Abstract
Growth hormone (GH) responses to GRF (1 μg/kg BW i.v.) were investigated. Comparison between GRF(1–40) and GRF(1–29)NH2 in 11 young adult volunteers gave identical results. One hundred and thirty-one children and adolescents (45 with idiopathic GHD) were tested with GRF (1–29)NH2. The maximal GH levels (max GH) in response to GRF during the 120 min test period were found suitable to characterize the response. In cases without GHD no correlation to age, sex and pubertal development was observed. A maximal GH level of above 10 ng/ml was found to be normal. In 3 out of 86 children without GHD (one with Turner syndrome; two with simple obesity) max GH fell short of 10 ng/ml, while 11 of 45 cases with GHD exceeded this margin. In GHD, max GH was inversely correlated with age. There was no difference in max GH between groups with or without perinatal pathology as a presumed cause of GHD. GH levels to GRF were positively correlated with maximal GH level during sleep in GHD, but not correlated with responses seen to insulin or arginine. The value of GRF testing for the confirmation of GHD is discussed in the light of other GH stimulatory tests and basal somatomedin C measurements. It is suggested that the combination of testing with GRF and the determination of a basal SmC level offers a safe and convenient way to diagnose GHD in clinically suspected cases, though in some cases further diagnostic tests may be needed.
Similar content being viewed by others
Abbreviations
- GH:
-
growth hormone
- GRF:
-
growth hormone releasing factor
- RIA:
-
radioimmunoassay
- SmC:
-
somatomedin C
- SDS:
-
standard deviation score =\(\frac{{x - \bar x}}{{SD_{\bar x} }}\)
- CA:
-
chronological age
- BA:
-
bone age
- GHD:
-
growth hormone deficiency
- CDGA:
-
constitutional delay of growth and adolescence
- IGHD:
-
isolated growth hormone deficiency
References
Arimura A, Culler MD (1985) Regulation of growth hormone secretion. In: Imura H (ed) The Pituitary Gland. Raven Press, New York, pp 221–259
Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L, Hintz RL (1981) Somatomedin C mediates growth hormone negative feed-back by effects on both the hypothalamus and the pituitary. Science 212:1279–1281
Bierich JR (1972) On the aetiology of hypopituitary dwarfism. In: Pecile A, Müller EE (eds) Growth and Growth Hormone. Excerpta Medica, Amsterdam, pp 408–415
Bierich JR (1983) Minderwuchs. Monatsschr Kinderheilkd 131: 180–193
Binoux M, Seurin D, Lassarre C, Gourmelen M (1984) Preferential measurement of Insulin-like growth factor (IGF) I-related peptides in serum with the aid of IGF-binding proteins (IGF BPs) produced by rat liver in culture. Estimation in serum IGF BP levels. J Clin Endocrinol Metab 59:453–462
Blum WF, Ranke MB, Bierich JR (1986) Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV. Acta Endocrinol 111:271–284
Borges JL, Gelato MC, Rogol AD, Vance ML, Loriaux DL, Rivier J, Blizzard RM, Furnaletto R, Evans WS, Kaiser DL, Merriam GR, Spiess J, Vale W, Thorner MO (1983) Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency. Lancet 119–124
Brandt I (1979) Perzentilenkurven für die Gewichtsentwicklung. Bei Früh- und Reifgeborenen in den ersten fünf Jahren. der kinderarzt 10:713–718
Brandt I (1980) Perzentilenkurven für das Längenwachstum. Bei Früh- und Reifgeborenen in den ersten fünf Jahren. der kinderarzt 11:43–51
Chihara K, Kashio Y, Abe H, Minamitani N, Kaji H, Kita T, Fujita T (1985) Idiopathic growth hormone (GH) dificiency, and GH deficiency secondary to hypothalamic germinomas: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity level in cerebrospinal fluid. J Clin Endocrinol Metab 60:269–278
Dacou-Voutetakis C, Drakopoulou N, Maniati M (1983) Growth hormone levels during sleep in children. In: Laron Z, Butenandt O (eds) Evaluation of growth hormone secretion. Karger, Basel, pp 45–52
Daughaday WH, Maritz IK, Blethen SL (1980) Inhibition of access of bound somatomedin to membrane receptor and immuno-binding sites: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol-extracted serum. J Clin Endocrinol Metab 51:781–788
Dean HJ, Kellett JG, Bala RM, Guyda HJ, Bhaumick B, Posner BI, Friesen HG (1982) The effect of growth hormone treatment on the somatomedin levels in growth hormone-deficient children. J Clin Endocrinol Metab 55:1167–1173
Finkelstein JW, Roffwarg HP, Boyar RM, Kream J, Hellman L (1972) Age-related changes in the twenty-four hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 35:665–670
Furnaletto RW, Underwood LE, Van Wyk JJ, D'Ercole AJ (1977) Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest 60:648–657
Frasier SA (1974) A review of growth hormone stimulation tests in children. Pediatrics 53:929–934
Grossman A, Lytras N, Savage MO, Wass JAH, Coy DH, Rees LH, Jones AE, Besser GM (1984) Growth hormone releasing factor. Comparison of two analogues and demonstration of hypothalamic defect in growth hormone release after radiotherapy. Br Med J 288:1785–1787
Grossman A, Savage MO, Lytras N, Preece MA, Sueiras-Diaz J, Coy DH, Rees LH, Besser GM (1984) Responses to analogues of growth hormone releasing hormone in normal subjects, and in growth hormone deficient children and young adults. Clin Endocrinol 21:321–330
Grossman A, Savage MO, Blacklay A, Ross RM, Plowman PN, Preece MA, Coy DH, Besser GM (1985) The use of growth hormone-releasing hormone in the diagnosis and treatment of short stature. Horm Res 22:52–57
Gelato MC, Pescovitz OH, Cassorla F, Loriaux DL, Merriam GR (1984) Dose-response relationship for the effects of growth-hormone-releasing factor-(1–44)-NH2 in young adult men and women. J Clin Endocrinol Metab 59:197–201
Greulich WW, Pyle SI (1962) Radiographic atlas of skeletal development of hand and wrist, 2nd edn. Stanford University Press, Calif
Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB (1982) Growth hormone releasing factor from a human pancreatic tumor that caused acromegaly. Science 218:585–587
Kaplanowitz PB, D'Ercole AJ, Van Wyk JJ, Underwood LE (1982) Plasma somatomedin-C during the first year of life. J Pediatr 100:932–934
Losa M, Schipohl J, Müller OA, von Werder K (1984) Stimulation of growth hormone secretion with human growth hormone releasing factors (GRF 1–44, GRF 1–40, GRF 1–29) in normal subjects. Klin Wochenschr 62:1140–1143
Moore DC, Ravulcaba RHA, Smith EK, Kelley VC (1982) Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents. Horm Res 16:49–55
Penny R, Blizzard RM (1972) The possible influence of puberty on the release of hGH in three males with isolated hGH deficiency. J Clin Endocrinol Metab 34:82–84
Ranke MB, Weber J, Bierich JR (1979) Long-term response to human growth hormone in 36 children with idiopathic growth hormone deficiency. Eur J Pediatr 132:221–238
Reiter EO, Lovinger RD (1981) The use of a commercially available somatomedin-C radioimmunoassay in patients with disorders of growth. J Pediatr 99:720–724
Rivier J, Spiess J, Thorner MO, Vale W (1982) Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature 300:276–278
Rogol AD, Blizzard RM, Johanson AJ, Furnaletto RW, Evans WS, Rivier J, Vale WW, Thorner MO (1984) Growth hormone release in response to human pancreatic tumor growth hormone-releasing hormone 1–40 in children with short stature. J Clin Endocrinol Metab 59:580–585
Rosenthal SM, Schriock EA, Kaplan SL, Guillemin R, Grumbach MM (1983) Synthetic human pancreas growth hormone-releasing factor (hp GRF 1–44 NH2) stimulates growth hormone secretion in normal men. J Clin Endocrinol Metab 57:677–679
Schriock EA, Lustig RH, Rosenthal SM, Kaplan SL, Grumbach MM (1984) 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 58: 1043–1049
Shibasaki T, Shizume K, Nakahara M, Masuda A, Jibiki K, Demura H, Wakabajashi I, Ling N (1984) Age-related changes in plasma growth hormone response to growth hormone-releasing factor in man. J Clin Endocrinol Metab 58:212–214
Takano K, Hizuka N, Shizume K, Asakawa K, Miyokawa M, Herose N, Shibasaki T, Ling NC (1984) Plasma growth hormone (GH) response to GH-releasing factor in normal children with short stature and patients with pituitary dwarfism. J Clin Endocrinol Metab 58:236
Takano K, Hizuka N, Shizume K, Honda N, Ling NC (1985) Plasma growth hormone (GH) response to single and repetitive subcutaneous administration of GH releasing factor (HpGRF-44) in normal and GH deficient children. Acta Endocrinol 108:11–19
Tanner JM, Whitehouse RH, Takaishi M (1966) Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children 1965. Arch Dis Child 41:454–471, 613–635
Thorner MO, Reschke J, Chitwood J, Rogol AD, Furnaletto R, Rivier J, Vale W, Blizzard RM (1985) Acceleration of growth in two children treated with human growth hormone-releasing factor. N Engl J Med 3:4–9
Trygstad O (1977) Transitory hGH deficiency successfully treated with hGH. Acta Endocrinol 84:11–22
Van Vliet G, Bosson D, Robyn C, Craen M, Malvaux P, Vander-schueren-Lodewyckx M, Wolter R (1985) Effect of growth hormone-releasing factor on plasma growth hormone, prolactin and somatomedin C in hypopituitary and short normal children. Horm Res 22:32–45
Van Vliet G, Bosson D, Rummens E, Robyn C, Wolter R (1985) Effect of growth hormone releasing factor (GRF) on plasma growth hormone (GH) and prolactin (PRL) levels in obese children. Pediatr Res: 604 (Abstr 3)
Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W, Frohman LA (1984) Impaired growth hormone response to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 311:1403–1407
Wood SM, Chung JLC, Adams EF, Webster JD, Joplin GF, Mashiter K, Bloom SR (1983) Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF(1–44)) in acromegaly and hypopituitarism. Br Med J 286:1687–1691
Youlton R, Kaplan SL, Grumbach MM (1969) Growth and growth hormone. IV: Limitations of the growth hormone response to insulin and arginine and of the immunoreactive insulin response to arginine in the assessment of growth hormone deficiency in children. Pediatrics 43:989–1004
Author information
Authors and Affiliations
Additional information
Dedicated to Professor A. M. Bongiovanni, M.D.
Rights and permissions
About this article
Cite this article
Ranke, M.B., Gruhler, M., Rosskamp, R. et al. Testing with growth hormone-releasing factor (GRF(1–29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency. Eur J Pediatr 145, 485–492 (1986). https://doi.org/10.1007/BF02429048
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02429048