Background: The diagnosis of growth hormone (GH) deficiency is based on a reduced peak GH response to provocative tests. However, the provocative tests are poorly reproducible and GH secretion is regulated by physiological parameters, such as body weight and puberty. The aim of this study was to assess the influence of body mass index (BMI) on GH response to provocative testing and to analyze the reproducibility of GH stimulation test. Methods: Clinical data were collected retrospectively by chart review from the Pediatric Endocrine Unit at the Ajou University Hospital. A total of 187 subjects with short stature who completed a GH stimulation testing between 2003 and 2009 were included in the study. Results: Of the 187 subjects, 66 (35.3%) had GH deficiency, while 121 (64.7%) were categorized as having idiopathic short stature. Reliability was calculated for 48 patients with idiopathic short stature who underwent the GH stimulation test twice. A GH response ≧10 ng/ml after retesting was found in 39 patients (81.3%) and a GH response <10 ng/ml was found in 9 patients (18.7%). In a stepwise multivariate analysis, BMI was a significantly independent predictor of peak GH. Elevated BMI was negatively associated with peak plasma GH levels. Conclusions: The lack of reliability of GH values in response to pharmacological stimuli should be taken into account in the diagnosis of GH deficiency. Also, higher BMI is associated with lower GH secretion. BMI should be measured and GH results appropriately interpreted for all subjects undergoing GH stimulation testing.

Carel JC, Tresca JP, Letrait M, Chaussain JL, Lebouc Y, Job JC, Coste J: Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab 1997;82:2117–2121.
Vestergaard P, Hoeck HC, Jakobsen PE, Laurberg P: Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults. Horm Metab Res 1997;29:106–110.
Hilczer M, Smyczynska J, Lewinski A: Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul 2006;40:69–75.
Mazzola A, Meazza C, Travaglino P, Pagani S, Frattini D, Bozzola E, Corneli G, Aimaretti G, Bozzola M: Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency. J Endocrinol Invest 2008;31:159–162.
Ho KY, Evans WS, Blizzard RM, Veldhuis JD, Merriam GR, Samojlik E, Furlanetto R, Rogol AD, Kaiser DL, Thorner MO: Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 1987;64:51–58.
Iranmanesh A, Lizarralde G, Veldhuis JD: Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991;73:1081–1088.
Qu XD, Gaw Gonzalo IT, Al Sayed MY, Cohan P, Christenson PD, Swerdloff RS, Kelly DF, Wang C: Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 2005;90:1563–1569.
Van Dam EW, Roelfsema F, Helmerhorst FH, Frolich M, Meinders AE, Veldhuis JD, Pijl H: Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:4225–4230.
Micmacher E, Assumpcao RP, Redorat RG, Spina LD, Cruz IC, Silva CA, Vaisman M, Conceicao FL: Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men. Arq Bras Endocrinol Metabol 2009;53:853–858.
Tzanela M, Zianni D, Bilariki K, Vezalis A, Gavalas N, Szabo A, Drimala P, Vassiliadi D, Vassilopoulos C: The effect of body mass index on the diagnosis of GH deficiency in patients at risk due to a pituitary insult. Eur J Endocrinol 2010;162:29–35.
Growth Hormone Research Society: Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 2000;85:3990–3993.
Song AK, Kim HJ, Suk HJ, Hwang JS, Hong CH: Serum IGF-1 and IGFBP-3 in 919 healthy Korean children and adolescents: normal values and correlations with age, sex, height, body mass index and bone age. J Korean Soc Pediatr Endocrinol 2005;10:35–41.
Greulich WW, Pyle SI: Radiologic Atlas of Skeletal Development of the Hand and Wrist, ed 2. Standford, Stanford University Press, 1959.
Moon JS, Lee SY, Nam CM, Choi JM, Choe BK, Seo JW, Oh K, Jang MJ, Hwang SS, Yoo MH, Kim YT, Lee CG: 2007 Korean National Growth Charts: review of developmental process and an outlook. Korean J Pediatr 2008;51:1–25.
Colao A, Di Somma C, Savastano S, Rota F, Savanelli MC, Aimaretti G, Lombardi G: A reappraisal of diagnosing GH deficiency in adults: role of gender, age, waist circumference, and body mass index. J Clin Endocrinol Metab 2009;94:4414–4422.
Makimura H, Stanley T, Mun D, You SM, Grinspoon S: The effects of central adiposity on growth hormone (GH) response to GH-releasing hormone-arginine stimulation testing in men. J Clin Endocrinol Metab 2008;93:4254–4260.
Bonert VS, Elashoff JD, Barnett P, Melmed S: Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 2004;89:3397–3401.
Corneli G, Di Somma C, Baldelli R, Rovere S, Gasco V, Croce CG, Grottoli S, Maccario M, Colao A, Lombardi G, Ghigo E, Camanni F, Aimaretti G: The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 2005;153:257–264.
Martha PM Jr, Gorman KM, Blizzard RM, Rogol AD, Veldhuis JD: Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass. J Clin Endocrinol Metab 1992;74:336–344.
Albertsson-Wikland K, Rosberg S, Karlberg J, Groth T: Analysis of 24-hour growth hormone profiles in healthy boys and girls of normal stature: relation to puberty. J Clin Endocrinol Metab 1994;78:1195–1201.
Stanley TL, Levitsky LL, Grinspoon SK, Misra M: Effect of body mass index on peak growth hormone response to provocative testing in children with short stature. J Clin Endocrinol Metab 2009;94:4875–4881.
Luque RM, Kineman RD: Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function. Endocrinology 2006;147:2754–2763.
Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF, Schally AV, Fernandez-Cruz A: Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. J Clin Endocrinol Metab 1987;65:634–642.
Pontiroli AE, Lanzi R, Monti LD, Sandoli E, Pozza G: Growth hormone (GH) autofeedback on GH response to GH-releasing hormone. Role of free fatty acids and somatostatin. J Clin Endocrinol Metab 1991;72:492–495.
Maccario M, Procopio M, Loche S, Cappa M, Martina V, Camanni F, Ghigo E: Interaction of free fatty acids and arginine on growth hormone secretion in man. Metabolism 1994;43:223–226.
Lee EJ, Nam SY, Kim KR, Lee HC, Cho JH, Nam MS, Song YD, Lim SK, Huh KB: Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects. J Clin Endocrinol Metab 1995;80:2495–2498.
Kok P, Buijs MM, Kok SW, Van Ierssel IH, Frolich M, Roelfsema F, Voshol PJ, Meinders AE, Pijl H: Acipimox enhances spontaneous growth hormone secretion in obese women. Am J Physiol Regul Integr Comp Physiol 2004;286:R693–R698.
Coutant R, Lahlou N, Bouvattier C, Bougneres P: Circulating leptin level and growth hormone response to stimulation tests in obese and normal children. Eur J Endocrinol 1998;139:591–597.
Tannenbaum GS, Gurd W, Lapointe M: Leptin is a potent stimulator of spontaneous pulsatile growth hormone (GH) secretion and the GH response to GH-releasing hormone. Endocrinology 1998;139:3871–3875.
Ozata M, Dieguez C, Casanueva FF: The inhibition of growth hormone secretion presented in obesity is not mediated by the high leptin levels: a study in human leptin deficiency patients. J Clin Endocrinol Metab 2003;88:312–316.
Loche S, Bizzarri C, Maghnie M, Faedda A, Tzialla C, Autelli M, Casini MR, Cappa M: Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency. J Pediatr 2002;140:445–449.
Cacciari E, Tassoni P, Cicognani A, Pirazzoli P, Salardi S, Balsamo A, Cassio A, Zucchini S, Colli C, Tassinari D, et al: Value and limits of pharmacological and physiological tests to diagnose growth hormone (GH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient. J Clin Endocrinol Metab 1994;79:1663–1669.
Zadik Z, Chalew SA, Gilula Z, Kowarski AA: Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation. J Clin Endocrinol Metab 1990;71:1127–1130.
Badaru A, Wilson DM: Alternatives to growth hormone stimulation testing in children. Trends Endocrinol Metab 2004;15:252–258.
Hilczer M, Smyczynska J, Stawerska R, Lewinski A: Stability of IGF-1 concentration despite divergent results of repeated GH stimulating tests indicates poor reproducibility of test results. Endocr Regul 2006;40:37–45.
Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA: Significance of basal IGF-1, IGFBP-3 and IGFBP-2 measurements in the diagnostics of short stature in children. Horm Res 2000;54:60–68.
Boquete HR, Sobrado PG, Fideleff HL, Sequera AM, Giaccio AV, Suarez MG, Ruibal GF, Miras M: Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-1 and IGFBP-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Metab 2003;88:4702–4708.
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