Higher incidence of thyropathy in patients with oesophageal achalasia. Genetic, autoimmune, regional or just a random association?

Czech version

Authors: R. Kroupa; K. Starý; A. Hep; J. Suchánková; J. Dolina
Authors‘ workplace: Interní gastroenterologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jan Lata, CSc.
Published in: Vnitř Lék 2008; 54(4): 341-345
Category: Original Contributions

Overview

Introduction:
The etiology of esophageal achalasia is still largely unknown. Inflammatory response to an initial stimulus on the level of genetic and/or immune predisposition may be the underlying cause of the disease. The final result is progressive disappearance of ganglion cells in the myenteric plexus and motility disorder. Autoimmune thyropathy (AIT) is a typical disease involving genetic background and immune response disorder.

Patients and methods:
44 patients (of which 30 women and 14 men) with diagnosed esophageal achalasia and a control group of patients with esophageal reflux of corresponding age and sex were screened for thyroid disease.

Results:
Thyroid disease was diagnosed in 15 out of 44 patients with achalasia (34%). Thyropathy was detected in 11 women (37%) and 4 men (28%). AIT was detected in 10 patients, in 4 of whom with hypfunction, nontoxic cystic or nodular goitre was detected in 4 patients, 1 patient was after strumectomy for benign node. Positive antithyroid antibody was newly detected in 4 patients with achalasia; subclinical hypothyreosis was found in one of them. There were two cases of AIT with subclinical hypofunction and 1 case of nontoxic goitre in the control group (7%). The difference was statistically significant (p < 0.01).

Conclusion:
The incidence of thyroid disease proved higher in patients with achalasia than in the controls. The rate of occurrence of thyroid disease exceeded significantly the occurrence in the population. The association of achalasia with prevailingly autoimmune thyropathy may corroborate the importance of autoimmunity in the etiopathogenesis of the disease.

Key words:
achalasia – esophageal motility – tyroid gland – genetic – autoimmunity

Sources

1. Kroupa R, Hep A. Achalázie jícnu - aktuální přehled etiopatogeneze a dostupné terapie. Čes a Slov Gastroent a Hepatol 2006; 60: 135-138.

2. Fountoulakis S, Tstsoulis A. On the pathogenesis of autoimune thyroid disease: A unifying hypothesis. J Clin Endocrinol. 2004; 60: 397-409.

3. Guarneri F, Benvenga S. Environmental factors and genetic background that interact to cause autoimmune thyroid disease. Curr Opin Endocrinol Diabetes Obes 2007; 14: 398-409.

4. Jiskra J. Význam autoimunity u onemocnění štítné žlázy. In: Límanová Z. Trendy soudobé endokrinologie 2. Štítná žláza. Praha: Galén 2006: 79-114.

5. Dvořáková M, Bílek R, Čeřovská J et al. Štítná žláza od minulosti k současnosti u dětské a dospělé populace v České republice. Diabet Metabol Endokrin Výž 2007; 10: 43-48.

6. Zamrazil V, Němec J. Diagnostika a léčba uzlové strumy. In: Stárka L (ed). Pokroky v endokrinologii. Praha: Maxdorf 2007: 369-387.

7. Park W, Vaezi MF. Etiology and pathogenesis of achalasia: The current understanding. Am J Gastroenterol 2005; 100: 1404-1414.

8. Zarate N, Mearin F, Gil-Vernet JP et al. Achalasia and Down´s syndrome: coincidental association or something else? Am J Gastroenterol 1999; 94: 1974-1977.

9. Tullio-Pelet A, Salomon R, Hadj-Rabia Set al. Mutant WD-repeat protein in triple-A syndrome. Nat Genet 2000; 26: 332-335.

10. Brooks BP, Kleta R, Stuart C et al. Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. Clin Genet 2005; 68: 215-221.

11. Di Nardo G, Tullio-Pelet A, Annese V et al. Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus. Dig Liver Disease 2005; 37: 312-315.

12. Karlsson B, Gustafsson J, Hedov G et al. Thyroid dysfunction in Downʼs syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 1998; 79: 242-245.

13. Jara LJ, Navarro C, Brito-Zerón M P del et al. Thyroid disease in Sjögrenʼs syndrome. Clin Rheumatol 2007; 26: 1601-1606.

14. Verne GN, Hahn AB, Pineau BC et al. Association of HLA-DR and -DQ alleles with idiopathic achalasia. Gastroenterology 1999; 117: 26-31.

15. Ruiz de Leon A, Mendoza J, Sevilla-Mantilla C et al. Myenteric antiplexus antibodies and class II HLA in achalasia. Dig Dis Sci 2002; 47: 15-19.

16. Latiano A, De Giorgio R, Volta U et al. HLA and enteric antineuronal antibodies in patients with achalasia. Neurogastroenterol Motil 2006; 18: 520-525.

17. Šterzl I, Hrdá P, Matucha P et al. Autoimunitní tyreoiditida - vybrané etiopatogenetické mechanizmy. Vnitř Lék 2006; 52: 891-899.

18. Jacobson EM, Tomer Y. The genetic basis of thyroid autoimmunity. Thyroid 2007; 17: 949-961.

19. Moses PL, Ellis LM, Anees MR et al. Antineuronal antibodies in idiopathic achalasia and gastro-esophageal reflux disease. Gut 2003; 52: 629-636.

20. Bruley des Varannes S, Chevalier J, Pimont S et al. The serum of achalasia patients alters neurochemical coding in the myenteric plexus and NO-mediated motor response in normal human fundus. Gut 2006; 55: 319-326.

21. Hermann M, Magee M, Kleniv RJ et al. Differential autoantibody response to thyroid peroxidase in patiens with Gravesʼ disease and Hashimotosʼ thyroiditis. J Clin Endocrinol Metab 1993; 77: 1098-1101.

22. Eastwood GL, Braverman LE, White EM et al. Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism. J Clin Gastroenterology 1982; 4: 307-310.

23. Pustorino S, Calipari G, Foti M et al. Esophageal transit and esophageal motility disorders in patients with nontoxic goiter and recurrent dysphagia. Recenti Prog Med 2002; 93: 235-239.

24. Volter F, Fain O, Mathieu E et al. Esophageal function and Sjögrenʼs syndrome. Dig Dis Sci 2004; 49: 248-253.

25. Ebert EC. Esophageal disease in scleroderma. J Clin Gastroenterol 2006; 40: 769-775.

26. Srbová L. Tyreopatie a vnější vlivy. In: Stárka L (ed). Pokroky v endokrinologii. Praha: Maxdorf 2007: 345-357.

27. Emami MH, Raisi M, Amini J et al. Achalasia and thyroid disease. World J Gastroenterol 2007; 13: 594-599.

28. Santiago JL, Martínez A, Benito MS et al. Gender-specific association of the PTPN22 C1858T polymorphism with achalasia. Hum Immunol 2007; 68: 867-870.