Abstract
In man the GH response to GHRH is variable within and between subjects. Pyridostigmine (PD), an acetylcholinesterase inhibitor, has been shown to reduce the variability of the GH response to GHRH in normal subjects. The aim of this study was to assess the existence of either inter- or intraindividual variability in the GH response to GHRH in type 1 diabetic patients. Moreover, we investigated the effect of PD on such variability in the same patients. Seven (4 females-3 males) nonobese type 1 diabetic patients underwent two experiments performed in consecutive days according to a single-blind protocol: 1) 120 mg oral PD 60 min before iv injection of human (h) GHRH-(1-29) NH2, 100 μg in 2 ml of sterile water; 2) oral placebo 60 min before iv injection of 100 μg hGHRH. The two experiments were then repeated, following the same procedure, one and two weeks after the start of the study. The GH peaks after GHRH were variable within different subjects but also in the same subject on different occasions. However, the mean GH peak levels after GHRH in the three tests were not significantly different (14.2±3.5, 15.3±3, 16.5±6.4 μg/L, respectively), the coefficient of variation for each test was 65%, 51.8%, 102.4%, respectively (mean 73.1±15.1%). The GH response to GHRH was always significantly enhanced by PD administration: the mean GH peak levels in the three tests were 31.9±7.1, 44.8±10.4, 49.9±13.1 μg/L, respectively, without significant differences between tests. After PD+GHRH the interindividual variability in the GH response was still present but significantly lower than after GHRH alone. The coefficient of variation for each test was 58.7%, 61.3%, 69.3%, respectively (mean 63.1±3.2%). It can be hypothesized that PD may reduce the interindividual variability of the GH response to GHRH in the diabetic population by decreasing somatostatin tone only in diabetic patients with normal-high hypothalamic somatostatin.
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Hayford J.T., Danney M.M., Hendrix J.A., Thompson R.G. Integrated concentration of growth hormone in juvenile-onset diabetes. Diabetes 29:391, 1980.
Hansen A.P. Abnormal serum growth hormone responses to exercise in juvenile diabetics. J.Clin. Invest. 49:1467, 1970.
Holland P.M., Landers M.B., Lebovitz H.E., Wolbarsht M.L. Levodopa-stimulated growth hormone secretion and diabetic retinopathy. Am. J. Ophthalmol. 82:612, 1976.
Cremer G.M., Molnar G.D., Taylor W.F., Rosevear J.W., Ackerman E. Growth hormone release in unstable diabetes. Tests with saline, arginine, glucagon and epinephrine. Acta Diabetol. Lat. 10:1216, 1973.
Valentini U., Cimino A., Rotondi A., Rocca L., Pelizzari R., Giustina A., Marchetti C., Romanelli G. Growth hormone response to thyrotropin releasing hormone and placebo in a group of insulin dependent diabetics. J. Endocrinol. Invest. 12:643, 1989.
Wehrenberg W.B., Ling N., Bohlen P., Esch F., Brazeau P.R., Guillemin R. Physiologic role of somatocrinin and somatostatin in the regulation of growth hormone secretion. Biochem. Biophys. Res. Commun. 109:562, 1982.
Pietschmann P., Schernthaner G., Prskavec F., Gisinger C., Freyler H. No evidence for increased growth hormone responses to growth hormone-releasing hormone in patients with diabetic retinopathy. Diabetes 36:159, 1987.
Krassowsky J., Felber J.P., Rogala H., Jeske W., Zgliczynski S. Exaggerated growth hormone response to growth hormone-releasing hormone in type 1 diabetes mellitus. Acta Endocrinol. (Copenh.) 117:225, 1988.
Giustina A., Bossoni S., Cimino A., Pizzocolo G., Romanelli G., Wehrenberg W.B. Impaired growth hormone (GH) responses to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. J. Clin. Endocrinol. Metab. 71:1486, 1990.
Press M., Tamborlane W.V., Thorner M.O., Vale W., Rivier J., Gertner J.M., Shervin R. Pituitary response to growth hormone-releasing factor in diabetes. Failure of glucose-mediated suppression. Diabetes 33:804, 1984.
Giampietro O., Ferdeghini M., Miccoli R., Locatelli V., Cerri M., Yanaihara N., Navalesi R., Müller E.E. Effect of growth hormone-releasing hormone and Clonidine on growth hormone release in type 1 diabetic patients. Horm. Metab. Res. 19:636, 1987.
Massara F., Ghigo E., Demislis K., Tangolo D., Mazza E., Locatelli V., Müller E.E., Molinatti G.M., Camanni F. Cholinergic involvement in the growth hormone releasing hormone-induced growth hormone release. Studies in normal and acromegalic subjects. Neuroendocrinology 43:670, 1986.
Giustina A., Bossoni S., Bodini C., Doga M., Girelli A., Buffoli M.G., Schettino M., Wehrenberg W.B. The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man. Metabolism 40:519, 1991.
Penalva A., Muruais C., Casanueva F.F., Diegue C. Effect of enhancement of endogenous cholinergic tone with pyridostigmine on the dose-response relationships of growth hormone (GH)-releasing hormone-induced GH secretion in normal subjects. J. Clin. Endocrinol. Metab. 70:324, 1990.
Wehrenberg W.B., Wiviott S.D., Voltz D.M., Giustina A. Pyridostigmine mediated growth hormone release: evidence for somatostatin involvement. Endocrinology 130:1445, 1992.
Giustina A., Bossoni S., Bodini C., Cimino A., Pizzocolo G., Schettino M., Wehrenberg W.B. Effects of exogenous growth hormone pretreatment on the pituitary growth hormone response to growth hormone-releasing hormone alone or in combination with pyridostigmine in Type 1 diabetic patients. Acta Endocrinol. (Copenh.) 125:510, 1991.
Mazza E., Ghigo E., Goffi S., Procopio M., Imperiale E., Arvat E., Bellone J., Boghen M.F., Müller E.E., Camanni F. Effect of the potentiation of cholinergic activity on the variability in individual GH response to GH-releasing hormone. J. Endocrinol. Invest. 12:795, 1989.
Steel R.G.D., Torrie J.H. Principles and Procedures of Statistics. Mc Graw-Hill, New York, 1960.
Tannenbaum G.S., Ling N. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 115:1952, 1984.
Hansen A.P. Normalization of growth hormone hyperresponse to exercise in juvenile diabetics after “normalization” of blood sugar. J.Clin. Invest. 50:1806, 1971.
Würzburger M.I., Prevelic G.M., Sonksen P.H., Peric L.A., Till S., Morris R.W. Effects of improved blood glucose on insulin-induced hypoglycaemia, TRH, Gn-RH and exercise tests in insulin-dependent diabetes. Clin. Endocrinol. (Oxf.) 32: 799, 1990.
Topper E., Gertner J., Amiel S., Press M., Genel M., Tamborlane W. Deranged alpha-adrenergic regulation of GH secretion in poorly controlled diabetes. Reversal of the exaggerated response to Clonidine after continuous subcutaneous insulin infusion. Pediatr. Res. 19:534, 1985.
Press M., Caprio S., Tamborlane W.V., Bhushan R., Thorner M., Vale W., River J., Sherwin R.S. Pituitary response to growth hormone-releasing hormone in IDDM. Diabetes 41:17, 1992.
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Giustina, A., Bodini, C., Bossoni, S. et al. Variability in the growth hormone response to growth hormone-releasing hormone alone or combined with pyridostigmine in type 1 diabetic patients. J Endocrinol Invest 16, 585–590 (1993). https://doi.org/10.1007/BF03347676
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DOI: https://doi.org/10.1007/BF03347676