Changes in retinal microvasculature and serum Gremlin-1 levels in acromegaly: A case-control study

There are controversial results about the effects of GH/IGF-1 on retinal vasculature. Gremlin-1 has roles in both pituitary tumorigenesis and angiogenesis. Therefore, we aimed to detect retinal micro-vascular changes in acromegaly with OCTA and examine its association with serum Gremlin-1 levels.

A cross-sectional, case-control study METHODS: We included 53 acromegaly patients and age/gender-matched 31 healthy controls. To evaluate retinal structure, optical coherence tomography angiography (OCTA) imaging was performed. Gremlin -1 levels were measured by the ELISA method.

Acromegaly patients had significantly lower superficial total density (p< 0.001), superficial parafoveal density (p = 0.002), superficial perifoveal density (p < 0.001); deep total density (p < 0.001), deep parafoveal density (p < 0.001), deep perifoveal density (p < 0.001). Total thickness and perifoveal thickness were significantly lower in the acromegaly group. Gremlin-1 levels were significantly lower in acromegaly patients (1.22(0.13) vs 1.38(0.29); p = 0.015, for acromegaly and control groups, respectively). We assessed study groups based on glucose tolerance status. Normal glucose tolerance (NGT) acromegaly patients had significantly lower superficial total density (p = 0.036), superficial perifoveal density (p = 0.003), deep total density (p = 0.023), and deep perifoveal density (p = 0.023) compared to NGT controls. According to backward linear regression analysis, the presence of acromegaly itself consistently showed a significant negative impact on all types of vascular density.

Patients with acromegaly have decreased vascular density and lower levels of Gremlin-1 independent of glucose tolerance status. Acromegaly may cause a reduction in gremlin-1 as a compensatory mechanism due to high IGF-1 levels known as an angiogenic factor, which in turn leads to the decrease in vascular density, or gremlin-1 may already have shown a decline in response to chronic inflammation and endothelial dysfunction in acromegaly resulting in a reduction in vascular density.