functional and morphological changes of thyroid

Nowiny Lekarskie 2009, 78, 2, 95–98
MAREK RUCHAŁA1, EDYTA GURGUL1, MACIEJ BĄCZYK1, MACIEJ GEMBICKI1, LESZEK PIETZ1, PAWEŁ
URUSKI2, JERZY SOWIŃSKI1
FUNCTIONAL AND MORPHOLOGICAL CHANGES OF THYROID GLAND
IN 14–18 YEARS OF AGED CHILDREN IN WESTERN POLAND AT THE TRANSITION PERIOD
FROM IODINE DEFICIENCY TO IODINE SUFFICIENCY
ZMIANY CZYNNOŚCIOWE I MORFOLOGICZNE TARCZYCY U 14–18-LETNICH DZIECI
Z REGIONU POLSKI ZACHODNIEJ W OKRESIE PRZEJŚCIOWYM
POMIĘDZY NIEDOBOREM JODU A DOSTATECZNĄ SUPLEMENTACJĄ
1
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poland
Chairman of the Department: professor Jerzy Sowiński
2
Department of Hypertension, Angiology and Internal Medicine, Poznan University of Medical Sciences, Poland
Chairman of the Department: professor Andrzej Tykarski
Summary
Aim. The aim of the study was to assess thyroid morphological and functional changes in school-aged children after the introduction of obligatory iodine prophylaxis with iodinated salt in 1997.
Methods. The examined group consisted of 706 children divided into two age groups: 14–16 year-olds (first group) and 16–18 year-olds (second
group). Iodine nutrition was assessed by means of urine iodine excretion. In both groups serum TSH, free T3, free T4 levels and aTPO titer were
measured. Thyroid gland morphology was evaluated in ultrasound examination.
Results. Iodine supplementation increased urine iodine concentration – the principal marker of iodine nutrition. The incidence of goiter was
higher in older group, in which iodine prophylaxis was introduced later. Compared to the studies conducted before obligatory iodine supplementation the occurrence of elevated aTPO was more frequent.
Conclusions. The prevalence of goiter was high, especially in older children, which suggests, that the later the iodine supplementation is introduced, the higher is the risk of thyroid gland enlargement. Elevated aTPO and autoimmune diseases result from the obligatory prophylaxis introduced in 1997 and are typical for the first years of iodine supplementation.
KEY WORDS: thyroid, goiter, iodine deficiency, iodine prophylaxis, iodine deficiency disorders, thyroid autoimmunological disorders.
Streszczenie
Cel badania. Celem badania była analiza czynnościowych i morfologicznych zmian gruczołu tarczowego u dzieci w wieku szkolnym po wprowadzeniu obowiązkowej profilaktyki jodowej w 1997 r.
Metodyka. Grupa badana składała się z 706 dzieci i została podzielona na dwie podgrupy wiekowe: dzieci w wieku od 14 do 18 lat zakwalifikowano do pierwszej podgrupy, a dzieci w wieku od 16–18 lat do drugiej podgrupy. Stan zaopatrzenia w jod określono poprzez ocenę wydalania
tego pierwiastka z moczem. U wszystkich dzieci oznaczono stężenie TSH, fT3, fT4 oraz przeciwciał aTPO. Gruczoł tarczowy został zobrazowany w badaniu ultrasonograficznym.
Wyniki. Profilaktyka jodowa spowodowała poprawę stanu zaopatrzenia w jod, co odzwierciedla wzrost wydalania tego pierwiastka z moczem.
Częstość występowania wola była większa wśród dzieci starszych, u których suplementację jodu wprowadzono w późniejszym wieku. W porównaniu do badań przeprowadzonych przed 1997 r. częściej odnotowywano podwyższone stężenie przeciwciał aTPO.
Wnioski. Częstość występowania wola była wysoka, zwłaszcza wśród starszych dzieci, co świadczy o tym, że im później suplementacja jodem
zostaje wprowadzona, tym wyższe ryzyko powstania wola. Podwyższone stężenie aTPO i występowanie zaburzeń autoimmunologicznych
wynika z wprowadzonej profilaktyki jodowej i jest typowe dla pierwszych lat po wprowadzeniu suplementacji.
SŁOWA KLUCZOWE: tarczyca, wole, niedobór jodu, profilaktyka jodowa, zespół niedoboru jodu, zaburzenia autoimmunologiczne
tarczycy.
Introduction
Thyroid gland comprises the majority of human body
iodine, which is an essential structural element of thyroid
hormones (65% and 59% of the weight of thyroxine and
triiodothyronine, respectively). Therefore, insufficient iodine intake results in inadequate thyroid hormones production (hypothyroidism) and leads to many adverse effects on
growth and development, known as iodine deficiency disorders (IDD) [1].
The principal marker of iodine intake is urine iodine excretion (UIE). Since more than 90% of ingested iodine is
ultimately excreted in the urine, UIE is highly sensitive to
recent changes in iodine intake [2]. WHO/ICCIDD recommends, that the median UIE for a population should be ≥
100ug of iodine per litre of urine. Mild iodine deficiency is
defined as UIE in the range 50–99ug/l, moderate 20–49 ug/l
and severe less than 20 ug/l [2].
Goiter is a consequence of adaptive processes in
chronic iodine deficiency. Low iodine supply increases
Marek Ruchała et. al.
TSH production to improve uptake of available iodine.
TSH stimulates hypertrophy and hyperplasia of thyroid
gland, leading to diffuse and nodular goiter formation [3].
Other goitrogenic factors (food components: cabbage,
cauliflower, broccoli, soy; industrial pollutants: perchlorate, smoking) may also interfere with thyroid function
and aggravate the effect. Nevertheless, most of them do
not exert major clinical effect, until iodine intake is appropriate [4]. In endemic areas, although thyroid volume
decreases in response to increased iodine intake, goiter
rate may not return to normal for months or years after
correction of iodine deficiency (ID) [5]. Therefore, goiter
rate reflects iodine nutrition in long term.
Thyroid hormones abnormalities cannot be considered as iodine deficiency indicators. Increased TSH level
stimulates the growth and metabolic activity of thyroid
follicular cells, which combined with the reduction of
iodine stores in the thyroid gland leads to a decreased T4
level and relatively high triiodothyronine (T3) synthesis.
However, these changes often remain within the normal
ranges [1].
Iodine deficiency is a worldwide problem. In 2003
nearly 2 billion people had inadequate iodine nutrition,
285 million of these were school-aged children [6]. In
nearly all countries, the best strategy to control iodine
deficiency is salt iodination, because salt is widely consumed with relatively consistent intake through the year.
This method has been proven to reduce the prevalence of
goiter [7]. Indeed, in Poland the obligatory prophylaxis
of IDD with iodinated salt (30 ± 10 mg of potassium
iodide per 1 kg of salt) was introduced in 1997 and a
research conducted in 2007 on a study group of children
from Wielkopolska revealed median value of UIE reaching appropriate values (107 µg/l) [8].
The aim of the study was to assess thyroid morphological and functional changes in school-aged children at
the transition period from iodine deficiency to iodine
sufficiency.
The results of the study were compared to the previous researches. The study in 1990 was conducted in view
of Chernobyl nuclear power station accident in 1986 [9].
The second research was conducted at the moment of
iodine supplementation introduction in 1997 [10].
Data revealed in the study were analyzed using Chi2
with Yates correction test.
Results
Median urine iodine excretion in the first group of
our study was 86 µg/l and in the second group – 78 µg/l,
indicating mild iodine deficiency. 61.3% of examined
had UIE below 100 µg/l. We noted an increase of UIE in
comparison to the previous research conducted before
iodine prophylaxis (in 1990 median UIE was 44 µg/l).
However, the most significant rise in iodine intake was
noted at the moment of the introduction of iodine supplementation in 1997 (Fig. 1).
100
60
86
1997
I group (2004)
78
44
40
20
0
1990
II group (2004)
Figure 1. Median urine iodine excretion before and during
iodine supplementation (μg/L).
Rycina 1. Mediana wydalania jodu z moczem przed i po rozpoczęciu profilaktyki jodowej (μg/L).
Goiter rate was higher in the second group (p = 0.01)
(Table 1). The focal lesions in thyroid gland were also
more frequent in older subjects (p = 0.003).
Table 1. The prevalence of goiter in the study group
Tabela 1. Występowanie wola w grupie badanej
Materials and methods
The study was conducted in 2000–2004 in 706 children from the region of Wielkopolska during a regular
screening examination in schools. Children were divided
into two age groups: 14–16 year-olds were included to
the first (I) group (228 girls and 204 boys) and 16–18
year-olds to the second (II) group (138 girls and 136
boys). The study was approved by the Ethical Committee of Poznan University of Medical Sciences.
Iodine nutrition was assessed by urinary iodine excretion (UIE) measured by Ce-As method in morning urine
samples. Serum TSH, free T4 and free T3 were determined
by electrochemiluminescence immunoassay (ECLIA) with
Modular Analytics E170 system (Roche Diagnostic, Germany). Anti-thyroid peroxidase autoantibodies (aTPO)
level was measured with the solid-phase radioimmunoassay
(RIA) method (Brahms Diagnostica, Berlin, Germany).
Thyroid gland was evaluated by ultrasound (Aloka SSD1100) with a 7.5 MHz linear transducer.
82
80
UIE ug/L
96
I group
II group
Girls
(%)
17.1
23.2
Boys
(%)
2.5
11.0
Mean
(%)
10.2
17.2
Nodular
goiter (%)
6.3
13.1
The autoimmunological disorders meant as increased
anti-thyroid peroxidase autoantibodies (aTPO) level
have risen since 1990 (p < 0.001) and occurred more
often in older children (p = 0.001) (Fig. 2).
The occurrence of Hashimoto thyroiditis (increased
aTPO level combined with hypoechogenicity of the thyroid gland and biochemical clinical manifestations of
thyroid malfunction) in both groups was also much higher
than before the introduction of IDD prophylaxis (p <
0.001) (Fig. 3).
Functional and morphological changes of thyroid gland in 14–18 years of aged children in Western Poland
13,1
10
8
5,7
6
4
2,1
2
0
1990
I group (2004) II group (2004)
Figure 2. The prevalence of increased aTPO level.
Rycina 2. Częstość występowania podwyższonego stężenia aTPO.
Hashimoto thyroiditis (%)
1,2
12
hyperthyroidism (%)
increased aTPO (%)
14
4
3,5
3
2,5
2
1,5
1
0,5
0
3,6
2004
Figure 3. The prevalence of Hashimoto thyroiditis before and
during iodine supplementation (%).
Rycina 3. Częstość występowania zapalenia tarczycy typu Hashimoto przed i po rozpoczęciu profilaktyki jodowej (%).
hypothyroidism (%)
The incidence of thyroid functional disorders (hypothyroidism or hyperthyroidism) has increased since 1990
(hypothyroidism: p < 0.001, hyperthyroidism: p = 0.8)
(Fig. 4; Fig. 5).
2
1,6
1,8
1,5
1
0,5
0,1
0
1990
I group
(2004)
1
1
0,8
0,6
0,5
0,5
0,4
0,2
0
1990
I group
II group
Figure 5. The prevalence of hyperthyroidism before and during
iodine supplementation (%).
Rycina 5. Częstość występowania nadczynności tarczycy przed
i po rozpoczęciu profilaktyki jodowej (%).
Discussion
0,1
1990
97
II group
(2004)
Figure 4. The prevalence of hypothyroidism before and during
iodine supplementation (%).
Rycina 4. Częstość występowania niedoczynności tarczycy przed
i po rozpoczęciu profilaktyki jodowej (%).
Our study demonstrated a great improvement in iodine nutrition since the introduction of IDD prophylaxis.
However, the median urinary iodine excretion still remained below 100 µg/l. Thus, the research was conducted at the transition period from iodine deficiency to
iodine sufficiency reached in 2007 [8].
The prevalence of both diffuse and nodular goiter
was high in both age groups, with significant superiority
in older children. These results suggest, that iodine supplementation should begin early in childhood as the later
iodine prophylaxis is introduced, the higher is the risk of
thyroid gland enlargement. However, the adolescents
belonging to the second group were at risk of goiter also
due to increased estrogen level in the age of puberty.
Many studies have revealed a reduction of goiter rate
after the suplementation of iodized salt [11–14]. As
mentioned above, goiter rate is a long-term indicator of
iodine intake, which consequently decreases, but is still
observed for months or years after the introduction of
appropriate iodine supply [15].
Autoimmunological thyroid disorders meant as increased aTPO level were much more frequent than in
1990, especially in the second group. The prevalence of
Hashimoto thyroiditis also has risen since the introduction of iodine prophylaxis. Several clinical studies revealed, that iodine supplementation is connected with
thyroid autoimmunity [16–18]. These disorders are considered to be typical for the first years of iodine prophylaxis in previously deficient areas and afterwards they
subside [19].
Hypothyroidism and hyperthyroidism in the study
group might have resulted from immunological changes
observed after the introduction of iodine supplementation. When aTPO level rises, TSH firstly remains on
lower levels and later increases, what may influence
thyroid hormones production. Iodine-induced hyperthyroidism is a well known term for the transient disorder, which
98
Marek Ruchała et. al.
occurs when iodine intake increases in previously iodine
deficient populations [20].
Elimination of iodine deficiency disorders is an essential health and social goal. However, it is important to
watch the consequences of iodine supplementation. High
salt consumption may result in hypertension followed by
vascular remodelling, cardiac hypertrophy and increased
stroke incidence [21–24]. To avoid such consequences,
iodization of other food like milk, bread, processed rice
or drinking water to increase iodine intake should be
considered.
Conclusions
The study indicated, that iodine supplementation
with salt iodinated improved iodine nutrition. High
prevalence of goiter in both age groups, especially in
older children suggests, that iodine supplementation
should begin early in childhood. The improvement of
iodine intake was followed by increase of thyroid autoimmunity, which is typical for the first years of iodine
prophylaxis and then subsides.
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Address for correspondence:
prof. UM dr hab. Marek Ruchała
60-355 Poznań, ul. Przybyszewskiego 49
Katedra i Klinika Endokrynologii,
Przemiany Materii i Chorób Wewnętrznych
tel.: +48 61 867-55-14 (869-13-30), fax: +48 61 869-16-82
e-mail: [email protected]