We agree with Klein and colleagues that objective testing is very important in assessment of cognitive functioning. They raise an important question with regard to the stra-tegy of elucidating possible cognitive deterioration in patients receiving postoperative radiotherapy to the pituitary gland.
Klein et al. state that numerous studies found discrepancies between self-report measures of cognitive functioning and objective tests. This finding is likely subject to publication bias. In addition, several studies mentioned by Klein are flawed by comparing global measures of self-report cognitive functioning with a single global objective neurocognitive score calculated as the mean of all the (standardized) scores1-3. This is far from a balanced comparison. In fact, when analyzed in a proper way, Middleton found that patients’ perceptions of their performance on specific tasks correlated with their objective performance on those tasks2. Podewils and colleagues reported similar results and concluded that individuals experiencing changes in cognitive function appeared to have some awareness of their condition4.
Further, in a cross-sectional study design, patients with non-functioning pitui-tary adenomas show differences in baseline characteristics, in treatment (type of surgery, radiotherapy), and in outcome (presence of residual non-functioning adenoma, hypopituitarism). In addition, this group receives multiple substitution therapy e.g. growth hormone, hydrocortisone and thyroid hormone, with all the intrinsic imperfections of hormone replacement strategies in mimicking normal hormone secretion5. Sometimes patients and doctors choose not to substitute sex steroid or growth hormone deficiencies. Effects of endogenous hormone deficiencies and exogenous substitution therapy may not be the same with respect to cognitive functioning. Moreover, different surgical routes may damage different parts in the brain. And putative deleterious effects of radiotherapy will differ in time. Radiotherapy used to be given several decades ago with two opposing lateral fields, potentially damaging the temporal lobes. Modern radiotherapy evolved to use a multiple-field technique in order to spare more normal surrounding tissue from the effects of ionizing radiation6,7. Thus, multiple factors are present that are likely to affect multiple different parts of the brain and therefore different cognitive domains. As a result, objective testing (even screening) in this group is far from easy. Based on previous study reports, no obvious deficits in cognitive functioning were expected. It is a logical next step and common practice to ask the patient if they experience deficits in their own cognitive functioning. We chose the Cognitive Failures Questionnaire and found no differences with regard to the application of radiotherapy8. Further studies are warranted and should include interviewing partners for cognitive problems in their spouses. Subsequently, formal testing can be performed with special attention the reported problems in cognitive functioning. Attention should be paid to the choice of these tests because many show a high inter-rater variability and lack of validation.

Yours sincerely,

André P van Beek, Alphons C.M. van den Bergh, Linda M. van den Berg, Gerrit van den Berg,
Joost C. Keers, Johannes A. Langendijk,Bruce H.R. Wolffenbuttel.