Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Abstract

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.

Morphometric changes correlate with poor psychological outcomes in patients with acromegaly

“…An irreversible effect of excess GH on cognitive functioning cannot be excluded (26), but future studies should also focus on various interventions, both psychological and cosmetic, to assess the impact of such strategies on improving psychopathological outcomes.…”

Neuropsychological functioning in acromegaly: towards identification of modifiable factors to improve long-term care after remission

“…At present, the number of reported patients that underwent neuropsychological evaluation after being considered adequately treated for acromegaly is still limited. Most studies evaluating cognitive function found worse scores on memory and executive functioning both in patients treated for acromegaly and for non-functioning adenomas, when compared to controls [10][11][12][13][14]. In the cohort of patients successfully treated for acromegaly at our center, cognitive function did not differ between acromegaly patients and matched controls or between acromegaly patients and patients treated for non-functioning adenomas [15].…”

Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumours: past, present and future

“…The clinical burden of acromegaly is further compounded by the substantial impairment in quality of life (QoL) (Rowles et al 2005, Trepp et al 2005, T'Sjoen et al 2007. Additionally, patients with acromegaly may experience neurocognitive (Leon-Carrion et al 2010, Martin-Rodriguez et al 2013) and neuropsychiatric dysfunctions (Sievers et al 2009a,b).…”

“…Indeed, in some patients, cognitive (Martin-Rodriguez et al 2013) and psychosocial (Biermasz et al 2004, van der Klaauw et al 2008) impairment may be irreversible. Despite the urgency to diagnose and treat, many patients with acromegaly still have uncontrolled disease, and there may be many more undiagnosed (Katznelson et al 2011).…”