Assessment And Variations Of Thyroid Biology Essay

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Nepal being situated far away from sea, mountainous and receiving a high annual rainfall, contributes to low soil iodine content, has a rather high percentage incidence of iodine deficiencies disorders which contributes to hypothyroidism. The aim of the study was to find out the variations of thyroid hormones and lipid profile in different categories of thyroidism.

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 1 July 2009 and 30 June 2010. The variables collected were age, sex, total T4, total T3, TSH, fT4, total cholesterol and triglycerides.

Of the 365 subjects selected for the study, 122 had thyroid disorder. Among the 122 thyroid disorder cases, 40 were of hyperthyroidism, 42 were of hypothyroidism and the remaining 40 were diagnosed of subclinical hypothyroidism. The result showed that most of the variables T3, T4, TSH, fT4, total cholesterol, triglycerides except age were statistically significant when compared with cases and the frequency of predisposal to thyroid disorders were much higher in females when compared to the counterpart males.

Thyroid dysfunction is very common both in elderly and younger age groups 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.

Thyroid hormones are crucial for growth, use of energy and regulation of protein, carbohydrate and fat metabolism. Hyperthyroidism is known to be the most commonest disorder revealing a prevalence in the UK of around 2.7% in females which accounts approximately >10 times in males and around 0.5% of women still remains undiagnosed of thyroid disorders 1. In a finding based on community survey comprising of 1210 participants (age≥ 60 yrs) from UK, the prevalence of undiagnosed overt hyperthyroidism was very low 2. Where as in Sweden, out of 1442 participants (age ≥ 60 yrs) only 2% of subjects diagnosed of thyrotoxicosis 3. Hypothyroidism is more common among elderly females, having 15 to 20 times higher risk for developing the disease when compared to men and its incidence is 0.3 to 5 people /1000/yr in America.4 Women are at 10 times higher risk of hypothyroidism compared to men, with the difference being significant after thirty-four yrs of age because the symptoms of hypothyroidism and menopause goes hand in hand, leaving behind more chances of missing hypothyroid cases 5. Pregnant women are also at higher risk 6. About 6.5 million Americans have undiagnosed and underactive or subclinical hypothyroidism and majority would be at the risk of progression to overt hypothyroidism. The hypo and subclinical thyroidism patients are at the higher risk of developing atherogenic lipid profile. The replacement of thyroid hormone will lower down the increased total cholesterol and triglycerides levels. However, the atherogenicity does not change much in male patients according to the American association of clinical endocrinologists (AACE)7. The higher risk of cardiovascular disease is bound to be associated with patients who have thyroid disorders due to abnormal lipid metabolism. The increase TSH levels with fT4 in reference range defines the grading of subclinical hypothyroidism. The prevalence of subclinical hypothyroidism in the world ranges from 1% to 10% and women with ≥ 60 yrs of age approaching 20% in some reports.8 The major cause of hypothyroidism is hashimotos disease (chronic autoimmune thyroiditis) and other causes could be due to the iodine deficiency, overtreated graves disease, antithyroid drugs and radioactive therapy9.

Nepal being situated far away from sea, mountainous and receiving a high annual rainfall, contributes to low soil iodine content, has a rather high percentage incidence of iodine deficiencies disorders which contributes to hypothyroidism 10. The prevalence of hyperthyroidism and hypothyroidism was reported to be 13.68 and 17.19% respectively in Nepal (WHICH YEAR??, must mention the report). About 172 million people, or 12% in South-East Asia, are affected by goiter and prevalence in Nepal surpasses all South East Asian countries and 41% are at risk of goiter, and improvement is anticipated by the increased consumption of iodized salt. The majority of patients with thyroid dysfunctions falls within 21-40 years age group11. The survey in Nepal in 1996 indicated 55% of the population had goiter localized to mountainous region like Khumbhu, Jumla 12. Subclinical hypothyroidism is a more common disorder than overt hypothyroidism with a prevalence of 1.4-7.8% in elderly population and even greater percentiles among women 13. A recent study by Walsh, et al. confirmed that subclinical hypothyroidism, but not subclinical hyperthyroidism, is associated with an increased risk of fatal and nonfatal coronary heart disease14. The aim of the current study was to find out the variations of thyroid hormones and lipid profile in different categories of thyroidism.

Materials and Methods

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

Analysis of hormones i.e. total T4, total T3, TSH, fT4 was done by ELISA(HUMAN)15,16,17. Estimation of total cholesterol and triglycerides was done by semi autoanalyser Human 3500, Germany18. The commercial 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 oral corticosteroids, antifolates, 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

Out of 365 subjects 122 were having the thyroid disorder. Among the 122 thyroid disorder cases, 40 were of hyperthyroidism, 42 were of hypothyroidism and 40 were of subclinical hypothyroidism.

Table 1: comparison of biochemical variables in cases and controls

Variables

Controls

(243)

Thyroid

P value

Cases

Mean ± SD

Age

37.95 ± 15.54

Hyper T

34.85 ± 16.59

0.248

Hypo T

40.88 ± 15.32

0.258

SCHypo T

39.08 ± 17.4

0.678

T3

1.03 ± 0.42

Hyper T

2.37 ± 0.74

0.001**

Hypo T

0.37 ± 0.19

0.001**

SCHypo T

1.00 ± 0.29

0.571

T4

7.62±1.75

Hyper T

14.15 ± 3.7

0.001**

Hypo T

2.21 ± 0.85

0.001**

SCHypo T

6.27 ± 1.17

0.001**

TSH

3.0 ± 1.99

Hyper T

0.32 ± 0.10

0.001**

Hypo T

20.5 ± 11.4

0.001**

SCHypo T

10.04 ± 1.46

0.001**

fT4

1.38 ± 0.36

Hyper T

2.66 ± 0.48

0.001**

Hypo T

0.56 ± 0.29

0.001**

SCHypo T

1.15 ± 0.21

0.001**

TCHO

167.21±25.90

Hyper T

143.12 ± 9.43

0.001**

Hypo T

279.31 ± 34.65

0.001**

SCHypo T

257.88 ± 22.29

0.001**

TG

123.53±22.66

Hyper T

87.32 ± 18.31

0.001**

Hypo T

168.43 ± 45.02

0.001**

SCHypo T

152.35 ± 53.55

0.001**

Hyper T -40, Hypo T -42, SCHypo T -40

Hyper T (Hyperthyroidism), Hypo T (Hypothyroidism), SCHypo T (SubClinical Hypothyroidism)

** Statistically significant (p value<0.05)

The result showed that most of the variables T3, T4, TSH, fT4, Total Cholesterol, Triglycerides except age had statistically significance when compared with cases. The TSH values was markedly increased while T4 and T3 values were found to be less than the reference range in cases of hypothyroidism .The fT4 value was in normal limit associated with increased TSH levels which was the sensitive indicator in sub clinical hypothyroidism. The T4 and T3 levels were raised associated with decreased levels of TSH in hyperthyroidism. The total cholesterol values were moderately increased and there was no gross derangement of TG levels both in cases of hypo and sub clinical hypothyroidism. In hyperthyroidism total cholesterol and triglycerides levels were mildly decreased but within the reference range.

Table 2: Comparison of gender in normal and cases

Variable

Male

Female

P value

Hyper T

10

30

0.001**

Hypo T

6

36

0.001**

SC Hypo T

6

34

0.001**

Normal

58

185

0.001**

** Statistically significant (p value<0.05)

The above results had shown that frequency of getting the disorders related to thyroid was much higher in females when compared to males.

Table 3: gender wise comparison of biochemical variables in cases

Variables

cases

Male

Female

P value

Mean ± SD

Mean ± SD

Age

Hyper T

33.00 ±20.07

35.47 ± 15.61

0.729

Hypo T

53.33 ± 21.80

38.81 ± 13.26

0.168

SC Hypo T

56.83 ± 25.57

35.94 ± 13.95

0.10

T3

Hyper T

2.49 ±.77

2.33 ± 0.74

0.58

Hypo T

0.40 ± 0.10

0.37 ± 0.20

0.66

SC Hypo T

0.86 ± 0.29

1.02 ± 0.29

0.26

T4

Hyper T

14.68 ±4.76

13.97 ± 3.36

0.67

Hypo T

2.65 ± 0.53

2.13 ± 0.88

0.08

SC Hypo T

5.86 ± 0.60

6.33 ± 1.24

0.16

TSH

Hyper T

0.34 ±0.11

0.32 ± 0.10

0.62

Hypo T

14.70 ± 5.40

21.48 ± 11.89

0.03**

SC Hypo T

19.98 ± 9.00

15.34 ± 8.31

0.28

fT4

Hyper T

2.5 ± 0.54

2.7 ± 0.47

0.41

Hypo T

0.45 ± 0.25

0.58 ± 0 .30

0.28

SC Hypo T

1.10 ± 0.60

1.15 ± 0.22

0.25

TCHO

Hyper T

145.4 ± 10.12

142.37 ± 9.25

0.42

Hypo T

265.00 ± 23.15

281.69 ± 35.89

0.16

SC Hypo T

283.50 ± 16.15

265.12 ± 22.25

0.04**

TG

Hyper T

84.40 ± 15.98

88.30 ± 19.18

0.53

Hypo T

152.17 ± 42.16

171.14 ± 45.47

0.35

SC Hypo T

167.50 ± 67.85

176.74 ± 50.59

0.35

Hyper T m-10,f-30: Hypo T m-6,f-36: SC Hypo T m-6,f-34

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

The results had shown that variables T3, T4, TSH, fT4, total cholesterol, triglycerides did not have any statistical significance when compared with gender. males and females had almost equal variation among the biochemical parameters and did 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. The single most important biochemical parameter for confirming the hyperthyroidism (the most common being graves disease or thyrotoxicosis) was to assess the levels of serum TSH and was associated with increased mortality in individuals >60 yrs of age particularly from circulatory incompetence and atrial fibrillation 19. Other effects of hyperthyroidism includes decreased systemic vascular resistance, increased cardiac output, heart rate and blood pressure. Our results showed low or undetectable serum TSH, well below the reference range along with raised serum thyroxine (T4) and T3 levels. The values obtained was specific for diagnosis of thyrotoxicosis20. The total cholesterol and TG values were lowered but not below the normal range. The values obtained were 143.12 ± 9.43mg/dl, 87.32 ± 18.31 mg/dl which were quite close to other studies i.e.155±10mg/dl, 106±10mg/dl, of total cholesterol and TG respectively in hyperthyroidism.20 The thyroid hormones could mildly decrease plasma TG due to increase in lipoprotein lipase (LPL) activity in hyperthyroidism21.

Hypothyroidism was separated into either overt or subclinical disease and that diagnosis was determined on the basis of the TSH laboratory blood tests .The hypothyroidism was characterized by low T3 and T4 values with raised TSH levels. The decrease levels of T4 and T3 due to iodine deficiency during the first trimester could result in abnormal fetal development. Neurological cretinism was characterized by poor cognitive ability, deaf mutism, speech defects, and proximal neuromotor rigidity and was associated with increased levels of TSH. The mothers with very low serum T4 had higher incidence of still births, abortions, and congenital abnormalities. Contributing to the higher rate of perinatal deaths as thyroid hormones T4 and T3 had strong modulating effect on the immune system.

Hypothyroidism was mostly associated with abnormal lipid metabolism, cardiac dysfunction, diastolic hypertension conferring the elevated risk of artherosclerosis and if ignored as in most of the undiagnosed cases could results in ischaemic heart disease and myocardial infarction19 Our study showed significant lower levels of T4 and T3 with raised TSH levels 20.5 ± 11.4 mU/L. Other studies revealed that most sensitive indicator for hypothyroidism was TSH, more than 10mU/L along with reduced levels of T421. In our study, there was significant increase in the mean conc. of total cholesterol 279.31 ± 34.65mg/dl and triglycerides 168.43 ± 45.02mg/dl in cases of hypothyroidism. In hypothyroidism, there was increased in cholesterol synthesis and absorption from intestines. Other studies had shown that hypothyroidism could significantly increase the levels of most of lipids most importantly was that of cholesterol and LDL and in contrast hyperthyroidism was not associated with plasma lipid variation22. The mean and SD of cholesterol in hypothyroid subjects was 289 ± 18mg/dl, for TG was 183 ± 37mg/dl, which were quite similar to our values23 The normal range of TSH concentration falls between 0.45 - 4.5 mU/L. The mildly underactive (subclinical) thyroid had TSH levels of 4.5 - 10mU/L and levels >10mU/L were considered to have overt hypothyroidism24 The fT4 levels (.8-2 pg/ml) with in reference range with raised TSH levels define the subclinical hypothyroidism. In our study mildly underactive (subclinical) thyroid patients had fT4 (1.15 ± 0.21pg/ml) and TSH (10.04 ± 1.46 mU/ L and those values were quite close to values of other studies i.e TSH (11.43 ± 5.50 mU/L) and fT4 (1.05 ± 0.21 pg/ml) in cases of subclinical hyperthyroidism25. Our results had shown the total cholesterol was moderately raised (257.88 ± 22.29mg/dl) while the TG levels were near the upper limit of the reference range (152.35 ± 53.55mg/dl). 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 results26. The similar results had obtained from the other studies that serum levels of total cholesterol and LDL were increased in patients of subclinical hypothyroidism in comparison to the normal controls (euthyroid) 27. Rarely hypertriglyceridemia occurs in hypothyroidism despite of fact that hypothyroid patients had abnormally low levels of post-heparin hepatic triglyceride lipase, low clearance of chylomicrons. Thus, TG metabolism is not grossly deranged in hypothyroidism28.

Conclusion

Thyroid dysfunction is very common both in elderly and younger age groups so regular screening shall be there to minimize the problem of undiagnosed cases particularly the patients having the 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 continued to be a major problem in Nepal and demanded a clear control strategy, combining ongoing iodine supplementation and education.

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