{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:24:01Z","timestamp":1761542641052,"version":"build-2065373602"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"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","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>Introduction<\/jats:title>\n                    <jats:p>We report the case of a 71-year-old woman with acromegalic facies, referred following bilateral idiopathic lens luxation (LL). Subsequent investigations revealed a 15-mm pituitary adenoma, along with biochemical evidence of massive growth hormone hypersecretion (Growth Hormone (GH): 93.22 \u00b5g\/L; insulin-like growth factor 1 [IGF-1]: 748 \u00b5g\/L), consistent with acromegaly. She exhibited multiple comorbidities, including arterial hypertension, chronic heart failure secondary to dilated cardiomyopathy\u2014compatible with acromegalic heart disease (AHD)\u2014osteoporosis, and type 2 diabetes mellitus (T2DM), reflecting a long-standing and high-burden disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Treatment and clinical course<\/jats:title>\n                    <jats:p>Since the patient was not eligible for surgery and daily subcutaneous injections were unfeasible due to the patient\u2019s lack of autonomy and limited caregiver support, therapy with lanreotide was initiated despite complete resistance to high doses of the classic analogue. We switched to pasireotide, achieving excellent disease control with 60 mg administered every 28 days. Progressive reduction in IGF-1 levels subsequently allowed a dose tapering to 40 mg every 28 days. Biochemical control of acromegaly was accompanied by improvement in disease-related complications (most notably T2DM), as well as the development of secondary hypocortisolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ocular complications<\/jats:title>\n                    <jats:p>Bilateral lens dislocation is not a known acromegaly complication; however, its bilateral occurrence suggests an underlying systemic cause. A plausible pathogenetic mechanism may involve chronic GH hypersecretion and IGF-1 overexpression, with subsequent interaction with ocular receptors. IGF-1 exerts an antiapoptotic and pro-proliferative action on lenticular cells through interaction with the IGF-1 receptor and the intracellular PI3K\/Akt pathway. It is a regulatory factor in the synthesis and degradation of fibrillin-1, a glycoprotein abundantly expressed in the extracellular matrix of the ciliary zonule, whose altered synthesis may underlie weakness of the lens suspensory apparatus. This is the first reported case of its genre, although bilateral intraocular lens subluxation (LS) in a patient with acromegaly and elevated intraocular pressure has previously been reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bilateral lens dislocation may represent an atypical presentation of acromegaly. It may indicate advanced disease and, if confirmed in other cohorts, could be considered among the suggestive signs of acromegaly. In our case, the use of pasireotide allowed adherence to therapy and optimal therapeutic response in a multicomplicated, non-self-sufficient patient.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1666425","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:19:16Z","timestamp":1761542356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Bilateral lens dislocation as an atypical presentation of acromegaly and review of the ocular effects of GH\/IGF-1 excess"],"prefix":"10.3389","volume":"16","author":[{"given":"Laura","family":"Vitale","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia Maria","family":"Fatti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Bonomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Frara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Persani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biagio","family":"Cangiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41572-019-0071-6","article-title":"Acromegaly","volume":"5","author":"Colao","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11102-023-01360-1","article-title":"Acromegaly consensus group. Consensus on criteria for acromegaly diagnosis and remission","volume":"27","author":"Giustina","year":"2024","journal-title":"Pituitary"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002-0022","article-title":"Systemic complications of acromegaly: epidemiology, pathogenesis, and management","volume":"25","author":"Colao","year":"2004","journal-title":"Endocr Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.577173","article-title":"Hypertension in acromegaly in relationship to biochemical control and mortality: global ACROSTUDY outcomes","volume":"11","author":"Vila","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2019.08.008","article-title":"Hypertension and acromegaly","volume":"48","author":"Puglisi","year":"2019","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01281.x","article-title":"Characterization of premature atherosclerosis of carotid arteries in acromegalic patients","volume":"54","author":"Otsuki","year":"2001","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-018-0911-5","article-title":"Preclinical markers of atherosclerosis in acromegaly: a systematic review and meta-analysis","volume":"21","author":"Parolin","year":"2018","journal-title":"Pituitary"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000545875","article-title":"Prevalence and characteristics of heart disease in patients with acromegaly in Colombia (RAPACO HEART study)","volume":"10","author":"Abreu-Lomba","year":"2025","journal-title":"Cardiology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1210\/er.2018-00115","article-title":"Systemic complications of acromegaly and the impact of the current treatment landscape: an update","volume":"40","author":"Gadelha","year":"2019","journal-title":"Endocr Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0027","article-title":"Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects","volume":"30","author":"M\u00f8ller","year":"2009","journal-title":"Endocr Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-024-00993-x","article-title":"Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management","volume":"20","author":"Esposito","year":"2024","journal-title":"Nat Rev Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-016-0758-6","article-title":"Acromegalic osteopathy","volume":"20","author":"Mazziotti","year":"2017","journal-title":"Pituitary"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.5114\/wo.2012.28790","article-title":"Risk of neoplasms in acromegaly","volume":"16","author":"Rucha\u0142a","year":"2012","journal-title":"Contemp Oncol (Pozn)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-025-01148-2","article-title":"Consensus on acromegaly therapeutic outcomes: an update","volume":"21","author":"Melmed","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70169-X","article-title":"Pasireotide C2402 Study Group. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial","volume":"2","author":"Gadelha","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-024-01461-5","article-title":"Efficacy and safety of pasireotide treatment in acromegaly: A systematic review and single arm meta-analysis","volume":"27","author":"Aliyeva","year":"2024","journal-title":"Pituitary"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-025-02642-0","article-title":"Impact of pasireotide on lipid and glucose metabolism in patients with acromegaly: a systematic review and meta-analysis","volume":"7","author":"Costanza","year":"2025","journal-title":"J Endocrinol Invest"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.648411","article-title":"Pasireotide in the personalized treatment of acromegaly","volume":"12","author":"Puig-Domingo","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-024-01391-2","article-title":"Hypopituitarism and bone disease: pathophysiology, diagnosis and treatment outcomes","volume":"27","author":"Akirov","year":"2024","journal-title":"Pituitary"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2480","article-title":"Pasireotide C2305 Study Group: pasireotide versus octreotide in acromegaly: a head-to-head superiority study","volume":"99","author":"Colao","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70169-X","article-title":"Pasireotide C2402 Study Group: pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial","volume":"2","author":"Gadelha","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00434.2001","article-title":"Somatostatin-28 regulates GLP-1 secretion via somatostatin receptor subtype 5 in rat intestinal cultures","volume":"283","author":"Chisholm","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0084","article-title":"Italian Study Group of Acromegaly. Predictors of morbidity and mortality in acromegaly: an Italian survey","volume":"167","author":"Arosio","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.11.27","article-title":"Elevated IGF-1 and GH levels are correlated with a thicker iris and wider anterior chamber angle in treatment-na\u00efve acromegaly patients","volume":"63","author":"Zhang","year":"2022","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2023.103773","article-title":"Corneal parameters, ocular biometers, and retinal and choroidal thickness in acromegaly patients","volume":"44","author":"Batur","year":"2023","journal-title":"Photodiagnosis Photodyn Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3109\/02713689408999885","article-title":"Insulin-like growth factor-1 (IGF-1) specifically binds to bovine lens epithelial cells and increases the number of fibronectin receptor sites","volume":"13","author":"Palmade","year":"1994","journal-title":"Curr Eye Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1046\/j.1432-0436.1996.6120077.x","article-title":"Cellular and molecular features of lens differentiation: a review of recent advances","volume":"61","author":"Wride","year":"1996","journal-title":"Differentiation"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0279","article-title":"Phosphatidylinositol 3-kinase (PI-3K)\/Akt but not PI-3K\/p70 S6 kinase signaling mediates IGF-1-promoted lens epithelial cell survival","volume":"45","author":"Chandrasekher","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B29","article-title":"IGF-1 enhancement of FGF-induced lens fiber differentiation in rats of different ages","volume":"34","author":"Richardson","year":"1993","journal-title":"Invest Ophthalmol Visual Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060497","article-title":"Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin","volume":"170","author":"Schaefer","year":"2007","journal-title":"Am J Pathol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4103\/tjo.tjo_76_19","article-title":"Late spontaneous bilateral intraocular lens subluxation accompanied with intraocular pressure elevation in a patient with acromegaly","volume":"10","author":"Chang","year":"2020","journal-title":"Taiwan J Ophthalmol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1666425\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:19:17Z","timestamp":1761542357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1666425\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":31,"alternative-id":["10.3389\/fendo.2025.1666425"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1666425","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2025,10,27]]},"article-number":"1666425"}}