Celiac disease and short stature in children

Abstract

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

Acknowledgements

The authors are grateful to Laurene Kelly for revising the English of the paper.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Celiac disease (CD) is characterized by a permanent sensitivity to gluten, resulting in an inflammatory enteropathy with various degrees of severity in genetically susceptible individuals. 95% of patients have specific HLA-DQ alleles, namely DQ2 (90%) and/or DQ8 (5%).

• Treatment of CD is based on the lifelong exclusion of gluten-containing cereals from the diet.

• CD prevalence in Italian schoolchildren is 1.2%.

• Nowadays, short stature is one of the most common symptoms of CD in children, and CD prevalence in short children varies from 2.9 to 8.3%.

• Within 1–2 years after starting a gluten-free diet (GFD), the CD child usually returns to his/her normal growth curve for weight and height, depending on the extent of the disease, the age of onset and the extent of height deficit compared with the target height.

• Many studies report an endocrine axis dysfunction in children with CD: low response of growth hormone (GH) secretion after pharmacological stimulation tests, reduction in IGF-I and IGF-binding protein (IGFBP)-3 and increase in IGFBP-2 and IGFBP-1.

• A remarkable number of cases testing positive for anti-pituitary antibodies has been reported in newly diagnosed CD patients, associated with height impairment and reduction of IGF-I levels.

• Ghrelin could serve as a reliable marker for monitoring adhesion to GFD in children with CD, since serum ghrelin levels are high in CD patients and decrease after at least 6 months of a GFD.

• The evaluation of GH secretion should be performed in CD children who show no catch-up growth after at least 1 year on a strict GFD, result negative for anti-tTG and when endomysium antibodies have been confirmed. In order to obtain complete catch-up growth in these subjects, substitutive therapy with GH should be promptly started at standard doses.

Notes