In a pilot therapeutic trial, four patients with amyotrophic lateral sclerosis 
(ALS) were treated with long term, continuous infusions of TRH, three 
intrathecally and one epidurally. They had prompt increases in serum TSH and 
thyroid hormone concentrations, averaging 120% for TSH, 49% for serum T4, 68% 
for the serum free T4 index, 49% for serum T3, and 67% for the serum free T3 
index. These elevations were statistically significant for all but serum T3 and 
persisted for the duration of treatment (4-7 months). Mean values during 
treatment were near the upper limit of normal for each of these hormone 
measurements. After TRH withdrawal, serum TSH fell transiently below the normal 
range. A comparison group of four patients with ALS treated by twice weekly 
intrathecal bolus doses of TRH had no significant changes in serum TSH, T4, or 
T3. During continuous TRH treatment, the responsiveness of both TSH and PRL to a 
standard iv TRH stimulation test was blunted, but not abolished. Basal serum PRL 
was occasionally elevated in the two women during continuous TRH treatment, but 
was normal in the men, and serum GH was normal in all patients. In the patients 
receiving continuous TRH treatment, indexes of end-organ effects of thyroid 
hormone were inconclusive; none had a rise in serum ferritin, one of four had a 
rise in serum sex hormone-binding globulin, and three had increased creatinuria. 
These results provide direct evidence in man that chronic TRH administration can 
cause modest sustained increases in serum TSH and thyroid hormones, though the 
metabolic consequences of these changes are uncertain, and appears to raise the 
set-point of the pituitary-thyroid axis, i.e. the serum T4 and T3 concentrations 
needed for a given degree of suppression of basal TSH secretion.