Harvey's Garden

Hyperparathyroidism

3 min read

Etiology

  • Primary: Autonomous overproduction of Parathyroid Hormone (PTH).
    • Most common cause: Parathyroid adenoma (~85%).
    • Other causes: Parathyroid hyperplasia (~15%), parathyroid carcinoma (<1%).
    • Associated with MEN 1 and MEN 2A syndromes.
  • Secondary: Compensatory PTH secretion due to chronic hypocalcemia.
  • Tertiary: Autonomous PTH secretion after prolonged secondary hyperparathyroidism.
    • The parathyroid glands become hyperplastic and no longer respond to normal feedback mechanisms.
    • Typically seen in patients with end-stage renal disease (ESRD), often after a renal transplant.

Parathyroid function

  • Bone: Increases bone resorption by indirectly activating osteoclasts (via RANKL on osteoblasts), releasing Ca2+ and PO4(3-).
  • Kidney: Increases Ca2+ reabsorption in the distal convoluted tubule. Decreases PO4(3-) reabsorption in the proximal convoluted tubule (“Phosphate trashing”). Stimulates 1-alpha-hydroxylase to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol).
  • Gut: Active Vitamin D increases intestinal absorption of both Ca2+ and PO4(3-).

Clinical features

Symptomatic patients often have clinical features of hypercalcemia

Clinical features

  • Nephrolithiasis, nephrocalcinosis (calcium oxalate > calcium phosphate stones)
  • Bone pain, arthralgias, myalgias, fractures
    • Because most of the calcium is released from bones
  • Constipation
    • Increase in extracellular Ca2+ → membrane potential outside is more positive → more amount of depolarization is needed to initiate action potential → decreased excitability of muscle and nerve tissue
  • Abdominal pain
  • Nausea and vomiting
  • Anorexia
  • Peptic ulcer disease
    • hypercalcemia-induced increase of gastric acid secretion and gastrin levels.
  • Neuropsychiatric symptoms such as anxiety, depression, fatigue, and cognitive dysfunction
  • Diminished muscle excitability
    • Cardiac arrhythmias
    • Muscle weakness, paresis
  • Polyuria and dehydration
    • Due to acquired renal ADH resistance. Although ADH is being secreted, the kidneys no longer respond to it adequately (nephrogenic diabetes insipidus).

Link to original

Diagnostics

  • Labs
    • Primary hyperparathyroidism: ↑ Serum Ca2+, ↑ PTH, ↓ Serum PO₄³⁻, ↑ Urinary Ca2+, ↑ Urinary cAMP
      • The severe hypercalcemia overwhelms the kidney’s ability to reabsorb calcium, resulting in a net increase in urinary calcium (hypercalciuria).
      • PTH acts on the kidney via a Gs-coupled receptor, which increases cAMP. This cAMP is then excreted, leading to ↑ Urinary cAMP.
  • Neck imaging
    • For surgical planning to determine the location of the abnormal glands and evaluate for concomitant thyroid disease
    • Options include ultrasound neck and nuclear imaging, i.e., Tc-99m sestamibi scan.
  • X-ray
    • Decreased bone mineral density
    • Cortical thinning: especially prominent in the phalanges of the hand; manifests as acroosteolysis (a subperiosteal pattern of bone resorption)
      • Unlike the typical osteoporosis of aging, which predominantly affects trabecular bone
    • Salt and pepper skull: granular decalcification manifesting as diffusely distributed lytic foci on imaging of the calvarium
    • Features of osteitis fibrosa cystica

Complications

Osteitis fibrosa cystica (OFC)

  • A rare skeletal disorder seen in advanced hyperparathyroidism characterized by replacement of calcified bone with fibrous tissue
  • Most commonly seen in primary hyperparathyroidism but can also occur in secondary hyperparathyroidism
  • ↑ PTH → ↑ RANK ligand expression → activation of osteoclasts → bone resorption, cortical bone destruction, and fibrous tissue deposition
  • Features include bone pain, subperiosteal thinning, and bone cysts; multiple bone cysts in the skull may result in a salt and pepper skull (pepper pot) appearance on x-ray.
  • In advanced OFC, large, cystic, vascular cavities with a tumor-like appearance on x-ray and a brown color due to hemosiderin deposition (brown tumors) can form in long bones.

Graph View

Backlinks