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Parathyroid adenomas are comprised of distinct cellular subpopulations of variable clonal status that exhibit differing degrees of calcium responsiveness. To gain a clearer understanding of the relationship among cellular identity, tumour composition and clinical biochemistry in <jats:styled-content style=\"fixed-case\">PHPT<\/jats:styled-content>, we developed a novel single cell platform for quantitative evaluation of calcium sensing behaviour in freshly resected human parathyroid tumour cells. Live\u2010cell intracellular calcium flux was visualized through Fluo\u20104\u2010<jats:styled-content style=\"fixed-case\">AM<\/jats:styled-content> epifluorescence, followed by <jats:italic>in situ<\/jats:italic> immunofluorescence detection of the calcium sensing receptor (<jats:styled-content style=\"fixed-case\">CASR<\/jats:styled-content>), a central component in the extracellular calcium signalling pathway. The reactivity of individual parathyroid tumour cells to extracellular calcium stimulus was highly variable, with discrete kinetic response patterns observed both between and among parathyroid tumour samples. <jats:styled-content style=\"fixed-case\">CASR<\/jats:styled-content> abundance was not an obligate determinant of calcium responsiveness. Calcium <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>50 values from a series of parathyroid adenomas revealed that the tumours segregated into two distinct categories. One group manifested a mean <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>50 of 2.40 mM (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 2.37\u20132.41), closely aligned to the established normal range. The second group was less responsive to calcium stimulus, with a mean <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>50 of 3.61 mM (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>: 3.45\u20133.95). This binary distribution indicates the existence of a previously unappreciated biochemical sub\u2010classification of <jats:styled-content style=\"fixed-case\">PHPT<\/jats:styled-content> tumours, possibly reflecting distinct etiological mechanisms. Recognition of quantitative differences in calcium sensing could have important implications for the clinical management of <jats:styled-content style=\"fixed-case\">PHPT<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jcmm.12732","type":"journal-article","created":{"date-parts":[[2015,12,6]],"date-time":"2015-12-06T08:28:19Z","timestamp":1449390499000},"page":"351-359","source":"Crossref","is-referenced-by-count":15,"title":["Single\u2010cell functional analysis of parathyroid adenomas reveals distinct classes of calcium sensing behaviour in primary hyperparathyroidism"],"prefix":"10.1111","volume":"20","author":[{"given":"James","family":"Koh","sequence":"first","affiliation":[{"name":"Department of Surgery Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce A.","family":"Hogue","sequence":"additional","affiliation":[{"name":"Department of Surgery Duke University Medical Center Durham NC 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