Assessment Of Thyroid Hormones In Thyroid Disorders Biology Essay

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Thyroid dysfunction is one of the major public health problems in Nepal. Laboratory measurements of T3, T4 and TSH are crucial in helping clinicians to diagnose thyroid abnormalities. Historically, hypercholesterolemia and Low Density Lipoprotein cholesterol levels have been found to be associated with subclinical hypothyroidism, therefore assessment of altered lipid profile plays a supportive role in thyroid dysfunction. The aim of the study was to find out the variations of thyroid hormones and lipid profile in hyperthyroidism, subclinical hypothyroidism and hypothyroidism.

Material and methods

It was a hospital based retrospective study carried out from the data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st July, 2009 and 30th June, 2010. The variables collected were age, sex, total T4, total T3, TSH, fT4, total cholesterol and triglycerides.

Result

122 out of the 365 subjects selected for the study had some form of thyroid disorder. Among these 122 cases, 40 had hyperthyroidism, 42 had hypothyroidism and the remaining 40 were diagnosed to have subclinical hypothyroidism. Our results showed that all the variables (T3, T4, TSH, fT4, total cholesterol and triglycerides) except for age were statistically significant when compared to cases. The frequency of thyroid disorders was much higher in females as compared to their male counterparts.

Conclusion

Thyroid dysfunction is found to be common across all age groups and shows a strong female preponderance in Pokhara Valley. Total cholesterol is escalating in Hypothyroidism and Subclinical Hypothyroidism cases. Therefore, timely screening and check up is a must in order to curtail the problem of undiagnosed cases, giving specific consideration to patients who have high artherogenic profile.

Key Words: Hyperthyroidism, Hypothyroidism, Subclinical Hypothyroidism, Thyroid hormones, Lipid profile

Introduction

Thyroid hormones are crucial for growth and to regulate the metabolism of protein, carbohydrates and fat. Thyroid disorders are commonly separated into two major categories, hyperthyroidism and hypothyroidism, depending on whether serum thyroid hormone levels (T4 and T3) are increased or decreased, respectively and it can be due to congenital factors, genetic predisposition, inadequate levels of dietary iodine intake, pregnancy, radiotherapy, viral infection, surgery, underlying disease such as infiltrative disorders, or autoimmunity 1-3. Graves Disease (diffuse toxic goitre) is common cause of hyperthyroidism due to overactivity of the immune system (autoimmunity). Other causes are sub-acute (painful, viral) thyroiditis, silent thyroiditis (painless or postpartum thyroiditis) and toxic multinodular goiter 4. In the UK, hyperthyroidism has a prevalence of around 2.7% in females which is approximately 10 times more than the prevalence in males. Thyroid disorders remain undiagnosed in nearly 0.5% of the female population in the UK 5. In a community survey comprising of 1210 participants (age≥ 60 years) from the UK, the prevalence of undiagnosed overt hyperthyroidism was very low 6. In a similar study conducted in Sweden, out of 1442 participants (age ≥ 60 yrs), only 2% of subjects were diagnosed to have thyrotoxicosis 7. The leading cause of primary hypothyroidism in iodine deficient areas is Hashimoto's disease (chronic autoimmune thyroiditis) 8. Pathophysiologically, there is cell-mediated and antibody-mediated destruction of the thyroid gland 9. Other causes are mainly due to iodine deficiency, over treated Graves disease, anti-thyroid drugs and radioactive therapy. The prevalence of subclinical hypothyroidism ranges from 1% to 10% worldwide, with prevalence in women above 60 years of age approaching 20% in some reports 10. In the United States National Health and Nutrition Examination Survey (NHANES III), the prevalence of overt hypothyroidism was found to be 0.3%; prevalence of subclinical hypothyroidism was found to be 4.3% 11. The annual incidence of primary hypothyroidism in women is 3.5 per 1000 and in men 0.6 per 1000 in the UK 12. Women are 10 times at higher risk of developing hypothyroidism compared to men, with the difference being significant after thirty-four years of age. This is because the symptoms of hypothyroidism and menopause go hand in hand, leaving behind more chances of missing hypothyroid cases 13. Pregnant women are also at higher risk of developing thyroid dysfunction 14. Nepal is a mountainous landlocked area, situated far away from the sea. The geographical placement of the country along with high annual rainfall leads to low soil iodine content. These factors lead to a very high incidence of iodine deficiency disorders. The detection of hyperthyroidism and hypothyroidism in hospital based thyroid screening of suspected patient in eastern part of Nepal was reported to be 13.68% and 17.19% respectively in 2002 and both same 8.3% in 2010 15.

Both hypothyroidism and hyperthyroidism have potentially fatal systemic manifestations. Therefore, accurate and timely diagnosis of thyroid abnormalities is critical for clinicians as well as medical laboratories worldwide for appropriate management. Laboratory measurements of T3, T4 and TSH are crucial in helping clinicians to diagnose thyroid abnormalities. Historically, hypercholesterolemia and Low Density Lipoprotein cholesterol levels have been found to be associated with subclinical hypothyroidism, therefore assessment of altered lipid profile plays a supportive role in thyroid dysfunction 16. The aim of the current study was to find out the variations of thyroid hormones and lipid profile in hyperthyroidism, subclinical hypothyroidism and hypothyroidism.

Materials and Methods

It was a hospital based retrospective study carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st July 2009 and 30th June 2010. The variables collected were age, sex, T3, T4, TSH, fT4, total cholesterol and triglycerides.

Analysis of T3, T4, TSH and fT4 levels was done by ELISA (HUMAN) 17-19. Estimation of total cholesterol and triglycerides was done by semi autoanalyser Human 3500, Germany 20. The commercially available kits of Human, Germany were used for all biochemical parameters.

Selection of Subjects:

Inclusion Criteria: Patients with abnormal thyroid profile

Exclusion Criteria: Patients having hepatic or renal dysfunction; history of heart failure, diabetes mellitus, stroke or ischemic heart disease; malignancy; alcohol or drug abuse were excluded from the study. Patients who had used any medications (within the previous six months) that might have contained corticosteroids, antifolates and lipid lowering agents were also excluded from the study.

The data collected was analyzed using Excel 2003, R 2.8.0, Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and EPI Info 3.5.1 Windows Version. Z-test was used to compare the significance difference between two variables. A p-value of < 0.05 (two-tailed) was used to establish statistical significance.

Result

122 out of the 365 subjects selected for the study had some form of thyroid disorder. Among these 122 cases, 40 had hyperthyroidism, 42 had hypothyroidism and the remaining 40 were diagnosed to have subclinical hypothyroidism.

Our results showed that all the variables (T3, T4, TSH, fT4, total cholesterol and triglycerides) except for age were statistically significant when compared to cases. The TSH values were markedly increased while T4 and T3 values were found to be less than the reference range in cases of hypothyroidism. The increase in TSH levels with fT4 in reference range defines the grading of subclinical hypothyroidism. Elevated levels of T3 and T4 associated with decreased TSH levels were found in cases of hyperthyroidism. In hypothyroidism and subclinical hypothyroidism, the total cholesterol values were moderately increased and there was no gross derangement of TG levels. In hyperthyroidism, total cholesterol and triglycerides levels were mildly decreased but remained within the reference range.

Table 2: Comparison of gender in controls and cases

Variable

Male

Female

P value

hyper

10

30

0.001**

hypo

6

36

0.001**

schypo

6

34

0.001**

Normal

58

185

0.001**

** Statistically significant (p value<0.05)

The above results show that the frequency of developing thyroid disorders is much higher in females in comparison to males.

Table 3: Gender wise comparison of biochemical variables in cases

Variables

Cases

Male

Female

P value

Mean ± SD

Mean ± SD

Age

hyper

33.00 ±20.07

35.47 ± 15.61

0.729

hypo

53.33 ± 21.80

38.81 ± 13.26

0.168

schypo

56.83 ± 25.57

35.94 ± 13.95

0.10

T3

hyper

2.49 ±.77

2.33 ± 0.74

0.58

hypo

0.40 ± 0.10

0.37 ± 0.20

0.66

schypo

0.86 ± 0.29

1.02 ± 0.29

0.26

T4

hyper

14.68 ±4.76

13.97 ± 3.36

0.67

hypo

2.65 ± 0.53

2.13 ± 0.88

0.08

schypo

5.86 ± 0.60

6.33 ± 1.24

0.16

TSH

hyper

0.34 ±0.11

0.32 ± 0.10

0.62

hypo

14.70 ± 5.40

21.48 ± 11.89

0.03**

schypo

19.98 ± 9.00

15.34 ± 8.31

0.28

fT4

hyper

2.5 ± 0.54

2.7 ± 0.47

0.41

hypo

0.45 ± 0.25

0.58 ± 0 .30

0.28

schypo

1.10 ± 0.60

1.15 ± 0.22

0.25

TCHO

hyper

145.4 ± 10.12

142.37 ± 9.25

0.42

hypo

265.00 ± 23.15

281.69 ± 35.89

0.16

schypo

283.50 ± 16.15

265.12 ± 22.25

0.04**

TG

hyper

84.40 ± 15.98

88.30 ± 19.18

0.53

hypo

152.17 ± 42.16

171.14 ± 45.47

0.35

schypo

167.50 ± 67.85

176.74 ± 50.59

0.35

hyper M-10,F-30: Hypo M-6,F-36: schypo M-6,F-34

** Statistically significant (p value<0.05), T Cho (Total Cholesterol), TG (Triglycerides)

The results show that these variables of T3, T4, TSH, fT4, total cholesterol, and triglycerides do not have any statistical significance with respect to gender. Males and females had almost equal variation among the biochemical parameters and the respective values do not show any significant difference.

Discussion

Our study was to stress upon the essentiality of laboratory diagnosis before any further investigation or treatment for thyroid disorders. Low or undetectable serum thyrotropin (TSH) concentrations are a sensitive indicator of hyperthyroidism 21. No laboratory findings are specific for the diagnosis of hyperthyroidism. Our results showed low serum TSH (0.32 ± 0.10 mU/L), well below the reference range, along with raised serum fT4 (2.66 ± 0.48 pg/ml), in cases of hyperthyroidism that observed in other studies 22. Hyperthyroidism is associated with increased mortality in individuals over 60 years of age, particularly from circulatory incompetence and atrial fibrillation21. Other effects of hyperthyroidism include decreased systemic vascular resistance, reduced bone mineral density, increased cardiac contractility, cardiac output, heart rate, left ventricular mass to cause diastolic dysfunction (delayed relaxation) and atrial arrhythmias. In our study, the total cholesterol and TG values were lowered but remained within normal range in cases of hyperthyroidism. The values obtained were 143.12 ± 9.43mg/dl, 87.32 ± 18.31 mg/dl which were quite close to the values found by Abrams et al i.e.155±10mg/dl, 106±10mg/dl, of total cholesterol and TG respectively 23. The decrease in serum total cholesterol was due to increase in post-heparin plasma hepatic lipase activity 24.

Hypothyroidism was separated into either overt or subclinical disease. The most sensitive indicator for hypothyroidism was TSH, more than10 mU/l, along with reduced levels of T4 25. Our study showed significant low levels of T4 and T3 with raised TSH levels (20.5 ± 11.4 mU/L). Hypothyroidism can affect people of all ages. The mothers with very low serum T4 have higher incidence of still births, abortions and congenital abnormalities, contributing to the higher rate of perinatal deaths as T4 and T3 have strong modulating effect on the immune system. Decreased levels of T4 and T3 due to iodine deficiency during the first trimester could result in abnormal foetal development. Neurological cretinism is characterized by poor cognitive ability, deaf mutism, speech defects and proximal neuromotor rigidity 26. In hypothyroidism, there is increased absorption of cholesterol from intestines, decreased clearance of cholesterol and low density lipoproteins from plasma and decreased synthesis of bile acids from cholesterol in the liver 23. In our study, there was significant increase in the mean concentration of total cholesterol (279.31 ± 34.65mg/dl) and triglycerides (168.43 ± 45.02mg/dl) in cases of hypothyroidism. In a similar study done by Texeira at al in 2008 showed that hypothyroidism could significantly increase the levels of most of lipids, most importantly that of cholesterol and LDL 27. In contrast hyperthyroidism was not associated with plasma lipid variation 28. In another study with thyroid dysfunction, the mean and SD of cholesterol in hypothyroid subjects was 283 ± 53 mg/dl which were quite similar to our values 15. The increase in levels of serum total cholesterol and triglycerides were due to reduced activity of post heparin plasma hepatic and lipoprotein lipase in cases of overt hypothyroidism 24. Unlike increased serum cholesterol levels, triglyceride metabolism is not grossly deranged in hypothyroidism 29. So, abnormal lipid metabolism in hypothyroidism accelerates the process of atherogenesis and elevates cardiovascular risk 30. The increase in TSH levels with fT4 in reference range defines the grading of subclinical hypothyroidism 31. In our study, fT4 (1.15 ± 0.21 pg/ml) levels were in reference range and TSH levels (10.04 ± 1.46 mU/L) were moderately raised in cases of subclinical hypothyroidism. These values were quite close to values found in other studies i.e. TSH (11.43 ± 5.50 mU/L) and fT4 (1.05 ± 0.21 pg/ml) 29. Our results showed that the levels of total cholesterol was increased (257.88 ± 22.29mg/dl) while triglyceride levels were near the upper limit of the reference range (152.35 ± 53.55mg/dl). The serum total cholesterol was increased while serum triglyceride levels, activity of post-heparin plasma hepatic lipase and lipoprotein lipase were normal in cases of subclinical hypothyroidism 24. In other studies, total cholesterol and TG levels were 237.50±1.01mg/dl and 168.53±0.89mg/dl respectively in cases of subclinical hypothyroidism, somewhat similar to above mentioned results 31. Thus, it is seen that patients with thyroid dysfunction had significant reversible alterations in levels of serum total cholesterol and triglycerides.

Conclusion

Thyroid dysfunction is found to be common across all age groups and shows a strong female preponderance in Pokhara Valley. Total cholesterol is escalating in Hypothyroidism and Subclinical Hypothyroidism cases. Therefore, timely screening and check up is a must in order to curtail the problem of undiagnosed cases, giving specific consideration to patients who have high artherogenic profile.

Future Directions of the Study

Multi-centered randomized and population based studies is needed to get the association between hypothyroidism and cardiovascular disorders. The maximum randomized, placebo-controlled trials of iodine supplementation should be started such as salt iodization. Regular checkups of women >50 years old to avoid confusion as the symptoms of menopause and hypothyroidism are similar. Early screening is inexpensive and would prevent progression to hypothyroidism. The antenatal checkups (particularly in the first trimester) help in preventing the premature delivery and birth defects. Maternal iodine supplementation is necessary before or during pregnancy. Iodine deficiency continues to be a major problem in Nepal and demands a clear control strategy, combining ongoing iodine supplementation and education.

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