Pathophysiology of Primary Hyperparathyroidism (PHPT)

• 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
• In primary hyperparathyroidism from parathyroid hyperplasia:
  • An increase in the cell numbers is probably the cause of the change in the set point
• 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
    • In severe cases, coma and death
  • Neuropsychiatric manifestations are particularly common and may include:
    • Depression
    • Confusion
    • 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
        • This suggests that hypercalcemia is the primary driver of an impaired quality of life

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