Hyperparathyroidism
Basics
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
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Citation
Domino, Frank J., et al., editors. "Hyperparathyroidism." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. 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; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism. Accessed November 5, 2024.
Hyperparathyroidism. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd 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; 2025. [cited 2024 November 05]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117547/all/Hyperparathyroidism.
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