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Editor,—Mauriac’s syndrome is a rare condition of insulin dependent diabetic children with long standing poor glycaemic control, growth retardation, and liver enlargement in whom improvement of diabetes control accelerates diabetic retinopathy.1 The cause of this paradoxical progression of diabetic retinopathy is unknown.
A 21-year-old man, diabetic since the age of 2, was first admitted to our hospital because of short stature and delayed sexual maturation. He presented with all signs of Mauriac’s syndrome: height 155 cm (below third percentile), body weight 41 kg, prepubertal sexual development (pubic hair Tanner stage 3, genital stage 2), liver enlargement, and subnormal serum concentration of insulin-like growth factor 1(IGF-1) of 162 ng/ml. His diabetes had been poorly controlled ever since, the actual HbA1c (normal < 5.6%, high performance liquid chromatography) being 13.3%, corresponding to an average glycaemia of about 20 mmol/l. Alkaline phosphatase was elevated (317 U/l) indicating delayed bone maturation; total cholesterol (314 mg/dl), low density lipoprotein cholesterol (263 mg/dl), triglycerides (375 mg/dl), and proteinuria (587 mg/l) were also abnormal as a consequence of poor diabetes control. Basal and stimulated levels of growth hormone, gonadotrophins, prolactin, and thyroid stimulating hormone were normal, as were testosterone, ‘free’ thyroxine and triiodothyronine, parathyroid hormone, osteocalcine, and vitamin D metabolites. Funduscopy revealed mild non-proliferative diabetic retinopathy, corresponding to retinopathy level 1.2 Visual acuity was 1.0. Treatment aimed at improving diabetes control was initiated by increasing the insulin dosage. Serum IGF-1, HbA1c, and retinopathy levels were followed prospectively. Eight months after intensifying insulin therapy, HbA1c had declined to 11.9% (corresponding to an average glycaemia of 18 mmol/l), serum IGF-1 had increased to 326 ng/ml, and the patient had grown by 2 cm. However, retinopathy had progressed to a severe non-proliferative state with substantial ischaemia at the posterior pole and diffuse macular oedema (level 3) with a drop in visual acuity to 0.8 (Fig 1A and B). Limited central laser coagulation was commenced, followed by panretinal laser coagulation. After a further 2 months, IGF-1 had further increased to 482 ng/ml (Fig 2), while longitudinal growth was continuing. Simultaneously, diabetic retinopathy progressed to the proliferative state (level 5). All neovascularisations regressed upon completion of panretinal laser coagulation, and visual acuity was restored (level 4). Shortly after that, growth velocity declined (yielding a final height after 2 years of observation of 161.5 cm) as did the IGF-1 concentration (227 ng/ml).
This is the first prospective and close follow up of serum IGF-1 concentrations and HbA1c in a poorly controlled diabetic patient, in whom deterioration of diabetic retinopathy in response to improving glycaemia was to be expected.1 3 IGF-1, which has growth promoting and angiogenic effects, was shown to increase after inducing improved glycaemic control, and this surge in serum IGF-1 concentration preceded retinal neovascularisation by 2 months. Exogenous IGF-1 can have serious side effects on the retinal circulation and can cause ‘papillopathy’, as has been described by Gallagher et al,4 and others.5Endogenous IGF-1 has been linked to proliferative retinopathy by other authors.6 Consistent with previous observations in diabetic patients7 8 we hypothesise from our case that an acceleration of diabetic retinopathy after abruptly improving glycaemic control in patients with IDDM and Mauriac’s syndrome may be induced by a surge in serum IGF-1 concentration. This may also explain progression of diabetic retinopathy in puberty9 and in pregnancy10; both conditions are associated with increasing IGF-1 levels. Increasing serum IGF-1 may, thus, have a role in the progression of diabetic retinopathy to the proliferative state.