We performed double-blind crossover trials to assess the effects of 
thyrotropin-releasing hormone (TRH) on amyotrophic lateral sclerosis patients. 
For acute intravenous trials, 500 mg TRH or placebo with norepinephrine was 
given at 1-week intervals (16 patients). CSF TRH concentration increased, and 
clinical side effects appeared with TRH. For chronic studies, 25 mg TRH and a 
saline placebo were given subcutaneously every day for 3 months (25 patients). 
CSF TRH level increased 29-fold after a single TRH injection, and mild transient 
side effects occurred. Vital signs, respiratory function, semiquantitative and 
quantitative neurologic function, muscle strength by manual and dynamometer 
testing, and EMG were studied. With daily TRH, 10 patients noted subjective 
improvement without objective evidence, and 10 patients complained of worsening 
of the disease with objective decline after TRH was stopped. Statistical 
analysis, however, showed no beneficial effects from either acute or chronic TRH 
trials.