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
- 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
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 I and MEN IIA
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Domino, Frank J., et al., editors. "Hyperparathyroidism." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2020. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism.
Hyperparathyroidism. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2020. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism. Accessed June 5, 2023.
Hyperparathyroidism. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism
Hyperparathyroidism [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2020. [cited 2023 June 05]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Hyperparathyroidism ID - 117547 ED - Domino,Frank J, ED - Baldor,Robert A, ED - Golding,Jeremy, ED - Stephens,Mark B, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -