The effect of long-term somatostatin analogue treatment on free and total insulin-like growth factor (IGF) -I, -II and IGF binding protein -1, -2 and -3 serum levels in euthyroid patients with active thyroid eye disease.

The aim of this study was to investigate the effect of long-term somatostatin analogue (SM-a) treatment on serum levels of free (F) and total (T) insulin-like growth factor (IGF)-I, -II and IGF binding protein (IGFBP) - 1, -2 and -3 in euthyroid patients with active thyroid ophthalmopathy. For this purpose, we measured the above-mentioned parameters in 21 patients (11M, 10F), aged 50.8+/-11.8 years (range 35-70) and 19 healthy individuals matched for age, gender and body mass index (BMI). A total of 4 SM-a (sandostatin LAR((R))-30) injections, each monthly, were administered in each patient and measurements were performed prior to treatment and 20-30 days after the last injection, while in control individuals the same determinations were performed only once. All patients had active thyroid eye disease (TED), with clinical activity scores (CAS) >/= 4 (5.3+/-1.1) and positive orbital octreoscan in both eyes. Serum F and T IGF-I and IGF-II were determined using non-competitive, time-resolved monoclonal immunofluorometric assays. IGFBP-1 and IGFBP-2 were determined by an in-house radioimmunoassay, while IGFBP-3 by commercially available IRMA. Our results showed that F and T IGF-I, -II and IGFBP-1, -2 and -3 levels in patients before and after administration of SM-a were comparable and the levels did not differ significantly from those of controls. Furthermore, no statistically significant differences emerged in the ratio between molar weights of TIGF-I/IGFBP-3 and TIGF-II/IGFBP-3, as well as in the ratio of F/TIGF-I and F/TIGF-II in patients before and after SM-a therapy. Fourteen patients (66%) experienced a decline in CAS of at least >1 point in each eye after SM-a administration, whereas in the remaining the CAS did not change. Finally, no relationship was found between the levels of the above-mentioned parameters (post therapy) and CAS, octreoscan scores and thyroid hormones levels. In conclusion, we showed that although SM-a administration in euthyroid patients with active TED had a beneficial effect in a significant percentage of patients, this effect was not associated with a decline in the circulating IGF-I, -II and IGFBP-1, -2 and -3 levels, at least under the conditions of the present study. It can be postulated that if the mechanism of action of SM-a is through reduction of IGF-I levels, this effect is possibly exerted in the retrobulbar tissues by local paracrine/autocrine action.