Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis

To evaluate the effect of severe head injury on both the secretion of basal pituitary hormones and the response to exogenous synthetic hypothalamic releasing factors administration.

Prospective, clinical study.

General intensive care unit in a university teaching hospital, Italy.

Comatose, head-injured patients (n = 22), all intubated and mechanically ventilated, invasively monitored without previous endocrinologic problems and substitutive therapies.

Routine neuroemergency procedures; administration of exogenous, synthetic hypothalamic releasing hormones.

Determinations of basal concentrations of growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine, and thyroxine were performed daily in the first week and on days 15 and 16 after the trauma. Plasma insulin-like growth factor-I and cortisol were also determined on days 2, 7, and 15. We carried out a thyrotropin-releasing hormone (TRH) test for the evaluation of the PRL, TSH, and GH responses on days 1 and 16 after the trauma and a growth hormone-releasing hormone (GHRH) test for the evaluation of GH and PRL responses on days 2, 7, and 15 after the trauma. Outcome was evaluated at 6 mos with the GOS. Triiodothyronine showed low values, even if in the normal range; thyroxine remained in the normal range. Significant increases in insulin-like growth factor-I concentrations were observed 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 days 7 and 15 than in the very acute phase (p< .01 comparing days 7 and 15 vs. day 2). We found a higher GH response to GHRH on day 7 in group 1 vs. group 2 (as both peak and area under the curve, p = .018 and p = .015, respectively). No 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 day 16. The GH peak response to TRH was greater on day 1 in those patients with an unfavorable course (group 1 vs. group 2, p < .05). The TSH response to TRH was not significantly correlated to the severity of trauma, but it was significantly (p < .04) higher in group 1 than in group 2. Finally, a "paradoxical" PRL response to GHRH administration was present on day 2 (basal vs. peak, p=.0003), day 7 (basal vs. peak, p = .01), and on day 15 after the trauma (basal vs. peak, p = .04).

Some of the responses to provocative tests have been identified 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 significantly correlated with outcome.