PROVOCATIVE HYPOTHALAMOPITUITARY AXIS TESTS IN SEVERE HEAD-INJURY - CORRELATIONS WITH SEVERITY AND PROGNOSIS

Objective: To evaluate the effect of severe head injury on both the se cretion of basal pituitary hormones and the response to exogenous synt hetic hypothalamic releasing factors administration. Design: Prospecti ve, clinical study. Setting: General intensive care unit in a universi ty teaching hospital, Italy.Patients: Comatose, head-injured patients (n = 22), all intubated and mechanically ventilated, invasively monito red without previous endocrinologic problems and substitutive therapie s. Interventions: Routine neuroemergency procedures; administration of exogenous, synthetic hypothalamic releasing hormones. Measurements an d Main Results: Determinations of basal concentrations of growth hormo ne (GH), prolactin (PRL), thyroid stimulating hormone (TSH), triiodoth yronine, and thyroxine were performed daily in the first week and on d ays 15 and 16 after the trauma. Plasma insulin-like growth factor-I an d cortisol were also determined on days 2, 7, and 15. We carried out a thyrotropin-releasing hormone (TRH) test for the evaluation of the PR L, TSH, and GH responses on days 1 and 16 after the trauma and a growt h hormone-releasing hormone (GHRH) test for the evaluation of GH and P RL responses on days 2, 7, and 15 after the trauma. Outcome was evalua ted at 6 mos with the GOS. Triiodothyronine showed low values, even if in the normal range; thyroxine remained in the normal range. Signific ant increases in insulin-like growth factor-I concentrations were obse rved on both days 7 and 15 compared with day 2 (p = .024 and p = .034, respectively). The GH response to GHRH was significantly greater on d ays 7 and 15 than in the very acute phase (p < .01 comparing days 7 an d 15 vs, day 2). We found a higher GH response to GHRH on day 7 in gro up 1 vs. group 2 (as both peak and area under the curve, p = .018 and p = .015, respectively). Na difference in GH response was detected on days 2 and 15. A ''paradoxical'' response of GH to TRH was observed on the day after the head trauma (basal vs, peak, p = .002) but not on d ay 16. The GH peak response to TRH was greater on day 1 in those patie nts with an unfavorable course (group 1 vs, group 2, p < .05). The TSH response to TRH was not significantly correlated to the severity of t rauma, but it was significantly (p < .04) higher in group 1 than in gr oup 2. Finally, a ''paradoxical'' PRL response to GHRH administration was present on day 2 (basal vs. peak, p = .0003), day 7 (basal vs. pea k, p = .01), and on day 15 after the trauma (basal vs. peak, p = .04). Conclusions: Some of the responses to provocative tests have been ide ntified as ''paradoxical'' and seem to have a great importance in the definition of prognosis in severe head-injured patients, specifically the GH response to TRH and the PRL response to GHRH that are significa ntly correlated with outcome.