{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:52Z","timestamp":1784527432238,"version":"3.55.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR-TR1-2023-12377089"],"award-info":[{"award-number":["PNRR-TR1-2023-12377089"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The term \u201cmicromegaly\u201d historically refers to patients with acromegalic features, elevated IGF-1, but normal growth hormone (GH) levels. The physiological mechanism, the appropriate clinical and treatment approaches, as well as its existence as a separate clinical entity are not well-defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively collected clinical and hormonal data from 30 patients with acromegaly and 30 with micromegaly (displaying high IGF-1 but GH &amp;lt; 0.4 \u00b5g\/L after glucose load), matched for age and sex. Data about acromegaly related comorbidities were collected (goiter, colonic polyps, malignancies, hypertension, cardiopathy, obstructive-sleep-apnea, carpal tunnel, and hyperglycemia). We performed a laboratory analysis of pituitary tissue samples from both groups, examining GH isoform expression and proliferative rate. We compared data of the two groups and described follow-up and treatment response in micromegalic patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with acromegaly exhibited higher IGF-1 values at diagnosis (+8.3 vs. +3.2 SDS,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01) and higher GH nadir levels after glucose load (6 vs. 0.15 \u03bcg\/L,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). All patients with acromegaly had a detectable pituitary adenoma (70% macroadenomas), whereas 52% of patients with micromegaly showed no evidence of pituitary adenoma. Despite different GH\/IGF-1 values, the prevalence of most comorbidities was similar in both groups, except for valve disease and diabetes mellitus, which were more frequent in acromegaly (valvopathy: 42.9% vs. 16.7%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006; diabetes: 56.7% vs. 23.3%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.016, respectively). Laboratory analyses in patients with micromegaly indicated a lower proliferative profile in tumor cells (D3 cyclin expression).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with a clinical diagnosis of acromegaly and high IGF-1 levels but a GH nadir &amp;lt; 0.4 \u00b5g\/L following glucose load exhibit a high burden of comorbidities and therefore require appropriate screening and follow-up. Therapeutic strategies in these cases should be individualized, considering the frequent absence of neuroradiological findings, which may reflect a lower proliferative profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1874123","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:37:33Z","timestamp":1784525853000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Micromegaly: a distinct clinical entity? Insights from a monocentric cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Alessandra","family":"Mangone","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]},{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Carosi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Sala","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Del Sindaco","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Mungari","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Cremaschi","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]},{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lotito","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]},{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Peverelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan","place":["Milan, Italy"]},{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2700","article-title":"Acromegaly: an endocrine society clinical practice 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