Age, Gender, and Seasonal Effects on Thyroid Profile Vol. 12 (1), June 2021
ISSN (Print): 2305 – 8722 ISSN (Online): 2521 – 8573
R A D S J . B i o l . R e s . A p p l . S c i . 17
Op e n Ac c e s s
F u l l L e n g t h A r t i c l e
Age, Gender, and Seasonal Effects on Thyroid Profile in
Adults with Normal Thyroid Functions
Sajjad Ahmad1,*, Haji Muhammad Rashid2, Hiza Hassan3, Muhammad Mujahid4, Maryam Gul5
1Department of Pathology, Quaid-e-Azam Medical College, Bahawalpur, Pakistan.
2Department of Chemical Pathology, University of Health Sciences, Lahore, Pakistan.
3Department of Medical Lab Technology, University of Haripur, Pakistan.
4Pathology Department, BSL-3 Lab, DHQ Hospital Sargodha, Pakistan.
5Microbiology Department, Kohat University of Sciences and Technology, Kohat, Pakistan.
A B S T R A C T
Background: Thyroid hormone variations have been observed according to age and sex. Seasonal effects also induce variations in
thyroid function even in people with normal thyroid levels. The majority of clinical laboratories follow a single reference range without
the consideration of age, gender, and especially seasonal variations in thyroid function tests.
Objectives: To evaluate age, gender, and seasonal variations in thyroid function tests in adults with normal thyroid functions.
Methodology: This cross sectional study was carried out at Pathology Department, Quaid-e-Azam Medical College, Bahawalpur. One
year data from Jan 2018 to Jan 2019 of thyroid function tests (TSH, T3 and T4) and demographic details were obtained for all those
patients whose Thyroid Stimulating Hormone (TSH) was in normal reference range (0.5-4.5mU/L). We found the data of 418 subjects
from 16 to 75 years of age, among them 196 were females and 222 were males.
Results: Serum TSH levels were higher in females (2.11mU/L ±1.54) than serum TSH levels of males (1.59mU/L ±1.2) with a p-value
of 0.0002. FT4 levels (normal range: 0.89-1.76ng/dL) were significantly lower (p-value 0.0018) in females (1.33ng/dL ±0.50) as
compared to males (1.48ng/dL ±0.48). In <20 years of the age group of both genders, serum TSH was at lowest levels, while highest
in 20-40 years of the age group of males and >60 years of females. The mean TSH of all subjects was high (2.98mU/L) in winters and
it was low (2.4mU/L) in autumn. FT4 was at the lowest level (1.16ng/dL) in winters and it was highest (1.46ng/dL) in summers. FT3
levels in the winter season were higher than in other seasons.
Conclusion: Age, gender, and season affects the thyroid hormones levels, and these factors should be considered while interpreting
the lab results of thyroid function tests.
Keywords
Age, FT3, FT4, Gender, Seasons, TSH.
*Address of Correspondence
sajjad.ahmadbwp@gmail.com
Article info.
Received: March 29, 2021
Accepted: April 20, 2021
Cite this article Ahmad S, Rashid HM, Hassan H, Mujahid M, Gul M. Age, Gender, and Seasonal
Effects on Thyroid Profile in Adults with Normal Thyroid Functions. RADS J Biol Res Appl Sci.
2021; 12(1):17-23.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in
any medium provided the original work is properly cited.
I N T R O D U C T I O N
The most important gland in the endocrine system is the
thyroid gland. It is situated below the larynx, on both
anterior sides of the trachea1. The thyroid gland secretes
two major hormones; Triiodothyronine (T3) and Thyroxin
(T4). The concentration of T3 is 7% and T4 is 93% of total
thyroid hormone secretion. Both thyroid hormones
circulate in the blood in a free and bound form. About 99%
of thyroid hormones are bound forms, and the major carrier
O R I G N A L A R T I C L E
Age, Gender, and Seasonal Effects on Thyroid Profile Vol. 12 (1), June 2021
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R A D S J . B i o l . R e s . A p p l . S c i . 18
of bound forms of T3 and T4 is thyroid binding globulin,
whereas a small amount is carried out by transthyretin and
albumin2. Free form is the active form of both hormones
and free T3 (FT3) is more active than free T4 (FT4)3. The
FT4 is involved in the control mechanism of thyroid
secretion and both FT3 and FT4 are indicators of thyroid
health of an individual4. These hormones are involved in
growth and metabolism of the body, therefore, in the
absence of thyroid hormones, the metabolism is decreased
and BMR fall to 50% below the range of normal5. Thyroid
hormones are very important in brain development6. Iodine
and a protein known as thyroglobulin are required for the
synthesis of T3 and T4 from the thyroid gland. Different
factors like age, sex, body weight, nutritional, climate and
health and disease condition effect the production of T3
and T47. The Thyroid Stimulating Hormone (TSH) which is
also called thyrotropin is released from the anterior
pituitary. TSH controls the production of T3 and T4 from
the thyroid gland through a negative feedback
mechanism7. TSH itself is regulated by Thyroid Releasing
Hormone (TRH) from the hypothalamus, by positive
feedback mechanism8. TSH measurement can accurately
assess the functions of the thyroid gland and it is used as
a screening test for thyroid disorders9.
In patients with normal pituitary function, an accurate
inverse association between free FT4 and the logarithm of
TSH can be calculated across the range of primary thyroid
disorders. According to the logarithmic response in the
concentration of TSH to variations in FT4 levels, TSH
measurement gives a more accurate estimation of thyroid
gland health than thyroid hormones measurement10.
Reference range for TSH is 0.5-4.5mU/L11. The application
of this reference normal range for thyroid function of all
normal populations has been much discussed over the last
20 years12. The normal reference range for FT4 is 0.89-
1.76ng/dL and FT3 is 2.3-4.2ng/dL11. Age influences T3,
T4 and TSH concentrations. It has been observed that the
tendency to develop auto-antibodies against the thyroid
gland and its components are gradually increased with
age, making people more prone to thyroid disorders.
Higher incidences of thyroid disorders are observed in
people exceeding 40yrs of age13. The variations in thyroid
hormone levels have also been observed in different
genders14. Asian women are involved in many activities
and they have more domestic responsibilities, therefore
malnutrition among poor and illiterate women and in their
children are more prevalent. They are at high risk to
develop goiter, anaemia and other disorders. The
decrease in the concentration of thyroid hormones with age
has been observed in both sexes, but the deprivation of
thyroid hormone is more in women than men15, 16. The
seasonal effect on T3, T4 and TSH has also been
observed. T3 and T4 levels in autumn and winter were
higher than in spring and summer17. In common clinical lab
practices here in Pakistan, almost a single reference value
of thyroid profile is applied for both genders, without the
consideration of age and seasonal variations. This study
was carried out to analyze age, gender and season related
variations in thyroid profile in adults with normal thyroid
functions, to provide sound data to a clinician to consider
such factors when interpreting the thyroid profile results.
M A T E R I A L A N D M E T H O D S
Required data for this cross sectional study was obtained
from Jan 2018 to Jan 2019 from Pathology Department,
Quaid-e-Azam Medical College, Bahawalpur. During one
year, a total of 1034 patients attended the pathology lab for
the thyroid profile (TSH, FT3 and FT4) test. In this study,
only data of those patients were collected whose TSH was
within the normal reference range (0.5-4.5mU/L)11. We
found the data of 418 subjects from 16 to 75 years of age,
included 196 females and 222 males.
Inclusion Criteria
Data of all patients with TSH in the normal reference range
(0.5-4.5mU/L) from Jan 2018 to Jan 2019 were included in
this study.
Exclusion Criteria
The patients with hyper or hypothyroidism, those who were
on medication for hyper or hypothyroidism, and those less
than 16 years were excluded from the study.
Measurements
Acess2, Beckman Coulter, a sophisticated fully automated
immunoassay analyzer was used for the measurement of
thyroid function tests. Test results of thyroid profile (TSH,
FT3 and FT4) of these subjects with age, sex and season
were statistically analyzed to explore the age, gender, and
seasonal variations. Four seasons were considered in one
year cycle, winter from Dec to Feb, spring from March to
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May, summer from June to Aug, and the autumn period
from Sep to Nov. Therefore, to present the seasonal
variations in thyroid profile, the obtained data were
distributed into four seasons according to the date of test
reports.
R E S U L T S
In our study, a total of 418 subjects was selected. The
frequency distribution according to age and gender is given
in Table 1, and gender wise comparison of the thyroid is
given in Table 2.
Two sample t-test was used to compare TSH, FT3 and FT4
between male and female groups. TSH and FT4 levels
were significantly different in both groups with a p-value
<0.05. FT3 levels between both groups were not
significantly different with a p-value >0.05. Age wise and
seasonal variations were presented in charts. Variations in
thyroid profile in males in different age groups were
presented in Fig. 1.
TSH levels were comparatively low in <20 years and high
in >60 years of age. FT3 levels were high in 20 to 60 years
of age, while FT4 levels were at a peak in <20 years of age
group and were low in >60 years of age group. Variations
in thyroid profile in a female with age groups were
presented in Fig. 2.
Table 1. Frequency Distribution According to Age and Gender.
Gender <20 year 20-40 41-60 >60 Total
Males 38 48 65 71 222
Females 29 44 55 68 196
Table 2. Gender wise Compression of Thyroid Profile.
Gender TSH (mU/L) FT3 (ng/dL) FT4 (ng/dL)
Male (222) 1.59 ± 1.2 2.4 ± 1.04 1.48 ± 0.48
Female (196) 2.11 ± 1.54 2.48 ± 0.8 1.33 ± 0.50
p- value 0.0002 0.3754 0.0018
Figure 1. Variations in thyroid profile of males in different age groups.
Age, Gender, and Seasonal Effects on Thyroid Profile Vol. 12 (1), June 2021
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Figure 2. Variations in thyroid profile of females in different age groups.
In females, TSH levels were low in <20 years and high in
>60 years age groups, while high levels were observed in
20 to 60 years of age. The highest FT3 levels were seen in
the>60 years of age group while there was little difference
in other age groups. FT4 mean levels in the <20 year age
group were significantly high. We observed a negative
relationship between TSH and FT4 in all groups of both
genders. Seasonal variations in all participants were
presented in Fig. 3.
Subjects were divided into four groups according to the
date of test result reports. TSH mean value was high in
winters and low in the summer season. FT3 levels were
also high in winters and comparatively low in autumn. FT4
levels in all four seasons were slightly different with
considerably low levels in winters.
Figure 3. Seasonal variations in thyroid profile.
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R A D S J . B i o l . R e s . A p p l . S c i . 21
D I S C U S S I O N
Iodine deficiency disorders (IDDs) are commonly prevalent
in developed and less-developed countries18. Pakistan has
overcome this problem to some extent but still, there are
some areas, where the IDDs are present with high
frequency. We need some serious steps to improve IDD
control program19. Iodine deficiency is the main cause of
hypothyroidism in both genders as well as in children and
elderly people20. Thyroid functions are decreased with the
increase of age17. The present study was conducted to
explore the effect of age, gender, and season on thyroid
profile. Gender wise comparison of thyroid profile (Table 2)
suggests that TSH levels were significantly higher in
females than the males, and FT4 levels were higher in
males as compared to females. FT3 in both genders was
not statistically different with a p-value of 0.375. Our study
presented the picture of slightly decreased thyroid
functions in females, similar findings about the variations in
thyroid hormone in two sexes were in accordance with
previous work by Razzak et al21 and Chaurasia et al.
201122. There is already evidence for the decrease of
thyroid functions during menstrual abnormalities. Elevated
TSH level in one of eight females during child bearing age,
high prevalence of hypothyroidism that is 4.8% in females,
and higher tendency towards primary hypothyroidism of
females with the increase of age support our findings23-25.
Some other studies also are in favor of our high FT4 results
in males, according to the findings of these studies, male
sex hormones increases the level of Thyroxin Binding
Globulin (TBG), which leads to increase in level of T417, 22.
Age-related variations were given in Fig. 1 for the male
group and Fig. 2 for females. In <20 years age group of
both genders, TSH level was comparatively low, whereas
FT4 was higher than all other age groups of both genders
except >60 year age group of males, where TSH was low.
A study carried out in India during 2011 also reflects similar
findings of>60 years male group22. In females of >60 years
of age group, the TSH level was significantly high with low
FT4, which indicates a decrease in the thyroid functions of
females after menopause and with an increase of age26 as
well as a high prevalence of subclinical and overt
hypothyroidism in females of advance age27.
Seasonal variations in the concentration of TSH, T3 and T4
is given in Fig. 3, which presents a higher level of TSH in
winters than in summers, while T3 is nearly similar in all
seasons but slightly higher in winters and slightly lower in
autumn. T4 is similar in all seasons but slightly lower in
winters and slightly high in summers. Summer and winter
results are comparable with the findings of Chaurasia et al.
201122 and are in accordance with a study done by Khan
et al. 200128. The season in which thyroid tests were
performed was independently related to the transition from
euthyroid status to subclinical hypothyroid status.
Seasonal variations in TSH concentration should be taken
into account before deciding on treatment for subclinical
hypothyroidism, especially in areas with a wide range of
annual temperatures29. The climatic components
contributed to the slight variance in hormone levels during
the different seasons and the effect was mainly on the
peripheral conversion of FT4 to FT3, rather than on the
pituitary-thyroid axis, leading to slightly more FT3 high in
winters30. Seasonal changes in TSH occurred
independently of the changes in peripheral thyroid
hormone, gender, age, and environmental temperatures.
The underlying physiological mechanism remain uncertain
and specific studies are necessary to clarify its impacting
role in humans31.
Serum-free T3 was significantly correlated with the
previous month's average outside temperature. Serum
TSH did not show any correlation with the average
temperature of the month or with free T3. A low level of free
T3 serum in winters suggests that the elimination of thyroid
hormones is accelerated by the cold, as described in Polar
T3 syndrome. Elevations in serum TSH are not taken into
account by changes in circulating thyroid hormones,
suggesting that other influences, such as photoperiod may
mediate this fluctuation32.
C O N C L U S I O N
From our study, it is concluded that gender, age, and
seasons have a significant effect on thyroid profile, and
females have high TSH levels as a whole, especially >60
years of age, while TSH is high in both genders during
winters. These factors should be observed while
interpreting the lab results of the thyroid profile.
C O N F L I C T S O F I N T E R E S T
None.
Age, Gender, and Seasonal Effects on Thyroid Profile Vol. 12 (1), June 2021
ISSN (Print): 2305 – 8722 ISSN (Online): 2521 – 8573
R A D S J . B i o l . R e s . A p p l . S c i . 22
F U N D I N G S O U R C E
None.
A C K N O W L E D G M E N T S
We are thankful to Professor Dr. Asma Shaukat, Head of
Pathology Department, Quaid-e-Azam Medical College,
Bahawalpur, for technical support.
L I S T O F A B B R E V I A T I O N S
FT3 Free T3
FT4 Free T4
T3 Triiodothyronine
T4 Thyroxin
TSH Thyroid Stimulating Hormone
TRH Thyroid Releasing Hormone
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