CLINICAL IMMUNOLOGY
The pre-treatment characteristics and evaluation of the effects of recombinant human growth hormone therapy in children with growth hormone deficiency and celiac disease or inflammatory bowel disease
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Submission date: 2017-11-08
Final revision date: 2017-12-20
Acceptance date: 2017-12-21
Publication date: 2018-03-30
Cent Eur J Immunol 2018;43(1):9-75
KEYWORDS
ABSTRACT
The aim of the study:
was to investigate the coincidence of growth hormone deficiency (GHD) and celiac disease (CD) or inflammatory bowel disease (IBD) in patients referred for short stature, and to evaluate the baseline anthropometric parameters and the effectiveness of recombinant human growth hormone (rhGH) therapy in the first year in those patients (GHD+CD/IBD subgroup) in comparison to patients with GHD without CD or IBD (GHD-CD/IBD subgroup).
Material and methods:
The study was retrospective and included 2196 short patients (height SDS [Standard Deviation Score] ≤ –1.2). 1454 patients had height SDS ≤ –2. Twenty-nine patients suffered from CD or IBD. GHD was confirmed in 419 patients with height SDS ≤ –2. The coexistence of GHD and CD or IBD was found in seven patients (GHD+CD/IBD subgroup).
Results:
At baseline the GHD-CD/IBD subgroup did not differ significantly in chronological age, height SDS, height velocity (HV) before rhGH therapy, body weight SDS, and body mass index SDS from the GHD+CD/IBD subgroup. The improvement in height SDS within the first year of rhGH therapy was higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup and the difference was statistically significant (p<0.05). HV in the first year of rhGH therapy was also significantly higher in the GHD+CD/IBD subgroup than in the GHD-CD/IBD subgroup (p < 0.05).
Conclusions:
In patients with chronic inflammatory disorders of the gastrointestinal tract, especially celiac disease, coexisting with GHD, rhGH therapy could be effective and should be administered together with therapy of primary gastrointestinal disease.
REFERENCES (70)
1.
Giovenale D, Meazza C, Cardinale GM, et al. (2006): The prevalence of growth hormone deficiency and celiac disease in short children. Clin Med Res 4: 180-183.
2.
Gasparetto M, Guariso G (2014): Crohn’s disease and growth deficiency in children and adolescents. World J Gastroenterol 20: 13219-13233.
3.
Ezri J, Marques-Vidal P, Nydegger A (2012): Impact of disease and treatments on growth and puberty of pediatric patients with inflammatory bowel disease. Digestion 85: 308-319.
4.
De Pascalis B, Bianchi A, Satta MA, et al. (2006): Growth hormone in inflammatory bowel disease. Eur Rev Med Pharmacol Sci 10: 13-16.
5.
Wong SC, Dobie R, Altowati MA, et al. (2016): Growth and the growth hormone-insulin like growth factor 1 axis in children with chronic inflammation: current evidence, gaps in knowledge, and future directions. Endocrine Reviews 37: 62-110.
6.
Soendergaard C, Young JA, Kopchick JJ (2017): Growth hormone resistance – special focus on inflammatory bowel disease. Int J Mol Sci 18: 1019.
7.
Katsanos KH, Tsianos EV (2002): Insulin-like growth factor system and inflammatory bowel disease. Annals of Gastroenterology 15: 11-17.
8.
Meazza C, Pagani S, Laarej K, et al. (2009): Short stature in children with coeliac disease. Pediatr Endocrinol Rev 6: 457-463.
9.
Meazza C, Pagani S, Gertosio C, et al. (2014): Celiac disease and short stature in children. Expert Rev Endocrinol Metab 9: 535-542.
10.
Vortia E, Kay M, Wyllie R (2011): The role of growth hormone and insulin-like growth factor-1 in Crohn’s disease: implications for therapeutic use of human growth hormone in pediatric patients. Curr Opin Pediatr 23: 545-551.
11.
Wong SC, Smyth A, McNeill E, et al. (2010): The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation. Clin Endocrinol (Oxf) 73: 220-228.
12.
Day AS, Ledder O, Leach ST, Lemberg DA (2012): Crohn’s and colitis in children and adolescents. World J Gastroenterol 18: 5862-5869.
13.
Jericho H, Sansotta N, Guandalini S (2017): Extraintestinal manifestations of celiac disease: effectiveness of the gluten-free diet. J Pediatr Gastroenterol Nutr 65: 75-79.
14.
Malik S, Mason A, Bakhshi A, et al. (2012): Growth in children receiving contemporary disease specific therapy for Crohn’s disease. Arch Dis Child 97: 698-703.
15.
Abraham BP, Mehta S, El-Serag HB (2012): Natural history of pediatric-onset inflammatory bowel disease: a systematic review. J Clin Gastroenterol 46: 581-589.
16.
Vasseur F, Gower Rousseau C, Vernier-Massouille G, et al. (2010): Nutritional status and growth in pediatric Crohn’s disease: a population-based study. Am J Gastroenterol 105: 1893-1900.
17.
Heuschkel R, Salvestrini C, Beattie RM, et al. (2008): Guidelines for the management of growth failure in childhood inflammatory bowel disease. Inflamm Bowel Dis 14: 839-849.
18.
Pfefferkorn M, Burke G, Griffiths A, et al. (2009): Growth abnormalities persist in newly diagnosed children with Crohn’s disease despite current treatment paradigms. J Pediatr Gastroenterol Nutr 48: 168-174.
19.
Shamir R, Philip M, Levine A (2007): Growth retardation in pediatric Crohn’s disease: pathogenesis and interventions. Inflamm Bowel Dis 13: 620-628.
20.
Boguszewski MCS, Cardoso-Demartini A, Geiger Frey MC, Celli A (2015): Celiac disease, short stature and growth hormone deficiency. Transl Gastrointest Cancer 4: 69-75.
21.
Wong SC, MacRae VE, McGrogan P, Ahmed SF (2006): The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation. J Pediatr Gastroenterol Nutr 43: 144-155.
22.
Radlović N, Mladenović M, Leković Z, et al. (2009): Effect of gluten-free diet on the growth and nutritional status of children with coeliac disease. Srp Arh Celok Lek 137: 632-637.
23.
Catassi C, Fasano A (2004): Coeliac disease as a cause of growth retardation in childhood. Curr Opin Pediatr 16:.
25.
Varghese S, Wyzga N, Griffiths AM, Sylvester FA (2002): Effects of serum from children with newly diagnosed Crohn disease on primary cultures of rat osteoblasts. J Pediatr Gastroenterol Nutr 35: 641-648.
26.
Diamanti A, Capriati T, Sole Basso M, et al. (2014): Celiac disease and overweight in children: an update. Nutrients 6: 207-220.
27.
Bozzola M, Meazza C, Villani A (2015): Auxo-endocrinological approach to celiac children. Diseases 3: 111-121.
28.
Walters TD, Gilman AR, Griffiths AM (2007): Linear growth improves during infliximab therapy in children with chronically active severe Crohn’s disease. Inflamm Bowel Dis 13: 424-430.
29.
Griffiths AM (2009): Growth retardation in early-onset inflammatory bowel disease: should we monitor and treat these patients differently? Dig Dis 27: 404-411.
30.
Sawczenko A, Ballinger AB, Savage MO, Sanderson IR (2006): Clinical Features affecting final adult height in patients with pediatric-onset Crohn’s disease. Pediatrics 118: 124-129.
31.
Giovenale D, Meazza C, Cardinale GM, et al. (2007): Growth hormone treatment in prepubertal children with celiac disease and growth hormone deficiency. J Pediatr Gastroenterol Nutr 45: 433-437.
32.
Bozzola M, Giovenale D, Bozzola E, et al. (2005): Growth hormone deficiency and coeliac disease: an unusual association? Clin Endocrinol (Oxf) 62: 372-375.
33.
Nemet D, Raz A, Zifman E, et al. (2009): Short stature, celiac disease and growth hormone deficiency. J Pediatr Endocrinol Metab 22: 979-983.
34.
Giannattasio A, Di Dato F, Minicucci V, et al. (2017): A retrospective evaluation of the association of celiac disease and growth hormone deficiency: more than a casual association? Minerva Endocrinologica 42: 24-29.
35.
Ballinger AB, Azooz O, El-Haj T, et al. (2000): Growth failure occurs through a decrease in insulin-like growth factor-1 which is independent of undernutrition in a rat model of colitis. Gut 46: 694-700.
36.
De Benedetti F, Alonzi T, Moretta A, et al. (1997): Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest 99: 643-650.
37.
Ballinger A (2002): Fundamental mechanisms of growth failure in inflammatory bowel disease. Horm Res 58 (Suppl 1): 7-10.
38.
Eivindson M, Nielsen JN, Gronbaek H, et al. (2005): The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease. Horm Res 64: 9-15.
39.
Street ME, de’Angelis G, Camacho-Hubner C, et al. (2004): Relationships between serum IGF-1, IGFBP-2, interleukin-1 and interleukin-6 in inflammatory bowel disease. Horm Res 61: 159-164.
40.
Kritsch KR, Murali S, Adamo ML, Ney DM (2002): Dexamethasone decreases serum and liver IGF-I and maintains liver IGF-I MRNA in parenterally fed rats. Am J Physiol Regul Integr Comp Physiol 282: R528-R536.
41.
Mazziotti G, Giustina A (2013): Glucocorticoids and the regulation of growth hormone secretion. Nat Rev Endocrinol 9: 265-276.
42.
Roberts-Thomson IC, Fon J, Uylaki W, et al. (2011): Cells, cytokines and inflammatory bowel disease: A clinical perspective. Expert Rev Gastroenterol Hepatol 5: 703-716.
43.
Neurath MF (2014): Cytokines in inflammatory bowel disease. Nat Rev Immunol 14: 329-342.
44.
Zhao Y, Xiao X, Frank SJ, et al. (2014): Distinct mechanisms of induction of hepatic growth hormone resistance by endogenous IL-6, TNF- and IL-1. Am J Physiol Endocrinol Metab 307: E186-E198.
45.
Wang P, Li N, Li JS, Li WQ (2002): The role of endotoxin, TNF-, and IL-6 in inducing the state of growth hormone insensitivity. World J Gastroenterol 8: 531-536.
46.
Theiss AL, Fruchtman S, Lund K (2004): Growth factors in inflammatory bowel disease. Inflamm Bowel Dis 10: 871-880.
47.
Mihara M, Hashizume M, Yoshida, H, et al. (2012): IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci Lond 122: 143-159.
48.
Yao X, Huang J, Zhong H, et al. (2014): Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther 141: 125-139.
49.
Reilly NR, Aguilar K, Hassid BG, et al. (2011): Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet. J Pediatr Gastroenterol Nutr 53: 528-531.
50.
Valletta E, Fornaro M, Cipolli M, et al. (2010): Celiac disease and obesity: need for nutritional follow-up after diagnosis. European Journal of Clinical Nutrition 64: 1371-1372.
51.
Alastair F, Emma G, Emma P (2011): Nutrition in inflammatory bowel disease. JPEN J Parenter Enteral Nutr 35: 571-580.
52.
Grønbek H, Thøgersen T, Frystyk J, et al. (2002): Low free and total insulinlike growth factor I (IGF-I) and IGF binding protein-3 levels in chronic inflammatory bowel disease: partial normalization during prednisolone treatment. Am J Gastroenterol 97: 673-678.
53.
Bannerjee K, Camacho-Hübner C, Babinska K, et al. (2004): Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease. J Pediatr Gastroenterol Nutr 38: 270-275.
54.
Beattie RM, Camacho-Hübner C, Wacharasindhu S, et al. (1998): Responsiveness of IGF-I and IGFBP-3 to therapeutic intervention in children and adolescents with Crohn’s disease. Clin Endocrinol (Oxf) 49: 483-489.
55.
Eivindson M, Grønbaek H, Skogstrand K, et al. (2007): The insulin-like growth factor (IGF) system and its relation to infliximab treatment in adult patients with Crohn’s disease. Scand J Gastroenterol 42: 464-470.
56.
Catassi C, Fasano A (2008): Is this really celiac disease? Pitfalls in diagnosis. Curr Gastroenterol Rep 10: 466-472.
57.
Cacciari E, Salardi S, Volta U, et al. (1985): Can antigliadin antibody detect symptomless coeliac disease in children with short stature? Lancet 29: 1469-1471.
58.
Stenhammar L, Fallstrom SP, Jansson G, et al. (1986): Coeliac disease in children of short stature without gastrointestinal symptoms. Eur J Pediatr 145: 185-186.
59.
Knudtzon J, Fluge G, Aksnes L (1991): Routine measurements of gluten antibodies in children of short stature. J Pediatr.
60.
Gastroenterol Nutr 12: 190-194.
61.
Rossi TM, Albini CH, Kumar V (1993): Incidence of coeliac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus. J Pediatr 123: 262-264.
62.
De Lecea A, Ribes-Koninckx C, Polanco I, Calvete JF (1996): Serological screening (antigliadin and antiendomysium antibodies) for non-overt coeliac disease in children of short stature. Acta Paediatr Suppl 412: 54-55.
63.
Tümer L, Hasanoglu A, Aybay C (2001): Endomysium antibodies in the diagnosis of coeliac disease in short statured children with no gastrointestinal symptoms. Pediatr Int 43: 71-73.
64.
Cacciari E, Salardi S, Lazzari R, et al. (1983): Short stature and celiac disease: a relationship to consider even in patients with no gastrointestinal tract symptoms. J Pediatr 103: 708-711.
65.
Iughetti L, De Bellis A, Predieri B, et al. (2006): Growth hormone impaired secretion and antipituitary antibodies in patients with coeliac disease and poor catch-up growth after a long gluten-free diet period: a casual association? Eur J Pediatr 165: 897-903.
66.
Malik S, Wong SC, Bishop J, et al. (2011): Improvement in growth of children with Crohn disease following anti-TNF-alpha therapy can be independent of pubertal progress and glucocorticoid reduction. J Pediatr Gastroenterol Nutr 52: 31-37.
67.
Collin P, Hakanen M, Salami J, et al. (2001): Autoimmune hypopituitarism in patients with coeliac disease: symptoms confusingly similar. Scand J Gastroenterol 36: 558-560.
68.
Delvecchio M, De Bellis A, Francavilla R, et al. Italian Autoimmune Hypophysitis Network Study (2010): Anti-pituitary antibodies in children with newly diagnosed celiac disease: a novel finding contributing to linear-growth impairment. Am J Gastroenterol 105: 691-696.
69.
Aguado R, Fernández S, Estévez OA, et al. (2014): Antiadenohypophysis autoantibodies in patients with nongluten-related gastroenteropathies. J Clin Lab Anal 28: 59-62.
70.
Meazza C, Pagani S, Messini B, et al. (2011): Celiac children treated for growth hormone deficiency reach normal final height. Clin Endocrinol (Oxf) 74: 791-792.