Abstract
Pubertal development is frequently delayed or disordered in children with chronic renal failure. Both neuroendocrine and peripheral alterations due to uremia have been hypothesized to explain the impairment in the pituitary gonadal axis. The aim of the present study was to evaluate quantitative (immunological) and qualitative (biological) LH secretion, as well as FSH and sex steroids, before and during 7 days of sc LHRH administration (136–150 ng/kg bw every 120 min) in 5 uremic children (13.1–14.8 yr) with delayed puberty. Six nonuremic children (13.2–17.8 yr) with delayed puberty underwent the same schedule and served as control group. On day 0 mean immunoreactive LH (l-LH) levels were higher in uremic (4.5±0.9 mlU/ml) than in nonuremic (1.9±03 mlU/ml; p<0.05) subjects while no differences were observed in bioactive LH (B-LH) levels (2.9±0.7 mlU/ml vs 2.4±0.3 mlU/ml). In both groups of subjects testosterone was at prepubertal levels. Spontaneous l-LH and B-LH pulses were observed sporadically in both uremic and nonuremic subjects. Short-term pulsatile LHRH ad-ministration induced significant increases in B-LH, I-LH, FSH and testosterone. The B/l LH ratio increased from day 0 (0.7±0.2) to day 7 (1.310.4; p<0.05) in uremics while it showed wide fluctuations in nonuremic subjects. On day 7, 4 uremic and 5 nonuremic subjects showed a pulsatile release of B-LH after exogenous LHRH pulses. Our data document that in uremia there are qualitative as well as quantitative abnormalities in pituitary gonadal secretion. Seven days of pulsatile LHRH administration seems to partially reverse the impaired activity of the pituitary gonadal axis. Uremic and nonuremic subjects showed the same responsiveness to the LHRH administration. A disturbed endogenous LHRH discharge could be hypothesized in delayed or disordered puberty in uremic children, as has already been suggested in nonuremic children with delayed puberty.
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References
Ducharme J.R. Normal puberty: clinical manifestations and their endocrine control. In: Collu R., Ducharme J.R., Guyda H.J. (Eds.), Pediatric Endocrinology. Raven Press, New York, 1989, p. 307.
Penny R., Olambiuwonnu N.O., Frasier S.P. Episodic fluctuations of plasma gonadotrophins in pre- and postpubertal girls and boys. J. Clin. Endocrinol. Metab. 45:307, 1977.
Jakacki R.I., Kelck R.P., Sauder S.E., Lloyd J.S., Hopwood N.J., Marshall J.C. Pulsatile secretion of luteinizing hormone in children. J. Clin. Endocrinol. Metab. 55:453, 1982.
Oerter K.E., Uriate M.M., Rose S.R., Barnes K.M., Cutler G.B. Jr. Gonadotropin secretory dynamics during puberty in normal girls and boys. J. Clin. Endocrinol. Metab. 71:1251, 1990.
Wu F.C.W., Butler G.E., Kelnar C.J.H., Stirling H.F., Huhtaniemi I. Pattern of pulsatile luteinizing hormone and follicle-stimulating hormone secretion in prepubertal (mid childhood) boys and girls and patients with idiopathic hypogonadotropic hypogonadism (Kallmann’s syndrome): a study using an ultrasensitive time-re-solved immunofluorometric assay. J. Clin. Endocrinol. Metab. 72:1229, 1991.
Wennink J.M.B., Delemarre-Van De Waal H.A., Schoemaker R., Schoemaker H., Schoemaker J. Luteinizing hormone and follicle stimulating hormone secretion patterns in boys throughout puberty measured using highly sensitive immuno radiometric assays. Clin. Endocrinol. (Oxf.) 31: 551, 1989.
Tsatsoulis A., Shalet S.M., Robertson W.R. Bioactive gonadotrophin secretion in man. Clin. Endocrinol. (Oxf.) 35:193: 1991.
Lucky A.W., Rich B.H., Rosenfield R.L, Fang V.S., Roche-Bender N. LH bioactivity increases more than immunoreactivity during puberty. J. Pediatr. 97:205, 1980.
Reiter E.O., Beitins I.Z., Ostrea T., Gutai J.P. Bioassayable luteinizing hormone during childhood and adolescence and in patients with delayed pubertal development. J. Clin. Endocrinol. Metab. 54:155, 1982.
Celani M.F., Montanini V., Baraghini G.F., Carani C., Cioni R., Resentini M., Morabito F., Marrama P. Biological and immunological profiles of serum luteinizing hormone (LH) during male sexual maturation. Acta Med. Auxol. 15:195, 1983.
Beitins I.Z., Padmanabhan V., Kasa-Vubu J., Bletter G.B., Sizonenko P.C. Serum bioactive follicle-stimulating hormone concentrations from prepuberty to adulthood: a cross-sectional study. J. Clin. Endocrinol. Metab. 71:1022, 1990.
Tsatsoulis A., Shalet S.M., Talbot A., Robertson W.R. Quantitative and qualitative changes in LH secretion following pulsatile GnRH therapy in a man with idiopathic hypogonadotrophic hypogonadism. Clin. Endocrinol. (Oxf.) 30:167, 1989.
Beitins I.Z., Dufau M.L., O’Loughlin K., Catt K.J., Mc Arthur J.W. Analysis of biological and immunological activities in the two pools of LH released during constant luteinizing hormone-releasing hormone (LHRH) in men. J. Clin. Endocrinol. Metab. 45:605, 1977.
Vourtsis R., Illig R. The use of a low-dose LHRH test for the distinction of delayed adolescence and isolated gonadotropin deficency. Helv. Paediatr. Acta 37: 437, 1982.
Ehrmann D.A., Rosenfield R.L., Cuttler L., Burstein S., Cara J.F., Levitsky L.L. A new test of combined pituitary-testicular function using the gonadotropin-releasing hormone agonist nafarelin in the differentiation of gonadotropin deficiency from delayed puberty: pilot studies. J. Clin. Endocrinol. Metab. 69:963, 1989.
Oertel P.J., Lichtwald K., Hafner S., Rauh W., Schonberg D., Scharer K. Hypothalamo-pituitary-gonadal axis in children with chronic renal failure. Kidney Int. 24(Suppl. 15): 534, 1983.
Lim V.S., Fang V.S. Gonadal dysfunction in uraemic men. A study of the hypothalamo-pituitary-testicular axis before and after renal transplantation. Am. J. Med. 58:655, 1975.
Scharer K., Schaefer F., Trott M., Kassmann K., Gilli G., Gerhard I., Klinga K., Schonberg D., Vecsei P. Pubertal development in children with chronic renal failure. In: Scharer K. (Ed.), Pediatric and adolescent endocrinology. Karger, Basel, 1989, p. 151.
Scharer K., Broyer M., Vecsei P., Roger M., Arnold-Schwender E., Usberti J. Damage to testicular function in chronic renal failure of children. Proc. Eur. Dial. Transplant. Assoc. 17:725, 1980.
Holdsworth S., Atkins R.C., De Kretser D.M. The pituitary testicular axis in men with chronic renal failure. N. Engl. J. Med. 296:1245, 1977.
Rodger R.S.C., Morrison L., Dewar U.H., Wilkinson R., Ward M.R., Kerr D.N.S. Loss of pulsatile luteinizing hormone secretion in men with chronic renal failure. Br. Med. J. 297:1598, 1985.
Wheatley T., Clark P.M.S., Clark J.D.A., Raglatt P.R., Evans D.B., Holder R. Pulsatility of luteinizing hormone in men with chronic renal failure: abnormal rather than absent. Br. Med. J. 294:482, 1987.
Schaefer F., Stanhope R., Sceil H., Schonberg D., Preece M.A., Scharer K. Pulsatile gonadotropin secretion in pubertal children with chronic renal failure. Acta Endocrinol. (Copenh.) 120: 14, 1989.
Giusti M., Perfumo F., Verrina E., Cavallero D., Piaggio G., Gusmano R., Giordano G. Biological activity of luteinizing hormone in uraemic children: spontaneous nocturnal secretion and changes after administration of exogenous pulsatile luteinizing hormone-releasing hormone preliminary observations. Pediatr. Nephrol. 5:559, 1991.
Schaefer F., Robertson W.R., Seidel C., Mitchell R., Scharer K. Pulsatile immunoreactive and bioactive luteinizing hormone secretion in adolescents with chronic renal failure. Pediatr. Nephrol. 5:566, 1991.
Warner B.A., Dufau M.L., Santen J.S. Effect of aging and illness on the pituitary testicular axis in men: qualitative as well as quantitative changes in luteinizing hormone. J. Clin. Endocrinol. Metab. 66:263, 1985.
Handelsman D.J., Spaliviero J.A., Turtle J.R. Bioactive luteinizing hormone in plasma of uraemic men and men with primary testicular damage. Clin. Endocrinol. (Oxf.) 24:259, 1986.
Dufau M.L., Pock R., Neubauer A., Catt K.J. In vitro bioassay of LH in human serum: the interstitial cell testosterone (RICT) assay. J. Clin. Endocrinol. Metab. 42:958, 1976.
Santen R.J., Bardin C.W. Episodic luteinizing hormone secretion in man pulse analysis, clinical interpretation, physiologic mechanisms. J. Clin. Invest. 52:2617, 1973.
Veldhuis J.D., Evans W.S., Johnson M.L., Wills M.R., Rogol A.D. Physiologic properties of the luteinizing hormone pulse signal: impact of intensive and extended venous sampling paradigms on its characterization in healthy men and women. J. Clin. Endocrinol. Metab. 62:881, 1986.
Giusti M., Marini G., Traverso L., Cavagnaro P., Granziera L., Giordano G. Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man. J. Endocrinol. Invest. 13:127, 1990.
Handelsman D.J., Spaliviero J.A., Turtle J.R. Testicular function in experimental uremia. Endocrinology 777: 1974, 1985.
Handelsman D.J., Spaliviero J.A., Turtle J.R. Hypothalamic-pituitary function in experimental uremic hypogonadism. Endocrinology 117:1984, 1985.
Wibullaksanakul S., Handelsman D.J. Regulation of hypothalamic gonadotropin-releasing hormone secretion in experimental uremia: in vitro studies. Neuroendocrinology 54: 353, 1991.
Medri G., Carella C., Rossi C.H., Amato G., De Santo N.G., Faggiano M., Beck-Peccoz P. Studies on the secretion of pituitary glycoprotein hormones and their common α-subunit in patients with chronic uremia: evidence for an automomous α-subunit production. J. Endocrinol. Invest. 10(Suppl. 1): 16, 1987.
Delamarre-Van De Waal H.A., Van Den Brande J.L., Schoemaker J. Prolonged pulsatile administration of luteinizing hormone-releasing hormone in prepubertal children: diagnostic and physiological aspects. J. Clin. Endocrinol. Metab. 67:859, 1985.
Gordon D., Cohen H.N., Beastall G.H., Perry B., Thomson J.A. Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration. J. Endocrinol. Invest. 11:77, 1988.
Spratt D.I., Finkelstein J.S., O’Dea L.S.L., Badge T.M., Rao P.H., Campbell J.D., Crowley W.F. Long-term administration of gonadotropin-releasin hormone in men with idiopathic hypogonadotropi hypogonadism: a model for studies of the hormone’s physiological effects. Ann. Intern. Med. 705:848, 1986.
Haavisto A-H., Dunkel L., Pettersson E., Huhtanien I. LH measurements by in vitro bioassay and a highly sensitive immunofluorometric assay improve the distinction between boys with constitutional delay of pi berty and hypogonadotropic hypogonadism. Pediatr. Res. 27:211, 1990.
Beitins I.Z., Axelrod L.J., Ostrea T., Little R., Badge T.M. Hypogonadism in a male with an immunological active, biological inactive luteinizing hormone: characterization of the abnormal hormone. J. Clin. Endocrinol. Metab. 52:1143, 1981.
Tsatsoulis A., Shalet S.M., Richardson P., Robertso W.R. Testosterone reduces the bioactivity of luteinizing hormone (LH) in man. Clin. Endocrinol. (Oxf.) 32:72, 1990.
Barkan A.L., Reame N.F., Kelck R.P., Marshall J.C Idiopathic hypogonadotropic hypogonadism in men: dependence of the hormone responses to gonadotropin-releasing hormone (GnRH) on the magnitude of endogenous GnRH secretory defect. J. Clin. Endocrinol. Metab. 67:1118, 1985.
Cossu M., Sorba G.B., Maioli M., Palermo M., Delita G. Effects of naloxone infusion on gonadotrophin an prolactin response in patients with chronic renal failure. Proc. Eur. Dial. Transplant. Assoc. 27:608, 1984.
Valenti S., Perfumo F., Cavallero D., Verrina E., Nicora D., Piaggio D., Pinducciu C., Giusti M. Pulsatile LHRH therapy in uremic children with delayed puberty. J. Endocrinol. Invest. 74(Suppl. 2): 95, 1991.
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Giusti, M., Perfumo, F., Verrina, E. et al. Delayed puberty in uremia: Pituitary-gonadal function during short-term pulsatile luteinizing hormone-releasing hormone administration. J Endocrinol Invest 15, 709–717 (1992). https://doi.org/10.1007/BF03347637
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DOI: https://doi.org/10.1007/BF03347637