PMID- 36245271 OWN - NLM STAT- MEDLINE DCOM- 20221129 LR - 20230415 IS - 1523-4681 (Electronic) IS - 0884-0431 (Print) IS - 0884-0431 (Linking) VI - 37 IP - 11 DP - 2022 Nov TI - Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism. PG - 2315-2329 LID - 10.1002/jbmr.4665 [doi] AB - In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT). PHPT is typically a disease of postmenopausal women, but its prevalence and incidence vary globally and depend on a number of factors, the most important being the availability to measure serum calcium and parathyroid hormone levels for screening. In the Western world, the change in presentation to asymptomatic PHPT is likely to occur, over time also, in Eastern regions. The selection of the population to be screened will, of course, affect the epidemiological data (ie, general practice as opposed to tertiary center). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs). Clonally dysregulated overgrowth of one or more parathyroid glands together with reduced expression of CaSRs is the most important pathophysiologic basis of PHPT. The spectrum of skeletal disease reflects different degrees of dysregulated bone remodeling. Intestinal calcium hyperabsorption together with increased bone resorption lead to increased filtered load of calcium that, in addition to other metabolic factors, predispose to the appearance of calcium-containing kidney stones. A genetic basis of PHPT can be identified in about 10% of all cases. These may occur as a part of multiple endocrine neoplasia syndromes (MEN1-MEN4), or the hyperparathyroidism jaw-tumor syndrome, or it may be caused by nonsyndromic isolated endocrinopathy, such as familial isolated PHPT and neonatal severe hyperparathyroidism. DNA testing may have value in: confirming the clinical diagnosis in a proband; eg, by distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH). Mutation-specific carrier testing can be performed on a proband's relatives and identify where the proband is a mutation carrier, ruling out phenocopies that may confound the diagnosis; and potentially prevention via prenatal/preimplantation diagnosis. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). CI - (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). FAU - Minisola, Salvatore AU - Minisola S AUID- ORCID: 0000-0001-6525-0439 AD - Department of Clinical, Internal, Anaesthesiologic and Cardiovascular Sciences, 'Sapienza', Rome University, Rome, Italy. FAU - Arnold, Andrew AU - Arnold A AUID- ORCID: 0000-0002-8821-8527 AD - Center for Molecular Oncology and Division of Endocrinology & Metabolism, University of Connecticut School of Medicine, Farmington, CT, USA. FAU - Belaya, Zhanna AU - Belaya Z AD - Department of Neuroendocrinology and Bone Disease, The National Medical Research Centre for Endocrinology, Moscow, Russia. FAU - Brandi, Maria Luisa AU - Brandi ML AUID- ORCID: 0000-0002-8741-0592 AD - F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy. FAU - Clarke, Bart L AU - Clarke BL AUID- ORCID: 0000-0002-3801-9546 AD - Mayo Clinic Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA. FAU - Hannan, Fadil M AU - Hannan FM AUID- ORCID: 0000-0002-2975-5170 AD - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Oxford, UK. AD - Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK. FAU - Hofbauer, Lorenz C AU - Hofbauer LC AUID- ORCID: 0000-0002-8691-8423 AD - Division of Endocrinology, Diabetes, and Bone Diseases & Center for Healthy Aging, Technische Universitat Dresden, Dresden, Germany. FAU - Insogna, Karl L AU - Insogna KL AUID- ORCID: 0000-0001-6973-5679 AD - Yale Bone Center Yale School of Medicine, Yale University, New Haven, CT, USA. FAU - Lacroix, Andre AU - Lacroix A AD - Division of Endocrinology, Department of Medicine and Research Center, Centre Hospitalier de l'Universite de Montreal (CHUM), Montreal, Canada. FAU - Liberman, Uri AU - Liberman U AD - Department of Physiology and Pharmacology, Tel Aviv University School of Medicine, Tel Aviv, Israel. FAU - Palermo, Andrea AU - Palermo A AUID- ORCID: 0000-0002-1143-4926 AD - Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico and Unit of Endocrinology and Diabetes, Campus Bio-Medico University, Rome, Italy. FAU - Pepe, Jessica AU - Pepe J AUID- ORCID: 0000-0002-3088-0673 AD - Department of Clinical, Internal, Anaesthesiologic and Cardiovascular Sciences, 'Sapienza', Rome University, Rome, Italy. FAU - Rizzoli, Rene AU - Rizzoli R AD - Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. FAU - Wermers, Robert AU - Wermers R AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition and Department of Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Thakker, Rajesh V AU - Thakker RV AUID- ORCID: 0000-0002-1438-3220 AD - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Oxford, UK. AD - Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20221017 PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - SY7Q814VUP (Calcium) RN - 0 (Receptors, Calcium-Sensing) RN - 0 (Parathyroid Hormone) SB - IM MH - Infant, Newborn MH - Female MH - Humans MH - *Hyperparathyroidism, Primary/complications/epidemiology/genetics MH - Calcium MH - *Hypercalcemia/genetics MH - Receptors, Calcium-Sensing/genetics MH - Parathyroid Hormone PMC - PMC10092691 OTO - NOTNLM OT - CALCIUM SENSING RECEPTOR OT - FAMILIAL PHPT OT - GENETIC TESTS OT - PARATHYROID HORMONE OT - PRIMARY HYPERPARATHYROIDISM COIS- We acknowledge unrestricted financial support from: Amolyt, Ascendis, Calcilytix and Takeda. They had no input into the planning or design of the project, the conduct of the reviews, evaluation of the data, writing or review of the manuscript, its content, conclusions, or recommendations contained herein. SM served: as speaker for Abiogen, Amgen, Bruno Farmaceutici, Diasorin, Eli Lilly, Shire, Sandoz, Takeda; and on advisory board of Abiogen, Kyowa Kirin, Pfizer, UCB. LCH has received honoraria for clinical trials to his institutions from Amgen. EDAT- 2022/10/18 06:00 MHDA- 2022/11/30 06:00 PMCR- 2023/04/12 CRDT- 2022/10/17 03:33 PHST- 2022/07/18 00:00 [revised] PHST- 2022/02/04 00:00 [received] PHST- 2022/07/29 00:00 [accepted] PHST- 2022/10/18 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/10/17 03:33 [entrez] PHST- 2023/04/12 00:00 [pmc-release] AID - JBMR4665 [pii] AID - 10.1002/jbmr.4665 [doi] PST - ppublish SO - J Bone Miner Res. 2022 Nov;37(11):2315-2329. doi: 10.1002/jbmr.4665. Epub 2022 Oct 17.