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Hypercalcemia Workup

  • Author: Mahendra Agraharkar, MD, MBBS, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Aug 02, 2016

Approach Considerations

Malignancy is one of the most common causes and must be excluded. Hyperparathyroidism and other causes of hypercalcemia can coexist with malignancy. If calcium levels have been mildly elevated for months or years, malignancy is an unlikely cause.

Hypercalcemia from malignancy usually is rapidly progressive; thus, rapidly rising calcium levels should increase suspicion of malignancy. If calcium levels have been elevated for an unknown duration, the patient should be evaluated for the presence of malignancy. Breast, lung, and kidney cancers should be considered, as should multiple myeloma, lymphoma, and leukemia. Testing in such cases might include a peripheral blood smear and/or serum and urine immunofixation electrophoresis. Biopsy samples may be taken from a solid tumor or from bone marrow for tissue histology studies.

Hyperparathyroidism is the most common cause of hypercalcemia in the population at large and usually is mild, asymptomatic, and sustained for years. Immunoreactive parathyroid hormone (PTH) and ionized calcium should be simultaneously measured. PTH levels should be suppressed in hypercalcemia; thus, the combination of normal PTH levels and elevated calcium levels suggests mild hyperparathyroidism. Hyperparathyroidism may be part of multiple endocrine neoplasia type 1, (ie, Wermer syndrome).

Other causes of hypercalcemia usually can be distinguished or at least considered on the basis of history and physical examination findings. Measurement of serum phosphate, alkaline phosphatase, serum chloride, serum bicarbonate, and urinary calcium may be useful in some cases. Renal function should be evaluated and thyroid-stimulating hormone should be checked to help rule out hyperthyroidism. In rare cases, measurement of vitamin D and its metabolites and measurement of parathyroid hormone–related peptide (PTHrP) may be necessary.

A flowchart of investigations is depicted in the image below.

Investigations flowchart. Investigations flowchart.

Imaging Studies

Chest radiographs always should be performed to help rule out lung cancer or sarcoidosis. Other radiographs should be considered to help evaluate for possible malignancies, metastases, or Paget disease.

Mammograms should be considered to help rule out breast cancer. Computed tomography (CT) and ultrasound should be considered to help rule out renal cancer.

When a biochemical diagnosis of primary hyperparathyroidism is made, CT scan, ultrasound, magnetic resonance imaging (MRI), and radionuclide imaging of the parathyroid gland may be helpful to assist with preoperative localization.

Contributor Information and Disclosures

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 is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Received ownership interest/medical directorship from South Shore DaVita Dialysis Center for other; Received ownership/medical directorship from Space City Dialysis /American Renal Associates for same; Received ownership interest from US Renal Care for other.


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, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

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Investigations flowchart.
Vitamin D metabolism.
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