The management of primary hyperparathyroidism (PHPT) has evolved with increased recognition of asymptomatic and normocalcemic disease, improved imaging, and greater understanding of multiglandular involvement. Parathyroidectomy remains the only definitive cure and is now recommended for all symptomatic and asymptomatic patients meeting guideline criteria. Focused parathyroidectomy guided by dual-modality imaging and intraoperative PTH monitoring is effective for single-gland disease, while bilateral exploration is essential for in cases of multiglandular disease. Cure rates exceed 97% in experienced hands, with low complication rates. Surgery leads to improvements in bone mineral density, quality of life, and long-term survival. Ongoing research is needed to optimize localization strategies and define outcomes in emerging disease variants.
MandlF. Therapeutischer Versuch bei Ostitis fibrosa generalista mittels Exstirpation eines Epithelkorperchentumors. Wien Klin Wochenschr. 1925;50:1343.
2.
McMullinJLCodnerJPatelSG, et al.Environmental chemicals and their association with hyperparathyroidism. World J Surg. 2023;47(2):296-303. doi:10.1007/s00268-022-06759-8
3.
PressDMSipersteinAEBerberE, et al.The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery. 2013;154(6):1232-1238. doi:10.1016/j.surg.2013.06.051
4.
CollierAPortelliMGhoshSNowellSClarkD. Primary hyperparathyroidism: increasing prevalence, social deprivation, and surgery. Endocr Res. 2017;42(1):31-35. doi:10.3109/07435800.2016.1169545
5.
MinisolaSArnoldABelayaZ, et al.Epidemiology, pathophysiology, and genetics of primary hyperparathyroidism. J Bone Miner Res. 2022;37(11):2315-2329. doi:10.1002/jbmr.4665
6.
YehMWItuartePHGZhouHC, et al.Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122-1129. doi:10.1210/jc.2012-4022
7.
GriebelerMLKearnsAERyuEHathcockMAMeltonLJWermersRA. Secular trends in the incidence of primary hyperparathyroidism over five decades (1965-2010). Bone. 2015;73:1-7. doi:10.1016/j.bone.2014.12.003
8.
HuXSaundersNSafleyS, et al.Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors. Surgery. 2021;169(1):102-108. doi:10.1016/j.surg.2020.06.010
9.
BalochZWLiVolsiVA. Pathology of the parathyroid glands in hyperparathyroidism. Semin Diagn Pathol. 2013;30(3):165-177. doi:10.1053/j.semdp.2013.06.003
10.
EricksonLAMeteOJuhlinCCPerrenAGillAJ. Overview of the 2022 WHO classification of parathyroid tumors. Endocr Pathol. 2022;33(1):64-89. doi:10.1007/s12022-022-09709-1
11.
MilasMWagnerKEasleyKASipersteinAWeberCJ. Double adenomas revisited: nonuniform distribution favors enlarged superior parathyroids (fourth pouch disease). Surgery. 2003;134(6):995-1003. doi:10.1016/j.surg.2003.07.009
12.
BarczyńskiMBränströmRDionigiGMihaiR. Sporadic multiple parathyroid gland disease—a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2015;400(8):887-905. doi:10.1007/s00423-015-1348-1
13.
BroomeDTNaplesRBaileyR, et al.Use of preoperative imaging in primary hyperparathyroidism. J Clin Endocrinol Metab. 2020;106(1):e328-e337. doi:10.1210/clinem/dgaa779
14.
SchneiderDFBurkeJFOjomoKA, et al.Multigland disease and slower decline in intraoperative PTH characterize mild primary hyperparathyroidism. Ann Surg Oncol. 2013;20(13):4205-4211. doi:10.1245/s10434-013-3190-4
15.
ParkHSLeeYHHongNWonDRheeY. Germline mutations related to primary hyperparathyroidism identified by next-generation sequencing. Front Endocrinol. 2022;13:853171. doi:10.3389/fendo.2022.853171
LakisMENockelPGaitanidisA, et al.Probability of positive genetic testing results in patients with family history of primary hyperparathyroidism. J Am Coll Surg. 2018;226(5):933-938. doi:10.1016/j.jamcollsurg.2018.01.007
18.
WilhelmSMWangTSRuanDT, et al.The American association of endocrine surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959-968. doi:10.1001/jamasurg.2016.2310
19.
RubinMRBilezikianJPMcMahonDJ, et al.The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab. 2008;93(9):3462-3470. doi:10.1210/jc.2007-1215
20.
CaronNRPasiekaJL. What symptom improvement can be expected after operation for primary hyperparathyroidism?World J Surg. 2009;33(11):2244-2255. doi:10.1007/s00268-009-9987-4
21.
FuleihanGEChakhtouraMCiprianiC, et al.Classical and nonclassical manifestations of primary hyperparathyroidism. J Bone Miner Res. 2022;37(11):2330-2350. doi:10.1002/jbmr.4679
22.
ŠiprováHFryšákZSoučekM. Primary hyperparathyroidism, with a focus on management of the normocalcemic form: to treat or not to treat?Endocr Pract. 2016;22(3):294-301. doi:10.4158/ep15704.or
23.
BilezikianJPKhanAASilverbergSJ, et al.Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022;37(11):2293-2314. doi:10.1002/jbmr.4677
24.
MadeoBKaraECioniK, et al.Serum calcium to phosphorous (Ca/P) ratio is a simple, inexpensive, and accurate tool in the diagnosis of primary hyperparathyroidism. JBMR Plus. 2017;2(2):109-117. doi:10.1002/jbm4.10019; Published 2017 Nov 2.
25.
YuYQiuJChuanFFengZLongJZhouB. The Ca∗Cl/P ratio: a novel and more appropriate screening tool for normocalcaemic or overt primary hyperparathyroidism. Endocr Pract. 2024;30(3):231-238. doi:10.1016/j.eprac.2023.12.004
26.
CusanoNEMaaloufNMWangPY, et al.Normocalcemic hyperparathyroidism and hypoparathyroidism in two community-based nonreferral populations. J Clin Endocrinol Metab. 2013;98(7):2734-2741. doi:10.1210/jc.2013-1300
27.
MarquesTFVasconcelosRDinizERêgoDGrizLBandeiraF. Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat?Arq Bras Endocrinol Metabol. 2011;55(5):314-317. doi:10.1590/s0004-27302011000500003
28.
ParnellKEOltmannSC. The surgical management of primary hyperparathyroidism: an updated review. Int J Endocr Oncol. 2018;05(01):IJE07. doi:10.2217/ije-2017-0019
29.
MarcocciCBollerslevJKhanAAShobackDM. Medical management of primary hyperparathyroidism: proceedings of the fourth international workshop on the management of asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab. 2014;99(10):3607-3618. doi:10.1210/jc.2014-1417
30.
YeZSilverbergSJSreekantaA, et al.The efficacy and safety of medical and surgical therapy in patients with primary hyperparathyroidism: a systematic review and meta‐analysis of randomized controlled trials. J Bone Miner Res. 2022;37(11):2351-2372. doi:10.1002/jbmr.4685
31.
SlatteryLHuntJP. Contemporary management of primary hyperparathyroidism. Surg Clin. 2022;102(2):251-265. doi:10.1016/j.suc.2021.12.009
32.
McManusC. Radiofrequency ablation for primary hyperparathyroidism: are we there yet?Gland Surg. 2023;12(8):1028-1030. doi:10.21037/gs-23-289
33.
SolorzanoCCCarneiro-PlaD. Minimizing cost and maximizing success in the preoperative localization strategy for primary hyperparathyroidism. Surg Clin. 2014;94(3):587-605. doi:10.1016/j.suc.2014.02.006
34.
WangTSCheungKFarrokhyarFRomanSASosaJA. Would scan, but which scan? a cost-utility analysis to optimize preoperative imaging for primary hyperparathyroidism. Surgery. 2011;150(6):1286-1294. doi:10.1016/j.surg.2011.09.016
35.
MonroeDPEdeiken‐MonroeBSLeeJEEvansDBPerrierND. Impact of preoperative thyroid ultrasonography on the surgical management of primary hyperparathyroidism. Br J Surg. 2008;95(8):957-960. doi:10.1002/bjs.6097
36.
SloanDADavenportDLEldridgeRJLeeCY. Surgeon-driven thyroid interrogation of patients presenting with primary hyperparathyroidism. J Am Coll Surg. 2014;218(4):674-683. doi:10.1016/j.jamcollsurg.2013.12.021
37.
Cunha‐BezerraPVieiraRAmaralF, et al.Better performance of four‐dimension computed tomography as a localization procedure in normocalcemic primary hyperparathyroidism. J Med Imag Radiat On. 2018;62(4):493-498. doi:10.1111/1754-9485.12728
38.
LimJYHermanMCBubisL, et al.Differences in single gland and multigland disease are seen in low biochemical profile primary hyperparathyroidism. Surgery. 2017;161(1):70-77. doi:10.1016/j.surg.2016.08.054
39.
IrvinGLCarneiroDMSolorzanoCC. Progress in the operative management of sporadic primary hyperparathyroidism over 34 years. Ann Surg. 2004;115(NA):130-137. doi:10.1097/01.sla.0000124448.49794.74
40.
IrvinGLDembrowVDPrudhommeDL. Operative monitoring of parathyroid gland hyperfunction. Am J Surg. 1991;162(4):299-302. doi:10.1016/0002-9610(91)90135-z
41.
LairdAMLibuttiSK. Minimally invasive parathyroidectomy versus bilateral neck exploration for primary hyperparathyroidism. Surg Oncol Clin. 2016;25(1):103-118. doi:10.1016/j.soc.2015.08.012
42.
SharmaJMilasMBerberEMazzagliaPSipersteinAWeberCJ. Value of intraoperative parathyroid hormone monitoring. Ann Surg Oncol. 2008;15(2):493-498. doi:10.1245/s10434-007-9683-2
43.
WharryLIYipLArmstrongMJ, et al.The final intraoperative parathyroid hormone level: how low should it go?World J Surg. 2014;38(3):558-563. doi:10.1007/s00268-013-2329-6
44.
FrakerDLHarsonoHLewisR. Minimally invasive parathyroidectomy: benefits and requirements of localization, diagnosis, and intraoperative PTH monitoring. long-term results. World J Surg. 2009;33(11):2256-2265. doi:10.1007/s00268-009-0166-4
45.
PatelSGLiuJSaundersNDWeberCJSharmaJ. Permanent hypoparathyroidism after thyroidectomy: an avoidable complication. Videoendocrinology. 2018;5(2):ve. doi:10.1089/ve.2018.0123
46.
ThielmannAKerrP. Validation of selective use of intraoperative PTH monitoring in parathyroidectomy. J Otolaryngology - Head Neck Surg. 2017;46(1):10. doi:10.1186/s40463-017-0188-0
47.
EligalSMekelMWeinbergerJM, et al.Minimally invasive parathyroidectomy: can intraoperative parathyroid hormone monitoring be omitted?World J Surg. 2022;46(8):1908-1914. doi:10.1007/s00268-022-06537-6
48.
LuiMSShiraliASHuangBLFisherSBPerrierND. Advances in endocrine surgery. Surg Oncol Clin. 2023;32(1):199-220. doi:10.1016/j.soc.2022.08.004
49.
WitteveenJEThielSVRomijnJAHamdyNAT. Therapy of endocrine disease: hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endocrinol. 2013;168(3):R45-R53. doi:10.1530/eje-12-0528
50.
SalmanMARabieeASalmanAA, et al.Role of vitamin D supplements in prevention of hungry bone syndrome after successful parathyroidectomy for primary hyperparathyroidism: a prospective study. Scand J Surg. 2020;110(3):329-334. doi:10.1177/1457496920962601
51.
TalutisSDDrakeFTSachsTRaoSRMcAnenyD. Evacuation of postoperative hematomas after thyroid and parathyroid surgery: an analysis of the CESQIP database. Surgery. 2019;165(1):250-256. doi:10.1016/j.surg.2018.04.087
52.
WermersRAGriebelerMLThapaPHathcockMAKearnsAE. Survival in primary hyperparathyroidism over five decades (1965-2010) a population-based retrospective study. Bone. 2021;152:116099. doi:10.1016/j.bone.2021.116099
53.
PalermoANaciuAMTabaccoG, et al.Clinical, biochemical, and radiological profile of normocalcemic primary hyperparathyroidism. J Clin Endocrinol Metab. 2020;105(7):e2609-e2616. doi:10.1210/clinem/dgaa174
54.
SharmaJItumDSMossLLiCChun-LiCWeberC. Predictors of bone mineral density improvement in patients undergoing parathyroidectomy for primary hyperparathyroidism. World J Surg. 2014;38(6):1268-1273. doi:10.1007/s00268-014-2555-6
55.
YehMWZhouHAdamsAL, et al.The relationship of parathyroidectomy and bisphosphonates with fracture risk in primary hyperparathyroidism: an observational study. Ann Intern Med. 2016;164(11):715-723. doi:10.7326/m15-1232
56.
LiuJYPeineBSMlaverE, et al.Neuropsychologic changes in primary hyperparathyroidism after parathyroidectomy from a dual-institution prospective study. Surgery. 2021;169(1):114-119. doi:10.1016/j.surg.2020.06.006
57.
PalermoAJacquesRGossielF, et al.Normocalcaemic hypoparathyroidism: prevalence and effect on bone status in older women. The OPUS study. Clin Endocrinol. 2015;82(6):816-823. doi:10.1111/cen.12732
58.
SomnayYRCravenMMcCoyKL, et al.Improving diagnostic recognition of primary hyperparathyroidism with machine learning. Surgery. 2017;161(4):1113-1121. doi:10.1016/j.surg.2016.09.044
59.
BroosWAMZantFMVDKnolRJJWondergemM. Choline PET/CT in parathyroid imaging: a systematic review. Nucl Med Commun. 2018;40(2):96-105. doi:10.1097/mnm.0000000000000952
