N Thalassinos

Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels.

ObjectiveTo investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. DesignProspective study. SettingGeneral intensive care unit in a university teaching hospital. PatientsForty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 ± 16 yrs) were studied the day after termination of mechanical ventilation (7–60 days after trauma). InterventionsFirst, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 &mgr;g of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels <18 &mgr;g/dL were defined as nonresponders to the low-dose stimulation test. Thirty-one patients underwent also a human corticotropin releasing hormone test. Measurements and Main ResultsIn traumatic brain injury patients, mean baseline and low-dose stimulation test-stimulated cortisol levels were 17.2 ± 5.4 &mgr;g/dL and 24.0 ± 6.6 &mgr;g/dL, respectively. The median increment in cortisol was 5.9 &mgr;g/dL. Basal corticotropin levels ranged from 3.9 to 118.5 pg/mL. Six of the 40 patients (15%) failed the low-dose stimulation test. The human corticotropin releasing hormone test (performed in 26 responders and five nonresponders) revealed diminished cortisol release only in the low-dose stimulation test nonresponder patients. Corticotropin responses to corticotropin releasing hormone were consistent with both primary (three patients) and/or secondary (two patients) adrenal dysfunction. In retrospect, nonresponders to the low-dose stimulation test more frequently required vasopressors (6/6 [100%] vs. 16/34 [47%]; p = .02) and for a longer time interval (median, 0 vs. 293 hrs; p = .006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p = .01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p = .53). ConclusionsAdrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.

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 &mgr;g) 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.

High prevalence of decreased cortisol reserve in brain-dead potential organ donors.

ObjectiveTo investigate the adrenocortical function in brain-dead patients, potential organ donors. DesignProspective study. SettingIntensive care units in two teaching hospitals. PatientsA total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 ± 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. InterventionsIn all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 &mgr;g of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 &mgr;g/dL after the administration of adrenocorticotropic hormone were defined as responders. Measurements and Main ResultsAfter the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 ± 6.2 vs. 17.0 ± 6.6 &mgr;g/dL, p < .001) and stimulated (16.9 ± 6.3 vs. 23.9 ± 5.7 &mgr;g/dL, p = .001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p < .001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r = .71, p = .001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = −.37, p = .15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 ± 11.4 vs. 6.8 ± 4.2 &mgr;g/dL, p = .003) and stimulated serum cortisol (28.8 ± 9.9 vs. 16.3 ± 4.3 &mgr;g/dL, p = .008). ConclusionsAdrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.

Bilateral Inferior Petrosal Sinuses Sampling in the Routine Investigation of Cushing's Syndrome: A Comparison with MRI

OBJECTIVE Identifying the cause of Cushings syndrome (CS) is a perplexing issue. Bilateral inferior petrosal sinuses sampling (BIPSS) is an invasive and elaborate but established procedure in distinguishing Cushings 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.

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 µg) 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.

Adrenal hyporesponsiveness to the low-dose stimulation test (LDST) is associated with a higher mortality in early sepsis and/or septic shock

The aim of the study was to determine the status of the hypothalamic–pituitary–adrenal axis in critically ill patients with early sepsis and/or septic shock and to investigate whether adrenal responses are related to mortality. Forty-two patients (32 male; median age 62 years; range 17–82 years) had cortisol, corticotropin (ACTH) and dehydroepiandrosterone sulphate (DHEAS) levels measured at onset of sepsis and/or septic shock. Adrenal responsiveness was assessed by the LDST. A peak cortisol < 18 μg/dl on the LDST was considered as representing an inadequate response. For the entire patient population, hormone concentrations were as follows (median or mean ± SD values): baseline cortisol 17.8 μg/dl, stimulated cortisol 24.8 ± 9.4 μg/dl, increment in cortisol 5.9 ± 4.4 μg/dl, ACTH 21.2 pg/ml and DHEAS 1553 ± 1157 ng/ml. Eight (19%) of the 42 patients had inadequate cortisol responses following the LDST. Overall, 21 patients died and 21 patients survived. There were no differences between survivors and nonsurvivors with regard to baseline cortisol (17.2 vs 18.9 μg/dl, P = 0.20), stimulated cortisol (23.5 vs 25.1 μg/dl, P = 0.94), ACTH (20.1 vs 26.1 pg/ml, P = 0.48) or DHEAS (1754 ± 1333 vs 1352 ± 939 ng/ml, P = 0.26) levels. In contrast, nonsurvivors had a lower increment in cortisol following the LDST compared with survivors (4.2 ± 3.5 vs 7.5 ± 4.7 μg/dl, P < 0.05). In conclusion, a substantial (19%) proportion of patients has evidence of adrenal hyporesponsiveness at onset of sepsis and/or septic shock. Attenuated adrenal responses are associated with a higher mortality rate in such patients.