We have demonstrated that critically ill patients have low IGF-I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF-I production and anabolism) and toward the direct effects (lipolysis and insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen in our patients may be important in this adaptation.

Pyridostigmine, an acetylcholinesterase inhibitor, stimulates growth hormone (GH) release and is thought to act by inhibiting hypothalamic somatostatin release. There are few data concerning the effect of pyridostigmine on other pituitary hormones apart from GH. We have studied the effect of pyridostigmine on basal GH, thyrotrophin (TSH), prolactin, adrenocorticotrophin and cortisol release, and thyrotrophin-releasing hormone (TRH)-stimulated TSH and prolactin release, in two studies involving nine healthy male subjects. Pyridostigmine stimulated GH release in all subjects but had no effect on adrenocortocotrophin or cortisol levels, or basal or TRH-stimulated TSH and prolactin levels.There are some data to suggest that somatostatin inhibits TRH-stimulated TSH release. Our findings, however, suggest that either endogenous somatostatin tone has little effect on the TSH response to TRH compared to its effects on GH or pyridostigmine acts through a mechanism other than altering somatostatin tone. Pyridostigmine did not alter adrenocorticotrophin or cortisol levels in the presence of a clear action on GH release, providing further evidence that the previously reported effects of cholinergic drugs on cortisol release are stress-relatedThe pulsatile release of growth hormone (GH) results from a d! namic equilibrium between the two hypothalamic hormones, Somatostatin and GH-releasing hormone (GHRH) (1). They act rehpectively to inhibit and stimulate GH release from the pituitary. The release of the hypothalamic peptides is in turn influenced by various neurotransmitters, for example cholinergic agonists increase and antagonists decrease GH release (2, 3). Data in animals suggest that the effects of altered cholinergic tone are mcdiated through alterations in hypothalamic somatostatin secretion (4, 5). Pyridostigmine, an acetylcholinesterase inhibitor, augments cholinergic tone, and increases both basal and GHRHstimulated GH release (6, 7). To date, there are few data concerning the effect of altered cholinergic tone on the release of other pituitary hormones. Exogenous somatostatin inhibits the thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TKH) (8,9), and therefore it might be expected that alterations in cholinergic tone could influence TSH release. In vitro, acetylcholine causes release of corticotrophin-releasing factor (10, 11) but its effects in vivo remain unclear (12). We have therefore studied the effect of pyridostigmine on basal GH, TSH, prolactin and adrenocorticotrophin (ACTH) release, and the TSH, GH and prolactin responses to TRH. Results Study IIn all six subjects GH levels rose 60 to 120 min after pyridostigmine and were higher than after placebo alone. After 60 min the mean peak serum GH level after placebo was 3.8 (range, < 1.0 to 9.0) mU/1 compared to 23.0 (5.5 to 52.6) mU/1 after pyridostigmine (P=O.O36). There was no consistent change in either ACTH or cortisol levels after pyridostigmine as compared to placebo (Fig. I), but in one subject ACTH levels rose from 13 ng/l at t...