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 causal association?
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Coeliac disease (CD) is usually associated with impaired growth in children. A gluten-free diet (GFD) induces a catch-up growth with the recovery of height in about 2 years.
Aim and discussion
The lack of the height improvement has been related to growth hormone (GH) secretion impairment. CD is an autoimmune disease often associated with other endocrine and non-endocrine autoimmune disease. The aim of this study was to evaluate antipituitary autoantibodies (APA) and antihypothalamus autoantibodies in CD children with poor clinical response to a GFD and growth hormone deficiency (GHD). We diagnosed CD on the basis of specific antibodies and endoscopic biopsies in 130 patients aged 1–15 years. Seven CD children, without catch-up growth after at least 12-months GFD, were tested for GH secretion and, in five out of seven patients, the diagnosis of GHD was made in the absence of metabolic and systemic diseases.
APA and antihypothalamus antibodies were detected by the indirect immunofluorescence method in the seven CD children without catch-up growth factor and in 25 CD children without growth impairment matched for sex and age, and in 58 healthy children as control groups. APA resulted positive at high titres in four out of five CD-GHD patients and were also positive at low titres (<1:8) in three of only CD children and in two out of 58 controls. Hypothalamic-pituitary magnetic resonance imaging (MRI) was normal in all patients except in one with cystic pineal. APA have been previously detected not only in adults with GHD, but also in idiopathic GHD children, suggesting the occurrence of an autoimmune hypophysitis in these patients.
In our study, the presence of APA in CD children without catch-up growth after GFD seems to be able to identify an autoimmune form of hypophysitis involving the somatotrophs cells.
KeywordsAntipituitary antibodies Coeliac disease Gluten-free diet Catch-up growth Idiopathic growth hormone deficiency
Body mass index
Growth hormone deficiency
Growth hormone releasing hormone
Insulin-like growth factor 1
IGF-binding protein 3
Magnetic resonance imaging
Type 1 diabetes mellitus
- 1.Barr DG, Shmerling DH, Prader A (1972) Catch-up growth in malnutrition, studied in celiac disease after institution of gluten-free diet. Pediatr Res 6(5):21–27Google Scholar
- 3.Betterle C, Dalpra C, Greggio N, Volpato M, Zanchetta R (2001) Autoimmunity in isolated Addison’s disease and in polyglandular autoimmune diseases type1, 2 and 4. Ann Endocrinol 62(2):193–201Google Scholar
- 5.Bosio L, Barera G, Mistura L, Sassi G, Bianchi C (1990) Growth acceleration and final height after treatment for delayed diagnosis of celiac disease. J Pediatr Gastroentrol Nutr 11(3):324–329Google Scholar
- 8.Cacciari E, Salardi S, Volta U, Biasco G, Lazzari R, Corazza GR, Feliciani M, Cicognani A, Partesotti S, Azzaroni D, Tassoni P, Pirazzoli P, Bianchi FB, Pisi E (1985) Can antigliadin antibody detect symptomless coeliac disease in children with short stature? Lancet 1(8444):1469–1471PubMedCrossRefGoogle Scholar
- 14.De Bellis A, Bizzarro A, Amoresano Paglionico V, Di Martino S, Criscuolo T, Sinisi AA, Lombardi G, Bellastella A (1994) Detection of vasopressin cell antibodies in some patients with autoimmune endocrine disease without overt diabetes insipidus. Clin Endocrinol 40(2):173–177Google Scholar
- 16.De Bellis A, Bizzarro A, Conte M, Perrino S, Coronella C, Solimeno S, Sinisi AM, Stile LA, Pisano G, Bellastella A (2003) Antipituitary antibodies in adults with apparently idiopathic growth hormone deficiency and in adults with autoimmune endocrine diseases. J Clin Endocrinol Metab 88(2):650–654PubMedCrossRefGoogle Scholar
- 17.De Bellis A, Bizzarro A, Perrino S, Coronella C, Conte M, Pasquali D, Sinisi AA, Betterle C, Bellastella A (2005) Characterization of antipituitary antibodies targeting pituitary hormone-secreting cells in idiopathic growth hormone deficiency and autoimmune endocrine diseases. Clin Endocrinol 63(1):45–49CrossRefGoogle Scholar
- 18.De Bellis A, Salerno M, Conte M, Coronella C, Tirelli G, Battaglia M, Esposito V, Ruocco G, Bellastella G, Bizzarro A, Bellastella A (2006) Antipituitary antibodies recognizing GH-producing cells in children with idiopathic growth hormone deficiency and in children with idiopathic short stature. J Clin Endocrinol Metab (in press) DOI 10.1210/jc.2006-0040
- 19.De Bellis A, Colao A, Bizzarro A, Di Salle F, Coronella C, Solimeno S, Vetrano A, Pivonello R, Pisano G, Lombardi G, Bellastella A (2002) Longitudinal study of vasopressin-cell antibodies and of hypothalamic-pituitary region on magnetic resonance imaging in patients with autoimmune and idiopathic complete central diabetes insipidus. J Clin Endocrinol Metab 87(8):3825–3829PubMedCrossRefGoogle Scholar
- 24.Farthing MJG, Rees LH, Edwards CRW, Byfield PGH, Himsworth RL, Dawson AM (1982) Thyroid hormones and the regulation of thyroid function in men with coeliac disease. Clin Endocrinol 16(6):525–535Google Scholar
- 26.Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford, CaliforniaGoogle Scholar
- 30.Karberg J, Henter JI, Tassin E, Lindblad BS (1988) Longitudinal analysis of infantile growth in children with coeliac disease. Acta Pediatr Scand 77(4):516–524Google Scholar
- 38.Maeda K, Kato Y, Yamaguchi N, Chihara K, Ohgo S (1976) Growth hormone release following thyrotropin-releasing hormone injection into patients with anorexia nervosa. Acta Endocrinol (Copenh) 81(1):1–8Google Scholar
- 39.Mauerhoff T, Mirakian R, Bottazzo GF (1987) Autoimmunity and the pituitary. In: Doniach D, Bottazzo GF (eds) Endocrine and other organ-oriented autoimmune disorders. Bailliere’s clinical immunology and allergy 1, Saunders, London, pp 217–235Google Scholar
- 42.Prader A, Shmerling D, Zachman M, Biro Z (1969) Catch-up growth in coeliac disease. Acta Paediatr Scand 58:311–319Google Scholar
- 43.Rosenbach Y, Dinari G, Zahavi I, Nitzan M (1986) Short stature as the major manifestation of celiac disease in older children. Clin Pediatr 25(1):13–16Google Scholar
- 44.Rosenberg R-WMC, Montzaris GZ, Jewell DP (1992) The immunology of coeliac disease. In: Branski D, Rozen P, Kagnoff MF (eds) Gluten-sensitive enteropathy. Frontiers of gastrointestinal research, vol 19. Karger, Basel, Switzerland, pp 29–43Google Scholar
- 45.Shmerling D, Prader A, Zachmann M (1968) The effect of dietary treatment on growth in celiac disease. In: McCance RA, Widdowson EM (eds) Calorie deficiencies and protein deficiencies. Churchill, London, p 159Google Scholar
- 48.Vanderschueren-Lodeweyckx M, Eggermont E, Cornette C, Beckers C, Malvaux P, Eeckels R (1977) Decreased serum thyroid hormone levels and increased TSH response to TRH in infants with coeliac disease. Clin Endocrinol 6(5):361–367Google Scholar
- 50.Ventura A, Magazzù G, Greco L for The SIGEP Study Group for Autoimmune Disorders in Celiac Disease: D’Andrea N, Lambertini A, Zaniboni G, Pensabene L, Guandalini S, Marani M, Miano A, Caruselli C, Mostaccio L, Bertolani P, Balli F, Ciccarelli G, Guariso G, Cataldo F, Chiaravalloti G, Ughi C, Martelossi S, Torre G (1999) Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. Gastroenterology 117(2):297–303PubMedCrossRefGoogle Scholar
- 51.Ventura A, Magazzù G, Greco L, Coordinators of the SIGEP Group: Balli F, Bertolani P, Caruselli C, Cataldo F, Chiaravalloti G, Ciccarelli G, D’Andrea N, Greco L, Guariso G, Lambertini A, Marani M, Martelossi S, Miano A, Mostaccio L, Pensabene L, Romano C, Torre G, Ughi C, Zaniboni G (1997) Autoimmune disorders in coeliac disease: relationship with duration of exposure to gluten. J Pediatr Gastroenterol Nutr 24:463CrossRefGoogle Scholar