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Hyperparathyroidism

MedGen UID:
6967
Concept ID:
C0020502
Disease or Syndrome
Synonyms: Elevated blood parathyroid hormone level; HPTH - Hyperparathyroidism; hyperparathyroidism
SNOMED CT: Hyperparathyroidism (66999008); HPTH - Hyperparathyroidism (66999008)
 
HPO: HP:0000843
Monarch Initiative: MONDO:0001741

Definition

Excessive production of parathyroid hormone (PTH) by the parathyroid glands. [from HPO]

Conditions with this feature

Multiple endocrine neoplasia type 2A
MedGen UID:
9958
Concept ID:
C0025268
Neoplastic Process
Multiple endocrine neoplasia type 2 (MEN2) includes the following phenotypes: MEN2A, FMTC (familial medullary thyroid carcinoma, which may be a variant of MEN2A), and MEN2B. All three phenotypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN2A and MEN2B involve an increased risk for pheochromocytoma; MEN2A involves an increased risk for parathyroid adenoma or hyperplasia. Additional features in MEN2B include mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and a marfanoid habitus. MTC typically occurs in early childhood in MEN2B, early adulthood in MEN2A, and middle age in FMTC.
McCune-Albright syndrome
MedGen UID:
69164
Concept ID:
C0242292
Disease or Syndrome
Fibrous dysplasia / McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G-protein, Gsa), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gsa signaling is ubiquitous, additional tissues may be affected. Café au lait skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include: Gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys; Testicular lesions with or without associated gonadotropin-independent precocious puberty; Thyroid lesions with or without non-autoimmune hyperthyroidism; Growth hormone excess; FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and Neonatal hypercortisolism. The prognosis for individuals with FD/MAS is based on disease location and severity.
Familial hypocalciuric hypercalcemia 1
MedGen UID:
137973
Concept ID:
C0342637
Disease or Syndrome
Familial hypocalciuric hypercalcemia (HHC) is a heritable disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. HHC is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone (PTH; 168450) level. Hypermagnesemia is typically present. Individuals with HHC are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults (summary by Hannan et al., 2010). Characteristic features of familial hypocalciuric hypercalcemia include mild to moderate hypercalcemia, nonsuppressed parathyroid hormone, relative hypocalciuria while hypercalcemic (calcium/creatinine clearance ratio less than 0.01, or 24-hr urine calcium less than 6.25 mmol), almost 100% penetrance of hypercalcemia from birth, absence of complications, persistence of hypercalcemia following subtotal parathyroidectomy, and normal parathyroid size, weight, and histology at surgery. However, atypical presentations with severe hypercalcemia, hypercalciuria with or without nephrolithiasis or nephrocalcinosis, kindreds with affected members displaying either hypercalciuria or hypocalciuria, postoperative normocalcemia, and pancreatitis have all been described in FHH (Warner et al., 2004). Genetic Heterogeneity of Hypocalciuric Hypercalcemia Familial hypocalciuric hypercalcemia type II (HHC2; 145981) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13, and HHC3 (600740) is caused by mutation in the AP2S1 gene (602242) on chromosome 19q13.
Parathyroid carcinoma
MedGen UID:
146361
Concept ID:
C0687150
Neoplastic Process
The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in up to 95% of affected individuals; onset is typically in late adolescence or early adulthood. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In approximately 10%-15% of individuals, primary hyperparathyroidism is caused by parathyroid carcinoma. Ossifying fibromas of the mandible or maxilla, also known as cementifying fibromas and cemento-ossifying fibromas, occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors can be locally aggressive and may continue to enlarge if not treated. Approximately 20% of individuals with HPT-JT syndrome have kidney lesions, most commonly cysts; renal hamartomas and (more rarely) Wilms tumor have also been reported. Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome. Parathyroid carcinoma. Most parathyroid carcinomas are functional, resulting in hyperparathyroidism and a high serum calcium level; however, nonfunctioning parathyroid carcinomas are also rarely described in individuals with a CDC73-related disorder. A germline CDC73 pathogenic variant has been identified in 20%-29% of individuals with apparently sporadic parathyroid carcinoma. Familial isolated hyperparathyroidism (FIHP). FIHP is characterized by primary hyperparathyroidism without other associated syndromic features. Individuals with CDC73-related FIHP tend to have a more severe clinical presentation and younger age of onset than individuals with FIHP in whom a CDC73 pathogenic variant has not been identified.
Hyperparathyroidism, transient neonatal
MedGen UID:
722059
Concept ID:
C1300287
Disease or Syndrome
Transient neonatal hyperparathyroidism is characterized by interference with placental maternal-fetal calcium transport, causing fetal calcium deficiency resulting in hyperparathyroidism and metabolic bone disease. Because 80% of calcium is transferred during the third trimester, abnormalities may not be detected on second-trimester ultrasounds. Affected infants present at birth with prenatal fractures, shortened ribs, and bowing of long bones, as well as respiratory and feeding difficulties. Postnatal recovery or improvement is observed once calcium is provided orally, with most patients showing complete resolution of skeletal abnormalities by 2 years of age (Suzuki et al., 2018).
Hyperparathyroidism 2 with jaw tumors
MedGen UID:
310065
Concept ID:
C1704981
Neoplastic Process
The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in up to 95% of affected individuals; onset is typically in late adolescence or early adulthood. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In approximately 10%-15% of individuals, primary hyperparathyroidism is caused by parathyroid carcinoma. Ossifying fibromas of the mandible or maxilla, also known as cementifying fibromas and cemento-ossifying fibromas, occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors can be locally aggressive and may continue to enlarge if not treated. Approximately 20% of individuals with HPT-JT syndrome have kidney lesions, most commonly cysts; renal hamartomas and (more rarely) Wilms tumor have also been reported. Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome. Parathyroid carcinoma. Most parathyroid carcinomas are functional, resulting in hyperparathyroidism and a high serum calcium level; however, nonfunctioning parathyroid carcinomas are also rarely described in individuals with a CDC73-related disorder. A germline CDC73 pathogenic variant has been identified in 20%-29% of individuals with apparently sporadic parathyroid carcinoma. Familial isolated hyperparathyroidism (FIHP). FIHP is characterized by primary hyperparathyroidism without other associated syndromic features. Individuals with CDC73-related FIHP tend to have a more severe clinical presentation and younger age of onset than individuals with FIHP in whom a CDC73 pathogenic variant has not been identified.
Hyperparathyroidism, neonatal self-limited primary, with hypercalciuria
MedGen UID:
344611
Concept ID:
C1855924
Disease or Syndrome
Bartter disease type 1
MedGen UID:
355727
Concept ID:
C1866495
Disease or Syndrome
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Multiple endocrine neoplasia type 4
MedGen UID:
373469
Concept ID:
C1970712
Neoplastic Process
Multiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands called the endocrine system. Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia typically involves tumors (neoplasia) in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, the condition can be life-threatening.\n\nThe major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.\n\nMany different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.\n\nMultiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.\n\nThe most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.
Hypophosphatemic rickets and hyperparathyroidism
MedGen UID:
383131
Concept ID:
C2677524
Disease or Syndrome
HELIX syndrome
MedGen UID:
1621482
Concept ID:
C4522164
Disease or Syndrome
HELIX syndrome is an autosomal recessive disorder characterized by Hypohidrosis, Electrolyte imbalance, Lacrimal gland dysfunction, Ichthyosis, and Xerostomia (summary by Hadj-Rabia et al., 2018).
Tumoral calcinosis, hyperphosphatemic, familial, 1
MedGen UID:
1642611
Concept ID:
C4692564
Disease or Syndrome
Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by: Ectopic calcifications (tumoral calcinosis) typically found in periarticular soft tissues exposed to repetitive trauma or prolonged pressure (e.g., hips, elbows, and shoulders); and Painful swellings (referred to as hyperostosis) in the areas overlying the diaphyses of the tibiae (and less often the ulna, metacarpal bones, and radius). The dental phenotype unique to HFTC includes enamel hypoplasia, short and bulbous roots, obliteration of pulp chambers and canals, and pulp stones. Less common are large and small vessel calcifications that are often asymptomatic incidental findings on radiologic studies but can also cause peripheral vascular insufficiency (e.g., pain, cold extremities, and decreased peripheral pulses). Less frequently reported findings include testicular microlithiasis and angioid streaks of the retina.
Osteopetrosis, autosomal dominant 3
MedGen UID:
1648454
Concept ID:
C4748197
Disease or Syndrome
Autosomal dominant osteopetrosis-3 (OPTA3) is characterized by phenotypic variability. Some patients have typical features of osteopetrosis, including fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density, whereas other patients exhibit localized osteosclerosis and generalized osteopenia. OPTA3 represents a relatively malignant form of osteopetrosis in some patients who develop significant pancytopenia and hepatosplenomegaly (Bo et al., 2016). For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634).
Osteopetrosis, autosomal recessive 9
MedGen UID:
1841123
Concept ID:
C5830487
Disease or Syndrome
Autosomal recessive osteopetrosis-9 (OPTB9) is characterized by increased bone density and bone fragility, as well as renal failure. Vision may be compromised due to compression of the optic nerve secondary to osteopetrotic stenosis of the optic nerve canal (Xue et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700).

Professional guidelines

PubMed

Bandeira F, de Moura Nóbrega J, de Oliveira LB, Bilezikian J
Arch Endocrinol Metab 2022 Nov 11;66(5):689-693. doi: 10.20945/2359-3997000000558. PMID: 36382758Free PMC Article
Bilezikian JP, Silverberg SJ, Bandeira F, Cetani F, Chandran M, Cusano NE, Ebeling PR, Formenti AM, Frost M, Gosnell J, Lewiecki EM, Singer FR, Gittoes N, Khan AA, Marcocci C, Rejnmark L, Ye Z, Guyatt G, Potts JT
J Bone Miner Res 2022 Nov;37(11):2391-2403. Epub 2022 Oct 17 doi: 10.1002/jbmr.4682. PMID: 36054638
Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, Wicart P, Bockenhauer D, Santos F, Levtchenko E, Harvengt P, Kirchhoff M, Di Rocco F, Chaussain C, Brandi ML, Savendahl L, Briot K, Kamenicky P, Rejnmark L, Linglart A
Nat Rev Nephrol 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5. PMID: 31068690Free PMC Article

Recent clinical studies

Etiology

Wang TS
Am J Surg 2024 Mar;229:196-197. Epub 2023 Nov 11 doi: 10.1016/j.amjsurg.2023.11.006. PMID: 37977977
Bilezikian JP, Khan AA, Silverberg SJ, Fuleihan GE, Marcocci C, Minisola S, Perrier N, Sitges-Serra A, Thakker RV, Guyatt G, Mannstadt M, Potts JT, Clarke BL, Brandi ML; International Workshop on Primary Hyperparathyroidism
J Bone Miner Res 2022 Nov;37(11):2293-2314. Epub 2022 Oct 17 doi: 10.1002/jbmr.4677. PMID: 36245251
Komaba H, Hamano T, Fujii N, Moriwaki K, Wada A, Masakane I, Nitta K, Fukagawa M
J Clin Endocrinol Metab 2022 Jun 16;107(7):2016-2025. doi: 10.1210/clinem/dgac142. PMID: 35277957
Newey PJ
Endocrinol Metab Clin North Am 2021 Dec;50(4):663-681. doi: 10.1016/j.ecl.2021.08.003. PMID: 34774240
Kowalski GJ, Buła G, Żądło D, Gawrychowska A, Gawrychowski J
Endokrynol Pol 2020;71(3):260-270. doi: 10.5603/EP.a2020.0028. PMID: 32797471

Diagnosis

Cusano NE, Cetani F
Arch Endocrinol Metab 2022 Nov 11;66(5):666-677. doi: 10.20945/2359-3997000000556. PMID: 36382756Free PMC Article
Kowalski GJ, Buła G, Żądło D, Gawrychowska A, Gawrychowski J
Endokrynol Pol 2020;71(3):260-270. doi: 10.5603/EP.a2020.0028. PMID: 32797471
Zhu CY, Sturgeon C, Yeh MW
JAMA 2020 Mar 24;323(12):1186-1187. doi: 10.1001/jama.2020.0538. PMID: 32031566
Messa P, Alfieri CM
Front Horm Res 2019;51:91-108. Epub 2018 Nov 19 doi: 10.1159/000491041. PMID: 30641516
Bilezikian JP, Bandeira L, Khan A, Cusano NE
Lancet 2018 Jan 13;391(10116):168-178. Epub 2017 Sep 17 doi: 10.1016/S0140-6736(17)31430-7. PMID: 28923463

Therapy

Ogata H, Fukagawa M, Hirakata H, Kagimura T, Fukushima M, Akizawa T; LANDMARK Investigators and Committees
JAMA 2021 May 18;325(19):1946-1954. doi: 10.1001/jama.2021.4807. PMID: 34003226Free PMC Article
Reiss AB, Miyawaki N, Moon J, Kasselman LJ, Voloshyna I, D'Avino R Jr, De Leon J
Atherosclerosis 2018 Nov;278:49-59. Epub 2018 Aug 30 doi: 10.1016/j.atherosclerosis.2018.08.046. PMID: 30253289
Jean G, Souberbielle JC, Chazot C
Nutrients 2017 Mar 25;9(4) doi: 10.3390/nu9040328. PMID: 28346348Free PMC Article
Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, Ketteler M, Kewalramani R, Martin KJ, Moe SM, Patel UD, Silver J, Sun Y, Wang H, Chertow GM
JAMA 2017 Jan 10;317(2):156-164. doi: 10.1001/jama.2016.19468. PMID: 28097356
Mizobuchi M, Ogata H
Curr Vasc Pharmacol 2014 Mar;12(2):324-8. doi: 10.2174/15701611113119990023. PMID: 23713875

Prognosis

Reitz RJ 3rd, Dreimiller A, Khil A, Horwitz E, McHenry CR
Surgery 2021 Mar;169(3):513-518. Epub 2020 Sep 9 doi: 10.1016/j.surg.2020.08.007. PMID: 32919783
Kakani E, Sloan D, Sawaya BP, El-Husseini A, Malluche HH, Rao M
Semin Dial 2019 Nov;32(6):541-552. Epub 2019 Jul 16 doi: 10.1111/sdi.12833. PMID: 31313380
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Ryhänen EM, Leijon H, Metso S, Eloranta E, Korsoff P, Ahtiainen P, Kekäläinen P, Tamminen M, Ristamäki R, Knutar O, Löyttyniemi E, Niskanen L, Väisänen M, Heiskanen I, Välimäki MJ, Laakso M, Haglund C, Arola J, Schalin-Jäntti C
Acta Oncol 2017 Jul;56(7):991-1003. Epub 2017 Mar 31 doi: 10.1080/0284186X.2017.1306103. PMID: 28362521
Khan AA, Hanley DA, Rizzoli R, Bollerslev J, Young JE, Rejnmark L, Thakker R, D'Amour P, Paul T, Van Uum S, Shrayyef MZ, Goltzman D, Kaiser S, Cusano NE, Bouillon R, Mosekilde L, Kung AW, Rao SD, Bhadada SK, Clarke BL, Liu J, Duh Q, Lewiecki EM, Bandeira F, Eastell R, Marcocci C, Silverberg SJ, Udelsman R, Davison KS, Potts JT Jr, Brandi ML, Bilezikian JP
Osteoporos Int 2017 Jan;28(1):1-19. Epub 2016 Sep 9 doi: 10.1007/s00198-016-3716-2. PMID: 27613721Free PMC Article

Clinical prediction guides

Wang TS
Am J Surg 2024 Mar;229:196-197. Epub 2023 Nov 11 doi: 10.1016/j.amjsurg.2023.11.006. PMID: 37977977
Pappachan JM, Buch HN
Adv Exp Med Biol 2017;956:215-237. doi: 10.1007/5584_2016_26. PMID: 27864805
Delorme S, Raue F
Recent Results Cancer Res 2015;204:91-116. doi: 10.1007/978-3-319-22542-5_4. PMID: 26494385
Duan K, Gomez Hernandez K, Mete O
J Clin Pathol 2015 Oct;68(10):771-87. Epub 2015 Jul 10 doi: 10.1136/jclinpath-2015-203186. PMID: 26163537
McBiles M, Lambert AT, Cote MG, Kim SY
Semin Nucl Med 1995 Jul;25(3):221-34. doi: 10.1016/s0001-2998(95)80012-3. PMID: 7570042

Recent systematic reviews

Roser P, Leca BM, Coelho C, Schulte KM, Gilbert J, Drakou EE, Kosmas C, Ling Chuah L, Wassati H, Miras AD, Crane J, Aylwin SJB, Grossman AB, Dimitriadis GK
Endocr Relat Cancer 2023 Apr 1;30(4) Epub 2023 Mar 22 doi: 10.1530/ERC-22-0287. PMID: 36621911
Xergia SA, Tsarbou C, Liveris NI, Hadjithoma Μ, Tzanetakou IP
Phys Sportsmed 2023 Dec;51(6):506-516. Epub 2022 Jun 10 doi: 10.1080/00913847.2022.2085505. PMID: 35670156
Bilezikian JP, Khan AA, Silverberg SJ, Fuleihan GE, Marcocci C, Minisola S, Perrier N, Sitges-Serra A, Thakker RV, Guyatt G, Mannstadt M, Potts JT, Clarke BL, Brandi ML; International Workshop on Primary Hyperparathyroidism
J Bone Miner Res 2022 Nov;37(11):2293-2314. Epub 2022 Oct 17 doi: 10.1002/jbmr.4677. PMID: 36245251
Witteveen JE, van Thiel S, Romijn JA, Hamdy NA
Eur J Endocrinol 2013 Mar;168(3):R45-53. Epub 2013 Feb 20 doi: 10.1530/EJE-12-0528. PMID: 23152439
McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR
Lancet 2012 Feb 25;379(9817):721-8. Epub 2012 Jan 20 doi: 10.1016/S0140-6736(11)61516-X. PMID: 22265699

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