Journal of Endocrinological Investigation

, Volume 15, Issue 10, pp 709–717 | Cite as

Delayed puberty in uremia: Pituitary-gonadal function during short-term pulsatile luteinizing hormone-releasing hormone administration

  • Massimo Giusti
  • F. Perfumo
  • E. Verrina
  • D. Cavallero
  • G. Piaggio
  • S. Valenti
  • R. Gusmano
  • G. Giordano


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.


Uremia delayed puberty gonadotropins sex-steroids LHRH pulsatile administration 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    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.Google Scholar
  2. 2.
    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.PubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    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.CrossRefGoogle Scholar
  7. 7.
    Tsatsoulis A., Shalet S.M., Robertson W.R. Bioactive gonadotrophin secretion in man. Clin. Endocrinol. (Oxf.) 35:193: 1991.CrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    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.Google Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.CrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.Google Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.Google Scholar
  19. 19.
    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.PubMedGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    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.CrossRefGoogle Scholar
  22. 22.
    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.CrossRefGoogle Scholar
  23. 23.
    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.Google Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.CrossRefGoogle Scholar
  27. 27.
    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.CrossRefGoogle Scholar
  28. 28.
    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.PubMedCrossRefGoogle Scholar
  29. 29.
    Santen R.J., Bardin C.W. Episodic luteinizing hormone secretion in man pulse analysis, clinical interpretation, physiologic mechanisms. J. Clin. Invest. 52:2617, 1973.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedGoogle Scholar
  32. 32.
    Handelsman D.J., Spaliviero J.A., Turtle J.R. Testicular function in experimental uremia. Endocrinology 777: 1974, 1985.CrossRefGoogle Scholar
  33. 33.
    Handelsman D.J., Spaliviero J.A., Turtle J.R. Hypothalamic-pituitary function in experimental uremic hypogonadism. Endocrinology 117:1984, 1985.PubMedCrossRefGoogle Scholar
  34. 34.
    Wibullaksanakul S., Handelsman D.J. Regulation of hypothalamic gonadotropin-releasing hormone secretion in experimental uremia: in vitro studies. Neuroendocrinology 54: 353, 1991.PubMedCrossRefGoogle Scholar
  35. 35.
    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.Google Scholar
  36. 36.
    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.CrossRefGoogle Scholar
  37. 37.
    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.PubMedGoogle Scholar
  38. 38.
    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.CrossRefGoogle Scholar
  39. 39.
    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.PubMedCrossRefGoogle Scholar
  40. 40.
    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.PubMedCrossRefGoogle Scholar
  41. 41.
    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.CrossRefGoogle Scholar
  42. 42.
    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.CrossRefGoogle Scholar
  43. 43.
    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.Google Scholar
  44. 44.
    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.Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1992

Authors and Affiliations

  • Massimo Giusti
    • 1
  • F. Perfumo
    • 2
  • E. Verrina
    • 2
  • D. Cavallero
    • 1
  • G. Piaggio
    • 2
  • S. Valenti
    • 1
  • R. Gusmano
    • 2
  • G. Giordano
    • 1
  1. 1.DISEMUniversity of GenovaGenovaItaly
  2. 2.Divisione Nefrologica e DialisiIstitute GasliniGenovaItaly

Personalised recommendations