History

The mnemonic "stones, bones, abdominal moans, and psychic groans" describes the constellation of symptoms and signs of hypercalcemia. These may be due directly to the hypercalcemia, to increased calcium and phosphate excretion, or to skeletal changes.

The presentation in a patient with hypercalcemia varies with how fast and how far the calcium level rises, as well as the sensitivity of the individual to elevated calcium levels. Mild prolonged hypercalcemia may produce mild or no symptoms, or recurring problems such as kidney stones. Sudden-onset and severe hypercalcemia may cause dramatic symptoms, usually including confusion and lethargy, possibly leading quickly to death.

Central nervous system effects include the following:

Lethargy
Weakness
Confusion
Coma

Renal effects include the following:

Polyuria
Nocturia
Dehydration
Renal stones
Renal failure

Gastrointestinal effects include the following:

Constipation
Nausea
Anorexia
Pancreatitis
Gastric ulcer

Cardiac effects include syncope from arrhythmias.

Physical Examination

Most patients with hypercalcemia do not have any specific findings on physical examination. Those with higher calcium levels may have findings that are more striking. Evidence of the underlying cause may be found, such as a suggestive breast mass in someone with hypercalcemia secondary to malignancy.

Nervous system findings include the following:

Confusion
Hypotonia
Hyporeflexia
Paresis
Coma

Renal findings include the following:

Volume depletion
Signs of renal failure

Gastrointestinal findings include the following:

Fecal impaction (from constipation)
Signs of pancreatitis
Signs of malignancy (eg, enlarged liver or masses)

Cardiovascular findings include the following:

Arrhythmias
Hypotension

Ophthalmic findings may include band keratopathy, which is calcium precipitation in a horizontal band across the cornea in the palpebral aperture.

Differential Diagnoses

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Hoenderop JG, Nilius B, Bindels RJ. Molecular mechanism of active Ca2+ reabsorption in the distal nephron. Annu Rev Physiol. 2002. 64:529-49. [QxMD MEDLINE Link].
McKay CP, Portale A. Emerging topics in pediatric bone and mineral disorders 2008. Semin Nephrol. 2009 Jul. 29(4):370-8. [QxMD MEDLINE Link].
Guarnieri V, Canaff L, Yun FH, et al. Calcium-Sensing Receptor (CASR) Mutations in Hypercalcemic States: Studies from a Single Endocrine Clinic Over Three Years. J Clin Endocrinol Metab. 2010 Feb 17. [QxMD MEDLINE Link].
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Haridas K, Holick MF, Burmeister LA. Hypercalcemia, nephrolithiasis, and hypervitaminosis D precipitated by supplementation in a susceptible individual. Nutrition. 2020 Jun. 74:110754. [QxMD MEDLINE Link].
Griebeler ML, Kearns AE, Ryu E, Thapa P, Hathcock MA, Melton LJ 3rd, et al. Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades. J Clin Endocrinol Metab. 2016 Mar. 101 (3):1166-73. [QxMD MEDLINE Link].
Vargas-Poussou R, Mansour-Hendili L, Baron S, et al. Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences. J Clin Endocrinol Metab. 2016 May. 101 (5):2185-95. [QxMD MEDLINE Link].
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Gastanaga VM, Schwartzberg LS, Jain RK, Pirolli M, Quach D, Quigley JM, et al. Prevalence of hypercalcemia among cancer patients in the United States. Cancer Med. 2016 Jun 5. [QxMD MEDLINE Link].
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Schutt RC, Bibawy J, Elnemr M, Lehnert AL, Putney D, Thomas AS, et al. Case report: Severe hypercalcemia mimicking ST-segment elevation myocardial infarction. Methodist Debakey Cardiovasc J. 2014 Jul-Sep. 10 (3):193-7. [QxMD MEDLINE Link]. [Full Text].
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Media Gallery

Investigations flowchart.
Vitamin D metabolism.

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Author

Mahendra Agraharkar, MD, MBBS, FACP, FASN Clinical Associate Professor of Medicine, Baylor College of Medicine; President and CEO, Space City Associates of Nephrology

Mahendra Agraharkar, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

O David Dellinger, III, MD Assistant Professor, Departments of Family Medicine and Internal Medicine, University of Alabama School of Medicine at Birmingham

O David Dellinger, III, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians-American Society of Internal Medicine, American Geriatrics Society, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Addiction Medicine

Disclosure: Nothing to disclose.

Arun Kumar Gangakhedkar, MD, FRACP Consultant in General Pediatrics, Starship Children's Hospital/Waitakere Hospital, New Zealand

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Hypercalcemia Clinical Presentation

History

Physical Examination

References

Tables

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