This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by HAYMOND, M. W. Articles by PAGLIARA, A. S. Search for Related Content PubMed PubMed Citation Articles by HAYMOND, M. W. Articles by PAGLIARA, A. S.

The Role of Growth Hormone and Cortisone on Glucose and Gluconeogenic Substrate Regulation in Fasted Hypopituitary Children

Edward Mallinckrodt Department of Pediatrics and the Department of Medicine, Washington University School of Medicine, Division of Endocrinology and Metabolism, St. Louis Children's Hospital St. Louis, Missouri

Reprint address: Morey W. Haymond, M. D., St. Louis Children's Hospital, 500 South Kingshighway, St. Louis, Missouri 63110.

Panhypopituitarism may be associated with spontaneous hypoglycemia and marked insulin sensitivity. Five children with both growth hormone (GH) and adrenocorticotrophin (ACTH) insufficiency were studied in three periods: a) on no therapy; b) during cortisone acetate; and c) during GH and cortisone acetate replacement.

With total caloric restriction prior to therapy, all patients became hypoglycemic (109 ± 18 37 ± 3.5 mg/dl, mean ± SEM) and ketonemic (β-hydroxybutyrate 0.10 ± 0.02 3.04 ± 0.63 mM and acetoacetate 0.05 ± .01 0.80 ± 0.15 mM) within 30 hours. Glutamine and alanine concentrations fell with fasting (511 ± 13 293 ± 26 µM and 394 ± 58 137 ± 12 µM, respectively) but to levels lower than in normal children. However, only alanine was significantly lower (P < 0.05). With cortisone plus GH therapy, fasting glycemia was improved (73 ± 6 mg/dl) at 30 hours fasting and was associated with increased alanine and glutamine concentrations (206 ± 28 µM and 448 ± 40 µM, respectively) and less ketonemia (β-hydroxybutyrate 1.13 ± 0.39 mM). Cortisone therapy alone resulted in intermediate improvement of these values. Only combined therapy resulted in increased lactate and pyruvate concentrations, which fell to normal with fasting. Fasting urinary ammonia excretion was unchanged whereas urea nitrogen excretion decreased significantly with therapy. The responses to alanine infusions following each study period in one patient were normal. The glycemic response to iv glucose was similar during each study period; however, post-prandial and glucose-stimulated insulin responses were increased with cortisone and cortisone plus GH therapy.

We suggest that the hypoglycemia observed in hypopituitary patients is a substrate-mediated phenomenon, and that cortisone and growth hormone replacement therapy improve fasting glucose homeostasis, increase circulating alanine and glutamine concentrations, and decrease hepatic gluconeogenesis. These effects may be mediated through an increase in fat catabolism.

A portion of this work was presented to the Endocrine Society, Chicago, Illinois, June 1973.

Supported by Grant No. HD-AM06355-03, National Institutes of Health and Grant No. RR-36, General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health.

Received July 9, 1975.

This article has been cited by other articles:

				F. Mochel, A. Slama, G. Touati, I. Desguerre, I. Giurgea, D. Rabier, M. Brivet, P. Rustin, J.-M. Saudubray, and P. DeLonlay Respiratory Chain Defects May Present Only with Hypoglycemia J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3780 - 3785. [Abstract] [Full Text] [PDF]

				H. Norrelund, C. Djurhuus, J. O. L. Jorgensen, S. Nielsen, K. S. Nair, O. Schmitz, J. S. Christiansen, and N. Moller Effects of GH on urea, glucose and lipid metabolism, and insulin sensitivity during fasting in GH-deficient patients Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E737 - E743. [Abstract] [Full Text] [PDF]

				H. Norrelund, N. Moller, K. S. Nair, J. S. Christiansen, and J. O. L. Jorgensen Continuation of Growth Hormone (GH) Substitution during Fasting in GH-Deficient Patients Decreases Urea Excretion and Conserves Protein Synthesis J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3120 - 3129. [Abstract] [Full Text] [PDF]

				N. S. Glaser, A. C. Shirali, D. M. Styne, and K. L. Jones Acid-base Homeostasis in Children With Growth Hormone Deficiency Pediatrics, December 1, 1998; 102(6): 1407 - 1414. [Abstract] [Full Text] [PDF]

				A. Kauschansky, M. Genel, and G. J. W. Smith Congenital Hypopituitarism in Female Infants: Its Association With Hypoglycemia and Hypothyroidism Arch Pediatr Adolesc Med, February 1, 1979; 133(2): 165 - 169. [Abstract] [PDF]