The low-dose (1 microg) adrenocorticotropin stimulation test in kidney and kidney-pancreas transplant patients: a potential guideline for steroid withdrawal.

Chronic steroid treatment is known to impair the hypothalamic-pituitary adrenal axis (HPA) but the need to assess HPA function prior to withdrawal of steroid therapy in post-transplant patients has not been uniformly accepted. We evaluated the status of the HPA axis in 48 kidney or kidney-pancreas transplant patients who were considered for possible discontinuation of glucocorticoid therapy using a recently validated dynamic test of HPA integrity, the low-dose (1 microg) adrenocorticotropin (ACTH) test. HPA suppression was detected in 29 (60%) of the patients, four of which had severe hypoadrenalism prohibitive of steroid withdrawal. Neither the duration of steroid treatment nor 8:00 am serum cortisol was a useful marker of hypoadrenalism. 8:00 am cortisol in subjects with normal HPA reserve and subjects with partial hypoadrenalism overlapped considerably but levels <5 microg/dL were indicative of severe hypoadrenalism. Pre-withdrawal diagnosis of partial hypoadrenalism allowed the identification of subjects requiring no further steroid replacement under regular daily circumstances. However glucocorticoid supplementation was prescribed in the event of stress such as infection, exceptional effort, trauma or surgery. Individuals with partial HPA impairment, but not patients with severe HPA suppression, improved upon retesting 3 months later. Patients exhibiting normal response to 1 mcg ACTH enjoyed an uneventful course following steroid withdrawal. Since hypoadrenalism is extremely common in post-transplant patients, we recommend the use of the low-dose ACTH test as a convenient method to identify patients with various degrees of hypoadrenalism prior to steroid withdrawal.

Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits.

Signal shortening of the motor cortex in T2-weighted MR images is a frequent finding in patients with amyotrophic lateral sclerosis (ALS). The cause of signal shortening in ALS is unknown, although iron deposits have been suggested. To test this hypothesis, we acquired T2*-weighted gradient-echo (GRE) MR images in addition to T2-weighted turbo spin-echo in 69 patients with ALS. Signal shortening in T2-weighted images was found in 31 patients. In T2*-weighted GRE images, only three patients had signal shortening. One patient with additional bifrontal haemorrhage had frontal but no motor cortex signal shortening. Iron deposits do not cause cortical signal shortening in patients with ALS predominantly. Other factors are presumably more important in the generation of cortical T2 shortening in ALS.

High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study.

UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.