J. Endocrinol. Invest. 14: 383-389, 1991
Altered growth hormone response after growth hormone releasing hormone administration in chronic renal failure R.v.G. Garcia*, A. Andrade*, J. Perez**, M. Courel, and FF Casanueva*** *Endocrine Section and **Nephrology Unit, Hospital General de Vigo, Vigo, and ***Department of Medicine and Endocrine Section Hospital General de Galicia, Faculty of Medicine, Santiago University, Santiago de Compostela, Spain This sustained secretion of both GH and PRL in uremia could be attributed to reduced kidney clearance. However, when subjects were examined individually both the GHRH- and the TRH-induced hormonal peaks and the subsequent fall were not different in both groups. Unlike with controls, in uremic patients GHRH-stimulated GH and TRH-stimulated PRUGH peaks were dispersed throughout the 120 min period. In controls GH and PRL peaks clustered around 15-30 min. The peak dispersion created a false impression of flattened curves or sustained hypersecretion in uremia. In conclusion, though we cannot rule out an altered hormonal clearance as contributing mechanism, the abnormal GH or PRL secretion after either TRH or GHRH administration in uremia suggest a hypothalamo-pituitary alteration. In endocrine studies with large peak dispersion the method of representation of mean ± SE could be extremely misleading.
ABSTRACT. Eleven chronic renal failure patients and 11 matched controls, received growth hormone GHRH (1~g/kg iv) or TRH (400 ~g iv) on separate occasions, immediately before undergoing hemodialysis. GHRH-induced GH peak in uremics (22.7 ± 5.2 ~g/I) was not different from that obtained in control subjects (16.0 ± 4.3 ~g/I). However, the uremic patients did not show the habitual post-peak fall, remaining GH levels over 10 ~gli till the end of the test. Differences between the two groups were significant (p < 0.05). Uremic patients showed PRL values higher than in controls, however their TRH-induced PRL peak (20.6 ± 6.6 ~g/I) was not different from that of controls (26.5 ± 3.0 ~g/I). Again chronic renal failure patients showed PRL plasma values abnormally elevated till the end of the test. Differences between the two groups were significant (p < 0.05). Administration of placebo to a different group of seven uremic patients did not alter GH and PRL plasma levels.
INTRODUCTION
sponses of GH have been reported in uremia after insulin-induced hypoglycemia (10), but almost normal GH responses have been obtained after arginine infusion (11). As the kidney actively participates in GH catabolism (12), it has been suggested that the increases in plasma half-life could be due to impaired renal function. Nevertheless, the half-life of .1251-labeled rat growth hormone injected in short-term nephrectomized animals is normal, with altered turnover developing only when a severe uremic syndrome takes place (13). As the underlying mechanisms for disturbed GH regulation in ehronic renal failure have not been elucidated, the responses of pituitary GH after GHRH administration in uremic subjects and in controls were studied. As an internal control, a study was performed to analyze whether also the responses of GH and prolactin (PRL) to TRH challenge were altered in uremic patients. A further study after placebo administration was conducted in a different group of uremic subjects.
A variety of endocrine and metabolic disturbances are associated with chronic renal failure, adversely affecting long-term survival and quality of life (1). Uremia is associated with growth disturbances in children, and severe wasting in adults (2, 3). Furthermore, several alterations in growth hormone (GH) regulation have been reported in chronic renal failure, ie basal GH levels are high or at the upper limit of normality (4,5), associated with normal somatomedinC levels, and a paradoxical increase in GH levels may be seen after either thyrotropin releasing hormone (TRH) administration (5, 7) or glucose IQading (8, 9). In addition, abnormal re-
Key-words: Chronic renal failure. uremia. GHRH. TRH. GH. PRL. Correspondence: F.F. Casanueva M.D., PhD., PO Box 563, Santiago de Compostela, Spain. Received September
15780
20, 1990; accepted February 11, 1991.
383
R. V.G. Garcia, A. Andrade, J. Perez, et al.
SUBJECTS AND METHODS
persion of peaks in uremics vs control subjects was compared by using both a Mann-Whitney test and a chi-square test. The significance level was established at p
Altered growth hormone response after growth hormone releasing hormone administration in chronic renal failure R.v.G. Garcia*, A. Andrade*, J. Perez**, M. Courel, and FF Casanueva*** *Endocrine Section and **Nephrology Unit, Hospital General de Vigo, Vigo, and ***Department of Medicine and Endocrine Section Hospital General de Galicia, Faculty of Medicine, Santiago University, Santiago de Compostela, Spain This sustained secretion of both GH and PRL in uremia could be attributed to reduced kidney clearance. However, when subjects were examined individually both the GHRH- and the TRH-induced hormonal peaks and the subsequent fall were not different in both groups. Unlike with controls, in uremic patients GHRH-stimulated GH and TRH-stimulated PRUGH peaks were dispersed throughout the 120 min period. In controls GH and PRL peaks clustered around 15-30 min. The peak dispersion created a false impression of flattened curves or sustained hypersecretion in uremia. In conclusion, though we cannot rule out an altered hormonal clearance as contributing mechanism, the abnormal GH or PRL secretion after either TRH or GHRH administration in uremia suggest a hypothalamo-pituitary alteration. In endocrine studies with large peak dispersion the method of representation of mean ± SE could be extremely misleading.
ABSTRACT. Eleven chronic renal failure patients and 11 matched controls, received growth hormone GHRH (1~g/kg iv) or TRH (400 ~g iv) on separate occasions, immediately before undergoing hemodialysis. GHRH-induced GH peak in uremics (22.7 ± 5.2 ~g/I) was not different from that obtained in control subjects (16.0 ± 4.3 ~g/I). However, the uremic patients did not show the habitual post-peak fall, remaining GH levels over 10 ~gli till the end of the test. Differences between the two groups were significant (p < 0.05). Uremic patients showed PRL values higher than in controls, however their TRH-induced PRL peak (20.6 ± 6.6 ~g/I) was not different from that of controls (26.5 ± 3.0 ~g/I). Again chronic renal failure patients showed PRL plasma values abnormally elevated till the end of the test. Differences between the two groups were significant (p < 0.05). Administration of placebo to a different group of seven uremic patients did not alter GH and PRL plasma levels.
INTRODUCTION
sponses of GH have been reported in uremia after insulin-induced hypoglycemia (10), but almost normal GH responses have been obtained after arginine infusion (11). As the kidney actively participates in GH catabolism (12), it has been suggested that the increases in plasma half-life could be due to impaired renal function. Nevertheless, the half-life of .1251-labeled rat growth hormone injected in short-term nephrectomized animals is normal, with altered turnover developing only when a severe uremic syndrome takes place (13). As the underlying mechanisms for disturbed GH regulation in ehronic renal failure have not been elucidated, the responses of pituitary GH after GHRH administration in uremic subjects and in controls were studied. As an internal control, a study was performed to analyze whether also the responses of GH and prolactin (PRL) to TRH challenge were altered in uremic patients. A further study after placebo administration was conducted in a different group of uremic subjects.
A variety of endocrine and metabolic disturbances are associated with chronic renal failure, adversely affecting long-term survival and quality of life (1). Uremia is associated with growth disturbances in children, and severe wasting in adults (2, 3). Furthermore, several alterations in growth hormone (GH) regulation have been reported in chronic renal failure, ie basal GH levels are high or at the upper limit of normality (4,5), associated with normal somatomedinC levels, and a paradoxical increase in GH levels may be seen after either thyrotropin releasing hormone (TRH) administration (5, 7) or glucose IQading (8, 9). In addition, abnormal re-
Key-words: Chronic renal failure. uremia. GHRH. TRH. GH. PRL. Correspondence: F.F. Casanueva M.D., PhD., PO Box 563, Santiago de Compostela, Spain. Received September
15780
20, 1990; accepted February 11, 1991.
383
R. V.G. Garcia, A. Andrade, J. Perez, et al.
SUBJECTS AND METHODS
persion of peaks in uremics vs control subjects was compared by using both a Mann-Whitney test and a chi-square test. The significance level was established at p
