Thyrotropin-releasing hormone in critical illness: from a dopamine-dependent test to a strategy for increasing low serum triiodothyronine, prolactin, and growth hormone concentrations.
OBJECTIVE
The aim of this study was to examine the effect of dopamine infusion on the thyrotropin (TSH), thyroid hormone, prolactin, and growth hormone responses to thyrotropin-releasing hormone (TRH) in critically ill patients.


METHODS
Prospective, randomized, controlled, open-labeled clinical study.


METHODS
The intensive care unit, University Hospital Gasthuisberg, Leuven, over a 1-month period.


METHODS
In 15 critically ill patients receiving dopamine treatment (5 micrograms/kg/min) for a mean of 43.3 +/- 1.2 (SEM) hrs after trauma or cardiac surgery, we studied the TSH, thyroid hormone, prolactin, and growth hormone responses to the administration of two consecutive intravenous TRH boluses of 200 micrograms, with a 6-hr interval. The dopamine infusion was continued in the control group and discontinued in the study group. Serum concentrations of TSH, prolactin, and growth hormone were measured before and 20, 40, 60, and 120 mins after TRH administration. Serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse T3, and thyroid hormone binding globulin were determined before and 120 mins after each TRH injection.


RESULTS
There was a > 100-fold interindividual variation in the baseline TSH concentration and in the TSH peak value after TRH administration. Two consecutive doses of TRH evoked a mean 16% increase in serum T4 concentration (p = .003) and a mean 47% increase in T3 (p = .001), whereas serum reverse T3 and thyroid hormone binding globulin values remain unaltered. Each of the TRH boluses increased serum growth hormone concentrations in the continued dopamine and discontinued dopamine groups, by a median of 60% (p = .001) and 68% (p = .001), respectively. Three hours after dopamine withdrawal, there was a three-fold increase of the peak TSH response (p = .001), a higher T3 response (p = .01), and a ten-fold increase of the peak prolactin value (p = .001) in response to TRH administration.


CONCLUSIONS
The TSH response to TRH administration in critical illness presents a striking interindividual variation and dopamine dependent. Repeated TRH administration results in a repetitive increase of TSH, prolactin, growth hormone, T4, and T3, without increasing reverse T3. These observations point toward a potential for TRH as a strategy for reversing the euthyroid sick syndrome, growth hormone deficiency, and immune dysfunction associated with critical illness.
Van den Berghe
G
G
Department of Intensive Care Medicine, University Hospital Gasthuisberg, Leuven, Belgium.
de Zegher
F
F
Vlasselaers
D
D
Schetz
M
M
Verwaest
C
C
Ferdinande
P
P
Lauwers
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D016638:Critical Illness / Q000628:therapy*; D004298:Dopamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood* / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011388:Prolactin / Q000097:blood* / Q000187:drug effects; D011446:Prospective Studies; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage*; D013997:Time Factors; D014284:Triiodothyronine / Q000097:blood* / Q000187:drug effects
D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D013006:Growth Hormone; D004298:Dopamine