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ISSN 1007-9327 CN 14-1219/R  World J Gastroenterol  2007 January 28;13(4):594-599

Achalasia and thyroid disease

Mohammad Hassan Emami, Mostafa Raisi, Jaleh Amini, Hamed Daghaghzadeh


Mohammad Hassan Emami, Hamed Daghaghzadeh, Isfahan University of Medical Sciences and Poursina Hakim Research Institution, Isfahan, Iran
Mostafa Raisi, Jaleh Amini, Poursina Hakim Research Institution, Isfahan, Iran
Supported by Poursina Hakim Research Institution, Isfahan, Iran
Correspondence to: Mostafa Raisi, Poursina Hakim Research Institution, PO Box: 81465-1798, No9- Behesht building- Bozorgmehr Av. Isfahan, Iran. mostafaraisi@yahoo.com
Telephone: +98-913-3154000  Fax: +98-311-2667542
Received: 2006-11-12             Accepted: 2006-12-21

Abstract
AIM: To investigate some possible etiologies of achalasia by screening patients with achalasia for some autoimmune diseases such as thyroid disease.

METHODS: We examined 30 known cases of achalasia (20 females, 10 males). Their age ranged 15-70 years. All of them were referred to our institute for treatment. Their sera were evaluated to detect some possible associations with rheumatoid disease, thyroid disease, inflammatory process, anemia, etc.

RESULTS: Seven out of 30 patients (23%) had thyroid disease including four patients with hypothyroidism (13.3%), two patients with hyperthyroidism (6.6%), and one had only thyroid nodule but was in euthyroid state (3.3%). Two of these hypothyroid patients had no related clinical symptoms (subclinical) and two had clinical manifestations of hypothyroidism. There were no correlations between the intensity of thyroid diseases and the severity of achalasia symptoms.

CONCLUSION: The etiology of achalasia is unknown although autoimmunity has been implicated and is supported by several studies. Thyroid disease presents concomitantly with achalasia in about one fourth of our patients who may have a common etiology.

© 2007 The WJG Press. All rights reserved.

Key words: Achalasia; Thyroid disease; Hypothyroidism; Esophageal motility; Etiology

Emami MH, Raisi M, Amini J, Daghaghzadeh H. Achalasia and thyroid disease. World J Gastroenterol 2007; 13(4): 594-599

 http://www.wjgnet.com/1007-9327/13/594.asp

INTRODUCTION
Achalasia is a common and well characterized primary motility disorder of the esophageal body and lower esophageal sphincter (LES), causing impaired progressive peristalsis in the esophageal body, incomplete relaxation of LES during swallowing, and sometimes increased abnormal relaxation of the LES pressure. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown that the presence of myenteric inflammation is a consistent and early pathologic change in patients with achalasia[1,.2]. The disorder is observed in both genders primarily in the fifth and sixth decades of life, although achalasia can present at any age[3,4]. The cause of the degeneration of neurons in achalasia is not known. The observations that achalasia is associated with HLA-DQw1 and that affected patients often have circulating antibodies to enteric neurons suggest that achalasia may be an autoimmune disorder[5-7]. Nonspecific degeneration of smooth muscle cells and a loss of small nerve fibers have been reported[8-10]. Another controversial issue is the role of inflammatory infiltrates in the pathogenesis of the disease. A study has suggested that complement activation is involved in the autoimmune pathogenesis of achalasia[11]. Achalasia is associated with extra esophageal autonomic nervous dysfunction that involves cardiovascular and papillary function as well as regulation of mesenteric arterial blood flow[12]. Some investigators have proposed that achalasia may result from chronic infections with herpes zoster or measles viruses, but modern studies have not confirmed an association between achalasia and any recognized viral disease[13,14]. However, a recent study also showed that there is no association between the most common viruses and achalasia[15]. As myenteric neurons synthesizing nitric oxide are responsible for the inhibitory component of esophageal peristalsis and LES relaxation, it is considered likely that these neurons are involved in this disease[16,17].
    Since there is no consistent single abnormality in achalasia, this study was designed to evaluate the relationship between achalasia and some of the commonest autoimmune diseases.

MATERIALS AND METHODS
Patients
All 42 newly diagnosed patients referred between 2001 and 2005 to our research center (Poursina Hakim Research Institution, Gastroenterology Division, Isfahan, Iran) were examined prospectively and enrolled in the study. Poursina Hakim Institution is a reference tertiary care center that services a population of about 4 000 000 individuals in the central area of Iran. Of the 42 enrolled cases in the study based on clinical and radiological findings, 6 patients with pseudoachalasia but without endoscopic features of achalasia were excluded due to non-compliance (one case) or some other reasons such as loss of follow-up due to changing their address or phone number, immigration to other provinces and admission by other physicians far from our institution. Finally 30 cases were included. Their symptoms, laboratory results, and historical and functional data were recorded. Achalasia was defined by clinical criteria, namely prolonged (more than 1 year) intermittent or progressive dysphagia to liquids and solids in addition to some other minor symptoms such as regurgitation, chest pain and nocturnal cough plus barium swallow with a typical beak like appearance. We obtained posterior-anterior chest x ray radiographies at 1, 5, and 20 min after a single barium meal to assess barium column and measure its heights and widths as well as the delay time of esophageal clearance (timed barium swallow). Upper gastrointestinal endoscopy was done to confirm the diagnosis and to rule out secondary achalasia (such as esophageal tumors of cardia and fundus, submucosal tumor of distal esophagus, peptic stricture and other mucosal or infiltrative lesions of the esophagus or gastric cardia). Endoscopic findings suggestive of achalasia may be seen and are very helpful if endoscopy is done carefully by experts in this field. Some of the suggestive criteria for achalasia are as following: esophageal dilation, esophageal dysmotility or aperistalsis in response to air insufflations, abnormal LES opening and high pressure LES during scope passage. Manometery although very helpful especially in early stages of the disease, was not available in our province at the time of the study, so it was not done for most of them.
    Exclusion criteria included those found to have an underlying malignancy during the study, any types of generalized neuropathies, diabetes mellitus, non-compliance or unwillingness of patients to continue the study, and finally those lost to follow up by any reason.
    The patients’ history was taken using a structured questionnaire. We interviewed, examined and completed a questionnaire designed to detect possibility of connective tissue and autoimmune diseases, other gastrointestinal motility disorders, diabetes mellitus, use of immunosuppressive medications, chronic viral illnesses, thyroid problems, usage of a regular immunosuppressive medication and also habits and addictions for all patients. Informed consent was obtained from all patients. None of the patients underwent surgical therapy.

Laboratory methods
After diagnosis of achalasia, all patients were screened for a set of selected autoimmune disease and other markers as shown in Table 1. Serum factors were evaluated by biochemical techniques. A double check of laboratory tests was conducted by a second laboratory to assure validity of abnormal results. Equivocal laboratory results were rechecked by a reference laboratory.

Symptoms
Clinical data regarding symptoms of dysphagia, regurgitation, and chest pain, nocturnal cough and pyrosis were collected by means of a validated questionnaire. Dysphagia was described as difficulty in swallowing, and regurgitation as the sensation of stomach contents going up the esophagus. The frequency of each symptom was graded on a scale ranging from 0 to 5 (0 = none, 1 = once per month or less, 2 = once per week up to three to four times a month, 3 = two to four times per week, 4 = once per day, 5 = several times per day). This scoring system is similar, but with some modifications, to that used by Eckardt et al[18] and modified by Vaezi et al[19].

Statistical analysis
For comparison between patients with achalasia and normal population, Student’s t-test assuming equal variance was used. In addition, we analyzed the symptoms using the non-parametric Mann-Whitney test, because the data were not normally distributed.

RESULTS
Of the 42 newly suspected achalasia patients referred to our institution, 36 (11 men and 25 women) fulfilled the participating criteria in the study, but only 30 (20 females, 10 males) finished the study. The remaining six patients were statistically similar by age and gender to the 30 cases and they had no unusual reason for their loss of follow-up.

Thyroid disease
Of the 30 patients, 7 had thyroid disease (23.7%), 4 had hypothyroidism (13.3%), 2 had hyperthyroidism (6.7%) and one (3.3%) had only a thyroid nodule in euthyroid state. Two of these hypothyroidism patients had no related clinical symptoms (subclinical) and two had clinical manifestations of hypothyroidism. Both patients with subclinical hypothyroidism were diagnosed in our screening. One patient experienced hypothyroid shock after balloon dilation therapy (cool skin, hypothermia, hypotension and bradicardia not responsive to volume expansion and intravenous atropine injection). She had clinical symptoms of hypothyroidism which was not detected before balloon dilation therapy. The results of laboratory tests are listed in Table 2.

Patients’ ethnicity
There were 21 (70%) Fars (the major Persian ethnicity), 7 Bakhtiari, an Iranian tribe, living in west of Isfahan Province) (23%), one Gilaki (another group of Iranians originating from northern Iran) (3.3%), and one patient was Turkish inhabitant in the central area of Iran (3.3. 0%).

Age and symptoms
The median age of onset of symptoms was 37 years (range 15-80 years). The mean age of patients with thyroid disease and other patients with achalasia was 35.8 and 38.5 years (P: 0.9). All patients complained of dysphagia to both liquids and solids. Regurgitation, weight loss, chest discomfort and heartburn were reported in 28 (93.3%), 18 (60%), 15 (50%) and 8 (26.6%) patients, respectively.
    The symptoms of patients were compared (Table  2). Correlations between the intensity of thyroid disease and the severity of achalasia symptoms were statistically insignificant by Mann-Whitney test.

Prevalence and incidence of achalasia
In 2002 -2005, 42 cases of suspected achalasia were identified in or referred to our center. Of these, 19 were residents of Isfahan during the period of the study. The population of Isfahan was about 4 million in 2006. The overall ethnic- and gender-specific incidences of achalasia in our cases are shown in Table 3. No strong history of rheumatic disease or neuropathy in patients and their family was detected in our study.

Serological study
All serum samples were evaluated with sensitive tests for autoimmune diseases but we did not find any positive test except for 2 positive anti nuclear antibody tests (6.6%). Evaluation for vasculitis, some electrolyte disturbances, and anemia did not show any important finding (Table 4).

DISCUSSION
Although achalasia is a historically recognized clinical entity, its fundamental pathophysiology remains poorly understood. Primary achalasia accounts for the majority of cases. The etiology of primary achalasia is not entirely clear and probably multidimensional[20] including genetic predisposition (supported by the concordance for the disease in monozygotic twins[21] and associations with some HLA loci[7]), inflammation (myopathy of the smooth muscle cells[22], neuropathy[23,24] and inflammatory changes in esophageal specimens[25]), infections (virus[14], Chagas’ disease, poliomyelitis[26,27], varicella zoster virus[28] and Helicobacter[29]), ischemia, toxicity and autoimmune disease[20]. Some other diseases postulate these etiologies such as concomitant appearance of achalasia and Guillain-Barré syndrome [30], Parkinson’s disease[31], triple A syndrome[32], etc.
    There are some reports about thyroid and esophageal problems in animals[33] but we have not found any reports about such problems in humans in English articles. Although it has been reported that there is a correlation between achalasia and autoimmune diseases, this is the first cross sectional study evaluating the relative prevalence of these problems (rheumatic disease, thyroid disease, inflammatory disease, etc) in a consecutive series of patients affected by achalasia which led us to a few interesting points. First, the results of serological tests obtained from this study confirmed some literature data that predict a potential autoimmune etiology of achalasia. Second, an association was found between thyroid problems and achalasia. Third, the frequency of thyroid disease was higher in patients with achalasia than in normal population.
It was reported that the prevalence of hypothyroidism is 4.6% (0.3% clinical and 4.3% subclinical) in the United States of America[34]. Whickham showed that the prevalence of spontaneous hypothyroidism in community is 1.5% in females and less than 0.1% in males [35]. These prevalence rates are similar to those reported in Finland[36], Japan[37], and in another US survey[38-40]. Heydarian and Azizi reported that the prevalence of hyperthyroidism, overt and subclinical hypothyroidism is 0.45%, 0.35% and 2.2% in Iran, respectively[41]. The prevalence of hypothyroidism and benign thyroid diseases (hypothyroidism, hyperthyroidism and thyroid nodules) in our patients was significantly higher than that reported in latter study (P value and confidence interval for each group were 0.025 and 0.000, 1.3-43.4 and 2.9-76.5 respectively).
The mean age of our patients is one -two decades lower than reported in other studies[3,4]. It may have a role in these findings. We found about a 5-fold rise in the prevalence of thyroid dysfunction in this study. Since our center is the only center offering balloon dilation therapy in Isfahan, we can assume that the overall population with achalasia in this area is very similar to that registered in our center and therefore these data are repeatable in our future study, but they may not be generalized in all cases of achalasia in other societies. Hence we suggest a similar study in all centers working in this subject. We should direct our future studies to find the possible genetic and environmental risk factors for earlier disease in this geographic area.
    The reason why there is such a relatively strong association between these diseases can be explained by the literature describing most thyroid problems as probable autoimmune diseases[42-45]. Autoimmune etiology of achalasia is also supported by the presence of circulating autoantibodies against the myenteric plexus and inflammatory T-cell infiltrates in the myenteric plexus, as well as the increased prevalence of HLA class Ⅱ antigens. Possibly the initiating event may be an unknown environmental insult due to a viral infection resulting in inflammation of the myenteric plexus in susceptible patients. Not all affected individuals develop achalasia[46]. However, autommunity at least has a concomitant or susceptible role in pathogenesis.
    Is there a symptomatic mimicry between achalasia and thyroid diseases? There is some evidence in animal model that a mega esophagus may occur in hypothyroidism which is a criterion of achalasia[33]. We had one clinical hypothyroid patient and one clinical hyperthyroid patient detected before balloon dilation therapy. We treated these two patients with levothyroxine and methimazole respectively for 6 mo after achievement of euthyroid state. No clinical or radiological improvements were obtained in symptomatology and radiological findings of achalasia after treatment, suggesting that what we found is actually a true association rather than a symptomatic mimicry or a transient neurological dysfunction. We also found a 6% positive ANA in this series which is similar to that in general population[47]. These findings may give some stronger evidence for certain autoimmune bases of achalasia. However, more and larger groups are necessary and a larger spectrum of autoimmune markers must be tested to make it possible to establish the utility of the issue in the early diagnosis of achalasia and identification of different etiologic mechanisms, which would allow us to think about novel outline of management since the existing treatments are only partially palliative.
    We also found a hypothyroid shock after balloon dilation therapy which was fortunately well managed because we were alert to the problem. Therefore we recommend clinical evaluation of thyroid disease for all patients and thyroid function test for suspicious cases to control thyroid function before any invasive therapy. Clinical severity was statistically similar in both groups of patients with normal and abnormal thyroid function tests. Therefore we cannot predict the possibility of thyroid disease on the basis of severity indexes.
    In conclusion, achalasia may be associated with thyroid diseases (hypothyroidism, hyperthyroidism and thyroid nodules), and this association should be kept in mind when a new case of achalasia is diagnosed. More accurate and extensive immunopathological studies should be performed to assess the possibility of a common immunopathogenesis or a cause and effect relationship in these diseases.

ACKNOWLEDGMENTS
The authors thank Ziba Farajzadegan MD, Hamid Tavakoli MD, Mehran Haghighi MD, Abbas Esmaeili MD, Peyman Adibi MD, Ali Akbar Vosughi MD, Mandana Soleymani MS, and other Poursina Hakim colleagues for their superb assistance in executing, coordinating and analyzing this project.

REFERENCES
1     Goldblum JR, Rice TW, Richter JE. Histopathologic features in esophagomyotomy specimens from patients with        achalasia. Gastroenterology 1996; 111: 648-654   PubMed
2     Clark SB, Rice TW, Tubbs RR, Richter JE, Goldblum JR. The nature of the myenteric infiltrate in achalasia: an        immunohistochemical analysis. Am J Surg Pathol 2000; 24: 1153-1158   PubMed
3     Paterson WG. Etiology and pathogenesis of achalasia. Gastrointest Endosc Clin N Am 2001; 11: 249-266, vi   PubMed
4     Vaezi MF, Richter JE. Diagnosis and management of achalasia. American College of Gastroenterology Practice Parameter        Committee. Am J Gastroenterol 1999; 94: 3406-3412   PubMed
5     Wong RK, Maydonovitch CL, Metz SJ, Baker JR Jr. Significant DQw1 association in achalasia. Dig Dis Sci 1989; 34: 349-       352   PubMed
6     Verne GN, Sallustio JE, Eaker EY. Anti-myenteric neuronal antibodies in patients with achalasia. A prospective study. Dig        Dis Sci 1997; 42: 307-313   PubMed
7     Verne GN, Hahn AB, Pineau BC, Hoffman BJ, Wojciechowski BW, Wu WC. Association of HLA-DR and -DQ alleles with i       diopathic achalasia. Gastroenterology 1999; 117: 26-31   PubMed
8     Casella RR, Ellis FH Jr, Brown AL. Fine structure changes in achalasia of the esophagus. II. Esophageal smooth muscle.        Am J Pathol 1965; 46: 467-486   PubMed
9     Friesen DL, Henderson RD, Hanna W. Ultrastructure of the esophageal muscle in achalasia and diffuse esophageal        spasm. Am J Clin Pathol 1983; 79: 319-325   PubMed
10   Mosley RG, Reichelderfer M, Sengupta A, Singaram C. Innervation of an esophageal ectatic submucosal blood vessel in        achalasia and a comparison with normals. Am J Gastroenterol 1994; 89: 1874-1879   PubMed
11   Storch WB, Eckardt VF, Junginger T. Complement components and terminal complement complex in oesophageal        smooth muscle of patients with achalasia. Cell Mol Biol (Noisy-le-grand) 2002; 48: 247-252   PubMed
12   von Herbay A, Heyer T, Olk W, Kiesewalter B, Auer P, Enck P, Haussinger D, Frieling T. Autonomic dysfunction in        patients with achalasia of the oesophagus. Neurogastroenterol Motil 1998; 10: 387-393   PubMed
13   Niwamoto H, Okamoto E, Fujimoto J, Takeuchi M, Furuyama J, Yamamoto Y. Are human herpes viruses or measles virus        associated with esophageal achalasia? Dig Dis Sci 1995; 40: 859-864   PubMed
14   Birgisson S, Galinski MS, Goldblum JR, Rice TW, Richter JE. Achalasia is not associated with measles or known herpes        and human papilloma viruses. Dig Dis Sci 1997; 42: 300-306   PubMed
15   Birgisson S, Galinski MS, Goldblum JR, Rice TW, Richter JE. Achalasia is not associated with measles or known herpes        and human papilloma viruses. Dig Dis Sci 1997; 42: 300-306   PubMed
16   De Giorgio R, Di Simone MP, Stanghellini V, Barbara G, Tonini M, Salvioli B, Mattioli S, Corinaldesi R. Esophageal and        gastric nitric oxide synthesizing innervation in primary achalasia. Am J Gastroenterol 1999; 94: 2357-2362   PubMed
17   Mearin F, Mourelle M, Guarner F, Salas A, Riveros-Moreno V, Moncada S, Malagelada JR. Patients with achalasia lack        nitric oxide synthase in the gastro-oesophageal junction. Eur J Clin Invest 1993; 23: 724-728   PubMed
18   Eckardt VF, Aignherr C, Bernhard G. Predictors of outcome in patients with achalasia treated by pneumatic dilation.        Gastroenterology 1992; 103: 1732-1738   PubMed
19   Vaezi MF, Richter JE, Wilcox CM, Schroeder PL, Birgisson S, Slaughter RL, Koehler RE, Baker ME. Botulinum toxin versus        pneumatic dilatation in the treatment of achalasia: a randomised trial. Gut 1999; 44: 231-239   PubMed
20   Podas T, Eaden J, Mayberry M, Mayberry J. Achalasia: a critical review of epidemiological studies. Am J Gastroenterol        1998; 93: 2345-2347   PubMed
21   Zilberstein B, de Cleva R, Gabriel AG, Neto SG, Gama-Rodrigues JJ. Congenital achalasia: facts and fantasies. Dis        Esophagus 2005; 18: 335-337   PubMed
22   Gockel I, Bohl JR, Junginger T. Achalasia: new insights in pathogenesis. Am J Gastroenterol 2006; 101: 202-203          PubMed
23   Csendes A, Smok G, Braghetto I, Gonzalez P, Henriquez A, Csendes P, Pizurno D. Histological studies of Auerbach's        plexuses of the oesophagus, stomach, jejunum, and colon in patients with achalasia of the oesophagus: correlation with        gastric acid secretion, presence of parietal cells and gastric emptying of solids. Gut 1992; 33: 150-154   PubMed
24   Storch WB, Eckardt VF, Wienbeck M, Eberl T, Auer PG, Hecker A, Junginger T, Bosseckert H. Autoantibodies to        Auerbach's plexus in achalasia. Cell Mol Biol (Noisy-le-grand) 1995; 41: 1033-1038   PubMed
25   Raymond L, Lach B, Shamji FM. Inflammatory aetiology of primary oesophageal achalasia: an immunohistochemical and        ultrastructural study of Auerbach's plexus. Histopathology 1999; 35: 445-453   PubMed
26   Dantas RO, Meneghelli UG. Achalasia occurring years after acute poliomyelitis. Arq Gastroenterol 1993; 30: 58-61          PubMed
27   Benini L, Sembenini C, Bulighin GM, Polo A, Ederle A, Zambito A, Vantini I. Achalasia. A possible late cause of postpolio        dysphagia. Dig Dis Sci 1996; 41: 516-518   PubMed
28   Castex F, Guillemot F, Talbodec N, Colombel JF, Paris JC, Cortot A. Association of an attack of varicella and an achalasia.        Am J Gastroenterol 1995; 90: 1188-1189   PubMed
29   Kountouras J, Zavos C, Chatzopoulos D. Apoptosis and autoimmunity as proposed pathogenetic links between        Helicobacter pylori infection and idiopathic achalasia. Med Hypotheses 2004; 63: 624-629   PubMed
30   Firouzi M, Keshavarzian A. Guillain-Barre syndrome and achalasia: two manifestations of a viral disease or coincidental        association? Am J Gastroenterol 1994; 89: 1585-1587   PubMed
31   Johnston BT, Colcher A, Li Q, Gideon RM, Castell JA, Castell DO. Repetitive proximal esophageal contractions: a new        manometric finding and a possible further link between Parkinson's disease and achalasia. Dysphagia 2001; 16: 186-189          PubMed
32   Allgrove J, Clayden GS, Grant DB, Macaulay JC. Familial glucocorticoid deficiency with achalasia of the cardia and        deficient tear production. Lancet 1978; 1: 1284-1286   PubMed
33   Jaggy A, Oliver JE. Neurologic manifestations of thyroid disease. Vet Clin North Am Small Anim Pract 1994; 24: 487-494          PubMed
34   Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of        thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977; 7: 481-493   PubMed
35   Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and        thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey
       (NHANES III). J Clin Endocrinol Metab 2002; 87: 489-499   PubMed
36   Gordin A, Heinonen OP, Saarinen P, Lamberg BA. Serum-thyrotrophin in symptomless autoimmune thyroiditis. Lancet        1972; 1: 551-554   PubMed
37   Okamura K, Ueda K, Sone H, Ikenoue H, Hasuo Y, Sato K, Yoshinari M, Fujishima M. A sensitive thyroid stimulating        hormone assay for screening of thyroid functional disorder in elderly Japanese. J Am Geriatr Soc 1989; 37: 317-322          PubMed
38   Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune        diseases in the United States. Clin Immunol Immunopathol 1997; 84: 223-243   PubMed
39   Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;        160: 526-534   PubMed
40   Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the        Framingham Study. Arch Intern Med 1985; 145: 1386-1388   PubMed
41   Heydarian P, Azizi F. Thyroid dysfunction and autoantibodies 10 years after implementation of universal salt iodization:        Tehran Thyroid Study, Irn J Endocrinol Metab 2003; 4: 229-241
42   Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996; 335: 99-107   PubMed
43   Knobel M, Barca MF, Pedrinola F, Medeiros-Neto G. Prevalence of anti-thyroid peroxidase antibodies in autoimmune and        nonautoimmune thyroid disorders in a relatively low-iodine environment. J Endocrinol Invest 1994; 17: 837-842   PubMed
44   Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J        Clin Endocrinol Metab 1990; 71: 661-669   PubMed
45   Feldt-Rasmussen U. Analytical and clinical performance goals for testing autoantibodies to thyroperoxidase,        thyroglobulin, and thyrotropin receptor. Clin Chem 1996; 42: 160-163   PubMed
46   Park W, Vaezi MF. Etiology and pathogenesis of achalasia: the current understanding. Am J Gastroenterol 2005; 100:        1404-1414   PubMed
47   Azizah MR, Azila MN, Zulkifli MN, Norita TY. The prevalence of antinuclear, anti-dsDNA, anti-Sm and anti-RNP antibodies        in a group of healthy blood donors. Asian Pac J Allergy Immunol 1996; 14: 125-128   PubMed

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