{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:52:49Z","timestamp":1783745569002,"version":"3.55.0"},"reference-count":18,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although primary hyperparathyroidism today is often a relatively asymptomatic disease, it has distinct biochemical and skeletal features. These features are present at diagnosis and are generally stable over time, leading to the theory of a biphasic disease course in which alterations occur during a preclinical phase. Measurement of calciotropic hormones in individuals undergoing skeletal evaluation has led to the identification of normocalcemic individuals with elevated PTH levels. We hypothesize that these patients represent the earliest manifestations of primary hyperparathyroidism<\/jats:p>\n               <jats:p>Twenty-two patients had hyperparathyroidism (94 \u00b1 29 pg\/ml) and normal corrected serum calcium levels (2.40 \u00b1 0.02 mmol\/liter). No secondary causes of hyperparathyroidism were found. PTH levels did not correlate with urinary calcium concentration, renal function, vitamin D concentrations, or bone density. The relationship between PTH and serum calcium (regression slope, +0.004) was identical in normocalcemic and hypercalcemic hyperparathyroid patients. Preferential cortical bone loss, characteristic of patients with primary hyperparathyroidism, was not seen (T-score: spine, \u22121.6; hip, \u22121.8; distal one-third radius, \u22121.3). In up to 12 months of observation, three patients have developed hypercalcemia, and one has had two adenomas removed.<\/jats:p>\n               <jats:p>These patients with elevated PTH levels in the absence of hypercalcemia may provide a window into this previously unrecognized stage of the disease and permit investigators to track its evolution in ways that have not heretofore been possible.<\/jats:p>","DOI":"10.1210\/jc.2003-031014","type":"journal-article","created":{"date-parts":[[2003,11,6]],"date-time":"2003-11-06T13:11:05Z","timestamp":1068124265000},"page":"5348-5352","source":"Crossref","is-referenced-by-count":169,"title":["\u201cIncipient\u201d Primary Hyperparathyroidism: A \u201cForme Fruste\u201d of an Old Disease"],"prefix":"10.1210","volume":"88","author":[{"given":"Shonni J.","family":"Silverberg","sequence":"first","affiliation":[{"name":"Departments of Medicine (S.J.S., J.P.B.), New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Bilezikian","sequence":"additional","affiliation":[{"name":"Departments of Medicine (S.J.S., J.P.B.), New York, New York 10032"},{"name":"Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613501010100_R1","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1210\/jcem-67-6-1294","article-title":"Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism.","volume":"67","author":"Rao","year":"1988","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501010100_R2","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1056\/NEJM199910213411701","article-title":"A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery.","volume":"341","author":"Silverberg","year":"1999","journal-title":"N Engl J Med"},{"issue":"Suppl 2","key":"2020071613501010100_R3","first-page":"S97","article-title":"Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: clinical course and considerations bearing on the need for surgical intervention","volume":"6","author":"Parfitt","year":"1991","journal-title":"J Bone Miner Res"},{"key":"2020071613501010100_R4","first-page":"723","article-title":"Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism.","volume":"80","author":"Silverberg","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501010100_R5","first-page":"729","article-title":"Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism.","volume":"80","author":"Silverberg","year":"1995","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501010100_R6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jbmr.5650040302","article-title":"Skeletal disease in primary hyperparathyroidism.","volume":"4","author":"Silverberg","year":"1989","journal-title":"J Bone Miner Res"},{"key":"2020071613501010100_R7","first-page":"1075","article-title":"Primary hyperparathyroidism","author":"Silverberg","year":"2001","journal-title":"In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia: WB Saunders;"},{"key":"2020071613501010100_R8","first-page":"N81","article-title":"Immunoassays for the detection of parathyroid hormone","volume":"17","author":"Juppner","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2020071613501010100_R9","first-page":"173","article-title":"High prevalence of normal total calcium and intact PTH in 60 patients with proven primary hyperparathyroidism.","volume":"2","author":"Glendenning","year":"1998","journal-title":"Aust N Z J Med"},{"key":"2020071613501010100_R10","first-page":"644","article-title":"Vitamin D deficiency, insufficiency, sufficiency and intoxication","author":"Peacock","year":"1985","journal-title":"What do they mean? In: Norman A, Schaefer K, Grigoletti MG, Herrath DV, eds. Sixth workshop on vitamin D. New York: de Gruyter;"},{"key":"2020071613501010100_R11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1056\/NEJM199803193381201","article-title":"Hypovitaminosis D in medical patients.","volume":"338","author":"Thomas","year":"1998","journal-title":"N Engl J Med"},{"key":"2020071613501010100_R12","first-page":"349","article-title":"Clinical presentation of primary hyperparathyroidism","author":"Silverberg","year":"2001","journal-title":"In: Bilezikian JP, Marcus R, Levine MA, eds. The parathyroids. 2nd ed. San Diego: Academic Press;"},{"key":"2020071613501010100_R13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1093\/clinchem\/44.4.805","article-title":"A non-(1\u201384) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples.","volume":"44","author":"Lepage","year":"1998","journal-title":"Clin Chem"},{"key":"2020071613501010100_R14","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1210\/jcem.84.11.6236","article-title":"A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure.","volume":"84","author":"John","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501010100_R15","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1359\/jbmr.2001.16.4.605","article-title":"Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1\u201384: implications for improvement of accurate assessment of parathyroid function.","volume":"16","author":"Gao","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2020071613501010100_R16","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1210\/jc.2002-021266","article-title":"Clinical utility of an immunoradiometric assay for parathyroid hormone (1\u201384) in primary hyperparathyroidism.","volume":"88","author":"Silverberg","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613501010100_R17","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0085-2538(15)47156-X","article-title":"A novel mechanism for skeletal resistance in uremia.","volume":"58","author":"Slatopolsky","year":"2000","journal-title":"Kidney Int"},{"key":"2020071613501010100_R18","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1210\/endo.142.4.8093","article-title":"Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH\/PTH-related peptide receptor.","volume":"142","author":"Nguyen-Yamamoto","year":"2001","journal-title":"Endocrinology"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/11\/5348\/9062239\/jcem5348.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/88\/11\/5348\/9062239\/jcem5348.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:46:23Z","timestamp":1594946783000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/88\/11\/5348\/2656614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,1]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2003,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2003-031014","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,1]]}}}