BG, SS, OF and KS participated selleck chemical Imatinib Mesylate in the design of the study and helped to draft the manuscript. JMC and VM conceived of the study, and participated in its design and coordination and helped to draft the manuscript and performed the statistical analysis. All authors read and approved the final manuscript.
Briefly, the study was conducted prospectively between June 2003 and June 2005 in four ICUs (two medical, one surgical and one medicosurgical). Patients who required at least mechanical ventilation were screened daily for awakening and comprehension using five simple verbal commands as previously described [13,14]. Patients were enrolled in the study and hormonal assays were performed on the first day when awakening and comprehension were satisfactory (day 1).

Therefore, patients without successful awakening were not included. The study protocol was approved by the Ethics Committee of Saint-Germain-en-Laye, France. Informed consent was obtained from all patients.Demographic characteristics, category of admission, comorbidities and intensive care unit (ICU) admission diagnosis were recorded, as well as the severity of critical illness determined using the Simplified Acute Physiology Score II (SAPS II) [15] and the Organ Dysfunctions and/or Infection score [16]. The mean blood glucose levels and the cumulative dose of corticosteroids (expressed as hydrocortisone-equivalent dosage) between ICU admission and inclusion in the study were calculated for each patient.

Endocrinological measurementsPlasma follicle-stimulating hormone (FSH), lutenizing hormone (LH) and prolactin concentrations were measured using radioimmunometric assays (RIAs) (Access 2; Beckman Coulter, Villepinte, France) as described elsewhere [11]. Plasma concentrations of testosterone, estradiol and dehydroepiandrosterone (DHEA) were determined by performing RIA after ether extraction. Plasma concentrations of dehydroepiandrosterone sulfate (DHEAS), progesterone, cortisol and insulin-like growth factor 1 (IGF-1) were measured directly by RIA (CIS Bio International, Gif-sur-Yvette, France). Plasma cortisol levels measured in patients still being treated with hydrocortisone were not taken into account in the analysis. Plasma concentrations of thyroid-stimulating hormone were determined by using a third-generation sandwich immunoassay (Immunotech Beckman Coulter, Villepinte, France).

Plasma levels were considered abnormally low when they were below the lowest normal value.In men, independently of age, hypogonadism was considered when plasma testosterone levels Entinostat were below 3 ng/ml [17]. Hypogonadism was considered secondary (SH) when FSH and LH concentrations were below 5 mU/l and primary (PH) when FSH and LH levels were above 10 mIU/l [17].Women were considered postmenopausal if they were older than 55 years of age or if they reported amenorrhea for 1 year or more.