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Growth Hormone Deficiency and Antipituitary Antibodies in Celiac Disease« Back to Volume 23, Issue 1, March 2007 - Table of Contents Iughetti et al studied 130 patients (59 males, age 5.67 ± 3.6 years, height 0.32 ± 1.25 SDS) who had been diagnosed with celiac disease (CD) based on the presence of antigliadin, antiendomysial, and antitransglutaminase antibodies, as well as endoscopic biopsies of the distal duodenal mucosa. These children had a poor clinical response to a gluten-free diet (GFD) and a growth hormone deficiency (GHD); they presented to the pediatric clinic at the University of Modena and Reggio Emilia, Italy between 1999 and 2004. Their growth velocity was determined yearly and serum endomysial antibodies were measured after at least 12 months on a GFD. Those children showing no catch-up growth on a GFD were evaluated to exclude possible GHD. Studies included measurement of basal serum GH, insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, free T3 , free T4 , TSH, prolactin, cortisol, ACTH, LH, FSH, estradiol or testosterone, and repeat studies for antibodies. In addition, antipituitary and antihypothalamus antibodies were measured. On different days, arginine and L-dopa GH stimulation tests were performed in all 7 of the children identified as having poor catch-up growth. Bone age was determined as well. A diagnosis of GHD was based on short stature, decreased growth velocity, delayed skeletal maturation, and blunted GH response (<10 µg/L) to the 2 pharmacological tests. Antipituitary antibodies were detected by an immunofluorescent method that had been previously described. MRIs were performed in these 7 patients. Five of the 7 patients showed a blunted GH response to the different stimuli and met the criteria for GHD. Four of the 5 had high titers of antipituitary antibodies, 2 were additionally positive for antihypothalamus antibodies. Antipituitary antibodies were also positive in low titers in 3 out of 25 (12%) children with CD only, and in 2 out of 58 (3.4%) control children. None of the 7 children had any pituitary abnormalities on MRI. The authors stated that in the past an insufficient GH response to hypoglycemia had been reported in children with CD, which subsequently improved with a GFD. The hypothesis that autoimmunity could involve the pituitary gland was reported about 40 years ago; however, the nature and significance of antipituitary antibodies in GHD patients is still being discussed. The authors stated, however, that high titers of antipituitary antibodies could explain some cases of apparent idiopathic GDH. In patients with multiple autoimmune abnormalities, such as the children with CD, these antibodies may explain their GHD. Editor’s CommentWhether or not one subscribes to the significance of antipituitary antibodies (and/or antihypothalamic antibodies) and the development of isolated GHD, the finding that 5 of 7 children with CD who failed to have catch-up linear growth after 12 months of a GFD met all criteria for GHD is an important finding. Indeed, it is tempting to ascribe failure of catch-up growth following initiation of a GFD to lack of compliance with the meal plan; but, GHD may be present in those children. It is important for pediatric endocrinologists to perform stimulation tests to identify this deficiency. Indeed, low IGF-I levels would not be a surprising finding in children newly diagnosed with CD, as their nutritional status is often poor. However, the failure of IGF-I levels to rise when antiendomysial antibody levels have fallen (at approximately 12 months after the initiation of a GFD) should raise suspicions as to an additional cause for growth failure. As more and more children are being diagnosed with CD, it becomes even more important for the pediatric endocrinologist to be aware of other endocrinologic abnormalities that might be associated with this disease; any of these may be autoimmune in origin. William L. Clarke, MD
« Back to Volume 23, Issue 1, March 2007 - Table of Contents
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
