Celiac disease and short stature in children Expert Rev. Endocrinol. Metab. Early online, 1–8 (2014) Cristina Meazza 1 , Sara Pagani 1 , Chiara Gertosio 2 , Elena Bozzola 3 and Mauro Bozzola* 1 1 Internal Medicine and Therapeutics Department, Pediatrics and Adolescentology Unit, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy 2 Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy 3 Department of Pediatrics, Pediatric and Infectious Diseases Unit, Bambino Gesu ` Children’s Hospital, IRCCS, Piazza Sant’ Onofrio 4, 00165 Rome, Italy *Author for correspondence: Tel.: +39 0382 501270 Fax: +39 0382 502876 mauro.bozzola@unipv.it Celiac disease (CD) is a genetically determined gluten-sensitive enteropathy resulting in nutrient malabsorption, with an increasing incidence worldwide. In CD children, short stature may be the only presenting clinical feature, even in the absence of gastrointestinal symptoms. Generally, a gluten-free diet (GFD) leads to rapid catch-up growth within 1–2 years. The pathogenesis of CD-associated short stature is still unclear. Besides the involvement of the growth hormone (GH)/IGF-I axis, other pathogenetic mechanisms may include autoimmune disorders of the pituitary gland and altered ghrelin secretion. Furthermore, some CD patients do not show catch-up growth during a GFD, despite reversion to seronegativity for CD markers. These subjects may have GH deficiency and could benefit from GH therapy. This review deals with the problem of linear growth in CD children and points to the importance of the evaluation of GH secretion in those children who show no catch-up growth after the introduction of a GFD. KEYWORDS: catch-up growth • celiac disease • gluten free-diet • growth hormone deficiency • growth hormone treatment • IGF-I • short stature Relationships between the gastrointestinal and endocrine system have been long postulated, suggesting that the assessment of short stature in children requires a careful investigation of both gastrointestinal and endocrine function. Celiac disease (CD) is a permanent sensitivity to gluten, resulting in an inflammatory enterop- athy with various degrees of severity (villous atrophy, crypt hyperplasia and an increased intraepithelial lymphocyte count) and a wide range of gastrointestinal and extra-intestinal problems [1–3]. The intestinal damage is the end-stage lesion of an inappropriate T-cell- mediated immune response to gluten peptides that are modified in the lamina propria by transglutaminase enzymes [4]. In fact, in CD patients, a variable combination of elevated titers of celiac-specific autoantibodies such as anti-transglutaminase antibodies (anti-tTG) and anti-endomysium antibodies (EMAs) is present. CD is a multifactorial disease in which genetic predisposition along with environmen- tal factors contribute to the onset of the dis- ease. In fact, 95% of patients carry the HLA class II haplotype DQ2 (90%) or DQ8 (5%) [5]. Treatment of CD is based on the lifelong exclusion of gluten-containing cereals from the diet and adherence to a gluten-free diet (GFD); these are extremely important to pre- vent future complications. CD is one of the most common lifelong disor- ders in Europe and in the USA. The prevalence of clinically overt CD has been reported to be 1/99 in Finland [6] and 1/77 in Sweden [7]. A very recent study reported a CD prevalence of 1.2% in Italian schoolchildren [8]. In the USA, CD may affect 1/104 children by the ages of 5 years [9]. With the availability of highly specific and sensitive serological tests, screening for CD is now more readily available. As a result, the reported incidence of this disease has greatly increased worldwide with a concomitant decrease in the severity of the symptoms at diagnosis (FIGURE 1) [10]. Recently, the prevalence of atypical forms presenting with extra-intestinal symptoms or without symptoms has increased significantly both in adults and children. The extra-intestinal symptoms involve different systems, such as skel- etal, endocrine and central nervous systems (BOX 1). Iron-deficiency anemia appears to be the most frequent extra-intestinal symptom followed by short stature in children [11]. Thus, CD should be considered in all children with short stature. In these patients, the prevalence of CD varies from 2.9 to 8.3% and CD is by far more common than growth hormone deficiency (GHD) or any other organic disorder [12]. informahealthcare.com 10.1586/17446651.2014.932248 Ó 2014 Informa UK Ltd ISSN 1744-6651 1 Review Expert Review of Endocrinology & Metabolism Downloaded from informahealthcare.com by Universita' di Pavia on 06/26/14 For personal use only.