Adherence to the Mediterranean diet is linked to reduced psychopathology in female celiac disease patients.

Celiac disease (CD) is a chronic enteropathy, affecting approximately 1% of the population worldwide with a higher prevalence in women. Recent studies demonstrate that CD is associated with an increased prevalence of psychopathology. The present study was undertaken to investigate the relationship between adherence to the Mediterranean Diet (MD) and psychopathological symptoms among CD patients, since the MD is a physical and mental health protective dietary regimen, which can easily be rendered gluten-free. A total of 134 CD patients (28 males and 106 females) were included in the study. Psychopathology was evaluated with the Symptom Checklist-90-Revised (SCL-90-R), and MD adherence was calculated using the Mediterranean Dietary Serving Score (MDSS). As regards psychopathological symptoms, female patients presented with statistically significant higher depression and anxiety than males. The majority of patients (64.9%) had low adherence to the MD (MDSS <14) with a mean score of 9.44 ± 3.26 and 9.14 ± 3.07 for men and women, respectively, out of a total of 24 points. High MD adherence was observed in 35.7% of the male and 34.9% of the female patients, with a mean score of 16.40 ± 2.63 and 16.35 ± 2.12, respectively. Interestingly, MD adherence was inversely associated with the intensity of several psychopathological symptoms in female patients, which represented the majority of the sample. The results of the study underline the need to encourage CD patients to adapt to a Mediterranean-style GFD.

The Importance of Use of the On-line Databases as a Source for Systematic Review of Toxoplasmosis Screening During Pregnancy.

BACKGROUND: Infection with the parasite Toxoplasma gondii is a common infection in animals and humans worldwide. This infection can occur after ingestion of water or food contaminated with cat oocytes, ingestion of tissue cysts in mammalian and avian meat and congenitally. The prenatal infection can lead to Congenital Toxoplasmosis with miscarriage or stillbirth. After infection, laboratory tests are positive within 2-3 weeks and remain positive throughout life. However, testing for Toxoplasma infection during pregnancy is necessary in some countries, while in others it is not a mandatory "screening" test. OBJECTIVE: The aim of this study was to review systematically the screening of toxoplasmosis in pregnancy in different countries worldwide. METHODS: Cohorts, retrospective and cross-sectional studies were incorporated in our review, finally including 11 articles from an initial pool of 1532 related papers. RESULTS: The seroprevalence of pregnant women varies from countries with low prevalence to regions with high prevalence and screening policies also differ. Most countries worldwide have control policies, while Germany and Mexico that do not have systematic screening for Toxoplasma during the prenatal period. CONCLUSION: Our results show that Congenital Toxoplasmosis is very rare in some countries and it is very difficult to find a balance between potential risk and benefit of a screening program. For this reason, some countries are limited to prenatal counseling to reduce CT. In addition, the reduction of major sources of contamination especially in developing countries is the most important prevention measure.

Site-specific use of molecular markers could be a promising prognostic tool in colorectal cancer.

Proximal and distal colorectal carcinomas (CRCs) are generally considered as genetically and clinicopathologically distinct disease entities. Tumor location has been proposed as an additional prognostic indicator and -more recently- as a factor with significant influence on the prognostic value of particular molecular markers and/or combination of markers (KRAS, MSI, APC/MSI), allowing the discrimination of specific disease subsets with considerably disparate outcome and the identification of high risk cases. This article examines the clinical importance of particular recent proposals on this specific issue. Their strengths and limitations, as well as issues requiring further elucidation and practical problems hampering their clinical implementation are briefly discussed. Moreover, some suggestions intending to improve research methodology on this specific theme and to render the clinical use of this novel approach more effective and feasible, are presented. Hopefully, the assessment of certain molecular markers in a site-specific fashion could be another step towards personalized management of CRC, improving and complementing the molecular classification of the disease.

Proximal shift of colorectal cancer. A persistent phenomenon with multiple causes, patterns and clinical implications.

A considerable change in the anatomical distribution of colorectal cancer (CRC) towards more proximal sites has been observed in Western countries within the last 6-7 decades. As a result, tumors located proximally to the splenic flexure are now accounting for 30-40% (or even more) of overall CRC cases. This proximal migration is not always representing a true increase of proximal cancer, arising from various combinations of changes in the rates of proximal and distal cancer (e.g. proximal increase with distal stability/reduction, or decline in both sites albeit higher distally etc) in different areas and periods. Principal potential causes include ageing in Western populations (since proximal cancers are more common among the aged), various potentially site-specific exposures (lifestyle and medical) and systematic screening. Their effect is reflected in the particular shift patterns; for instance, widespread screening in USA has led to an overall CRC decline, more evident distally (for technical, anatomical and morphological reasons). Segmental disparities in particular characteristics (age, gender, morphology) and responses to various exposures are etiologically associated (for the most part) with underlying genetic differences between proximal and distal tumors. From clinical aspect, proximal shift necessitates a more generalized use of colonoscopy in screening programs. Potential interventions in treatment (segmental patient stratification) and prevention (identification of particular site-specific exposures) require further investigation.

A detailed immunohistochemical analysis of the PI3K/AKT/mTOR pathway in lung cancer: correlation with PIK3CA, AKT1, K-RAS or PTEN mutational status and clinicopathological features.

The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is upregulated in a number of human cancers, including non-small cell lung cancer (NSCLC). Its potential role in NSCLC progression provides an attractive target for anticancer therapy. The expression of phosphorylated mTOR (p-mTOR), phosphorylated AKT (p-AKT), p85α and p110γ subunits of PI3K, phosphorylated p70S6K (p-p70S6K), phosphatase and tensin homolog (PTEN) and phosphorylated 4E-BP1 (p­4E­BP1) was examined by immunohistochemistry in 102 NSCLC specimens. The results were correlated with clinicopathological features. We also examined 61 of our cases for the presence of PIK3CA, AKT1, PTEN and K-RAS mutations. A common PIK3CA mutation was detected at exon 9 in 2 samples (p.E545K), whereas another sample displayed a rare mutation (p.D1018N). Furthermore, 10 out of 54 cases (18.5%) had a K-RAS mutation at codon 12, 5 had a PTEN mutation (exons 7 and 8) and 1 case had an AKT1 mutation (p.E17K). PTEN mutations were associated with nodal metastases. The expression of p-mTOR positively correlated with that of p-AKT and p-p70S6K and was higher in adenocarcinomas along with nuclear p110γPI3K expression, whereas p-4E-BP1 expression was higher in squamous cell carcinomas. We also established a positive association between p85αPI3K or p110γPI3K and cytoplasmic p-AKT and its downstream effectors. An inverse correlation was noted between p-4E-BP1 immunoexpression and tumour status and nuclear p-AKT expression as regards tumour stage. Univariate survival analysis demonstrated that p-4E-BP1 expression, either alone or in combination with cytoplasmic p-AKT expression had an adverse prognostic significance in adenocarcinomas. The combination of p-4E­BP1 and cytoplasmic p-AKT expression remained significant in the multivariate analysis as a function of their interaction with histological type. Our data demonstrate the significance of p­4E­BP1 immunoexpression as a molecular marker of prognostic value in adenocarcinomas, particularly when combined with p-AKT.

Primary endobronchial non-Hodgkin lymphoma in an 80-year-old patient with prostate cancer.

The identification of a primary endobronchial non-Hodgkin lymphoma (NHL) is rare. We hereby present the case of a primary solitary endobronchial NHL lesion in an 80-year-old patient with prostate cancer who did not present any systemic involvement at the time of diagnosis.

[The importance of the tumor marker CYFRA 21-1 in patients with lung cancer after surgery or chemotherapy].

Lung cancer is the most common cancer worldwide with 900,000 new cases each year in men and 330,000 in women, being also the major cause of death from cancer. In Greece about 4,000 persons die every year due to lung carcinoma. One of the major problems in the follow up of these patients is the difficulty of early detection of recurrent disease. Tumor markers are of particular interest in this respect. Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins that show increased levels in patients with carcinomas. CYFRA 21-1 assays determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients with various types of lung cancer after surgery or chemotherapy. Ninety-six consecutive patients were studied during a two years period. Forty-five of them had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC). Moreover, 52 healthy individuals were studied to estimate the cut off value of CYFRA 21-1. Increased serum levels of the marker were found in patients with lung cancer compared to controls (P<0.001). The cut off value was estimated as 3.3 ng/ml with 96% specificity. Before the treatment there was no difference in the sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels, 52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC and especially in SCC among other histotypes of NSCLC when different stages of the disease were compared. Patients with extended disease, metastatic or recurrent disease had also more increased levels of the marker (P<0.001). One month after surgical ablation of the primary lung lesion, 28/58 patients showed a drop in the levels of the marker as an indication of the tumor ablation. From the 58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1 levels with a sensitivity of 92% and specificity of 95%. From the 38 patients that underwent chemotherapy treatment, 24 had a depravation of the disease and 21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer.

Pituitary-adrenal responses to human corticotropin-releasing hormone in critically ill patients.

OBJECTIVE: To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome. DESIGN AND SETTING: Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital. PATIENTS: The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years). INTERVENTIONS: A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured over a period of 2 h. MEASUREMENTS AND RESULTS: In the overall patient population baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5 microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors. CONCLUSIONS: Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.

Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study.

AIMS: We tested the hypothesis that renin-angiotensin system inhibition could reverse left ventricular diastolic dysfunction in patients with type 2 diabetes. METHODS AND RESULTS: Forty asymptomatic patients with type 2 diabetes were recruited in this double-blind cross-over trial. Left ventricular diastolic function was assessed at baseline with Doppler echocardiography; ratios of early to late peak flow velocity through the mitral orifice (E/A) and velocity time integral of early to late transmitral diastolic flow (VTIE/VTIA) were evaluated. In addition, plasma brain natriuretic peptide (BNP) was measured. Patients received randomly either ramipril (2.5 mg/day), or telmisartan (40 mg/day) or their combination for 3 months. Subsequently, every patient was crossed over to alternative regimens after a 2-week washout period. Measurements were repeated at the end of each treatment period. Both E/A and VTIE/VTIA ratios were increased (29 and 20% with ramipril, 25 and 23% with telmisartan and 36 and 28% with combination treatment, respectively, p < 0.001), whereas plasma BNP levels were significantly reduced with all 3 regimens (9% with ramipril, 25% with telmisartan and 36% with combination, p < 0.001). CONCLUSIONS: Both ramipril and telmisartan improve echocardiographic left ventricular diastolic indices and reduce plasma BNP levels in diabetic patients; their combination yields an even better therapeutic effect.

Bilateral inferior petrosal sinuses sampling in the routine investigation of Cushing's syndrome: a comparison with MRI.

OBJECTIVE: Identifying the cause of Cushing's syndrome (CS) is a perplexing issue. Bilateral inferior petrosal sinuses sampling (BIPSS) is an invasive and elaborate but established procedure in distinguishing Cushing's disease (CD) from ectopic adrenocorticotropic hormone (ACTH) syndrome. We compare the diagnostic performance of BIPSS and MRI in detecting an ACTH-secreting source, and we suggest the diagnostic protocol that we found beneficial for the management of patients with CS. MATERIALS AND METHODS: Seventy-eight consecutive patients with CS were included. All patients underwent biochemical investigation and pituitary MRI. Consequently, patients were routinely referred for BIPSS; 25 received stimulation with corticotropin-releasing hormone (CRH) and 53 with CRH and desmopressin. The diagnosis of CD was established on the basis of complementary biochemical, imaging, and BIPSS criteria. The diagnostic performances of BIPSS and MRI were calculated for patients with final diagnosis. RESULTS: A final diagnosis was available for 54 patients (46 CD confirmed, five ectopic confirmed, three adrenals). No (known) patient was misclassified based on our suggested diagnostic criteria. MRI rendered 25 false-negatives and two false-positives (incidentalomas). Successful BIPSS yielded two false-negatives and three false-positives (adrenals). The calculated accuracy for detecting a pituitary source of ACTH was 50% and 88% for MRI and successful BIPSS, respectively. CONCLUSION: MRI is of only limited diagnostic performance, while BIPSS is the most accurate way to establish the diagnosis of CD. The routine use of a multimodality diagnostic approach including BIPSS, MRI, and biochemical tests is suggested to avoid the risk of mismanagement for patients with CS.

Untreated hypopituitarism due to absence of the pituitary stalk with normal adult height: report of two cases.

Patients with congenital multiple pituitary hormones deficiency (MPHD) occasionally present with pituitary stalk interruption and ectopic posterior lobe on magnetic resonance imaging (MRI). Very rarely normal adult height despite growth hormone deficiency (GHD) has been described in these patients. We report two patients with evidence of congenital MPHD, who remained untreated until adulthood. They both failed to develop spontaneous puberty, and they demonstrated very low growth velocity until adulthood when they continued to grow, with a final height of 176 and 169 cm when they sought medical attention in our department at the age of 45 and 33 yr, respectively. At that time a hypoplastic pituitary, absence of pituitary stalk, and ectopic posterior pituitary lobe were found on MRI, and the laboratory investigations, including dynamic tests for pituitary hormone reserve, revealed MPHD with severe GHD. In conclusion, these cases illustrate that very rarely patients with untreated MPHD can reach normal adult height. Some postulations about the pathophysiology of this phenomenon are discussed.

Glucose and lipid fluxes in the adipose tissue after meal ingestion in hyperthyroidism.

BACKGROUND: Although insulin resistance is well established in hyperthyroidism, information on the effects of insulin on adipose tissue (AD) is limited. METHODS: To investigate this, a meal was given to 12 hyperthyroid (HR) and 10 euthyroid (EU) subjects. Blood was withdrawn for 360 min from veins draining the anterior abdominal sc AD and from the radial artery. Blood flow was measured with 133Xe. Lipoprotein lipase (LPL) was calculated as triglyceride flux across AD, and AD-lipolysis was calculated as glycerol flux minus LPL. RESULTS: Both groups displayed comparable postprandial glucose levels, with the HR having higher insulin levels than the EU. In AD of HR vs. EU: 1) blood flow was increased [area under curve 0-360 min (milliliters per 100 milliliters of tissue); 1746 +/- 208 vs. 1344 +/- 102, P = 0.001], but glucose uptake was normal [area under curve 0-360 min (micromoles per 100 milliliters of tissue); 501 +/- 114 vs. 368 +/- 48]; 2) fasting rates of lipolysis (nanomoles per minute per 100 milliliters of tissue; 329 +/- 75 vs. 89 +/- 22, P = 0.02) and nonesterified fatty acid (NEFA) release (nanomoles per minute per 100 milliliters of tissue; 841 +/- 146 vs. 316 +/- 97, P = 0.01), and plasma NEFA levels (micromoles per liter; 623 +/- 50 vs. 454 +/- 57, P = 0.03) were increased, but were all rapidly suppressed to levels similar to those in EU after the increase in plasma insulin levels after the meal; and 3) LPL was not stimulated by insulin. CONCLUSIONS: In hyperthyroidism, AD lipolysis and glucose uptake are resistant to insulin. The defect in lipolysis is manifested in the fasting state, whereas postprandially this rate is rapidly suppressed to normal. This may relieve tissues from the burden of NEFAs after the meal, thus facilitating muscle glucose disposal by insulin.

Prognostic significance of microalbuminuria in non-diabetic patients with acute myocardial infarction.

BACKGROUND: The aim of this study was to examine whether the presence of microalbuminuria (20-200 microg/min) can predict in-hospital morbidity and mortality in non-diabetic patients with acute myocardial infarction. METHODS: Two hundred twenty-three (172 men and 51 women) non-diabetic patients with acute myocardial infarction were studied prospectively. The main outcome measures of the study were based on a comparison of in-hospital mortality and major non-fatal in-hospital events (pulmonary edema, post-infarction angina, infarct extension, mechanical complications, conduction disturbances and ventricular arrhythmias) between microalbuminuric and normoalbuminuric patients. RESULTS: A significant proportion of patients (33.6%) had microalbuminuria. Seventy-six patients (34%) developed an in-hospital event (fatal or non-fatal). Six patients (2.7%) with acute myocardial infarction died in the hospital. Patients with microalbuminuria had a higher mortality rate in comparison with normoalbuminuric patients (6.6% vs. 0.68%, p = 0.01). For non-fatal events, the incidence of pulmonary edema and ventricular arrhythmias was significantly higher in patients with microalbuminuria (14.6% vs. 3.4%, p < 0.001 and 12% vs. 3.4%, p = 0.01, respectively). The combined end-point of the total number of fatal and non-fatal events was significantly higher in patients with microalbuminuria (57.3% vs. 22.3%, p < 0.001). In multiple logistic regression analysis, microalbuminuria (p < 0.001) and ejection fraction (p = 0.01) were independently related to the occurrence of major in-hospital events. CONCLUSIONS: Microalbuminuria is a significant predictor of in-hospital morbidity and mortality in non-diabetic patients with acute myocardial infarction.

Endocrine alterations in critically ill patients with stroke during the early recovery period.

INTRODUCTION: Endocrine abnormalities in critically ill patients with stroke during the early recovery period have not been well characterized. METHODS: To investigate this issue, 33 consecutive mechanically ventilated patients (27 men) with hemorrhagic (n = 21) or ischemic (n = 12) stroke having a mean age of 57 +/- 12 years were studied. Glasgow Coma Scale score on admission in the hospital was 8 +/- 3. The following basal hormones were measured within 72 hours postextubation: cortisol, corticotropin (ACTH), free thyroxine, tri-iodothyronine, thyroid-stimulating hormone, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor (IGF)-1. Subsequently, a low-dose (1 microg) ACTH stimulation test was performed. RESULTS: Twenty-six (79%) patients showed endocrine alterations. The most common change was low IGF-1 levels compatible with growth hormone deficiency (45%), followed by hypogonadism (39%), thyroid dysfunction (36%), and cortisol hyporesponsiveness (33%). CONCLUSION: Neuroendocrine changes occur with high frequency in critically ill patients with stroke during the early recovery period. It remains to be determined whether these changes have implications for functional and/or clinical outcome.

Microalbuminuria: a strong predictor of 3-year adverse prognosis in nondiabetic patients with acute myocardial infarction.

BACKGROUND: The aim of this study is to evaluate the significance of microalbuminuria (MA) as a 3-year prognostic index in nondiabetic patients with acute myocardial infarction (AMI). METHODS: One hundred seventy-five patients with AMI were followed prospectively for 3 years. The study end point was cardiac death or rehospitalization for an acute coronary event. RESULTS: Forty-two patients (24%) developed a new cardiac event during the follow-up. Microalbuminuria (P < .001), pulmonary edema during initial hospitalization (P < .001) and postinfarction angina (P = .0364), advanced age (P = .001), severe atherosclerosis (high Gensini score) (P = .036), ejection fraction <50% (P = .0013), history of bypass surgery (P = .0265), and early conservative management (P = .0214) were all associated with adverse prognosis. Cox proportional hazards regression analysis showed that MA was an independent predictor of 3-year adverse prognosis in all the models tested, with an adjusted relative risk for the development of a cardiac event ranging from 2.1 to 4.3. CONCLUSIONS: In nondiabetic patients with AMI, MA is a strong and independent predictor of an adverse cardiac event within the next 3 years.

Comparison of the effects of ramipril versus telmisartan in reducing serum levels of high-sensitivity C-reactive protein and oxidized low-density lipoprotein cholesterol in patients with type 2 diabetes mellitus.

The effect of ramipril (an angiotensin [AT]-converting enzyme inhibitor), telmisartan (an AT-II type 1 receptor blocker), or their combination on inflammation and lipid peroxidation was assessed in 37 patients with type 2 diabetes who were free of coronary artery disease. All regimens were associated with a significant reduction of C-reactive protein and oxidized low-density lipoprotein cholesterol serum levels (p <0.001). These results further enlighten the mechanisms underlying the cardiovascular beneficial effect of renin-AT system inhibition.

High incidence of neuroendocrine dysfunction in long-term survivors of aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: To investigate the incidence, pattern, and magnitude of neuroendocrine changes in long-term survivors of aneurysmal subarachnoid hemorrhage (SAH). METHODS: Thirty patients (16 women) with a mean age of 50+/-13 years underwent endocrine assessment between 12 and 24 months after aneurysmal SAH. SAH severity was graded clinically by the Hunt & Hess scale (median, II) and radiologically by the Fisher classification (median, II). Patients underwent measurement of basal hormone levels and dynamic assessment by the low-dose (1 microg) corticotropin stimulation test. Functional outcome was examined concurrently with endocrine testing by the modified Rankin Scale and the Barthel Index. RESULTS: Of the 30 patients tested, 14 patients (47%) showed isolated or combined endocrine abnormalities. These included low insulin-like growth factor 1 levels compatible with growth hormone deficiency in 37%, hypogonadism in 13%, and cortisol hyporesponsiveness to the low-dose corticotropin stimulation test in 10%; thyroid dysfunction in the form of subclinical hypothyroidism was observed in 7% of patients. Median modified Rankin Scale and Barthel Index at the time of endocrine testing were 1 and 100, respectively. There was no correlation between the presence of endocrine dysfunction and SAH severity indices or functional outcome scores. CONCLUSIONS: Long-term survivors of aneurysmal SAH frequently exhibit endocrine changes, with growth hormone and gonadal deficiencies predominating. Thus, screening of pituitary function is recommended in patients surviving SAH. The relationship between late hormonal alterations and functional outcome in patients with SAH warrants further study.

Comparison of the extent and severity of coronary artery disease in patients with acute myocardial infarction with and without microalbuminuria.

The extent and severity of coronary atherosclerosis were compared between 43 microalbuminuric and 87 normoalbuminuric nondiabetic patients with acute myocardial infarction. Patients with microalbuminuria had significantly greater scores of the severity (Gensini score) and extent (Hamsten score) of coronary artery disease (p <0.001).

Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors.

OBJECTIVE: To investigate the incidence and type of endocrine abnormalities in critical care patients with traumatic brain injury (TBI) and to examine their relationships to possible predisposing factors. DESIGN: Prospective study. SETTING: General intensive care unit in a university hospital. PATIENTS AND PARTICIPANTS: Thirty-four TBI patients (27 men, 7 women), having a mean age of 37+/-16 years, were studied after weaning from mechanical ventilation. INTERVENTIONS: Baseline endocrine assessment was carried out by measuring cortisol, corticotropin, dehydroepiandrosterone sulfate, free thyroxine, thyrotropin (TSH), testosterone, oestradiol, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, growth hormone and insulin-like growth factor I. Dynamic evaluation was performed by human corticotropin releasing hormone and growth hormone releasing hormone in all patients. Male patients underwent additional investigation with gonadotropin-releasing hormone. Severity of neurological derangement was graded according to Glasgow Coma Scale (GCS), Marshall Computerized Tomographic Classification and intracranial pressure (ICP) levels. MEASUREMENTS AND RESULTS: Eighteen of the 34 patients (53%) had an abnormal result in at least one hormonal axis tested, with cortisol hyporesponsiveness and gonadal dysfunction being equally common, affecting 24% of patients. Endocrine abnormalities were associated with a higher brain CT-scan classification score ( p=0.02). The GCS on admission correlated positively with baseline FSH (r=0.37, p=0.03), peak FSH (r=0.41, p=0.03), testosterone (r=0.44, p=0.02) and TSH (r=0.39, p=0.03). There were no relations between ICP(max) and any baseline or dynamic hormone measurements. CONCLUSIONS: Patients with TBI receiving critical care show changes in their neuroendocrine responses, which depend upon clinical and radiological measures of head injury severity. Most common abnormalities include cortisol hyporesponsiveness and hypogonadism.

The low-dose corticotropin stimulation test in acute traumatic and non-traumatic brain injury: incidence of hypo-responsiveness and relationship to outcome.

OBJECTIVE: To investigate adrenal responses to the low-dose corticotropin (ACTH) stimulation test in acute traumatic or non-traumatic brain injury (BI) and to assess its value in predicting outcome. DESIGN: Prospective study. SETTING. Intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: Seventy-five patients with acute BI, with a median age of 45 years were investigated. BI was due to trauma ( n=51), ischemic stroke ( n=17), subarachnoid hemorrhage ( n=4) or intracerebral hemorrhage (n=3). INTERVENTIONS: Blood was taken on day 16 (median) after admission to the ICU to determine baseline cortisol and ACTH. Thereafter, a low-dose stimulation test (LDST) was performed: 1 microg of tetracosactrin was injected and 30 min later a second blood specimen was obtained to measure stimulated cortisol. Patients having a stimulated cortisol below 500 nmol/l were defined as non-responders to the LDST. MEASUREMENTS AND RESULTS: Median baseline and stimulated cortisol were 491 nmol/l and 690 nmol/l, respectively. The median increment in cortisol was 154 nmol/l (range 5-579 nmol/l). Mean ACTH was 46+/-21 pg/ml. Ten (13%) patients were non-responders to the LDST; these had a higher mortality rate compared to patients with adequate cortisol production (70 vs 32%, p=0.034). Logistic regression analysis revealed that APACHE II ( p<0.001), Glasgow Coma Scale (GCS) ( p=0.04) and age ( p=0.02) were independent outcome predictors. In contrast, the increment in cortisol ( p=0.26) did not add to outcome prediction. CONCLUSIONS: Adrenal hypo-responsiveness in the setting of acute traumatic or non-traumatic BI is not an independent outcome predictor in the presence of high APACHE II, low GCS and older age.