MON-047 Coexistence of Marfanoid Features and Acromegaly: A Rare Clinical Presentation

Abstract Disclosure: M.C. Duarte: None. R. Mattos: None. T.R. Costa: None. I.S. Freitas: None. J.B. Drummond: None. B.S. Soares: None. Introduction: Marfan Syndrome (MFS) is an autosomal hereditary disorder with skeletal, ocular, and cardiovascular manifestations, while acromegaly results from excess growth hormone (GH), leading to skin thickening, extremity enlargement, and macroglossia. Both conditions are individually described, but their coexistence is rare. This case presents a unique instance of both MFS and acromegaly in one patient.Case: A 56-year-old male with classic features of MFS, including joint laxity, pectus carinatum, arm span-to-height ratio of 1.06, and positive thumb and wrist signs, also had significant cardiovascular involvement, having undergone aortic valve replacement and aneurysmectomy of the descending aorta. Despite a negative family history, his clinical features met MFS diagnostic criteria. Ten years after diagnosis, he noticed progressive changes in his hands, feet, and facial features, including a prominent nose, lips, and jaw.He sought endocrinological evaluation, and during the physical examination, signs of joint swelling and severe heart failure symptoms, including dyspnea, bilateral leg edema, and a grade V systolic murmur, were noted.Laboratory tests showed elevated IGF-1 (346 ng/mL) and GH (11 ng/mL) levels after an oral glucose tolerance test. MRI revealed a macroadenoma (1.2x0.8x0.8 cm). Due to his decompensated heart condition, surgery was postponed, and he began monthly lanreotide injections (120 mg), which reduced IGF-1 to 256 ng/mL and improved symptoms of aortic insufficiency and heart failure. One year later, cabergoline (1.5 mg/week) was added, and MRI showed tumor shrinkage (1.0x0.8x0.7 cm), though IGF-1 remained elevated at 296 ng/mL. After stabilizing his cardiac condition, the patient underwent transsphenoidal surgery. One month post-surgery, IGF-1 levels normalized, and he reported relief from swelling and pain.Whole exome sequencing (NGS) revealed no pathogenic variants linked to MFS, Multiple Endocrine Neoplasia type 1 and/or Isolated Familial Acromegaly. However, several potential pathogenic variants were identified in heterozygous form across six genes: WDR87 (p.Arg131Ter), POLR3A (c.1909+22G>A), CTNS (48 kb deletion), DUOX (p.Ser205Ter), FLG (p.Arg501Ter), and HFE (p.Cys282Tyr), though their clinical relevance is uncertain.Discussion:. In patients with Marfan-like phenotypes, fewer than 10% show pathogenic variants in the FBN1 gene, possibly due to complex genetic alterations. The identification of potential pathogenic variants in multiple genes highlights the complexity of genetic contributions to the patient’s condition, warranting further investigation. The coexistence of MFS and acromegaly in a single patient raises significant considerations about the diagnostic process, treatment strategies, and genetic evaluation for complex diseases. Presentation: Monday, July 14, 2025