Evidence of cognitive and neurophysiological impairment in patients with untreated naive acromegaly.

Context: Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions. However, very few human studies have challenged this hypothesis. Objective: The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions, particularly memory, and whether these alterations are accompanied by neurophysiological correlates. Design: We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls. Comparative analyses were carried out on major neurocognitive domains (executive functions, visual/verbal memory, attention, visuoconstructive abilities, and verbal fluency) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources. Results were correlated with GH and IGF-I hormone concentrations. Results: Short-and long-term memory were the most severely impaired cognitive functions. Moreover, memory performance correlated negatively with GH and IGF-I concentrations. No association was detected between depression and memory impairment, and only a marginal association was found with quality of life. Finally, acromegaly patients showed power attenuation in fast frequency electroencephalogram bands, as well as decreased activity in prefrontal and middle temporal cortices, that was associated to cognitive performance. Conclusions: Results provide evidence of cognitive and neurophysiological impairment, characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas. High levels of GH and IGF-I in acromegaly patients could be the basis for these findings. (J Clin Endocrinol Metab 95: 4367-4379, 2010)