Research Article
Open Access
Effect of Age, Gender and Season on Thyroid Hormones
Status in Children of East Delhi- A Hospital Based Study
Pradeep Kumar Dabla1,2, Shikha Sharma1* and Nakshi Sinha1
1Department of Biochemistry, Chacha Nehru Bal Chikitsalya, New Delhi, India.
2G.B Pant Institute of Postgraduate Medical Education & Research, Associated to Maulana Azad Medical College, New Delhi, India.
*Corresponding author: Shikha Sharma, Department of Biochemistry, Chacha Nehru Bal Chikitsalya Hospital, Associated to Maulana Azad Medical College, New Delhi, India, E-mail:
@
Received: March 15, 2018; Accepted: April 03, 2018; Published: April 06, 2018
Citation: Dabla PK, Sharma S, Sinha N (2018) Effect of Age, Gender and Season on Thyroid Hormones Status in Children of East Delhi- A Hospital Based Study. J Endocrinol Diab. 5(2): 1-11. DOI:
10.15226/2374-6890/5/1/00198
Abstract
Background: Thyroid hormones are the most commonly
prescribed tests in the clinical set up. Variations are observed in
individuals of different age, sex, race and nutritional status. However
few studies describe these changes in children. The aim of the present
study was to evaluate thyroid hormones in children of East Delhi with
respect to gender, age and season.
Methods: The study included 850 children up to 12 years of age of
both genders who attended the hospital for thyroid hormone analysis.
Subjects suffering from thyroid disorders or those on medication
affecting hormone status were excluded from the study. Non-fasting
venous samples were collected and serum FT3, FT4 and TSH levels
were estimated by chemiluminesence method. Statistical analysis was
done by using unpaired t-test and ANOVA.
Results: TSH levels were found to be statistically higher in
the female subjects (p = 0.049). On evaluating hormones age wise
FT3 levels were found to increase significantly with age (p = 0.000)
whereas FT4 and TSH levels significantly declined with age (p = 0.000
and p = 0.039). Significant seasonal variation in hormones was also
observed.
Conclusions: Our results shows that thyroid hormone levels
change markedly in childhood. Variation in thyroid hormone levels
has to be kept in mind during evaluation and treatment of thyroid
disorders in children.
Keywords: thyroxine (T4); tri-iodothyronine(T3); thyroid
stimulating hormone (TSH); thyroid hormones; age variation; gender
variation; seasonal variation; children
Introduction
The thyroid gland is an important endocrine gland crucial
for the growth and development of children. Its deficiency is
associated with severe physical and mental impairment. The
gland is responsible for the secretion of two metabolically active
hormones which include tetra-iodo-thyronine or thyroxin (T4)
and tri-iodo-thyronine (T3) with concentrations of 93% and 7%
respectively [1]. T3 is four times more potent than T4 but with a
shorter half life and is present in lesser concentration in the blood.
The gland is regulated by the anterior pituitary hormone TSH
whose secretion is further under control by the hypothalamus.
Iodine is required for hormone synthesis. Adequate dietary intake
of iodine is therefore essential and depends on the growth, body
weight, age, sex and nutritional status of the individual. Climate
and various disease conditions may also affect the requirement
of iodine [2]. In normal individuals the thyroid hormones show
variations with respect to age, sex, nutrition and race[3-5]. The
relationship of the gland with aging is of special interest because
of the importance of the organ in regulating the rates of various
body functions. Gradual increase in the autonomous tissue with
age makes the individual more susceptible to thyroid problems.
The concentration of the hormones decreases with age in both
sexes however the drop is observed to be more in the female than
males [6]. Interpretation of thyroid function tests can be difficult
at times. The correct understanding of these physiologically
related changes is important to clinically differentiate from
subclinical thyroidal illness or non-thyroidal disease and provide
appropriate and timely treatment. Age and gender dependent
variation among children and adolescents has been studied by
many workers, however with contradictory findings [7, 8, 9].
In view of these inconclusive findings the present study was
undertaken to evaluate the physiological changes in thyroid
hormones in children of East Delhi.
Materials and Methods
The present cross sectional study was conducted in the
Department of Biochemistry at Chacha Nehru Bal Chikitsalya
Hospital, New Delhi. Children up to 12 years of age who had
attended the hospital for thyroid hormone test for period of
one year were included in the study. The study was approved
by the scientific ethical committee and informed consent was
taken from all patients. Secondary data on age, gender, season,
FT3, FT4 and TSH level were analyzed. Children were excluded
if they had any personal or family history of thyroid disease,
goitre, hypothyroidism, hyperthyroidism or history of intake of
medication which could affect the thyroid status. Also patients
who had fever and chronic illness like nephrotic syndrome, renal
failure, malabsorption disorders like celiac disease or malignancy
etc were excluded from the study. In this way a total of 350 from
1200 subjects were excluded from the study. Informed consent
was taken from the remaining 850 subjects. The patients were
classified according to their age into neonates (0-1 month), infants
(1-12 months), preschool children (1-5 yrs) and school going
and adolescent group (6-12 yrs); males and females according
to their sex. Seasons were classified as winter (Nov-Jan), spring
(Feb-Apr), summer (May-July) and autumn (Aug-Oct) according
to their visit to the laboratory. The data were organised to know
the variations of thyroid hormones in different age, sex and
seasons. Blood samples were obtained from ante-cubital vein of
subjects under aseptic conditions. The samples of the newborns
were collected between 4th to 7th day after birth. 3ml of venous
blood was collected and allowed to clot. Serum was separated by
centrifugating at 2000 rpm for 5 mins. Samples were analyzed
for FT3, FT4 and TSH by chemiluminiscence method on Access-2
Beckman Coulter analyser. Analysis of thyroid hormones in male
and female subjects was done by using student’s unpaired t-test.
Whereas One-way analysis of variance (ANOVA) was used to
compare thyroid hormones in children of different age groups
along with comparison in different seasons. A p-value of < 0.05
was considered as statistically significant. Calculations were
done using SPSS software, version 15.0 for Windows.
Results
In the present study FT3, FT4 and TSH concentrations were
measured in serum samples of all evaluable study subjects. The
mean ± SD for FT3 in our study subjects was 3.43 ± 1.07 pg/mL,
for FT4 0.93 ± 0.51 ng/dL and 3.44 ± 2.75 μIU/mL for TSH.
(Table 1) shows the segregation of subjects according to
different age groups. Males made up 53.5 % of the study group
whereas females 46.5 % respectively. On evaluating the impact
of gender on thyroid hormone levels (Table 2), a significant
elevation of TSH was found in females (p = 0.049). FT4 levels
were slightly higher in females however the difference was not
statistically significant. No significant difference was found in
levels of FT3 in male and female subjects.
Table 1: Classification of subjects in different age groups
Age |
Male |
Female |
0 – 1 month |
56 (12.3%) |
43 (10.8%) |
1-12 months |
77 (16.9%) |
53 (13.4%) |
1-5 years |
139 (30.5%) |
105 (26.5%) |
6-12 years |
183 (40.2%) |
194 (49.1%) |
Total |
455 (53.5%) |
395 (46.5%) |
Table 2: Thyroid hormones in subjects of different gender
Gender |
FT3 |
FT4 |
TSH |
Male |
3.4 ± 1.08 |
0.91 ± 0.38 |
3.26 ± 2.31 |
Female |
3.37 ± 1.09 |
0.94 ± 0.62 |
3.63 ± 3.15 |
P-Value |
0.687 |
0.388 |
0.049 |
Hormone levels were also compared in children belonging to
different age groups. FT3 levels were found to be lowest amongst
neonates and highest levels were seen in children between 1-5
years. Levels were similar in children between 1-12 months and
6-12 years of age. There was a statistically significant variation in
FT3 level (p=0.000) in different age groups on applying ANOVA
test (Table 3 and Graph 1). On the other hand levels of FT4
were highest amongst neonates. Levels in the remaining groups
Table 3: Thyroid hormones in subjects of different age groups
Age |
FT3 |
FT4 |
TSH |
0-1mth |
2.45 ± 0.91 |
1.10 ± 0.5 |
3.42 ± 2.61 |
1-12mth |
3.41 ± 1.01 |
0.89 ± 0.37 |
3.28 ± 2.7 |
1-5yrs |
3.58 ± 1.02 |
0.88 ± 0.36 |
3.04 ± 2.13 |
6-12yrs |
3.44 ± 1.06 |
0.93 ± 0.51 |
3.57 ± 2.07 |
p-value |
p = 0.000 |
p = 0.000 |
p = 0.039 |
Graph 1: FT3 levels in different age groups
Graph 2: FT4 levels in different age groups
Graph 3: TSH levels in different age groups
remained stable with FT4 levels being slightly higher in 6-12 year
group. A statistically significant variation in FT4 level (p=0.000)
was also seen in different age groups on applying ANOVA test
(Table 3 and Graph 2). TSH level was found to be highest in
children of 6-12 years age. Neonates showed higher levels of TSH
followed by a decline in the first year of life and up till 5 years. A
statistically significant variation in TSH level (p = 0.039) was also
seen in different age groups on applying ANOVA test (Table 3 and
Graph 3).
On evaluating hormone levels in male and female subjects in
different age groups, FT3 and TSH levels were found to be higher
in the female subjects in all age groups. FT4 levels were higher in
the female subjects amongst the neonates as well as in the 6-12
years age group. However these differences were not statistically
significant as shown in Table.4.
The hormonal changes in different seasons are shown in
Table.4. TSH levels were highest in the winter season and lowest
during the monsoon. In summer and autumn months levels were
almost equal. A statistically significant variation in TSH level (p
= 0.045) was seen in different seasons on applying ANOVA test.
FT3 levels were found to be highest in the summer and lowest
in autumn. Levels were similar during the monsoon and winter
season. A statistically significant variation in FT3 level (p= 0.000)
was seen in different seasons on applying ANOVA test (Table.4).
FT4 levels were highest in the winter followed by the monsoon
season. Levels in summer and autumn were similar. A statistically
significant variation in FT4 level (p = 0.018) in different seasons
was also seen on applying ANOVA test.
Table 4: Thyroid hormones in male and female subjects of different age groups
Age |
FT3 |
FT4 |
TSH |
|
Male |
Female |
p-value |
Male |
Female |
p-value |
Male |
Female |
p-value |
0-1 mth |
3.43±1.08 |
3.44±1.06 |
0.961 |
0.92±0.38 |
0.94±0.63 |
0.851 |
3.29±2.34 |
3.63±3.18 |
0.541 |
1-12 mths |
3.35±1.10 |
3.58±1.00 |
0.232 |
0.95±0.59 |
0.91±0.36 |
0.664 |
3.36±2.47 |
3.59±3.14 |
0.642 |
1-5 yrs |
3.43±1.07 |
3.51±1.05 |
0.561 |
0.93±0.51 |
0.89±0.36 |
0.492 |
3.44±2.76 |
3.56±3.05 |
0.754 |
6-12 yrs |
3.43±1.08 |
3.44±1.05 |
0.933 |
0.92±0.39 |
0.95±0.63 |
0.584 |
3.32±2.35 |
3.64±3.17 |
0.271 |
Table 5: Thyroid hormones in subjects in different seasons
Seasons |
FT3 |
FT4 |
TSH |
Summer (N=230) |
3.64 ± 1.09 |
0.89 ± 0.49 |
3.47 ± 2.62 |
Monsoon (N=210) |
3.26 ± 1.04 |
0.94 ± 0.52 |
3.16 ± 1.99 |
Autumn (N=220) |
3.16 ± 0.89 |
0.89 ± 0.51 |
3.43 ± 2.70 |
Winter (N=190) |
3.25 ± 0.98 |
1.03 ± 0.52 |
3.89 ± 2.97 |
p-value |
p = 0.000 |
p = 0.018 |
p = 0.045 |
Discussion
India is a vast sub-tropical country with differences in its
ethnic background, topography and iodine nutrition. Thyroid
hormones are crucial for the growth and development of children.
Their biological activity in target cells is determined by the
intracellular concentration of T3, which is further dependent upon
the circulating levels of T3 and T4 [10]. With an increase in age
a decline in thyroid function is observed [11]. The present study
was conducted to evaluate the effect of gender, age and season on
thyroid function tests (FT3,FT4 and TSH) in children. Our study
showed a significant difference in the value of TSH (Table 2) in
male and female subjects. This observation was in accordance
by a study by Parra et al [8] that in childhood and adolescence
sex associated variations in thyroid hormone concentrations
may occur. Girls mature at an earlier chronological age than boys.
This may represent a partial response of the body to the different
qualitative and quantitative energy needs in girls as compared
to boys, consecutive to the differences in body composition first
appearing at the time of puberty [8]. On evaluating hormone
levels in different age groups, FT3 levels were found to be lowest
in the neonates followed by increase in level from one month till
five years of age and a decline in the 6-12 years age group (Table
3). Immediately after birth TT3 levels are high due to maternal
oestrogen induced increase in thyroxine-binding globulin (TBG).
In a study by Jacobsen et al [12] FT3 levels were found to increase
by 50-70 % in full term infants and reached a maximum value
by 50-79 days of life. Levels also markedly increase during early
infancy and childhood and tend to decline during adolescence
[11]. In the present study also FT3 value in the 6-12 years age
group fell to 3.44 ng/mL from 3.58 ng/mL in children (1-5 years).
Similar values of progressive decrease of T3 levels fom childhood
to adolescence have in observed in several studies [11, 13]. The
increased metabolic activity during infancy and childhood may
lead to increased peripheral utilisation of thyroid hormones [14].
Our study showed a progressive decline in the FT4 concentration
up to 5 years of age, with mean FT4 of 1.10 ng/dL in neonates, 0.89
ng/dL in infants, 0.88 ng/dL in children between 1-5 years and
0.93 ng/dL in 6-12 years age group. At birth TT4 levels are high
due to maternal oestrogen induced increase in TBG. Jacobsen et al
[12] showed serum T4 levels to decrease by 20% during the first
month of life. Levels decline gradually till 15 years of age. This was
in contrast to our study in which we found a decline in FT4 till five
years of age followed by an increase. On the other hand a Chinese
study indicated that the mean serum thyroxin concentration was
high in newborns for up to seven days which reduced in the preschool
ages within a few months [15]. Other studies in France [16,
17, 18] indicated that there was no alteration in mean T4 levels
between the ages of one month and 2 years, which is different
from the results of the Chinese study. Both studies have mostly
been carried on in subjects up to 2 years of age and contradict
each other, but rely on a key point that serum T4 levels gradually
decrease as the children get older. The common key point in the
above studies was also found in our investigation. In the present
study mean TSH levels in neonates was 3.42 μIU/mL. TSH levels
surge immediately within 30 minutes of birth from 60-700 μIU/
mL [19] to decline back by 3 days and reach normal adult values
after few weeks of life. The mean TSH level in infancy was 3.28
μIU/mL whereas in 1-5 years age group was 3.04 μIU/mL which
increased to 3.47 μIU/mL in the age group of 6-12 years. Our
findings were similar to a study by A. Dambal et al [20]. A prepubertal
surge of TSH between 9-9.5 years of age may account
for this finding [7]. No sex variations were observed for any of the
thyroid hormones in different ages of our subjects under study.
This finding was similar to a study by Elmlinger [21] et al, but
in contrast to a study by Hubner [22] and his co-workers who
found sex specific effects on FT3 residuals in the age group of
11-14 years. The effect of seasons on thyroid hormones FT3, FT4
and TSH was also observed. TSH levels were highest in the winter
and lowest during the monsoon season. TSH levels estimated
equal in summer and autumn months. FT3 levels were found to
be highest in the summer and lowest in autumn whereas similar
levels detected during the monsoon and winter season. FT4 levels
were highest in the winter and monsoon seasons with winter
values being detected slightly higher. FT4 levels in summer and
autumn were similar. This variation observed may be due to the
effect of cold which may accelerate the peripheral metabolism of
thyroid hormones during the winter months and therefore lead
to increase in levels of TSH and FT4. Seasonal changes therefore
also lead to variations in levels of thyroid hormones. Our findings
were in accordance to studies of Khan et al [23] and Chaurasia et
al [24].
Limitations of the present study
The main limitation in our study was that, it comprised of a
hospital based population. Physiological variations determined
from a large cohort of healthy subjects may give more insight.
However due to ethical and practical considerations in children,
hospital data was used to conduct the present study which
will serve as a base for further large scale evaluations. Since
reference groups are based in a hospital, our results may slightly
diverge from similar population. This concern was addressed
by excluding subjects with diagnosis and medication affecting
thyroid functions. Further studies are also required on a larger
sample size in adolescents to investigate the significance of
gender on thyroid hormone levels.
Conclusion
Our results coroborate with those of previous studies showing
that thyroid hormone levels change markedly in childhood.
Variations in thyroid hormones with respect to age, gender and
season should be carefully assessed in each country and even
each state of each country to prevent any misdiagnosis with
respect to thyroid hormones which are vital for growing children.
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