Statistics from Altmetric.com
Acromegaly is complicated by diabetes mellitus because of the action of growth hormone (GH) which induces the production of insulin-like growth factor I (IGF-I). IGF-I may contribute to the development of diabetic retinopathy in an autocrine and/or paracrine manner.1 In patients with acromegaly who demonstrate excessive secretion of GH, the incidence of retinopathy is reportedly very low and severe retinopathy is rare.2 3 This report describes a patient with severe proliferative diabetic retinopathy in both eyes associated with acromegaly. We performed pars plana vitrectomy and calculated the levels of angiogenic growth factors (IGF-I and vascular endothelial growth factor, VEGF) in the vitreous of both eyes to learn whether GH and/or IGF-I may influence the progression of diabetic retinopathy in proliferative diabetic retinopathy associated with acromegaly.4 5
A 62 year old woman presented with severe proliferative diabetic retinopathy and was admitted to Osaka Kaisei Hospital for a pars plana vitrectomy. The duration of her diabetic mellitus was about 10 years and her blood sugar level was between 140–320 mg/ml. HgA1c was 7.0–7.5%. The patient also had systemic hypertension. Corrected visual acuity was 30 cm/hand movement in the right eye and light perception in her left eye. Remarkable bilateral rubeosis iridis, active fibrovascular membranes, and extensive tractional retinal detachment were observed in both eyes (Fig 1). Physical examination revealed acromegaly in all four limbs (Fig2A). The patient’s serum GH level was 256 ng/ml and her serum IGF-I level was 726 ng/ml. Magnetic resonance imaging revealed the presence of pituitary adenoma (Fig 2B). Based on these findings acromegaly was diagnosed.
Pars plana vitrectomy was performed on both eyes. IGF-I levels in the vitreous obtained at the time of vitrectomy were determined by radioimmunoassay (assay range 0.3–2100 ng/ml) to be 14 ng/ml. VEGF levels in the vitreous were determined by an ELISA system (the lower limit of detection 2 pg/ml) to be 5.6 ng/ml. Trans-sphenoidal resection of the pituitary adenoma was indicated; however, the patient and her family refused to allow us to perform this treatment. After vitrectomy complete retinal attachment was achieved; however, rubeotic glaucoma was a complication in both eyes. Despite additional operations (trabeculectomy and cyclocryocoagulation) intraocular pressure was uncontrollable and light perception was ultimately lost in both eyes.
It is well known that diabetic retinopathy is an occasional complication of diabetic mellitus secondary to acromegaly,4 5 although the occurrence of proliferative diabetic retinopathy in association with this disease appears to be rare. But the present case of diabetic retinopathy accompanied by acromegaly was complicated by very active fibrovascular proliferation and tractional retinal detachment. Diabetic mellitus secondary to acromegaly is related to the oversecretion of GH. IGF-I, an angiogenic factor, is the mediating molecule that is influenced by GH in the pathogenesis of diabetic retinopathy. However, acromegalic patients who overexpress GH with or without concomitant diabetes do not demonstrate an increased incidence of retinopathy.4 5 The influence of the excessive secretion of GH and downstream effector IGF-I on diabetic retinopathy and neovascularisation in acromegalic patients remains unclear, although Smith and associates6 recently reported that inhibition of GH can inhibit ischaemia induced retinal neovascularisation in vivo via VEGF.
Other investigators have calculated the vitreous and serum levels of IGF-I in patients with proliferative diabetic retinopathy to be in the range of 5–8 ng/ml and 80–220 ng/ml respectively.7-9 In this case the vitreous level of IGF-I was 14 ng/ml and the serum level of IGF-I was 726 ng/ml. Both of these values are higher than in patients with proliferative diabetic retinopathy. This is the first report to calculate the vitreous IGF-I level in an acromegalic patient with severe proliferative diabetic retinopathy. The results suggest that the excessive production of local IGF-I or the breakdown of the blood-ocular barrier (which resulted in the diffusion of serum IGF-I into the vitreous cavity), occurred in this patient and accelerated the progression of the retinopathy. We also found a relatively higher level of VEGF (5.6 ng/ml), a major angiogenetic growth factor, in the vitreous of the patient.10 Some investigators reported that IGF-I accelerates the expression of VEGF in some cell lines.11 Thus, GH may have played a important role in the progression of diabetic retinopathy in combination with IGF-I and VEGF.9 Diabetic retinopathy associated with acromegaly should be further studied to examine the correlation among GH, IGF-I, VEGF, and other angiogenic factors.