{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:17:55Z","timestamp":1788866275704,"version":"build-2803163510"},"reference-count":68,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,8,1]]},"abstract":"<jats:p>C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe.<\/jats:p>\n               <jats:p>We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercalcitoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to analyze the methylation pattern of androgen receptor alleles and microsatellite regions (TP53, RB1, WT1, and NF1). Consecutive sections were selected for MIB-1, pRB1, p53, Mdm-2, and p21WAF1 immunostaining, DNA content analysis, and in situ end labeling. Appropriate tissue controls were run.<\/jats:p>\n               <jats:p>Only two patients had medullary thyroid carcinoma foci. Nine informative C-cell hyperplasia patients showed germline point mutation in RET, eight of them with the same androgen receptor allele preferentially methylated in both lobes. C-cell hyperplasia foci showed heterogeneous DNA deletions revealed by loss of heterozygosity of TP53 (12 of 20), RB1 (6 of 14), and WT1 (4 of 20) and hypodiploid G0\/G1 cells (14 of 20), low cellular turnover (MIB-1 index 4.5%, in situ end labeling index 0.03%), and significantly high nuclear area to DNA index ratio.<\/jats:p>\n               <jats:p>MEN 2A (germline point mutation in RET codon 634) C-cell hyperplasias are monoclonal and genetically heterogeneous and show down-regulated apoptosis, findings consistent with an intraepithelial neoplasia. Concordant X-chromosome inactivation and interstitial gene deletions suggest clone expansions of precursors occurring at a point in embryonic development before divergence of each thyroid lobe and may represent a paradigm for other germline mutations.<\/jats:p>","DOI":"10.1210\/jcem.86.8.7739","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:07:29Z","timestamp":1389200849000},"page":"3948-3957","source":"Crossref","is-referenced-by-count":29,"title":["Germline RET 634 Mutation Positive MEN 2A-related C-Cell Hyperplasias Have Genetic Features Consistent with Intraepithelial Neoplasia"],"prefix":"10.1210","volume":"86","author":[{"given":"Salvador J.","family":"Diaz-Cano","sequence":"first","affiliation":[{"name":"Departments of Pathology, Tufts University\u2013New England Medical Center (S.J.D.-C., R.T., H.J.W.), Boston, Massachusetts 02111"},{"name":"Barts and The London Queen Mary\u2019s School of Medicine and Dentistry (S.J.D.-C.), E1 1BB London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"de Miguel","sequence":"additional","affiliation":[{"name":"University Hospital of Seville (M.d.M.), 41009-Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Blanes","sequence":"additional","affiliation":[{"name":"University Hospital of Malaga (A.B.), 29010-Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Tashjian","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Tufts University\u2013New England Medical Center (S.J.D.-C., R.T., H.J.W.), Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert J.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Tufts University\u2013New England Medical Center (S.J.D.-C., R.T., H.J.W.), Boston, Massachusetts 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071619150606600_R1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.7824936","article-title":"Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN 2B.","volume":"267","author":"Santoro","year":"1995","journal-title":"Science"},{"key":"2020071619150606600_R2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/363458a0","article-title":"Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.","volume":"363","author":"Mulligan","year":"1993","journal-title":"Nature"},{"key":"2020071619150606600_R3","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1056\/NEJM199409293311302","article-title":"Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A.","volume":"331","author":"Lips","year":"1994","journal-title":"N Engl J Med"},{"key":"2020071619150606600_R4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1126\/science.959840","article-title":"The clonal evolution of tumor cell populations.","volume":"194","author":"Nowell","year":"1976","journal-title":"Science"},{"key":"2020071619150606600_R5","first-page":"283","article-title":"Clonal origin of human tumors.","volume":"458","author":"Fialkow","year":"1976","journal-title":"Biochim Biophys Acta"},{"key":"2020071619150606600_R6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/jcp.1040780106","article-title":"The 5-methylcytosine content of DNA: tissue specificity.","volume":"78","author":"Kappler","year":"1971","journal-title":"J Cell Physiol"},{"key":"2020071619150606600_R7","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/hmg\/3.suppl_1.1487","article-title":"DNA methylation and cancer.","volume":"3","author":"Laird","year":"1994","journal-title":"Hum Mol Genet"},{"key":"2020071619150606600_R8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev.ge.26.120192.000313","article-title":"Some milestones in the history of X-chromosome inactivation.","volume":"26","author":"Lyon","year":"1992","journal-title":"Annu Rev Genet"},{"key":"2020071619150606600_R9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1006\/bbrc.1994.1258","article-title":"A novel strategy for the investigation of clonality in precancerous disease states and early stages of tumor progression.","volume":"199","author":"Sternlicht","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071619150606600_R10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/00019606-200103000-00005","article-title":"PCR techniques for clonality assays.","volume":"10","author":"Diaz-Cano","year":"2001","journal-title":"Diagn Mol Pathol"},{"key":"2020071619150606600_R11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/BF02739690","article-title":"Clonality studies in the analysis of adrenal medullary proliferations: Application principles and limitations.","volume":"9","author":"Diaz-Cano","year":"1998","journal-title":"Endocr Pathol"},{"key":"2020071619150606600_R12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/00019606-199512000-00002","article-title":"Introduction to apoptosis.","volume":"4","author":"Salomon","year":"1995","journal-title":"Diagn Mol Pathol"},{"key":"2020071619150606600_R13","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0002-9440(10)64732-3","article-title":"Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex.","volume":"156","author":"Diaz-Cano","year":"2000","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R14","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1056\/NEJM197811022991804","article-title":"Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis.","volume":"299","author":"Graze","year":"1978","journal-title":"N Engl J Med"},{"key":"2020071619150606600_R15","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1056\/NEJM198802253180804","article-title":"The clinical outcome of prospective screening for multiple endocrine neoplasia type 2 a: an 18 year experience.","volume":"318","author":"Gagel","year":"1988","journal-title":"N Engl J Med"},{"key":"2020071619150606600_R16","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1365-2796.1995.tb01207.x","article-title":"Clinical use of molecular information in the management of multiple endocrine neoplasia type 2A.","volume":"238","author":"Gagel","year":"1995","journal-title":"J Intern Med"},{"key":"2020071619150606600_R17","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1001\/jama.1996.03540190047028","article-title":"The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis.","volume":"276","author":"Eng","year":"1996","journal-title":"JAMA"},{"key":"2020071619150606600_R18","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1056\/NEJM197308302890901","article-title":"C-cell hyperplasia preceding medullary thyroid carcinoma.","volume":"289","author":"Wolfe","year":"1973","journal-title":"N Engl J Med"},{"key":"2020071619150606600_R19"},{"key":"2020071619150606600_R20","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/(SICI)1097-0142(19960215)77:4<750::AID-CNCR22>3.0.CO;2-Z","article-title":"Physiologic versus neoplastic C-cell hyperplasia of the thyroid: separation of distinct histologic and biologic entities.","volume":"77","author":"Perry","year":"1996","journal-title":"Cancer"},{"key":"2020071619150606600_R21","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/0046-8177(95)90294-5","article-title":"Immunostains for collagen type IV discriminate between C-cell hyperplasia and microscopic medullary carcinoma in multiple endocrine neoplasia, type 2a.","volume":"26","author":"McDermott","year":"1995","journal-title":"Hum Pathol"},{"key":"2020071619150606600_R22","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/00019606-199712000-00006","article-title":"DNA extraction from formalin-fixed paraffin-embedded tissues: protein digestion as a limiting step for retrieval of high quality DNA.","volume":"6","author":"Diaz-Cano","year":"1997","journal-title":"Diagn Mol Pathol"},{"key":"2020071619150606600_R23","first-page":"501","article-title":"A polymerase chain reation assay for non-random X chromosome identifies monoclonal endometrial cancer and precancers.","volume":"146","author":"Mutter","year":"1995","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R24","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/nar\/23.8.1411","article-title":"PCR bias in amplification of AR alleles, a trinucleotide repeat marker used in clonality studies.","volume":"23","author":"Mutter","year":"1995","journal-title":"Nucleic Acids Res"},{"key":"2020071619150606600_R25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/labinvest.3780033","article-title":"Molecular evolution and intratumor heterogeneity by topographic compartments in muscle-invasive transitional cell carcinoma of the urinary bladder.","volume":"80","author":"Diaz-Cano","year":"2000","journal-title":"Lab Invest"},{"key":"2020071619150606600_R26","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH679>3.0.CO;2-B","article-title":"Clonal patterns in phaechromocytomas and MEN-2A adrenal medullary hyperplasias: histologic and kinetic correlates.","volume":"192","author":"Diaz-Cano","year":"2000","journal-title":"J Pathol"},{"key":"2020071619150606600_R27","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/bjc.1993.236","article-title":"Rapid detection of allele loss in colorectal tumours using microsatellites and fluorescent DNA technology.","volume":"67","author":"Cawkwell","year":"1993","journal-title":"Br J Cancer"},{"key":"2020071619150606600_R28","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/1096-9896(200008)191:4<343::AID-PATH617>3.0.CO;2-Y","article-title":"Designing a molecular analysis of clonality in tumours.","volume":"191","author":"Diaz-Cano","year":"2000","journal-title":"J Pathol"},{"key":"2020071619150606600_R29","first-page":"965","article-title":"Cell image analysis","author":"Bibbo","year":"1991","journal-title":"In: Bibbo M, ed. Comprehensive cytopathology. Philadelphia: W.B. Saunders Co.;"},{"key":"2020071619150606600_R30","first-page":"77","article-title":"Cell cycle analysis of apoptosis using flow cytometry","author":"Sherwood","year":"1995","journal-title":"In: Schwartz LM, Osborne BA, eds. Cell death. San Diego: Academic Press;"},{"key":"2020071619150606600_R31","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s004280050468","article-title":"Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression.","volume":"436","author":"Koch","year":"2000","journal-title":"Virchows Arch"},{"key":"2020071619150606600_R32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/41.1.7678025","article-title":"A new method to detect apoptosis in paraffin sections: In situ end-labeling of fragmented DNA.","volume":"41","author":"Wijsman","year":"1993","journal-title":"J Histochem Cytochem"},{"key":"2020071619150606600_R33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/00019606-199708000-00004","article-title":"Bcl-2 expression and DNA fragmentation in breast carcinoma, pathologic and steroid hormone receptors correlates.","volume":"6","author":"Diaz-Cano","year":"1997","journal-title":"Diagn Mol Pathol"},{"key":"2020071619150606600_R34","author":"Taylor","year":"1994"},{"key":"2020071619150606600_R35","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/0046-8177(92)90314-S","article-title":"Expression of mitosis per thousand cells and cell density in breast carcinomas. A proposal.","volume":"23","author":"Simpson","year":"1992","journal-title":"Hum Pathol"},{"key":"2020071619150606600_R36","first-page":"170","article-title":"Mitotic index quantification: different approaches and their value in adrenal cortical proliferative lesions.","volume":"74","author":"Diaz-Cano","year":"1996","journal-title":"Lab Invest"},{"key":"2020071619150606600_R37","first-page":"497","article-title":"Prominent expression of mRNA for proinflammatory cytokines in synovium in patients with juvenile rheumatoid arthritis or chronic lyme arthritis.","volume":"27","author":"Harjacek","year":"2000","journal-title":"J Rheumatol"},{"key":"2020071619150606600_R38","first-page":"571","article-title":"Clonality in Kaposi\u2019s sarcoma [Letter; comment].","volume":"337","author":"Diaz-Cano","year":"1997","journal-title":"N Engl J Med"},{"key":"2020071619150606600_R39","first-page":"2153","article-title":"Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome inactivation and cytogenetics of a clinically benign smooth muscle proliferation.","volume":"150","author":"Quade","year":"1997","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00019606-199704000-00005","article-title":"Aggressive fibromatosis (desmoid tumor) is a monoclonal disorder.","volume":"6","author":"Alman","year":"1997","journal-title":"Diagn Mol Pathol"},{"issue":"Suppl 138","key":"2020071619150606600_R41","first-page":"179","article-title":"Embryonic development of human thyroid gland and ultimobranchial body","volume":"179","author":"Sugiyama","year":"1969","journal-title":"Acta Endocr"},{"key":"2020071619150606600_R42","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/(SICI)1096-9896(199912)189:4<627::AID-PATH479>3.0.CO;2-K","article-title":"Influence of intratumour heterogeneity in the interpretation of marker results in phaeochromocytomas.","volume":"189","author":"Diaz-Cano","year":"1999","journal-title":"J Pathol"},{"key":"2020071619150606600_R43","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1182\/blood.V83.10.2899.2899","article-title":"Tissue specificity of X-chromosome inactivation patterns.","volume":"83","author":"Gale","year":"1994","journal-title":"Blood"},{"key":"2020071619150606600_R44","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0046-8177(99)90266-6","article-title":"Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR\/DGGE.","volume":"30","author":"Brady","year":"1999","journal-title":"Hum Pathol"},{"key":"2020071619150606600_R45","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s004390050339","article-title":"Polyclonal origin of medullary carcinoma of the thyroid in multiple endocrine neoplasia type 2.","volume":"99","author":"Ferraris","year":"1997","journal-title":"Hum Genet"},{"key":"2020071619150606600_R46","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.935869","article-title":"Clonal origin of inherited medullary thyroid carcinoma and pheochromocytoma.","volume":"193","author":"Baylin","year":"1976","journal-title":"Science"},{"key":"2020071619150606600_R47","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1126\/science.619463","article-title":"Inherited medullary thyroid carcinoma: a final monoclonal mutation in one of multiple clones of susceptible cells.","volume":"199","author":"Baylin","year":"1978","journal-title":"Science"},{"key":"2020071619150606600_R48","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/ng0894-480","article-title":"Cooperative tumorigenic effects of germline mutations in Rb and p53.","volume":"7","author":"Williams","year":"1994","journal-title":"Nat Genet"},{"key":"2020071619150606600_R49","first-page":"1407","article-title":"Bcl-2 and c-Myc, but not bax and p53, are expressed during human medullary thyroid tumorigenesis.","volume":"152","author":"Wang","year":"1998","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R50","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s004390050724","article-title":"Mutational analysis of the GDNF\/RET-GDNFR \u03b1 signaling complex in a kindred with vesicoureteral reflux.","volume":"102","author":"Shefelbine","year":"1998","journal-title":"Hum Genet"},{"key":"2020071619150606600_R51","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0959-437X(00)00125-8","article-title":"Cross-talk in kidney development.","volume":"10","author":"Schedl","year":"2000","journal-title":"Curr Opin Genet Dev"},{"key":"2020071619150606600_R52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000051850","article-title":"Molecular genetics of neuroendocrine tumors.","volume":"62","author":"Calender","year":"2000","journal-title":"Digestion"},{"key":"2020071619150606600_R53","first-page":"747","article-title":"Genetic markers and animal models of neurocristopathy.","volume":"10","author":"Nakamura","year":"1995","journal-title":"Histol Histopathol"},{"key":"2020071619150606600_R54","first-page":"1241","article-title":"Germline and somatic mutations in an oncogene: RET mutations in inherited medullary thyroid carcinoma.","volume":"56","author":"Marsh","year":"1996","journal-title":"Cancer Res"},{"key":"2020071619150606600_R55","first-page":"2167","article-title":"Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma.","volume":"56","author":"Eng","year":"1996","journal-title":"Cancer Res"},{"key":"2020071619150606600_R56","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1101\/gad.8.11.1300","article-title":"Apoptosis or retinoblastoma: Alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.","volume":"8","author":"Howes","year":"1994","journal-title":"Genes Dev"},{"key":"2020071619150606600_R57","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0065-230X(08)60100-1","article-title":"The natural somatic mutation frequency and human carcinogenesis.","volume":"71","author":"Simpson","year":"1997","journal-title":"Adv Cancer Res"},{"issue":"Suppl 5","key":"2020071619150606600_R58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1289\/ehp.93101s535","article-title":"DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis","volume":"101","author":"Ames","year":"1993","journal-title":"Environ Health Perspect"},{"key":"2020071619150606600_R59","first-page":"545","article-title":"Mutation of cell cycle regulators. Biological and clinical implications for human neoplasia.","volume":"147","author":"Cordon-Cardo","year":"1995","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R60","first-page":"1757","article-title":"Effects of mutation and growth rates on patterns of microsatellite instability.","volume":"148","author":"Li","year":"1996","journal-title":"Am J Pathol"},{"key":"2020071619150606600_R61","first-page":"3759","article-title":"Cell proliferation as a major risk factor for cancer: a concept of doubtful validity.","volume":"55","author":"Farber","year":"1995","journal-title":"Cancer Res"},{"key":"2020071619150606600_R62","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nm0397-313","article-title":"Adenovirally transferred p16INK4\/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death.","volume":"3","author":"Sandig","year":"1997","journal-title":"Nat Med"},{"key":"2020071619150606600_R63","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1101\/gad.9.5.600","article-title":"Growth factor modulation of p53-mediated growth arrest versus apoptosis.","volume":"9","author":"Canman","year":"1995","journal-title":"Genes Dev"},{"key":"2020071619150606600_R64","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/path.1711720305","article-title":"Expression of the ret proto-oncogene product in human normal and neoplastic tissues of neural crest origin.","volume":"172","author":"Nakamura","year":"1994","journal-title":"J Pathol"},{"key":"2020071619150606600_R65","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.7824936","article-title":"Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B.","volume":"267","author":"Santoro","year":"1995","journal-title":"Science"},{"key":"2020071619150606600_R66","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1093\/jnci\/84.7.506","article-title":"Heterogeneity for allelic loss in human breast cancer.","volume":"84","author":"Chen","year":"1992","journal-title":"J Natl Cancer Inst"},{"key":"2020071619150606600_R67","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1126\/science.274.5295.2057","article-title":"Loss of heterozygosity in normal tissue adjacent to breast carcinomas.","volume":"274","author":"Deng","year":"1996","journal-title":"Science"},{"key":"2020071619150606600_R68","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/jnci\/84.7.469","article-title":"Genetic heterogeneity in breast cancer.","volume":"84","author":"Wolman","year":"1992","journal-title":"J Natl Cancer Inst"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/86\/8\/3948\/9168670\/jcem3948.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/86\/8\/3948\/9168670\/jcem3948.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T04:23:04Z","timestamp":1594959784000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/86\/8\/3948\/2849067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,1]]},"references-count":68,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jcem.86.8.7739","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,1]]}}}