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This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are \u201casymptomatic\u201d and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.<\/jats:p>","DOI":"10.1002\/hed.26861","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T05:03:36Z","timestamp":1632114216000},"page":"3996-4009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-0756","authenticated-orcid":false,"given":"Jesus E.","family":"Medina","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery The University of Oklahoma College of Medicine  Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory W.","family":"Randolph","sequence":"additional","affiliation":[{"name":"Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology Massachusetts Eye and Ear Infirmary  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Angelos","sequence":"additional","affiliation":[{"name":"Department of Surgery and MacLean Center for Clinical Medical Ethics The University of Chicago  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Zafereo","sequence":"additional","affiliation":[{"name":"Head and Neck Endocrine Surgery The University of Texas M. 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