A dysfunction of the body’s normal regulatory feedback mechanisms resulting in 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 potential hypocalcemia and/or hyperphosphatemia. This is can be caused by vitamin D deficiency, kidney dysfunction, decreased calcium intake, decreased calcium absorption, and/or phosphate loading.
  • Tertiary HPT: autonomous hyperfunction of the parathyroid gland in the setting of long-standing secondary HPT



  • Predominantly postmenopausal females
  • Female > male (3:1)

Primary HPT is 1 in 500 to 1 in 1,000 in the United States.

Etiology and Pathophysiology

  • PTH is mostly regulated by calcium levels.
  • PTH is synthesized by the four parathyroid glands, which are located behind the four poles of the thyroid gland (locations can vary).
  • 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.
  • 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 hyperplasia (10–15%) of the four parathyroid glands, either sporadically or in association with multiple endocrine neoplasia (MEN) type I or MEN type IIA
    • Parathyroid carcinoma (<1%), a very rare and severe form
  • Secondary HPT: adaptive parathyroid gland hyperplasia and hyperfunction from decreased calcium
    • Dietary
      • Vitamin D deficiency causes decreased calcium absorption.
      • Calcium deficiency
    • Chronic renal disease resulting in the following:
      • Renal parenchymal loss causing hyperphosphatemia
      • Impaired calcitriol production causing hypocalcemia
      • General skeletal and renal resistance to PTH
  • Tertiary HPT: autonomous oversecretion of PTH following prolonged parathyroid stimulation


  • MEN type I and MEN type IIA: 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 alleles
  • Familial isolated HPT

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 I and MEN IIA

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