|
|
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
S- Editor Liu Y L- Editor Wang
XL E- Editor Liu WF
|
|
PubMed