Advertisement

Growth Hormone Neurosecretory Dysfunction: Update

  • Barry B. Bercu
Part of the Serono Symposia, USA book series (SERONOSYMP)

Abstract

The neuroregulation of GH secretion is complex involving the dual regulatory control of a GH releasing hormone (GHRH) and GH inhibiting hormone (somatostatin or SRIH) (see Figures 1 and 2). These neurohormones are further regulated by neurotransmitters (Fig. 1). Experimental evidence (animal and human) for anatomic distribution and the possible role of neurotransmitters (dopaminergic, catecholaminergic, cholinergic, serotonergic, histaminergic, gama-aminobutyric acidergic) are reviewed in greater detail elsewhere (1,2). We hypothesize that defects in the neuro- regulatory control of GH secretion results in decreased or disordered GH secretion which is, ultimately, expressed as poor growth velocity and short stature.

Keywords

Growth Hormone Growth Hormone Secretion Provocative Testing Peak Growth Hormone Idiopathic Short Stature 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bercu BB, Diamond F. A determinant of stature: regulation of growth hormone secretion. In: Barness L, ed. Advances in pediatrics. Chicago: Yearbook Medical Publishers, Inc, 1986: 331–80.Google Scholar
  2. 2.
    Bercu BB, Diamond F. Growth hormone neurosecretory dysfunction. In: Savage M, Randall R, eds. Growth disorders. Clin Endocrinol Metab 1986; 15: 537–90.Google Scholar
  3. 3.
    Richards GE, Wara WM, Grumbach MM, et al. Delayed onset of hypopitu¬itarism: sequelae of therapeutic irradiation of central nervous system, eye and middle ear tumors. J Pediatr 1976; 89: 553.PubMedCrossRefGoogle Scholar
  4. 4.
    Shalet SM. Disorders of the endocrine system due to radiation and cytotoxic chemotherapy. Clin Endocrinol (Oxf) 1983; 18: 637–59.CrossRefGoogle Scholar
  5. 5.
    Shalet SM, Beardwell CG, Morris-Jones PH, Pearson D. Growth hormone deficiency after treatment of acute leukemia in children. Arch Dis Child 1976; 51: 489–93.PubMedCrossRefGoogle Scholar
  6. 6.
    Shalet SM, Beardwell CG, Pearson D, Morris-Jones PH. The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clin Endocrinol (Oxf) 1976; 5: 287–90.CrossRefGoogle Scholar
  7. 7.
    Dacou-Vaitekakis C, Xypolyta A, Haidas ST, et al. Irradiation of the head: immediate effect on growth hormone secretion in children. J Clin Endocrinol Metab 1977; 44: 791–4.CrossRefGoogle Scholar
  8. 8.
    Swift PGF, Kearney PJ, Dalton RG, et al. Growth hormonal status of children treated for acute lymphoblastic leukemia. Arch Dis Child 1978; 53: 890–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Oliff A, Bode U, Bereu BB, et al. Hypothalamic-pituitary dysfunction following CNS prophylaxis in acute lymphocytic leukemia, correlation with CT scan abnormalities. Med Pediatr Oncol 1979; 7: 141–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Bode U, Oliff A, Bereu BB, DiChiro G, Glaubiger D, Poplack D. Absence of CT brain scan abnormalities with less intensive CNS prophylaxis. Am J Pediatr Hematol Oncol 1980; 2: 21–4.Google Scholar
  11. 11.
    Romehe CA, Zipf WB, Miser A, et al. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature. J Pediatr 1984; 104: 177–81.CrossRefGoogle Scholar
  12. 12.
    Dickinson WP, Berry DH, Dickinson L, et al. Differential effects of cranial radiation on growth hormone response to arginine and insulin infusion. J Pediatr 1978; 92: 754–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Blatt J, Bereu BB, Gillin JC, Mendelson WB, Poplack D. Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia. J Pediatr 1984; 104: 182–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Muhlendahl KEV, Gadner H, Riehm H, et al. Endocrine function after antineoplastic therapy in 22 children with acute lymphoblastic leukemia. Helv Paediatr Acta 1976; 31: 463–71.Google Scholar
  15. 15.
    Chrousos GP, Poplack D, Brown T, O’Neill D, Schwade JG, Bereu BB. Effects of cranial radiation on hypothalamic-adenohypophyseal function: abnormal growth hormone secretory dynamics. J Clin Endocrinol Metab 1982; 54: 1135–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Daniel PM, Prichard ML. Studies of the hypothalamus and the pituitary with special reference to the effects of transsection of the pituitary stalk. Acta Endocrinol [suppl] (Copenh) 1978; 201: 1–216.Google Scholar
  17. 17.
    Bloch B, Brazeau P, Esch F, et al. Immunohistochemical detection of growth hormone-releasing factor in brain. Nature 1983; 301: 607–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Cooper PE, Fernstrom MH, Rorstad OP, Leeman SE, Martin JB. The regional distribution of somatostatin, substance P and neurotensin in human brain. Brain Res 1981; 218: 219–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Rudman D, Kutner MH, Blackston RD, Jansen RD, Patterson JH. Normal variant short stature: subclassification based on responses to exogenous human growth hormone. J Clin Endocrinol Metab 1979; 49: 92–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Kowarski AA, Schneider J, Ben-Galim E, Weldon VV, Daughaday WH. Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH. J Clin Endocrinol Metab 1978; 47: 461–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Lanes P, Plotnick LP, Spencer ME, Daughaday WE, Kowarski AA. Dwarfism associated with normal serum growth hormone and increased bioassayable, receptorassayable, and immunoassayable somatomedin. J Clin Endocrinol Metab 1980; 50: 485–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Lanes P, Plotnick LP, Spencer ME, Daughaday WE, Kowarski AA. Dwarfism associated with normal serum growth hormone and increased bioassayable, receptorassayable, and immunoassayable somatomedin. J Clin Endocrinol Metab 1980; 50: 485–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Hayek A, Peake GT. Growth and somatomedin-C responses to growth hormone in dwarfed children. J Pediatr 1981; 99: 868–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Valenta LH, Siegel MB, Lesniak MA, et al. Pituitary dwarfism in a patient with circulating abnormal growth hormone polymers. N Engl J Med 1985; 312: 214–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Frazer TE, Gavin VR, Daughaday WH, Hillman RE, Weldon W. Growth hormone-dependent growth failure. J Pediatr 1982; 101: 12–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Van Vliet G, Styne DM, Kaplan SL, Grumbach MM. Growth hormone treatment for short stature. N Engl J Med 1983; 309: 1016–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Gertner JM, Genel M, Gianfredi SP, et al. Prospective clinical trial of human growth hormone in short children without growth hormone deficiency. J Pediatr 1984; 104: 172–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Grunt JA, Howard C, Daughaday WH. Comparison of growth and somatomedin C responses following growth hormone treatment in children with small-for-date short stature, significant idiopathic short stature and hypopituitarism. Acta Endocrinol (Copenh) 1984; 106: 168–74.Google Scholar
  29. 29.
    Spiliotis B, August G, Hung W, Sonis W, Mendelson W, Bercu BB. Growth hormone neurosecretory dysfunction: a treatable cause of short stature. JAMA 1984; 251: 2223–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Bercu BB, Shulman D, Root AW, Spiliotis BE. Growth hormone provocative testing frequently does not reflect endogenous growth hormone secretion. J Clin Endocrinol Metab 1986; 63: 709–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Tanner JM. Growth at adolescence. Springfield: Charles C. Thomas, 1962.Google Scholar
  32. 32.
    Greulich WW, Pyle SJ. Radiographic atlas of skeletal development of the hand and wrist. Palo Alto: Stanford University Press, 1973.Google Scholar
  33. 33.
    Root AW, Rosenfield RL, Bongiovanni AM, Eberlein WR. The plasma growth hormone response to insulin-induced hypoglycemia in children with retardation of growth. Pediatrics 1967; 39: 884–52.Google Scholar
  34. 34.
    Reiter EO, Root AW. The effect of pyridoxine on pituitary release of growth hormone and prolactin in childhood and adolescence. J Clin Endocrinol Metab 1978; 47: 689–90.PubMedCrossRefGoogle Scholar
  35. 35.
    Veldhuis JD, Johnson ML. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol 1986; E486–93.Google Scholar
  36. 36.
    Shulman DI, Bercu BB. The evaluation of growth hormone secretion: provocative testing vs endogenous 24 hour growth hormone profile. Acta Paediatr Scand (in press).Google Scholar
  37. 37.
    Costin G, Kaufman FR. Growth hormone secretory patterns in children with short stature. J Pediatr 1987; 110: 362–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Huseman CA, Hassing JM. Evidence for dopaminergic stimulation of growth velocity in some hypopituitary children. J Clin Endocrinol Metab 1984; 58: 419–25.PubMedCrossRefGoogle Scholar
  39. 39.
    Huseman CA. Growth enhancement by dopaminergic therapy in children with intrauterine growth retardation. J Clin Endocrinol Metab 1985; 61: 514–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Huseman CA, Hassing JM, Sibilia MG. Endogenous dopaminergic dysfunction: a novel form of human growth hormone deficiency and short stature. J Clin Endocrinol Metab 1986; 62: 484–90.PubMedCrossRefGoogle Scholar
  41. 41.
    Castro-Magana M, Angulo M, Fuentes B, et al. Effect of prolonged clonidine administration on growth hormone concentrations and rate of linear growth in children with constitutional growth delay. J Pediatr 1986; 109: 784.PubMedCrossRefGoogle Scholar
  42. 42.
    Pintor C, Cella SG, Corda R, et al. Clonidine accelerates growth in children with impaired growth hormone secretion. Lancet 1985; 1: 1482–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Loche S, Pintor C, Puggioni R, et al. Treatment of shorjf stature with clonidine: stimulatory effect in children with constitutional growth delay (CGD) [Abstract]. Presented at the 68th Annual Meeting of the Endocrine Society, Anaheim, California, 1986.Google Scholar
  44. 44.
    Bercu BB, Root AW, Shulman DI. Preservation of dopaminergic and alpha adrenergic function in children with growth hormone neurosecretory dysfunction. J Clin Endocrinol Metab 1986; 63: 968–73.PubMedCrossRefGoogle Scholar
  45. 45.
    Brammert M, Hokfelt B. Partial blockage by naloxone of clonidine- induced increase in plasma growth hormone in hypertensive patients. J Clin Endocrinol Metab 1984; 58: 374–7.CrossRefGoogle Scholar
  46. 46.
    Delitala G, Maioli M, Pacifico A, et al. Cholinergic receptor control mechanisms for L-dopa, apomorphine, and clonidine-induced growth hormone secretion in man. J Clin Endocrinol Metab 1983; 57: 1145–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Tater P, Vigas M. Role of alpha 1 and alpha 2 adrenergic receptors in the growth hormone and prolactin response to insulin induced hypoglycemia in man. Neuroendocrinology 1984; 39: 275–80.CrossRefGoogle Scholar
  48. 48.
    Tannenbaum GH, Ling N. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology 1984; 115: 1952–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Thorner MO, Speiss J, Vance ML, et al. Human pancreatic growth hormone releasing factor selectively stimulates growth hormone secretion in man. Lancet 1983; 1: 24–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Chalew S, Armour KM, Levin PA, Thorner MO, Kowarski AA. Growth hormone response to GH-releasing hormone in children with subnormal integrated concentrations of GH. J Clin Endocrinol Metab 1986; 62: 1110–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Gelato MC, Malözowski S, Caruso-Nicoletti M, et al. Growth hormone (GH) responses to GH-releasing hormone during pubertal development in normal boys and girls: comparison to idiopathic short stature and GH deficiency. J Clin Endocrinol Metab 1986; 174: 174–9.CrossRefGoogle Scholar
  52. 52.
    Schrioch EA, Lustig RH, Rosenthal SM, Kaplan SL, Grumbach MM. Effect of growth hormone (GH)-releasing hormone (GRH) on plasma GH in relation to magnitude and duration of GH deficiency in 26 children and adults with isolated GH deficiency or multiple pituitary hormone deficiencies: evidence for hypothalamic GRH deficiency. J Clin Endocrinol Metab 1984; 58: 1043–9.CrossRefGoogle Scholar
  53. 52A.
    Shulman DI, Root AW, Hu CS, Bereu BB. 24 hour prolactin secretion in short normal, classical growth hormone deficient and growth hormone neurosecretory dysfunction children [Abstract 790]. 69th Annual Endocrine Society Meeting, Indianapolis, Indiana, 1987: 218.Google Scholar
  54. 53.
    Mauras N, Blizzard RM, Link K, Johnson ML, Rogol AD, Veldhuis JD. Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab 1987; 64: 596–601.PubMedCrossRefGoogle Scholar
  55. 54.
    Zadik Z, Chalew SA, McCarter J Jr, Meistas M, Kowarski AA. The influence of age on the 24 hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 1985; 60: 513–6.PubMedCrossRefGoogle Scholar
  56. 55.
    Ross JL, Pescovitz OH, Barnes K, Loriaux DL, Cutler GB Jr. Growth hormone cccrctory dynamics in children with precocious puberty. J Pediatr 1987; 110: 369–72.PubMedCrossRefGoogle Scholar
  57. 56.
    Albertsson-Wikland K, Isaksson O, Rosberg S, et al. Secretory pattern of growth hormone in children of different growth rates [Abstract]. Acta Endocrinol (Copenh) 1983; 103 (suppl 256): 72.Google Scholar
  58. 57.
    Gourmelen M, Le Bouc Y, Girard F, et al. Serum levels of insulinlike growth factor (IGF) and IGF binding protein in constitutionally tall children and adolescents. J Clin Endocrinol Metab 1984; 59: 1197–203.PubMedCrossRefGoogle Scholar
  59. 58.
    Cacciari E, Cicognani A, Pirazzoli P, et al. Differences in somatomedin-C between short-normal subjects and those of normal height. J Pediatr 1985; 106: 891–4.PubMedCrossRefGoogle Scholar
  60. 59.
    Zadik F, Chalew SA, Raiti S, Kowarski AA. Do short children secrete insufficient quantities of growth hormone? Pediatrics 1985; 76: 355–60.PubMedGoogle Scholar
  61. 60.
    Eigenmann JE, Patterson DF, Zapf J, et al. Insulin-like growth factor I in the dog: a study in different dog breeds and in dogs with growth hormone elevation. Acta Endocrinol (Copenh) 1984; 105: 294–301.Google Scholar
  62. 61.
    Eigenmann JE, Patterson DF, Froesch ER. Body size parallels insulin-like growth factor I levels but not growth hormone secretory capacity. Acta Endocrinol (Copenh) 1984; 106: 448–53.Google Scholar
  63. 62.
    Bereu BB, Shulman DI, Root AW. High incidence of prenatal and perinatal complications associated with growth hormone neurosecretory dysfunction ( GHND) [Abstract]. Pediatr Res 1987; 224A.Google Scholar
  64. 63.
    Bierich JR. Treatment of constitutional delay of growth and adolescence with human growth hormone. Klin Padiatr 1983; 195: 309–16.PubMedCrossRefGoogle Scholar
  65. 64.
    Lanes R, Bohorquez L, Leal V, et al. Growth hormone secretion in patients with constitutional delay of growth and pubertal development. J Pediatr 1986; 109: 781–3.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Barry B. Bercu
    • 1
    • 2
  1. 1.Department of PediatricsUniversity of South Florida College of MedicineTampaUSA
  2. 2.All Children’s HospitalSt. PetersburgUSA

Personalised recommendations