{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:05:24Z","timestamp":1789517124799,"version":"build-2803163510"},"reference-count":38,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["PRIN 2022B5HC29"],"award-info":[{"award-number":["PRIN 2022B5HC29"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009702","name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","doi-asserted-by":"publisher","award":["DGOS\/PNMR3\/AP-HP"],"award-info":[{"award-number":["DGOS\/PNMR3\/AP-HP"]}],"id":[{"id":"10.13039\/501100009702","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rare National Disease Plan to the Reference Center"},{"DOI":"10.13039\/501100016394","name":"ANR","doi-asserted-by":"publisher","award":["IO-COHO-03"],"award-info":[{"award-number":["IO-COHO-03"]}],"id":[{"id":"10.13039\/501100016394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008784","name":"ESPE","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Clinical presentation of inactivating parathyroid hormone (PTH)\/PTH\u2013related protein (PTHrP) signaling disorders (iPPSDs, historically pseudohypoparathyroidism [PHP]) exhibits pronounced age-dependence. Indeed, main features, including PTH resistance and brachydactyly (BD), develop during late childhood, while other features (ectopic ossifications, obesity, and hypothyroidism) are most prevalent in toddlers. The latter are included among minor diagnostic criteria; therefore, a substantial diagnostic delay has been reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this work is to describe the early natural history of a large cohort of iPPSD\/PHP patients to improve diagnosis, with the final goal of proposing new diagnostic criteria for early infancy and reducing diagnostic delay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 117 patients regularly followed up at 2 European endocrinology tertiary centers, and we retrospectively collected data on the age of onset of main clinical and hormonal features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In our cohort the median age at diagnosis was 5.9 years. Age of onset of PTH resistance and BD, major criteria for diagnosis, was significantly different from that of both thyrotropin (TSH) resistance and obesity (median age 6.1, 5.8, 1.85, and 2 years, respectively). Minor diagnostic criteria were more represented than major criteria in children before age 2 years (P = .002). Indeed, in 64% of patients before age 2 years none of the major criteria were observed; conversely, 71% had already developed at least one minor criterion. In particular, 20% had developed TSH resistance and obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The clinical picture of iPPSD\/PHP in early infancy differs from that of mid-late infancy and adults, thus current diagnostic criteria may not be appropriate for children. We suggest that the combination of early-onset obesity and elevated TSH should raise suspicion and trigger genetic screening before age 2 years.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag132","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:45:36Z","timestamp":1775648736000},"page":"e2271-e2280","source":"Crossref","is-referenced-by-count":0,"title":["Clinical picture of early-infancy PTH resistance syndromes: is it time to improve diagnostic criteria?"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9050-0150","authenticated-orcid":false,"given":"Giulia","family":"Del Sindaco","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda \u2013 Ospedale Maggiore Policlinico , Milan 20122 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