Evaluation of growth hormone deficiency in children with cystic fibrosis


1 Department of Pediatrics, Faculty of Medicine, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pediatrics, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

4 Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Due to chronic respiratory and gastrointestinal problems, growth failure is a common issue in patients with cystic fibrosis (CF). The present study aimed to investigate the prevalence of growth hormone deficiency (GHD) in CF children with stable gastrointestinal and respiratory conditions. Materials and Methods: In this study, the growth indicators of all 4–16-year-old children referred to two CF clinics were monitored over 3 years. Children without severe gastrointestinal or pulmonary symptoms with weight <3% percentile or whose height increase were two standard deviations below their expected height growth over 6 months were selected for the growth hormone (GH) stimulation test by clonidine and L-dopa test. Some of the children without CF, who were also referred for height growth disorders and matched the CF group, were considered the control group. They underwent the GH stimulation test, and the results were compared. Results: From 150 patients with CF, growth failure was observed in 24 patients with stable gastrointestinal and respiratory conditions; in 10 of them, the GH stimulation test was deficient. The prevalence of GHD was 6.6% in CF patients. In the control group of 30 children without CF, but with growth failure, the GH was deficient in nine cases, implying no significant difference with the case group (P = 0.37). Conclusion: In our study, the prevalence of GHD was 6.6% in CF patients, whereas the prevalence GHD in the normal population of childhood is <1%. Therefore, further studies should be designed to investigate the cause of GHD in CF patients


Darrah R, Bederman I, Vitko M, Valerio DM, Drumm ML, Hodges CA. Growth deficits in cystic fibrosis mice begin in utero prior to IGF-1 reduction. PLoS One 2017;12:e0175467.  Back to cited text no. 1
Thaker V, Carter B, Putman M. Recombinant growth hormone therapy for cystic fibrosis in children and young adults. Cochrane Database Syst Rev 2018;12:CD008901.  Back to cited text no. 2
Le TN, Anabtawi A, Putman MS, Tangpricha V, Stalvey MS. Growth failure and treatment in cystic fibrosis. J Cyst Fibros 2019;18 Suppl 2:S82-7.  Back to cited text no. 3
Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry, 2019 Annual Data Report. Bethesda, Maryland: Cystic Fibrosis Foundation Publ.; 2020. p. 1-26.  Back to cited text no. 4
Scaparrotta A, Di Pillo S, Attanasi M, Consilvio NP, Cingolani A, Rapino D, et al. Growth failure in children with cystic fibrosis. J Pediatr Endocrinol Metab 2012;25:393-405.  Back to cited text no. 5
Kim RJ. Cystic fibrosis-related diabetes in children: An update. Pediatr Ann 2016;45:e321-6.  Back to cited text no. 6
Assael BM, Casazza G, Iansa P, Volpi S, Milani S. Growth and long-term lung function in cystic fibrosis: A longitudinal study of patients diagnosed by neonatal screening. Pediatr Pulmonol 2009;44:209-15.  Back to cited text no. 7
Konstan MW, Butler SM, Wohl ME, Stoddard M, Matousek R, Wagener JS, et al. Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis. J Pediatr 2003;142:624-30.  Back to cited text no. 8
Bidlingmaier M, Strasburger CJ. Growth hormone. Handb Exp Pharmacol 2010;195:187-200.  Back to cited text no. 9
Karami H, Kianifar HR, Khakshour A, Vakili R, Khalighi N, Jafari S, et al. Assessment of serum levels of growth factors IGF1 and IGFBP3 in children with cystic fibrosis. Iran J Pediatr 2019;29:1-6.  Back to cited text no. 10
Khalighi N, Vakili R, Jafari SA, Kianifar HR. Growth factors in cystic fibrosis. Reviews in Clinical Medicine. 2016;3:13-7.  Back to cited text no. 11
Rogan MP, Reznikov LR, Pezzulo AA, Gansemer ND, Samuel M, Prather RS, et al. Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth. Proc Natl Acad Sci U S A 2010;107:20571-5.  Back to cited text no. 12
Hardin DS, Adams-Huet B, Brown D, Chatfield B, Dyson M, Ferkol T, et al. Growth hormone treatment improves growth and clinical status in prepubertal children with cystic fibrosis: Results of a multicenter randomized controlled trial. J Clin Endocrinol Metab 2006;91:4925-9.  Back to cited text no. 13
Hardin DS, Rice J, Ahn C, Ferkol T, Howenstine M, Spears S, et al. Growth hormone treatment enhances nutrition and growth in children with cystic fibrosis receiving enteral nutrition. J Pediatr 2005;146:324-8.  Back to cited text no. 14
Stalvey MS, Anbar RD, Konstan MW, Jacobs JR, Bakker B, Lippe B, et al. A multi-center controlled trial of growth hormone treatment in children with cystic fibrosis. Pediatr Pulmonol 2012;47:252-63.  Back to cited text no. 15
Lutski M, Zucker I, Zadik Z, Libruder C, Blumenfeld O, Shohat T, et al. Prevalence of diabetes among children treated with growth hormone in Israel. Diabet Med 2019;36:1276-81.  Back to cited text no. 16
Ahmed H. Growth hormone stimulation tests. Physiol Rep 2018;6:e13563.  Back to cited text no. 17
Le TN, Schechter MS. Origins of growth deficiencies in cystic fibrosis. Thorax 2019;74:423-4.  Back to cited text no. 18
Lavi E, Gileles-Hillel A, Zangen D. Somatic growth in cystic fibrosis. Curr Opin Endocrinol Diabetes Obes 2020;27:38-46.  Back to cited text no. 19
Goyal A, Khadgawat R. Diagnosis of childhood growth hormone deficiency: Controversies, consensus and the need for new diagnostic tools. Neurol India 2018;66:1685-6.  Back to cited text no. 20
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Laursen EM, Lanng S, Rasmussen MH, Koch C, Skakkebaek NE, Müller J. Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients. Eur J Endocrinol 1999;140:315-21.  Back to cited text no. 21
Pascucci C, De Biase RV, Savi D, Quattrucci S, Isidori AM, Lubrano C, et al. Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis. J Endocrinol Invest 2018;41:591-6.  Back to cited text no. 22
Ciro D, Padoan R, Blau H, Marostica A, Fuoti M, Volpi S, et al. Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers. J Cyst Fibros 2013;12:165-9.  Back to cited text no. 23
Phung OJ, Coleman CI, Baker EL, Scholle JM, Girotto JE, Makanji SS, et al. Recombinant human growth hormone in the treatment of patients with cystic fibrosis. Pediatrics 2010;126:e1211-26.  Back to cited text no. 24
Yang A, Cho SY, Kwak MJ, Kim SJ, Park SW, Jin DK, et al. Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency. Sci Rep 2019;9:16181.  Back to cited text no. 25
Rosenberg LA, Schluchter MD, Parlow AF, Drumm ML. Mouse as a model of growth retardation in cystic fibrosis. Pediatr Res 2006;59:191-5.  Back to cited text no. 26