{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:13:41Z","timestamp":1791249221916,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,5,17]],"date-time":"2005-05-17T00:00:00Z","timestamp":1116288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C\u2010PTH fragments in circulation and present with a higher C\u2010PTH\/I\u2010PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high\u2010performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> A 55\u2010year\u2010old man with severe hypercalcaemia (Ca<jats:sup>2+<\/jats:sup>: 2\u00b701 mmol\/l), very high PTH levels (CA\u2010PTH 82\u00b71 and T\u2010PTH 72\u00a0pmol\/l) caused by a large parathyroid tumour (7\u00b735\u00a0g) and accompanied by significant bone involvement (alkaline phosphatase of 185 UI\/l and subperiostal bone resorption of hands) was referred to us. Blood was obtained at various time points during his medical treatment, before and after surgery, to measure parameters of calcium and phosphorus metabolism, and of bone turnover. HPLC separations of circulating PTH molecular forms were performed and analysed with PTH assays having 1\u20134 (CA), 12\u201318 (T), 26\u201332 (E) and 65\u201384 (C) epitopes.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Before surgery, serum Ca<jats:sup>2+<\/jats:sup> was nearly normalized with hydratation, intravenous (IV) pamidronate and oral vitamin\u00a0D administration. Despite a decrease in Ca<jats:sup>2+<\/jats:sup> to 1\u00b731\u00a0mmol\/l, CA\u2010PTH and T\u2010PTH levels decreased by half in relation to a threefold increase in basal 1,25\u2010dihydroxyvitamin\u00a0D [1,25(OH)<jats:sub>2<\/jats:sub>D] level (94 to 337\u00a0pmol\/l). After this initial positive response, hypercalcaemia and elevated CA\u2010 and T\u2010PTH levels recurred even if 1,25(OH)<jats:sub>2<\/jats:sub>D levels remained elevated. The tumour was removed surgically and proved to be poorly differentiated with nuclear atypia and mitosis. After surgery, the Ca<jats:sup>2+<\/jats:sup> level and PTH secretion normalized. The higher CA\u2010PTH level relative to the T\u2010PTH level observed before surgery in this patient was related to the oversecretion of an amino\u2010terminal (N) form of PTH recognized by PTH assays with (1\u20134) or (26\u201332) epitopes but not by the T\u2010PTH assay with a (12\u201318) epitope. This molecular form represented 50% of CA\u2010PTH measured in this patient, but only 7% in less severe cases of primary hyperparathyroidism. It was unaffected by medical therapy and disappeared after surgery.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> The relationship between the overexpression of this N\u2010PTH molecular form and severe primary hyperparathyroidism remains unclear. Further studies will be required in these rare patients to see whether N\u2010PTH is a marker of less well differentiated parathyroid tumours and\/or relates to the overproduction of C\u2010PTH fragments in the presence of severe hypercalcaemia.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2005.02286.x","type":"journal-article","created":{"date-parts":[[2005,6,8]],"date-time":"2005-06-08T16:17:17Z","timestamp":1118247437000},"page":"721-727","source":"Crossref","is-referenced-by-count":49,"title":["Overproduction of an amino\u2010terminal form of PTH distinct from human PTH(1\u201384) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery"],"prefix":"10.1111","volume":"62","author":[{"given":"Agn\u00e8s","family":"R\u00e4kel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Hugues","family":"Brossard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Victor","family":"Patenaude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Albert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgard","family":"Nassif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Cantor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"D\u2019Amour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012098651-4\/50020-1"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-196801000-00003"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012098651-4\/50022-5"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-46-2-267"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(79)90446-7"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(81)90207-2"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-56-3-572"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000181253"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.77.2.413"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1998.00447.x"},{"key":"e_1_2_6_12_2","first-page":"158","article-title":"Primary hyperparathyroidism in women: a table of two cities \u2013 New York and Beijing","volume":"45","author":"Bilezikian J.P.","year":"2000","journal-title":"International Journal of Fertility"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0007-1323.2001.01775.x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0730659"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-114-3-897"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-6-1305"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-71-5-1305"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-6009(08)80087-6"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.3.1054"},{"issue":"2","key":"e_1_2_6_20_2","first-page":"N75","article-title":"Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism. 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