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
- Primary HPT is 1 in 500 to 1 in 1,000 in the United States.
- 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 the 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 1 or MEN type 2A
- Parathyroid carcinoma (<1%), a very rare and severe form
- Secondary HPT: adaptive parathyroid gland hyperplasia and hyperfunction from decreased calcium
- 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 1 and MEN type 2A: 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
Chronic kidney disease, increasing age, poor nutrition, radiation, and/or family history
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
There's more to see -- the rest of this topic is available only to subscribers.