William Tormey

Neuroendocrine dysfunction in the acute phase of traumatic brain injury.

background  Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post‐TBI period is unknown.

The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage.

Background  Hyponatraemia is common following subarachnoid haemorrhage (SAH) but the pathogenesis is unclear.

Early detection of acute myocardial infarction: additional diagnostic information from serum concentrations of myoglobin in patients without ST elevation.

The value of the 12 lead electrocardiogram, serum total creatine kinase, creatine kinase MB isoenzyme, and myoglobin for the early detection of infarction was evaluated within one hour of admission to the coronary care unit in 82 consecutive patients with suspected myocardial infarction. The 51 patients in whom infarction was diagnosed during the first 24 hours after admission had a higher prevalence of ST elevation (64% v 11%), higher median serum myoglobin (136 micrograms/l v 34 micrograms/l), higher serum creatine kinase (77 IU/l v 34 IU/l), and higher MB isoenzyme (7 IU/l v 4 IU/l) than those in whom it was not. Stepwise logistic regression analysis in 70 patients in whom the electrocardiogram and serum myoglobin were suitable for analysis showed that serum myoglobin was the variable most closely associated with infarction, and contributed additional diagnostic information when ST elevation was entered into the model first. Serum myoglobin remained associated with myocardial infarction when patients who had had symptoms for less than six hours were analysed. An algorithm based on a rapid agglutination test for myoglobin and ST elevation on the electrocardiogram gave an accurate diagnosis in 82% of patients. This approach gave early and rapid recognition of acute myocardial infarction and warrants further examination.

Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients

Background: Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented. Objective: To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions. Methods: All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis. Results: Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12–28)) than normonatraemic patients (median 12 days (IQR 10.5–15)) (p<0.001). Conclusions: Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.

Acute Glucocorticoid Deficiency and Diabetes Insipidus Are Common After Acute Traumatic Brain Injury and Predict Mortality

CONTEXT Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. OBJECTIVES There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. DESIGN Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. SETTING The patients were recruited from the Irish National Neurosurgery Centre. PATIENTS One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. MAIN OUTCOME MEASURES PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. RESULTS Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. CONCLUSIONS Acute hypocortisolemia and CDI are predictive of mortality and long-term pituitary deficits in TBI.

Hyponatremia Following Mild/Moderate Subarachnoid Hemorrhage Is Due To SIAD and Glucocorticoid Deficiency and not Cerebral Salt Wasting

CONTEXT Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN This was a prospective cohort study. SETTING The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.

The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.

Over a five-and-a-half-year period, there were 298 laboratory requests for urinary 5-hydroxyindoleacetic acid (5-HIAA). The clinical and laboratory associations of the 24 patients in which there were 43 urinary 5-HIAA 24-h collection results greater than the laboratory upper reference limit are detailed. Four were confirmed carcinoid tumours and two were phaeochromocytomas. Flushing was a prominent symptom in 46% and diarrhoea or altered bowel habit in 37%. Associated with the raised urinary 5-HIAA values were increased levels of 4-hydroxy-3-methoxymandelic acid and homovanillic acid in 14.3% and 21%, respectively, of those collections where the metabolites were requested. Diagnostic imaging was performed in 57%. While the specificity was 88%, 5-HIAA is relatively insensitive in the diagnosis of carcinoid tumours and a more widespread use of diagnostic imaging including isotope scanning with labelled metaiodo-benzylguanidine, vasoactive intestinal peptide and octreotide is suggested.

Abnormal regulation of thirst and vasopressin secretion following surgery for craniopharyngioma

objective  In this study we aimed to establish the frequency of postoperative diabetes insipidus and the incidence and characteristics of abnormalities of thirst in a cohort of patients with craniopharyngioma, in whom neurosurgery had been performed.

Benzodiazepine premedication may attenuate the stress response in daycase anesthesia: a pilot study.

PurposePatients undergoing daycase surgery suffer from varying degrees of fear and anxiety. There is conflicting evidence in the literature regarding the benefit of benzodiazepine premedication in daycase surgery. We carried out a prospective, double-blind, randomized pilot study investigating the effect of benzodiazepine premedication on the stress response in patients undergoing daycase anesthesia and surgery.MethodsGroup I (n = 16) received diazepam 0.1 mg·kg−1 orally 60 min preoperatively; Group II (n = 15) received diazepam 0.1 mg·kg−1 orally 90 min preoperatively; Group III (n = 30) received a placebo. The stress response was measured by analyzing urinary catecholamine and cortisol levels and by scoring anxiety levels using state-trait anxiety inventory (STAI) scores and visual analogue scores (VAS).ResultsAnxiety scores (VAS and STAI scores) were not different between groups. We found a statistically significant reduction in urinary cortisol and noradrenaline levels in the groups receiving diazepam vs placebo.DiscussionThe reduction in stress hormones following diazepam premedication, in patients undergoing daycase surgery may support the role for benzodiazepine premedication in this setting. However, further studies are warranted to determine the clinical significance of these findings.RésuméObjectifLes patients de chirurgie d’un jour éprouvent des craintes et de l’anxiété à divers degrés. La documentation scientifique présente des arguments contradictoires concernant les bienfaits de la prémédication aux benzodiazépines en chirurgie d’un jour. Nous avons réalisé une étude pilote prospective, randomisée et à double insu pour vérifier l’effet de la prémédication à la benzodiazépine sur la réaction de stress chez des patients anesthésiés en chirurgie d’un jour.MéthodeLes patients du Groupe I (n = 16) ont reçu 0,1 mg·kg−1 de diazépam oralement 60 min avant l’opération; ceux du Groupe II (n = 15) ont eu 0,1 mg·kg−1 de diazépam oralement 90 min avant l’opération et ceux du Groupe III (n = 30), un placebo. La réaction de stress a été mesurée en analysant les niveaux de catécholamine et de cortisol urinaires et en cotant le degré d’anxiété à l’aide du questionnaire sur l’anxiété chronique et réactionnelle STAI (state-trait anxiety inventory) et l’échelle visuelle analogique (EVA).RésultatsLes scores d’anxiété (EVA et STAI) ont été comparables d’un groupe à l’autre. II existait une réduction statistiquement significative de cortisol et de noradrénaline urinaires chez les patients qui ont reçu du diazépam vs le placebo.DiscussionLa réduction des hormones de stress qui suit la prémédication avec du diazépam chez les patients de chirurgie d’un jour peut encourager la prémédication avec des benzodiazépines dans ce contexte. Toutefois, la valeur clinique de ces résultats doit être précisée.

Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency

background  Glucocorticoid therapy is associated with potentially serious side‐effects, but there is no information available regarding glucocorticoid requirement in adult hypopituitary patients with partial ACTH deficiency.