Gastrointestinal Manifestations of Primary Hyperparathyroidism (PHPT)

• The most frequent gastrointestinal manifestations of PHPT are:
  • Constipation:
    • That occurs in 33% of the cases
  • Heartburn:
    • That occurs in 30% of the cases
  • Nausea:
    • That occurs in 24% of the cases
  • Anorexia:
    • That occur in 15% of the cases
• A significant reduction in patient symptoms:
  • Is seen after parathyroidectomy
• The precise pathophysiology is not fully known:
  • Variations in gene expression secondary to sustained stimulation of PTH result:
    • In gut dysmotility:
      • That often leads to constipation and dyspepsia
• PHPT has been associated with increased incidence of malignancies:
  • Especially of the colon and rectum
• PHPT has been associated with peptic ulcer disease:
  • The incidence varies between:
    • 5% to 30 % of the cases
  • In animal models:
    • Elevated gastric levels have been shown to result from PTH infusion into blood vessels supplying the stomach:
      • Independent of its effects on serum calcium
• An increased incidence of pancreatitis has been reported in patients with PHPT:
  • PHPT as a cause of acute pancreatitis was first described by Cope et al, in 1957
  • In retrospective series:
    • The incidence of acute pancreatitis in patients with PHPT:
      • Has varied from 1% to 12%
  • In a study by Jacob et al:
    • They showed a 28-fold increase in the risk of developing pancreatitis in patients with PHPT compared to the general population
    • After removing all other causes:
      • The average serum calcium level seems to be the only predictive factor for pancreatitis development
    • In the diagnostic work-up of acute pancreatitis:
      • PHPT should be included in the differential diagnosis:
        • Although PHPT is found in less than 1% of individuals who present with acute pancreatitis
    • The mechanism of origin that leads to pancreatitis:
      • Seems to be related more to the hypercalcemia than to the PHPT
    • Experimental studies have validated that calcium ions cause calculus deposition within the pancreatic ducts:
      • With subsequent obstruction and inflammation
    • Calcium can also trigger the pancreatitis cascade:
      • By promoting conversion of trypsinogen to trypsin
• Patients with PHPT also have an increased incidence of cholelithiasis:
  • Presumably due to PTH inhibition of:
    • Gallbladder wall emptying, hepatic bile secretion and sphincter Oddi dysmotility, as well as modification of bile composition (increase in biliary calcium):
      • Which leads to the formation of calcium bilirubinate stones

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