Impact of rosiglitazone on serum IGF1 concentrations in uncontrolled acromegalic patients under conventional medical therapy: results from a pilot phase 2 study
Martina Lombardi1, Giuseppe Rossi2, Francesco Raggi1, Claudio Urbani1, Chiara Sardella1, Chiara Cosci1, Enio Martino1 & Fausto Bogazzi1
Current therapies for acromegaly are unsatisfactory for some patients. High dose thiazoledinedines have been reported to shrink tumor size and reduce serum GH levels in animal models of acromegaly. To study the effects of increasing doses of rosiglitazone on serum GH and IGF1 concentrations in acromegalic patients, we designed a phase two clinical trial. We enrolled five consecutive patients with active acromegaly uncontrolled under conventional therapies. They received increasing doses of rosiglitazone (4 mg each month starting from 8 mg up to 20 mg/day), added to previous therapies for acromegaly. Mean serum IGF1 concentrations reduced from 547±91 to 265±126 μg /l (P=0.043) during the 4 months-course with rosiglitazone; main reduction occurred with the higher dose of rosiglitazone; on the opposite, lower doses of rosiglitazone left serum IGF1 levels unaffected in 4/5 patients. IGF1 normalized in all patients. Serum GH concentrations did not significantly changed as well as all other pituitary hormones. No main side-effects were observed. Studies in Hep G2 cells showed that rosiglitazone reduced hepatic GH-dependent generation of IGF1. Conclusion: Rosiglitazone reduces serum IGF1 concentrations in patients with active acromegaly, likely acting on the GH-dependent hepatic synthesis of IGF1. Large studies are necessary to confirm whether rosiglitazone may have a role as a new adjuvant therapy for acromegalic patients.