overactivity of the parathyroid glands→ high PTH → Ca2+ release from bones, increase resorption from urine and GIT

• PRIMARY:
  • parathyroid adenoma 90% - increased PTH, increased Ca2+
  • Adults, females 4:1, asympt. → severe.
  • Rarely part of MEN type 1
  • lithium
• Secondary HPT: Chronic renal failure( also vit D def, cholestasis) → Ca2+ loss → increased PTH, decreased Ca2+
• Tertiary HPT: persistant Secondary → Hyperplasia. not responding to ca+ levels. increased PTH, incr Ca2+
• Quaternary HPT: Tertiary + Adenoma.

demographics

Women

Pathophysiology:

• Primary hyperparathyroidism: Overproduction of PTH by parathyroid chief cells.
  • ↑ PTH → ↑ bone resorption → ↑ release of calcium phosphate → ↑ calcium levels
    • PTH causes bone resorption as it induces RANKL expression in osteoblasts → binding of RANKL to RANK on osteoclasts → activation of osteoclasts → bone resorption
    • PTH also induces IL-1 expression in osteoblasts → activation of osteoclasts
  • ↑PTH on the kidneys → ↑ phosphate excretion (phosphaturia)
• Secondary hyperparathyroidism:
  • ↓calcium and/or ↑ phosphate blood levels → reactive hyperplasia of the parathyroid glands → ↑ PTH secretion
  • CKD
    • CKD→ impaired renal phosphate excretion → ↑ phosphate blood levels → ↑ PTH secretion
    • CKD → ↓ biosynthesis of active vitamin D → ↓ intestinal calcium resorption and ↓ renal calcium reabsorption → hypocalcemia → ↑ PTH secretion
• Tertiary hyperparathyroidism:  Chronic renal disease → refractory and autonomous secretion of PTH → hypercalcemia

Clinical Features

Variable, majority asymptomatic

• Hypercalcemia:

  

  • Painful bones: Classically osteitis fibrosa cystica
  • Renal stones: Kidney stones → renal failure. nephrogenic diabetes insipidis.
  • Abdo groans: Constipation, ileus, Anorexia, nausea, vomiting, abdo pain. Less commonly pancreatitis, PUD
  • Psychiatric moans: Lethargy weakness, fatigue, memory loss, psychosis depression, confusion, coma/stupor