THYROTROPIN AND PROLACTIN-RELEASE IN PROLONGED CRITICAL ILLNESS - DYNAMICS OF SPONTANEOUS SECRETION AND EFFECTS OF GROWTH HORMONE-SECRETAGOGUES

OBJECTIVE Infusion of GH secretagogues appears to be a novel endocrine approach to reverse the catabolic state of critical illness, through amplification of the endogenously blunted GH secretion associated with a substantial IGF-I rise. Here we report the dynamic characteristics of spontaneous nightly TSH and PRL secretion during prolonged critical illness, together with the concomitant effects exerted by the adminis tration of GH-secretagogues, GH-releasing hormone (GHRH) and GH-releas ing peptide-2 (GHRP-2) in particular, on night-time TSH and PRL secret ion. PATIENTS AND DESIGN Twenty-six critically ill adults (mean +/- SE M age: 63 +/- 2 years) were studied during two consecutive nights (210 0-0600 h). According to a weighed randomization, they received 1 of 4 combinations of infusions, within a randomized, cross-over design for each combination: placebo (one night) and GHRH (the next night) (n = 4 ); placebo and GHRP-2 (n = 10); GHRH and GHRP-2 (n = 6); GHRP-2 and GH RH + GHRP-2 (n = 6). Peptide infusions (duration 21 hours) were starte d after a bolus of 1 mu g/kg at 0900 h and infused (1 mu g/kg/h) until 0600 h. MEASUREMENTS Serum concentrations of TSH and PRL were determi ned by IRMA every 20 minutes and T4, T3 and rT3 by RIA at 2100 h and 0 600 h in each study night. Hormone secretion was quantified using deco nvolution analysis. RESULTS During prolonged critical illness, mean ni ght-time serum Concentrations of TSH (1.25 +/- 0.42 mIU/I) and PRL (9. 4 +/- 0.9 mu g/l) were low-normal. However, the proportion of TSH and PRL that was released in a pulsatile fashion was low (32 +/- 6% and 16 +/- 2.6%) and no nocturnal TSH or PRL surges were observed. The serum levels of T3 (0.64 +/- 0.06 nmol/l) were low and were positively rela ted to the number of TSH bursts (R-2 = 0.32; P = 0.03) and to the log of pulsatile TSH production (R-2 = 0.34; P = 0.03). GHRP-2 infusion fu rther reduced the proportion of TSH released in a pulsatile fashion to half that during placebo infusion (P = 0.02), without altering mean T SH levels. GHRH infusion increased mean TSH levels and pulsatile TSH p roduction, 2-fold compared to placebo (P = 0.03) and 3-fold compared t o GHRP-2 (P = 0.008). The addition of GHRP-2 to GHRH infusion abolishe d the stimulatory effect of GHRH on pulsatile TSH secretion. GHRP-2 in fusion induced a small increase in mean PRL levels (21%; P = 0.02) and basal PRL secretion rate (49%; P = 0.02) compared to placebo, as did GHRH and GHRH + GHRP-2. CONCLUSIONS The characterization of the specif ic pattern of anterior pituitary function during prolonged critical il lness is herewith extended to the dynamics of TSH and PRL secretion: m ean serum levels are low-normal, no nocturnal surge is observed and th e pulsatile fractions of TSH and PRL release are reduced, as was shown previously for GH. Low circulating thyroid hormone levels appear posi tively correlated with the reduced pulsatile TSH secretion, suggesting that they have, at least in part, a neuroendocrine origin. Finally, t he opposite effects of different GH-secretagogues on TSH secretion fur ther delineate particular linkages between the somatotrophic and thyro trophic axes during critical illness.