What causes hypercalcemia in primary hyperparathyroidism?

Answer

The causes of hypercalcemia that result in a concomitantly elevated parathyroid hormone level are few. These include familial benign (hypocalciuric) hypercalcemia (FHH) (see Related disorders), lithium-induced hypercalcemia, and tertiary hyperparathyroidism. A minority of patients (ie, 10-15%) with hyperparathyroidism have parathyroid hormone levels that are within the reference range but are inappropriately high in the presence of elevated serum calcium concentrations. A subset of patients has normal calcium levels with elevated parathyroid hormone, so-called normocalcemic hyperparathyroidism. However, when considering this diagnosis, all potential causes of secondary hyperparathyroidism (eg, low calcium intake, gastrointestinal disorders, renal insufficiency, vitamin D deficiency, hypercalciuria of renal origin) should be excluded. Patients with normal calcium levels and elevated parathyroid hormone levels in the absence of an identifiable secondary cause should be monitored for progression to hypercalcemia.

Secondary and tertiary hyperparathyroidism are typically diagnosed based on their clinical context. Cancer-induced hypercalcemia is associated with a low parathyroid hormone level but possibly a high parathyroid hormone–related peptide level.

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Media Gallery

Normal parathyroid glands as seen during a thyroidectomy. The large arrow points to the superior parathyroid. The thinner arrow points to the inferior parathyroid. The forceps points toward the recurrent laryngeal nerve. The patient's head is toward the top right.
Hyperparathyroidism. Technetium-99m (99mTc) sestamibi radionuclide scan. The early image (top left) shows uptake in the salivary glands and thyroid. The later images (right and bottom) show washout from the thyroid but persistence in the region of the right inferior thyroid lobe (arrows). This proved to be a right parathyroid adenoma.
Sestamibi parathyroid scan with SPECT scan. The orange indicates radionuclide accumulation. The findings indicate the presence of a right-sided parathyroid adenoma just behind the thyroid lobe. At exploration, this patient was found to have adjacent double adenomas on the right.
Sestamibi parathyroid scan with SPECT scan showing an ectopic mediastinal parathyroid adenoma adjacent to the aortic arch. This patient had undergone a failed neck exploration. A transthoracic, robotic excision was curative.
A small, left inferior parathyroid adenoma as demonstrated on a 4D-CT scan. The left panel is a single image from the early contrast phase showing intense enhancement. The right panel shows rapid washout of contrast. The white arrows point to the adenoma.
The panels show a transverse and longitudinal (sagittal) view of a left superior parathyroid adenoma on ultrasonography. The caliper marks designate the adenoma. Adenomas are typically homogeneous and hypoechoic.

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Author

Lawrence T Kim, MD, FACS, FACE Professor, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of North Carolina at Chapel Hill School of Medicine; Member, UNC Lineberger Comprehensive Cancer Center

Lawrence T Kim, MD, FACS, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Endocrinology, American College of Surgeons, American Thyroid Association, International Association of Endocrine Surgeons, Parkland Surgical Society, Society of Surgical Oncology, Southern Surgical Association, Surgical Discovery Club

Disclosure: Nothing to disclose.

Coauthor(s)

Michelle Whittier Krause, MD, MPH Associate Professor of Medicine, Division of Nephrology, University of Arkansas for Medical Sciences

Michelle Whittier Krause, MD, MPH is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, National Kidney Foundation

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.

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Daniel Einhorn, MD, FACP, FACE Medical Director, Scripps/Whittier Diabetes Institute; Associate Clinical Professor of Medicine, University of California, San Diego, School of Medicine

Daniel Einhorn, MD, FACP, FACE is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Phi Beta Kappa, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Elizabeth H Harris, MD, FACE Clinical Assistant Professor, Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine

Elizabeth H Harris, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Vitaly Kantorovich, MD Assistant Professor and Director of the UAMS Weight Control Program, Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences and Staff Physician, Central Arkansas Veterans Healthcare System

Vitaly Kantorovich, MD is a member of the following medical societies: The Endocrine Society

Disclosure: Nothing to disclose.

Antoine Makdissi, MD Assistant Professor of Medicine, University of Arkansas for Medical Sciences College of Medicine

Disclosure: Nothing to disclose.

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