alkali syndrome, Renal failure, Rhabdomyolysis
Rheum / Immune / Allergy	Chronic granulomatous disorders
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

3

References

↑ Peacock M (2002). "Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum". J. Bone Miner. Res. 17 Suppl 2: N87–94. PMID 12412783.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Template:WS Template:WH

[pmid12412783-1] Peacock M (2002). "Primary hyperparathyroidism and the kidney: biochemical and clinical spectrum". J. Bone Miner. Res. 17 Suppl 2: N87–94. PMID 12412783.

[pmid2763869-2] 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.

[pmid20614300-3] 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.

[pmid15507543-4] 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.

[pmid9780988-5] 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.

[pmid26713296-6] 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.

[pmid15673803-7] Stewart AF (2005). "Clinical practice. Hypercalcemia associated with cancer". N Engl J Med. 352 (4): 373–9. doi:10.1056/NEJMcp042806. PMID 15673803.

[pmid8120527-8] 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.

[pmid1313547-9] 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.

[pmid9215298-10] 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.

[pmid2918061-11] 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.

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