The paper by Morandi et al. (Reference Morandi2011), entitled “Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation,” is of great interest due to its lack of finding a correlation between serum levels of insulin-like growth factor-1 (IFG-1) and delirium in intensive care unit (ICU) patients.

As reviewed recently by Adamis and Meagher (Reference Adamis and Meagher2011), a large body of data supports the involvement of IGF-1 in the pathogenesis of delirium. A role for IGF-1 in delirium was first suggested by Wilson et al. (Reference Wilson2005). These investigators measured serum levels of IGF-1 in 100 acutely ill medical inpatients at the time of their admission and found that the 12 patients who later developed delirium had lower levels of IGF-1 (OR: 0.822, CI: 0.69, 0.97, p = 0.027). A role for lower levels of circulating IGF-1 in delirium has been confirmed by two studies from Adamis and Meagher (Reference Adamis and Meagher2011) and a study from our laboratory on postoperative delirium in knee replacement patients (Kwatra and Rivelli, Reference Kwatra and Rivelli2008).

From the foregoing, it is clear that a lack of an association between IGF-1 and delirium needs to be scrutinized. To their credit, Morandi et al. point out several factors that could have affected their not finding an association between circulating IGF-1 levels and delirium. However, one factor that Morandi et al. did not address is the nature of the IGF-1 assay that they employed. From the work of endocrinologists, we know that measuring IGF-1 in plasma/serum is full of pitfalls, and proper validation of the assay is needed. Unfortunately, Morandi et al. do not provide any details of the IGF-1 assay they used, and it is important to know whether they validated the assay according to the guidelines provided by Frystyk et al. (Reference Frystyk, Freda and Clemmons2010).