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Year : 2013 | Volume : 1 | Issue : 2 | Page : 37 - 40  


Original Articles
Thyroid Status in Relation to Age and Gender – A Cross Sectional Study

Amrut A. Dambal1, Samata Padaki.2, Anita Herur3, Sangappa V. Kashinakunti4, Manjula R5, Gurupadappa K6

1Assistant Professor, Dept of Biochemistry, 2Assistant Professor, Dept of Physiology, MRIMS, Hyderabad, AP., 3Associate Professor, Dept of Physiology, SNMC, Bagalkot, Karnataka, 4Associate Professor, Dept of Biochemistry, SNMC, Bagalkot, Karnataka, 5Assistant Professor, Dept of Community Medicine, SNMC, Bagalkot, Karnataka, 6Professor and Head, Dept of Biochemistry, SIMS, Shimoga, Karnataka

 

Abstract:

Background: Thyroid disorders have become much more common in the present days and so are its resultant complications or sequelae. There are marked variations in thyroid function with age and sex, evident in all of the in vitro hormone and protein measurements.

Objective: To correlate the thyroid status with age and gender.

Methods: 500 subjects of all age group and both genders from the general population of Bagalkot, Karnataka were included in the study. Subjects suffering from thyroid disorders were excluded. Non-Fasting venous samples were collected from all the subjects, serum T3, T4, and TSH levels were estimated by microplate immunoenzymometric assay. Statistical analysis was done by ANOVA and unpaired ‘t’ test.

Results: It was observed that T3 and T4 levels declined but TSH levels raised, as the age advanced. T3 and T4 levels were lower and TSH levels higher in female subjects as compared to male subjects, in the age group of 21 – 40 years.

Conclusion: The variability in the thyroid status has to be borne in mind during evaluation and treatment of thyroid disorders.

Key words: Age variation; Gender variation; Tri-iodo-thyronine (T3); Tetra-iodo-thyronine (T4); Thyroid stimulating hormone (TSH).

Corresponding Author: Dr. Samata Padaki, Assistant Professor, Dept of Physiology, MRIMS, Hyderabad, AP.    Email: drsamatapadaki@gmail.com

 

Introduction:

Thyroid is one of the larger endocrine glands[1] located immediately below the larynx on either side of the trachea. The principal hormones of thyroid gland are tetra-iodo-thyronine or thyroxine (T4) and tri-iodothyronine (T3). Thyroid stimulating hormone (TSH) is the anterior pituitary hormone regulating thyroid functions. In normal individuals, the thyroid hormones and TSH have physiological variations according to age[2], sex[3], nutrition[4] and race. The thyroid undergoes slight “physiological” changes with aging, either as a result of its participation in the senescence process or as an effect of changes in other systems.[5]

Sometimes, the interpretation of thyroid function tests is also difficult in aging individuals, because true “physiological” age-associated changes cannot be easily distinguished from the alterations secondary to subclinical thyroid disease or acute or chronic non-thyroidal illness and or drugs often taken by elderly patients. Human aging is often associated with an increased prevalence of thyroid autoantibodies that may not be the consequence of the aging process by itself but rather an expression of age-associated disease. Thyroid diseases in older patients differ from those observed in younger patients in their prevalence and clinical expression and their treatment often deserves special attention because of the increased risk of complications. Variations from euthyroid status affects all physiological systems and effects on the cardiovascular system are more pronounced.[6]   Changes in thyroid status are also associated with changes in autonomic regulation of the cardiovascular system.[7]

The definition of “physiological” age-associated thyroid changes and the correct understanding of these modifications are not merely speculative, since it greatly helps in differentiating “physiological” alterations from subclinical thyroid disease and in resolving the question of treatment of uncertain clinical situations.

Very few studies have been done to assess the physiological variations of thyroid hormones in India. Hence, we took up a study to compare the thyroid levels in different age groups, and to correlate them with the opposite gender, in apparently healthy individuals of Bagalkot, Karnataka.

Material and Methods:

Ethical clearance was obtained for the study by the Institutional Ethical Committee, SNMC, Bagalkot. An initial survey was done to list out 650 apparently healthy individuals from the general population residing in and around S.N.Medical College and Hospital, as it is served by the Institute. 175 males and 350 females in different age groups ranging from the newborn baby up to 80 year old were chosen using simple random sampling by lottery method, between June 2010 and May 2012 from the community. Informed consent was obtained from each of the subject. A thorough clinical examination was performed and 5 male and 20 female subjects were excluded as they had personal or family history of thyroid diseases like goiter, hypothyroidism, hyperthyroidism, or intake of medications which would interfere with the thyroid status. Also the presence of any fever, acute or chronic illnesses such as renal failure, malignant neoplasm, hepatic cirrhosis and diabetes mellitus and other diseases known to affect thyroid functions were ruled out. In this way, total 150 out of 650 subjects were excluded and referred to teaching hospital for further treatment. The procedure was explained to the remaining 500 subjects. Blood samples were obtained from antecubital vein of the subjects in the morning hours from 9am to 10am. The blood sample of 3 newborns was taken from different veins by the trained NICU staff nurses using 26 gauge needles in the hospital during their stay. The samples were collected between 4th to 7th days of their birth. 8 out of 83 women in the age group of 21-40 years were pregnant but their gestational period was not considered.

The blood sample was collected from non-fasting subjects as fasting causes a rapid fall in serum T3 concentration. 3 ml of venous blood sample was collected in plain vacutainer which was allowed to stand for 15 minutes to allow clotting. The serum was separated by centrifugation at 3000 rpm for 10 minutes. Serum T3, T4 and TSH levels were estimated by ELISA using Monobind. Inc kits in all the age groups.

The subjects were classified into five groups according to their age (Table 1).

 

Table 1: Classification of Subjects according to Age group.

Age group (years)

Number of subjects

0 – 10

50

11 – 20

120

21 – 40

130

41 – 60

140

61 – 80

60

 

Statistical analysis was made by ANOVA and unpaired ‘t’ test using SPSS (version 15.0). Serum T3, T4 and TSH levels of all the age groups were compared irrespective of the gender. Then serum T3, T4 and TSH levels were correlated between 70 male and 60 female adults within the age group of 21 – 40 years and the results were tabulated.

Results:

All 500 subjects were classified into different age groups (Table 1). On comparing the different thyroid hormone levels in different age groups, we found out that, T3 levels were more in the first decade, reduced in the 2nd and increased progressively in the later decades of life. On contrary, T4 levels were low in the first decade, increased in the second decade and progressively decreased in the later age groups. There was a statistically significant variation in T4 values with respect to different age groups on applying ANOVA test. TSH levels were higher in the first decade of life while there was a slight decrease in the second decade and it remained stable in the later decades but slightly on a higher side in the fifth decade (Table 2).

Table 2: Thyroid profile in different age groups

Age (years)

T3 (ng/ml)

T4 (µg/dl)

TSH (µIU/ml)

0 – 10

1.68 ± 1.2

6.12 ± 3.4

0.8 ± 3.1

11 – 20

0.81 ± 1.01

10.5 ± 4.57

1.3 ± 5.2

21 – 40

1.3 ± 0.58

9.1 ± 3.1

2.2 ± 15.8

41 – 60

1.4 ± 0.95

8.7 ± 3.2

2.3 ± 4.3

61 – 80

1.62 ± 0.24

7.1 ± 2.3

2.7 ± 2.9

F

0.838

3.06

0.01

P

0.36

0.08*

0.91

                        *Statistically significant

On correlating various thyroid hormone levels in both males and females lying within the age group of 21 – 40 years, we found out that there was a significant difference in the T3, T4 and TSH levels. T3 and T4 levels were higher in males whereas TSH was more in females (Table 3).

Table 3: Thyroid profile with respect to gender in the Age group of 21 – 40 years.

Gender

T3 (ng/ml)

T4 (µg/dl)

TSH (µIU/ml)

Male

1.4 ± 1.1

9.6 ± 4.1

2.7 ± 1.7

Female

1.2 ± 0.7

7.06 ± 3.1

3.8 ± 3.09

‘p’ value

< 0.05*

< 0.05*

< 0.05*

*Statistically significant

 

Discussion:

Thyroid function probably decreases with senescence and the decrease is probably the result of the aging process.[8,9,10] It is observed in several studies that during a normal human life span, serum T3 is low at the time of birth, increases markedly during early infancy, remains high during childhood and is reduced after adolescence, then remains stable until late middle age and ultimately decreases in old age.[9,10] Our study evaluated thyroid status in different age groups and in different gender.

In our study, the highest mean T3 value (1.68 ng/ml) was observed in the children (0-10 years), it fell to 0.81 ng/ml in adolescents and in adults and in elderly people it was 1.4 ng/ml and 1.62 ng/ml. At birth, serum total T3 levels are high because of maternal estrogen induced increase in serum TBG. Total T3 rise in first few hours of life and decline gradually until the age of 15 years. Similar findings of progressive decrease of T3 levels from childhood to adolescence were observed in several studies.[10,11] Some attributed these values to the progressive change in the relative thyroid output of T3 and T4 and not due to a decrease in Thyroid Binding Globulin (TBG), because there is no significant change in the levels of serum TBG concentration in young children and adults.[10,12] However, others observed that this change in T3 levels was due to decreasing TBG levels since T3 like T4 is largely transported bound to TBG; the fall in mean T3 and TBG approximated 29% and 30% respectively between 1 to 15 years in their studies.[13,14,15] In the present study also, the mean T3 value in adolescents (11-20 yrs) fell to 0.81ng/ml from 1.68 ng/ml in children (1-10 yrs). It has been observed that increased metabolic activity during infancy and childhood leads to increased peripheral utilization of thyroid hormones.[16]

There was significant difference in the levels of T3 between males and females in the age group of 21 – 40 years. T3 levels were more in males (1.4 ng/ml) as compared to females (1.2 ng/ml), which are consistent with stimulatory and suppressive effects of estrogen and androgens respectively on TBG serum concentrations.[9,10] This is in accordance with the studies done by Dalla Valle and Rossi. Some of the studies done previously by other authors contradicted these findings.[13,14,15,16] However, further studies done to correlate the relationship between thyroid growth (by ultrasonography) chronological age, and body surface area (BSA) showed varied results. It has been observed that marked changes occur in thyroid function during puberty as an adaptation to body and sexual development. Adaptation of the hypothalamic–pituitary–thyroid axis in response to increased energy expenditure may be the reason. A prepubertal surge of TSH between 9.0 and 9.5 years, followed by a transient increase in circulating thyroid hormones (T4 and T3) may account for this adaptation.[15] Several authors have identified sex steroid receptors in normal and pathological human thyroid tissues and suggested that estrogens might have a positive influence and androgens a rather restraining influence on the thyroid gland itself.[17,18]

Our study showed a progressive decrease in serum T4 concentration with mean T4 level of 6.12 µg/ml in children; 10.5 µg/ml in adolescents; 9.1 µg/ml in adults and 7.1 µg/ml in elderly. At birth, serum total T4 levels are high because of maternal estrogen induced increase in serum TBG. Total T4 rise abruptly in first few hours of life and decline gradually until the age of 15 years. In our study, though the mean T4 level in adolescents was higher than that of children, it decreased further in adults (P < 0.08). These results did not match with the results of some of the studies, which reported a gradual decrease of T4 levels from infancy till they reached lowest level towards the end of the adolescent growth period suggesting that during adolescence there is an increase in the cellular uptake of thyroxine because of increase in muscular mass, which coincides with an increase in the Basal Metabolic Rate (BMR).[10] Present study showed that the mean T4 concentration in the elderly group was lower than that of adults, and the difference was statistically significant. Similar age related decrease in serum T4 concentration in older people was reported by other studies. This decrease could be due to a primary retardation of hormone metabolism within the cell i.e. these changes could be a consequence of the hypo-metabolism associated with aging.[11,12]

Our study showed a significant difference in adult male and female T4 values. The mean T4 level in the adult males (9.6 µg/ml) was more than that of females (7.06 µg/ml), and the difference between the two was statistically significant. This is in relevance to other studies, which also found significant difference in serum T4 concentration in male and female adults.[9,10] This is explained by increased binding of T4 with TBG in adult females.

In the present study, mean TSH value in the children was 0.8 µIU/ml. TSH surges immediately after birth to 25 to 160 µIU/L, declines back by three days and reaches adult values by few weeks of life. In our study only 3 newborns were included whose thyroid status was not considered separately. The mean TSH value increased to 1.3 µIU/ml in adolescents was 2.2 µIU/ml in adults and 2.7 µIU/ml in the elderly. There was no significant difference between TSH values in adults and elderly age groups except between the children and adolescents. Similar results were reported in other studies.[19] It is possible that with increasing age there occurs a decrease in the sensitivity of the pituitary to slight deficiencies of thyroid hormone, so that more marked deficiency than younger individuals would be required to elicit hyper secretion of TSH.

It was observed that TSH values increased significantly in females over 60 years of age whereas males had stable TSH levels that were slightly higher than the females before sixty years and lower thereafter.[9] In our study, the mean TSH level of males and females in the age group 21 – 40 showed significant difference. Estrogens cause increased secretion of TBG. On the other hand, TBG levels are depressed by androgens.[20]

During pregnancy, there is increase in thyroid-binding globulin (TBG) secondary to an estrogenic stimulation and reduced hepatic clearance of TBG. Levels of bound proteins, total thyroxine, and total tri-iodothyronine are increased. This begins early in the first trimester, plateaus during mid gestation, and persists until shortly after delivery. Free T4 and T3 increase slightly during the first trimester in response to elevated HCG, decline in third trimester. HCG intrinsically activates TSH receptors to release TSH and thereby T3 and T4 by behaving like a thyrotropic hormone which could also be a reason for increase in the activity of T3 and T4 during the first trimester of pregnancy. In our study only 8 out of 83 women in the age group of 21-40 years were pregnant and their gestational period was not considered. Hence, the statistical analysis in evaluating physiological variations of T3, T4 and TSH among pregnant women in comparison with other women in the same age group was not considered.

Limitations:

Following were the limitations of our study.

  1. Less number of newborns and pregnant women was the main drawback for not considering the status of infancy and pregnancy in evaluating thyroid profile.
  2. Seasonal variation was not considered.
  • As it was a population based study and apparently healthy subjects were chosen, the effect of euthyroid sickness syndrome on thyroid profile was not considered.

 

Conclusion:

The activity of the thyroid gland depends on the age as well as gender. Hence, it can be concluded that this variability in the thyroid status has to be borne in mind during evaluation and treatment of thyroid disorders, and it becomes very essential that clinical laboratories should frame normal values for different age groups in order to avoid diagnostic misinterpretations and therapeutic failures.[10]

To summarize our observations, serum T3 levels are high in children and decline progressively with age while serum T4 levels decline significantly only from adolescent to adult group. The serum TSH levels, on the other hand, increase from children to adults. There is significant difference in the mean serum T3, T4 and TSH values in males and females in adult age group.

 

References:

  1. Barret K.E, Barman S.M, Boitano S, Brooks H.L: “Ganong’s Review of Medical Physiology”, 23rd edition, The McGraw Hill Companies, Inc;2010: 301.
  2. Blanco AC, Dehesa EM, Longas AF, Aizpun JIL, Lazaro RM. Reference values for thyroid hormones, thyrotropin and thyroglobulin in healthy children of Zaragoza. Anales Espanoles De Pediatria 1999;51(4):361-8.
  3. Marwaha RK, Tandon N, Desai A, Kanwar R, Grewal K, Aggarwal R. Reference range of thyroid hormones in normal Indian school-age children. Clin Endocrinol (Oxf) 2008;68(3):369-74.
  4. Jean D, Wilson MD, Daniel W, Foster MD. William’s Textbook of Endocrinology, 8th edition Philadelphia: WB. Saunders Co;1992:358-80.
  5. Latrofa F, Ricci D, Montanelli L, Rocchi R, Piaggi P, Sisti E, et al. Thyroglobulin autoantibodies in patients with papillary thyroid carcinoma: Comparison of different assays and evaluation of causes of discrepancies. J Clin Endocrin Metab. 2012;97(11):2012-406.
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  9. Lipson A, Nickoloff EL, Tah HH, Kasecamp WR, Drew HM, Shakir R et al. A study of age-dependent changes in thyroid function tests in adults. J Nuclear Medicine 1979;20:1124-30.
  10. Westgren U, Burger A, Ingemansson S, Melander A, Tibblin S, Wahlin E. Blood levels of 3,5,3'-triiodothyronine and thyroxine: Difference between children, adults and elderly subjects. Acta Med Scand 1976;200:493-5.
  11. Hishikawa M, Inada M, Naito K, Ishii H, Tanaka K, Mashio Y et al. Age related changes of serum 3,3’ iiodothyronine, 3,5’-diiodothyronine and 3,5 - diiodothyronine concentrations in man. J Clin Endocrinol Metab 1981:52;517-22.
  12. Anderson S, Pederson KM, Bruun NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of sub clinical thyroid disease. J Clin Endocrinol Metab. 2002;87:1068-72.
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Acknowledgement: I sincerely thank the Management, our Dean Dr. Chandrakant Shirole and staff of Department of Biochemistry, MRIMS for encouraging me in this work. I also thank the staff of S.N. Medical College and Hospital for allowing me to carry on the work. I immensely thank Dr. Prashant Kokiwar for his valuable suggestions.

Source of Support: Nil. Conflict of Interest: None.





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