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Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness.
Clin Endocrinol (Oxf). 1996 Sep; 45(3):341-51.CE

Abstract

OBJECTIVE

Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration.

PATIENTS AND DESIGN

Critically ill adults (n = 40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n = 10), GHRH and GHRP-2 (n = 10), GHRP-2 and GHRH+GHRP-2 (n = 10), GHRH+GHRP-2 and GHRH+GHRP-2 + TRH (n = 10). The GHRH and GHRP-2 doses were 1 microgram/kg and the TRH dose was 200 micrograms. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection.

MEASUREMENTS

Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA.

RESULTS

Critically ill patients presented a striking GH response to GHRP-2 (mean +/- SEM peak GH 51 +/- 9 micrograms/l in older patients and 102 +/- 26 micrograms/l in younger patients; P = 0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P = 0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P = 0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P = 0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response > ninefold (P = 0.005), elicited a 60% rise in serum T3 (P = 0.01) and an 18% increase in T4 (P = 0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P = 0.007). GHRP-2 increased basal serum cortisol levels (531 +/- 29 nmol/l) by 35% (P = 0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P = 0.05).

CONCLUSIONS

The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.

Authors+Show Affiliations

Department of Intensive Care Medicine, University of Leuven.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8949573

Citation

Van den Berghe, G, et al. "Pituitary Responsiveness to GH-releasing Hormone, GH-releasing Peptide-2 and Thyrotrophin-releasing Hormone in Critical Illness." Clinical Endocrinology, vol. 45, no. 3, 1996, pp. 341-51.
Van den Berghe G, de Zegher F, Bowers CY, et al. Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness. Clin Endocrinol (Oxf). 1996;45(3):341-51.
Van den Berghe, G., de Zegher, F., Bowers, C. Y., Wouters, P., Muller, P., Soetens, F., Vlasselaers, D., Schetz, M., Verwaest, C., Lauwers, P., & Bouillon, R. (1996). Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness. Clinical Endocrinology, 45(3), 341-51.
Van den Berghe G, et al. Pituitary Responsiveness to GH-releasing Hormone, GH-releasing Peptide-2 and Thyrotrophin-releasing Hormone in Critical Illness. Clin Endocrinol (Oxf). 1996;45(3):341-51. PubMed PMID: 8949573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness. AU - Van den Berghe,G, AU - de Zegher,F, AU - Bowers,C Y, AU - Wouters,P, AU - Muller,P, AU - Soetens,F, AU - Vlasselaers,D, AU - Schetz,M, AU - Verwaest,C, AU - Lauwers,P, AU - Bouillon,R, PY - 1996/9/1/pubmed PY - 1996/9/1/medline PY - 1996/9/1/entrez SP - 341 EP - 51 JF - Clinical endocrinology JO - Clin. Endocrinol. (Oxf) VL - 45 IS - 3 N2 - OBJECTIVE: Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN: Critically ill adults (n = 40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n = 10), GHRH and GHRP-2 (n = 10), GHRP-2 and GHRH+GHRP-2 (n = 10), GHRH+GHRP-2 and GHRH+GHRP-2 + TRH (n = 10). The GHRH and GHRP-2 doses were 1 microgram/kg and the TRH dose was 200 micrograms. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS: Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS: Critically ill patients presented a striking GH response to GHRP-2 (mean +/- SEM peak GH 51 +/- 9 micrograms/l in older patients and 102 +/- 26 micrograms/l in younger patients; P = 0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P = 0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P = 0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P = 0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response > ninefold (P = 0.005), elicited a 60% rise in serum T3 (P = 0.01) and an 18% increase in T4 (P = 0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P = 0.007). GHRP-2 increased basal serum cortisol levels (531 +/- 29 nmol/l) by 35% (P = 0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P = 0.05). CONCLUSIONS: The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine. SN - 0300-0664 UR - https://www.unboundmedicine.com/medline/citation/8949573/Pituitary_responsiveness_to_GH_releasing_hormone_GH_releasing_peptide_2_and_thyrotrophin_releasing_hormone_in_critical_illness_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0300-0664&date=1996&volume=45&issue=3&spage=341 DB - PRIME DP - Unbound Medicine ER -