Description

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

Epidemiology

Incidence

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

Prevalence
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

Genetics

• 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