What is the pathophysiology of 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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In primary hyperparathyroidism due to adenomas, the normal feedback on parathyroid hormone production by extracellular calcium seems to be lost, resulting in a change in the set point. However, this is not the case in primary hyperparathyroidism from parathyroid hyperplasia. An increase in the cell numbers is probably the cause.

The chronic excessive resorption of calcium from bone caused by excessive parathyroid hormone can result in osteopenia. In severe cases, this may result in osteitis fibrosa cystica, which is characterized by subperiosteal resorption of the distal phalanges, tapering of the distal clavicles, salt-and-pepper appearance of the skull, and brown tumors of the long bones. This is not commonly seen now. In addition, the chronically increased excretion of calcium in the urine can predispose to the formation of renal stones.

The other symptoms of hyperparathyroidism are due to the hypercalcemia itself and are not specific to hyperparathyroidism. These can include muscle weakness, fatigue, volume depletion, nausea and vomiting, and in severe cases, coma and death. Neuropsychiatric manifestations are particularly common and may include depression, confusion, or subtle deficits that are often characterized poorly and may not be noted by the patient (or may be attributed to aging). Increased calcium can increase gastric acid secretion, and persons with hyperparathyroidism may have a higher prevalence of peptic ulcer disease. Rare cases of pancreatitis have also been attributed to hypercalcemia.

A prospective cohort study by Ejlsmark-Svensson et al reported that in patients with primary hyperparathyroidism, quality-of-life questionnaire scores were significantly lower in association with moderate-severe hypercalcemia than in relation to mild hypercalcemia. However, quality of life did not seem to be related to the presence of organ-related manifestations of primary hyperparathyroidism, such as osteoporosis, renal calcifications, and renal function impairment. [4]  This suggests that hypercalcemia is the primary driver of an impaired quality of life.

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