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Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children

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Abstract

The hormonal diagnosis of GH deficiency in childhood is conventionally based on the GH response to at least two provocative stimuli. Among these, arginine (ARG) has long been considered a classical, centrally mediated stimulus of GH secretion. ARG is also able to potentiate the GH response to GHRH, likely inhibiting hypothala-mic somatostatin; this combined test is one of the most potent to explore the maximal secretory capacity of somatotroph cells. Based on these premises, we verified whether the sequential administration of ARG and ARG+GHRH could be feasible as single step provocative test to evaluate the GH relea-sable pool in short children. To this goal, 48 normal short children (35 M and 13 F, 12.0±0.4 yr, PS 1: 255 II–IV: 23) underwent a test with ARG (0.5 g/kg iv from 0 to +30 min) followed by a coadmini-stration of ARG (from +120 to 150 min) plus GHRH (1 μg/kg iv at +120 min). ARG alone elicited a clear GH response (mean peak vs baseline: 12.1±1.7 vs 2.0±0.4 μg/l, p<0.001, Cmax range 12–51.0 μg/l). Following this GH rise, the hormonal levels at +120 min approached to baseline levels (4.2±0.8 μg/l) but then showed marked response to the coadmi-nistration of ARG+GHRH. The GH peak following ARG+GHRH (mean peak: 47.8±3.3 μg/l, p<0.001; Cmax 22.4–150.0 μg/l) was clearly higher (p<0.001) than that recorded after ARG alone. The GH responses to both ARG and ARG+GHRH were independent of gender, puberty, height velocity, body mass index (BMI) and IGF-I levels. Nine normal short children (16%) had GH peaks lower than 7 μg/l after ARG alone, while none showed GH peak below 20 μg/l after ARG+GHRH. Thus, ARG alone is a good stimulus of GH secretion but false positive responses frequently occur in normal short children. ARG+GHRH is a more potent stimulus giving no false positive responses even after previous challenge with ARG alone. Testing with sequential administration of ARG and ARG+GHRH may allow the single step evaluation of the somatotroph response to central and pituitary stimuli in short children.

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References

  1. Shalet S.M., Toogood A., Rahim A., Brennan B.M.D. The diagnosis of growth hormone deficiency in children and adults. Endocr. Rev. 1998, 19: 203–223.

    Article  CAS  PubMed  Google Scholar 

  2. Frasier S.D. A review of growth hormone stimulation tests in children. Pediatrics 1974, 53: 929–937.

    CAS  PubMed  Google Scholar 

  3. Thomer M.O., Vance M.L., Horvath E., Kovacs K. The anterior pituitary. In: Wilson J.D., Foster D.W. (Eds.), William Textbook of Endocrinology. Saunders, Philadelphia, 1992, p. 221.

    Google Scholar 

  4. Tassoni R., Cacciari E., Cau M., Colli C., Tosi M.T., Zucchini S., Cicognani A., Pirazzoli R, Salardi S., Balsamo A., Frejaville E., Cassio A., Zappulla F. Variability of growth hormone response to pharmacological and sleep tests performed twice in short children. J. Clin. Endocrinol. Metab. 1990, 71: 230–234.

    Article  CAS  PubMed  Google Scholar 

  5. Cacciari E., Tassoni R., Parisi G., Pirazzoli R., Zucchini S., Mandini M., Cicognani A., Balsamo E. Pitfalls in diagnosing of impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient. J. Clin. Endocrinol. Metab. 1992, 74: 1284–1289.

    CAS  PubMed  Google Scholar 

  6. Zadik Z., Chalew S.A., Kowarski A.A. Assessment of growth hormone secretion in normal stature children using 24-hour integrated concentration and pharmacological stimulation. J. Clin. Endocrinol. Metab. 1990, 71: 932–937.

    Article  CAS  PubMed  Google Scholar 

  7. Donaldson D.L., Pan F., Hollowell J.C., Stevenson J.L., Gifford R.A., Moore W.V. Reliability of stimulated and spontaneous growth hormone (GH) levels for identifyng the child with low GH secretion. J. Clin. Endocrinol. Metab. 1991, 72: 648–652.

    Article  Google Scholar 

  8. Ghigo E., Bellone J., Aimaretti G., Bellone S., Loche S., Cappa M., Bartolotta E., Dammacco F., Camanni F. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J. Clin. Endocrinol. Metab. 1996, 81: 3323–3327.

    CAS  PubMed  Google Scholar 

  9. Alba Roth L., Muller A.O., Schopol L., von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin se cretion. J. Clin. Endocrinol. Metab. 1988, 67: 1186–1189.

    Article  CAS  PubMed  Google Scholar 

  10. Page M.D., Dieguez C., Valcavi R., Edwards C., Hall R., Scanlon M.F. Growth hormone (GH) responses to arginine and l-dopa alone and after GHRH pretreatment. Clin. Endocrinol. 1988, 28: 551–558.

    Article  CAS  Google Scholar 

  11. Ghigo E., Bellone J., Mazza E., Imperiale E., Procopio M., Valente F., Lala R., De Sanctis C., Camanni F. Arginine potentiates the growth hormone (GH)-re-leasing hormone but not the pyridostigmine-in-duced GH secretion in normal short children. Further evidence for a somatostatin suppressing effect of arginine. Clin. Endocrinol. 1990, 32: 763–767.

    Article  CAS  Google Scholar 

  12. Ghigo E., Arvat E., Goffi S., Bellone J., Valente F., Procopio M., Ghigo M.C., Camanni F. Repetitive GHRH and arginine administration to ex plore the maximal secretory capacity of somatotroph cells during lifespan. Exp. Clin. Endocrinol. (Life Sci. Adv.) 1991, 10: 191–198.

    Google Scholar 

  13. Bellone J., Aimaretti G., Valetto M.R., Bellone S., Baffoni C., Arvat E., Seminara S., Camanni F., Ghigo E. Acute administration of recombinant human growth hormone inhibits the somatotroph respon siveness to growth hormone-releasing hormone in childhood. Eur. J. Endocrinol. 1996, 135: 421–424.

    Article  CAS  PubMed  Google Scholar 

  14. Arvat E., Di Vito L., Gianotti L., Ramunni J., Boghen F., Deghenghi R., Camanni F., Ghigo E. Mechanism underlying the negative growth hormone (GH) autofeedback on the GH-releasing effect of Hexarelin in man. Metabolism 1997, 46: 83–88.

    Article  CAS  PubMed  Google Scholar 

  15. Ghigo E., Goffi S., Nicolosi M., Arvat E., Valente F., Mazza E., Ghigo M.C., Camanni F. Growth hormone responsiveness to combined administration of arginine and GH releasing hormone does not vary with age in man. J. Clin. Endocrinol. Metab. 1990, 71: 1481–1485.

    Article  CAS  PubMed  Google Scholar 

  16. Ghigo E., Imperiale E., Boffano G.M., Mazza E., Bellone J., Arvat E., Procopio M., Goffi S, Barreca A., Chiabotto P., Lala R., de Sanctis C., Boghen M.T., Muller E.E., Camanni F. A new test for diagnosis of growth hormone (GH) deficiency due to primary pituitary impairment: combined administration of pyridostigmine and GH-releasing hormone. J. Endocrinol. Invest. 1990, 13: 307–316.

    CAS  PubMed  Google Scholar 

  17. Valetto M.R., Bellone J., Baffoni C., Savio P., Aimaretti G., Gianotti L., Arvat E., Camanni F., Ghigo E. Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur. J. Endocrinol. 1996, 135: 568–572.

    Article  CAS  PubMed  Google Scholar 

  18. Muller E.E., Nisticò G. Neurotransmitter regulation of the anterior pituitary. In: Muller E.E., Nisticò G., (Eds.), Brain messengers and the pituitary. Academic Press, San Diego, 1989 p. 404.

    Google Scholar 

  19. Spiliotis B.E., August G.P., Hung W., Sonis W., Mendelson W., Bercu B. Growth hormone neurosecretory dysfunction. A treatable cause of short stature. JAMA 1984, 251: 2223–2230.

    Article  CAS  PubMed  Google Scholar 

  20. Bercu B.B., Shulman D., Root A.W., Spiliotis B.E. Growth hormone (GH) provocative testing frequent ly does not reflect GH secretion. J. Clin. Endocrinol. Metab. 1986, 63: 709–715.

    Article  CAS  PubMed  Google Scholar 

  21. Zadik Z., Chalew S.A., Raiti A., Kowarsky A.A. Do short children secrete insufficient growth hormone? Pediatrics 1985, 76: 355–360.

    CAS  PubMed  Google Scholar 

  22. Albertsson-Wikland K., Rosberg S. Analysis of 24 hour growth hormone profiles in children: relation to growth. J. Clin. Endocrinol. Metab. 1988, 67: 493–500.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to E. Ghigo M.D..

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Bellone, J., Aimaretti, G., Bellone, S. et al. Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children. J Endocrinol Invest 23, 97–101 (2000). https://doi.org/10.1007/BF03343686

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