What causes hypercalcemia in primary hyperparathyroidism?

Updated: Dec 24, 2020
  • Author: Lawrence T Kim, MD, FACS, FACE; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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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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