Bilateral lens dislocation as an atypical presentation of acromegaly: case report and review of the ocular effects of GH/IGF-1 excess

Laura Vitale¹Letizia Maria Fatti²Marco Bonomi^1,2Stefano Frara^2,3Giovanni Vitale^1,2Luca Persani^1,2Biagio Cangiano^1,2*

• ¹Department of Medical Biotechnology and Translational Medicine, Faculty of Medicine and Surgery, University of Milan, Milan, Italy
• ²Istituto Auxologico Italiano Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
• ³Link Campus University, Rome, Italy

Introduction: 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 (GH: 93.22 µg/L; IGF-1: 748 µg/L), consistent with acromegaly. She exhibited multiple comorbidities, including arterial hypertension, chronic heart failure secondary to dilated cardiomyopathy -compatible with acromegalic heart disease (AHD)- osteoporosis and type 2 diabetes mellitus (T2DM), reflecting a long-standing and high-burden disease. Treatment and clinical course: Since the patient was not eligible for surgery and daily subcutaneous injections were unfeasible due to patient's lack of autonomy and limited caregiver support, therapy with lanreotide was initiated, with 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. Ocular complications: 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 anti-apoptotic 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 synthesis and degradation of fibrillin-1, a glycoprotein abundantly expressed in the extracellular matrix of the ciliary zonule, whose altered synthesis may be responsible for the lens suspensory apparatus weakness. 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 been previously reported. Conclusions: Bilateral lens dislocation could represent an atypical presentation of acromegaly. It could be a sign of advanced disease and, if confirmed in other cohorts, could be among the suggestive signs of acromegaly. In our case, the use of pasireotide allowed correct compliance and optimal response to therapy in a multicomplicated and not self-sufficient patient.