The Turkish Journal of Pediatrics
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The frequency of autoimmune thyroid disorders in juvenile idiopathic arthritis
Erbil Ünsal1, Oğuz Ören1, Koray Salar2, Balahan Makay1, Ayhan Abacı1 Bayram Özhan2, Ece Böber1
1Departments of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey
2Tepecik Training Hospital, İzmir, Turkey
|Ünsal E, Ören O, Salar K, Makay B, Abacı A, Özhan B, Böber E.
The frequency of autoimmune thyroid disorders in juvenile idiopathic arthritis.
Turk J Pediatr 2008; 50: 462-465.
Few studies have been performed to investigate autoimmune diseases associated
with organ non-specific rheumatological disorders in children, such as juvenile
idiopathic arthritis (JIA). The objective in this study was to determine the
frequency of autoimmune diseases of the thyroid gland in children with JIA.
Eighty patients with JIA and 81 healthy sex- and age-matched controls were
enrolled in the study. Serum free T3, free T4, thyroid stimulating hormone
(TSH), anti-thyroglobulin antibodies, and anti-peroxidase antibodies were
evaluated. The mean age was 11.5±5.5 years in the patient group and 10.5±4.9
years in the control group. Twenty-seven of the cases were classified as
oligoarticular, 26 as polyarticular, 17 as enthesitis-related, 6 as systemic, and
4 as psoriatic arthritis. Autoimmune thyroid disease was found in 4 patients
in the JIA group (5%). There were no significant differences between the
study and control groups regarding the existence of anti-thyroid antibodies
(p=0.17). Girls were more likely to develop autoimmune thyroiditis (3 girls,
1 boy). Autoimmune thyroiditis was more frequent in patients who had a
family history of thyroid disease (p=0.02). There was no statistical correlation
between rheumatoid factor (RF) and antinuclear antibody (ANA) positivity
and autoimmune thyroiditis (p>0.05). We conclude that there is no need for
routine screening of serum thyroid function tests and thyroid antibody levels
in patients with JIA in the absence of clinical symptoms.
autoimmune thyroid disease, juvenile idiopathic arthritis.
|Autoimmune thyroiditis is more frequent
than in the normal population in the course
of rheumatoid autoimmune diseases such as
rheumatoid arthritis, in which specific organ
involvement is rare. A common autoimmune
pathogenesis or a strong genetic association
among these diseases, such as the expression
of certain types of major histocompatibility
complexes, has been put forward[1,2]. However,
there are very few studies about the association
of autoimmune thyroid disorders and juvenile
idiopathic arthritis (JIA), which is a rheumatoid
autoimmune disease of childhood[3-6]. The goal
of this study was to determine the frequency
of autoimmune diseases of the thyroid gland
in a group of children with JIA.|
|Material and Methods |
|This prospective study was performed at the
Department of Pediatrics, Division of Immunology
and Rheumatology of Dokuz Eylül University,
Faculty of Medicine, and İzmir Tepecik Training
Hospital between September 2004 and June
2005. During this period, 80 patients (41 male,
39 female) (mean age: 11.5±4.1 years) who
were diagnosed as JIA between January 1999 and
January 2005 according to the revised criteria of
JIA were enrolled in the study after informed
parental consent was obtained.
For each patient, demographic data, JIA subgroup,
and family history of thyroid diseases
up to second-degree relatives were recorded.
Rheumatoid factor (RF) and antinuclear antibody
(ANA) titers were examined in the JIA
Thyroid Function and Autoimmunity Screening
Serum concentrations of free T3, free T4, thyroid
stimulating hormone (TSH), and thyroglobulin
(TgA) and thyroperoxidase antibodies (TPOA)
were determined by chemiluminescence
assays (Diagnostic Products Corporation, Los
Angeles, CA, USA). Reference values were
0.35-4.9 µIU/L for TSH, 0.8-2.3 ng/dl for
fT4 and 2.1-4.4 pg/ml for fT3. TgA values
>50 IU/ml and TPOA values >50 IU/ml were
considered as positive. Patients with positive
autoantibodies were further evaluated with
thyroid ultrasonography. Hypothyroidism was
defined as low fT3 and/or fT4 with elevated
TSH levels; subclinical hypothyroidism was
defined as elevated TSH with normal thyroid
hormone levels; and thyrotoxicosis was defined
as high fT3 and/or fT4 levels accompanying
suppressed TSH. Hypothyroid and thyrotoxic
patients also had signs and symptoms of thyroid
dysfunction, while subclinical hypothyroid and
euthyroid groups were clinically symptom-free.
Autoimmune thyroiditis was defined as positive
TPOA and/or TgA.
Control group: 81 patients (41 male, 40 female,
mean age: 10.5±4.9 years) who were admitted
to our hospital for non-autoimmune diseases
served as control group. None of these patients
had the signs and symptoms of thyroid disease
or a chronic disease.
The study protocol was approved by the Ethics
Committee of Dokuz Eylül University, Faculty
SPSS 10.0 version was used. Results are expressed
as mean ± SD. The Mann-Whitney U test was
used for non-normally distributed variables
whereas Yates chi-square test and Fisher's exact
test were used for normally distributed data. P
value <0.05 was considered significant.
|The sex and age distribution were comparable in
the study and control groups. The mean age at
JIA diagnosis was 8.6±3.8 years and the mean
age at study entry was 11.4±4 years. The mean
disease duration at study entry was 34.7±31
months. Twenty-seven out of 80 JIA patients
had oligoarticular, 26 RF-negative polyarticular,
17 enthesitis-related, 6 systemic onset, and 4
psoriatic type of the disease (Table I).
| ||Table I. Characteristics and Presence of Thyroid Disease in JIA vs Control Group|
Anti-thyroid antibodies were detected in 4 of
80 (5%) JIA patients. The onset of JIA was
systemic in 1 of them, enthesitis-related in
1, and polyarticular in the remaining 2. None
of the 27 cases with oligoarthritis (OA) had
anti-thyroid antibodies; 7 were ANA-positive.
Four cases with psoriatic arthritis also did not
Table II presents important demographic
and laboratory data of the four patients with
anti-thyroid antibodies: Girls were more
prone to develop autoimmune thyroiditis
(3 girls vs 1 boy). The four patients had
subclinical hypothyroidism, hypothyroidism,
hyperthyroidism and euthyroidism, respectively.
In the control group, one patient had a positive
TPOA with normal FT3, FT4, and TSH, and
one patient had subclinical hypothyroidism
without thyroid antibodies. There were no
significant differences between the study and
control groups regarding the existence of antithyroid
| ||Table II. Clinical and Laboratory Data of JIA Patients with Positive Anti-Thyroid Antibodies|
Autoimmune thyroiditis was more frequent in
patients who had a family history related to
thyroid disease (p=0.02).
There was no statistical correlation between RF
and ANA positivity and autoimmune thyroiditis
|The association between rheumatoid arthritis and
autoimmune thyroid disease is well established;
however, most literature studies on this topic
are focused on adult series[9-12]. There are only a
few studies evaluating the relationship between
JIA and autoimmune thyroiditis[3-6]. All of them
have reported a high prevalence of anti-thyroid
antibodies in JIA when compared to healthy
controls. This study could not demonstrate any
significant differences between the JIA patients
and age-matched healthy controls regarding the
existence of anti-thyroid antibodies. Autoimmune
thyroiditis is four to seven times more frequent
in girls than in boys. Similarly, three of four
patients with autoimmune thyroiditis were
female in this study.
In the previous studies[3-6], the majority of the
patient population was female. However, in our
study, 51% of the patients were male. Özdoğan
et al. also reported a male predominance
among JIA patients in a Turkish population.
The rate of male patients was 56% in their
147 patients. The male predominance due to
patients with enthesitis-related arthritis (ERA),
a subgroup mostly defined in boys, might
explain the low frequency of autoimmune
thyroiditis in our study. Twenty-two percent of
the study population consisted of patients with
ERA. None of the mentioned studies included
patients with ERA except the study of Harel
et al.. Only a minority of 66 patients (3%)
had ERA in that study and 75% of the study
population was female.
Recently, Harel et al. reported a higher
incidence of anti-thyroid antibodies in patients
with oligoarticular JIA. All of the patients
with positive anti-thyroid antibodies, which
composed 39% of the patient population, had
OA. Another study by Alpigiani et al., in which
66% of patients were female, demonstrated
significantly higher anti-thyroid antibody
positivity, particularly in the OA type. The
majority of the patients (64%) were OA. The
largest series investigating the coexistence of
JIA and autoimmune thyroiditis was reported
by Stagi et al.. They evaluated 151 patients,
of whom 80% were female, and found a
higher prevalence of autoimmune thyroiditis
as well as subclinical hypothyroidism in OA
type. Fifty-eight percent of the patients had
OA. In contrast to these studies, none of the
patients with OA had autoimmune thyroiditis
in this study. The lower incidence of OA
(33%) and female ratio than previous reports
may contribute to the lower frequency of
autoimmune thyroiditis in this study.
In conclusion, this study demonstrated that
there was no significant increase in autoimmune
thyroiditis in a group of JIA patients, when
compared to a sex- and age-matched control
group. Despite the statistical insignificance,
the presence of four patients with autoimmune
thyroiditis should not be underestimated
regarding the evaluation of JIA patients for
autoimmune thyroid diseases. Screening for
anti-thyroid antibodies is recommended in the
presence of clinical symptoms and a positive
family history. Further studies with a larger
group of patients are needed to demonstrate the
frequency of autoimmune thyroiditis in JIA.
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