Excess production of parathyroid hormone (PTH)

  • Primary hyperparathyroidism (HPT): intrinsic parathyroid gland dysfunction resulting in excessive secretion of PTH with a lack of response to feedback inhibition by elevated calcium
  • Secondary HPT: appropriate increased secretion of PTH in response to hypocalcemia and/or hyperphosphatemia; can be caused by vitamin D deficiency, kidney dysfunction, decreased calcium intake or absorption, and/or phosphate loading
  • Tertiary HPT: autonomous hyperfunction of the parathyroid gland in the setting of long-standing secondary HPT



  • Primary HPT is 1 in 500 to 1 in 1,000 in the United States.
  • Primary HPT is the etiology for 90% of patients with hypercalcemia.
  • Predominantly postmenopausal females

Etiology and Pathophysiology

PTH is synthesized by the four parathyroid glands, which are located behind the thyroid gland, and mostly regulated by calcium levels.

  • Ectopic (abnormal locations and most common is the thymus) or supernumerary glands (more than four glands)
  • PTH releases calcium from bone by osteoclastic stimulation (increasing bone resorption).
  • PTH increases reabsorption of calcium in the distal tubules of the kidneys.
  • PTH increases phosphorus excretion by decreasing reabsorption in the proximal tubules of the kidneys.
  • PTH stimulates conversion of 25-hydroxycholecalciferol (25[OH]D) to 1,25-dihydroxycholecalciferol (1,25[OH]2D or active vitamin D) in the kidneys. 1,25(OH)2D increases calcium and phosphate absorption from the GI tract and kidneys and stimulates osteoclastic activity and bone resorption.
  • Primary HPT: unregulated PTH production and release due to the loss of normal feedback control by extracellular calcium, causing increase in serum calcium
    • Solitary adenoma (80–85%)
    • Diffuse parathyroid gland hyperplasia (10–15%), either sporadically or in association with multiple endocrine neoplasia
    • Parathyroid carcinoma (<1%)
  • Secondary HPT: adaptive parathyroid gland hyperplasia and hyperfunction from decreased calcium
    • Dietary from vitamin D deficiency causes decreased calcium absorption or calcium deficiency.
    • Chronic renal disease including renal parenchymal loss causing hyperphosphatemia; impaired calcitriol production causing hypocalcemia
  • Tertiary HPT: autonomous oversecretion of PTH following prolonged parathyroid stimulation


  • A genetic basis of primary HPT is identified in about 10% of all cases.
  • Patients with multiple gland hyperplasia in the absence of renal disease should be screened for MEN-I gene mutation.
  • Neonatal severe primary HPT: infants born without both calcium sensing receptor (CaSR) gene alleles
  • HPT—jaw tumor syndrome
  • Familial hypocalciuric hypercalcemia (FHH): loss of one CaSR gene allele

Risk Factors

Chronic kidney disease, increasing age, poor nutrition, radiation, and/or family history

General Prevention

Adequate intake of calcium and vitamin D may help prevent secondary HPT.

Commonly Associated Conditions

  • Vitamin D deficiency
  • Chronic renal failure
  • MEN syndromes: MEN type 1 and MEN type 2A

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