Hyperparathyroidism

Description

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

Epidemiology

Prevalence

• 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

Genetics

• 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