Largest Of The Endocrine Glands Biology Essay

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The thyroid gland, located immediately below the larynx on each side of and anterior to the trachea, is one of the largest of the endocrine glands, normally weighing 15 to 20 grams in adults. (1)

The normal adult thyroid gland secretes about 90 micrograms of thyroxine (T4) and less than 10 micrograms of triiodothyronine (T3) per day. Somewhat less than half of the T4 is converted to T3 by several tissues especially in the liver. (2)Converting T4 into T3 is necessary for life, and there is no evidence that this metabolic derangement can be acquired later in life. Anyone who could not convert T4 into T3 would not be alive, as this conversion is necessary for fetal development and birth. (3)

In the circulation, almost all of the thyroid hormones (99.98 percent of T4 and 99.5 percent of T3) are tightly bound to the proteins thyroxine binding globulin (TBG), albumin, and transthyretin. However, the free T3 and T4 are responsible for the biological effects of the thyroid hormones. (4)

Thyroxine and T3 have the same functions for regulation of energy production and protein synthesis, which contribute to growth of the body and to normal body functioning throughout life. Thyroxine and T3 increase cell respiration and metabolism of all food types (carbohydrates, fats, and excess amino acids) and thereby increase energy and heat production. (5)

Circulating levels of thyroid hormones regulate both the pituitary and blood levels of TSH. This provides a tight control of the hormogenic activity of the thyroid gland. Excess thyroid hormone in blood has been shown to decrease the levels of TSH both in the pituitary and in the blood. (6)

Figure (1): Pituitary-thyroid axis hormones and their regulation (7)

Mechanism of actions:

It is now understood that the action of thyroid hormone on target cells is tissue specific and regulated through membrane transporter and intracellular enzymatic activity. Firstly, thyroid hormone uptake into cells is controlled by unique hormone receptors on the plasma membrane of different cells. (8) The sensitivity or responsiveness of a particular cell to thyroid hormones correlates to some degree with the number of receptors for these hormones. The cells of the CNS appear to be an exception. The thyroid hormones play an important role in CNS development during fetal and neonatal life, and developing nerve cells in the brain are important targets for thyroid hormones. In the adult, however, brain cells show little responsiveness to the metabolic regulatory action of thyroid hormones, although they have numerous receptors for these hormones. The reason for this discrepancy is unclear.

Thyroid hormone receptors (TR) are located in the nuclei of target cells bound to thyroid hormone response elements (TRE) in the DNA. TRs are protein molecules of about 50 kDa that are structurally similar to the nuclear receptors for steroid hormones and vitamin D. Thyroid receptors bound to the TRE in the absence of T3 generally act to repress gene expression. The free forms of T3 and T4 are taken up by target cells from the blood through a carrier-mediated process that requires ATP. Once inside the cell, T4 is deiodinated to T3. (9)

Once T3 is produced inside the target cells, it enters the nucleus and binds to a nuclear receptor. The T3-receptor complex then binds to a thyroid-regulatory element on DNA, where it stimulates DNA transcription. The newly transcribed mRNAs are translated, and new proteins are synthesized. These new proteins are responsible for the multiple actions of thyroid hormones. Other T3 receptors located in ribosomes and mitochondria mediate posttranscriptional and posttranslational events.

A vast array of new proteins are synthesized under the direction of thyroid hormones, including Na+-K+ ATPase, transport proteins, β1-adrenergic receptors, lysosomal enzymes, proteolytic proteins, and structural proteins. The nature of the protein induced is specific to the target tissue. In most tissues, Na+-K+ ATPase synthesis is induced, which leads to increased oxygen consumption, BMR, and heat production. In myocardial cells, myosin, β1-adrenergic receptors, and Ca2+ ATPase are induced, accounting for thyroid hormone-induced increases in heart rate and contractility. In liver and adipose tissue, key metabolic enzymes are induced, leading to modifications in carbohydrate, protein, and fat metabolism. (10)

Figure (2): Mechanism of action of thyroid hormones (11)

Metabolism:

T4 and T3 are deiodinated in the liver, the kidneys, and many other tissues. These deiodination reactions serve not only to catabolize the hormones, but also to provide a local supply specifically of T3, which is believed to be the primary mediator of the physiological effects of thyroid secretion. One third of the circulating T4 is generally converted to active T3 in adult humans, and 45% is converted to RT3. Only about 13% of the circulating T3 is secreted by the thyroid while 87% is formed by deiodination of T4; similarly, only 5% of the circulating rT3 is secreted by the thyroid and 95% is formed by deiodination of T4. It should be noted as well that marked differences in the ratio of T3 to T4 occur in various tissues. Two tissues that have very high T3/T4 ratios are the pituitary and the cerebral cortex, due to the expression of specific deiodinases. (12)

Figure (3): thyroxin deiodination (13)

Three selenoprotein iodothyronine monodeiodinase enzymes have been described. Two of these enzymes, deiodinase Dl and D2, are activating enzymes because they deiodinate the outer ring; there is one inactivating deiodinase, D3, which deiodinates the inner ring. Dl is also capable of inner ring monodeiodination, particularly of sulfated iodothyronines. These deiodinases are developmentally regulated and differ in their tissue distribution and properties. In the cerebral cortex, for example, > 50% of the intracellular T3 is derived from the intracellular conversion of T4 to T3. In contrast, in liver, only 25% of the intracellular T3 is generated from T4, the remainder being derived from plasma. As a consequence of these variations in deiodinase activity, the relative amounts of T4 and T3 in the serum do not necessarily correspond to their intracellular proportions.

D1, responsible for most of the circulating T3, is expressed predominantly in liver and kidney. In contrast, the highest concentration of D2 is in brain, pituitary, placenta, and brownadipose tissue. D3 is present predominantly in fetal tissues and the utero-placental unit, underlying the importance of protecting the fetus from the effects of thyroid hormone excess. Adaptive mechanisms in the activity of these deiodinases at a cellular level are an important prereceptor level of control that results in the preferential shunting of thyroid hormone to areas of need. For example, increased conversion of T4 to T3 by the fetal brain in the presence of hypothyroidism is a critical protective mechanism that accounts, in part, for the normal or near-normal cognitive outcome of babies with congenital hypothyroidism as long as postnatal therapy is early and adequate. (14)

Figure (4): Metabolism of thyroid hormones (15)

Hormonal disturbance in renal failure:

The kidney has a central role in producing and metabolizing a variety of hormones. (16) So uremia can interfere with the metabolism and regulation of hormones at each level of the regulatory cascade by various mechanisms. Only a minority of these changes can be accurately detected by routine laboratory tests and the interpretation of clinical and laboratory findings in uremic patients may be extremely difficult. (17)

Abnormal metabolism of thyroid hormones is an important pathogenetic factor not only in primary or secondary diseases of the thyroid gland but also in many pathological states primarily not connected with this endocrine organ. In recent years, abnormal plasma concentrations of thyroid hormones were reported in acute febrile states of viral or bacterial origin, neoplastic diseases, in different pathological states of the liver, kidneys and in systemic diseases. (18)

Patients with renal failure often have signs & symptoms suggestive of thyroid dysfunction. These findings include dry skin, pale face, low temperature, cold intolerance, decreased basal metabolic rate, lethargy, fatigue, edema & hyporeflexia. Various studies of thyroid functions in uremic patients have been carried out which have shown conflicting results. Hyperthyroidism, hypothyroidism & euthyroid state have all been reported by various workers. (19)

Subjects and methods

Subject selection:

This study was performed on 65 individuals, classified into 2 groups:

Group (A): Control group:

This group includes 11 (6 males and 5 females) apparent healthy adults, with normal clinical picture including normal kidney and thyroid functions. Their age ranges from 21 to 40 years.

Group (B): Renal failure group:

This group consists of 54 (25 males and 29 females) adults with end stage renal disease and undergoing periodic hemodialysis three times per week for a period of time ranging from 3 months to 120 months. Their age ranges from

Subject specimens:

Renal failure samples were collected from The National Institute of Urology and Nephrology (El-Matareya, Cairo, Egypt). The control samples were collected from normal volunteers.

Blood samples were drawn from individuals at fasting state; samples were processed within one hour of sampling. Separation of serum was obtained by centrifugation at 4000 rpm for 10 minutes. The samples were stored at -20°C until analyzed.

Determination of serum creatinine:

Serum creatinine was determined by kinetic method according to the principle of Heny, (1974). the kits were supplied by dp International co.

Principle:

Creatinine in alkaline solution reacted with picrate to form a colored complex. The rate of complex formation was measured photometrically at 492 nm.

Reagents:

R1

Creatinine standard

2 mg/dl

R2

Picric acid

38 mmol/l

R3

Sodium hydroxide

0.4 mmol/l

Method:

The working solution was prepared by mixing equal volumes of picric acid (R2) and sodium hydroxide (R3). 1 ml of working solution was added to standard tube and sample tubes. 100 μl of standard solution or sample was added then a gentle mixing was performed. The absorption of standard solution and samples were measured after 30 seconds (A1) and after 2 minutes (A2) at 492 nm. (20)

Calculations:

The value of (A = A2 - A1) was calculated and then the serum creatinine can be calculated from this formula:

Serum Cr = (A sample / A standard) x 2 = mg/dl

Determination of serum urea:

Serum urea was determined by enzymatic method according to the principle of patton, and Crouch, (1977). The kits were supplied by dp International co.

Principle:

Enzymatic determination of urea according to the following reaction:

Urea + H2O Urease 2 NH3 + CO2

In an alkaline medium, the ammonium ions reacted with the salicylate and hypochlorite to form a green colored indophenol.

Reagents:

R1

Urea standard

50 mg/ dl

R2

Enzyme reagent:

 

 

Urease

> 5000 U/l

R3

Buffer reagent:

 

 

Phosphate buffer PH8

100 mmol/l

 

Sodium salicylate

52 mmol/l

 

Sodium nitroprusside

2.9 mmol/l

 

EDTA

2.0 mmol/l

R4

Alkaline reagent:

 

 

Sodium hydroxide

80 mmol/l

 

Sodium hypochlorite

4.0 mmol/l

Method:

1 ml of buffer reagent (R3) was added to each of three tubes, the first for reagent blank, second for standard and third for sample. One drop of urease (R2) was added to the three tubes. 10 μl of standard was added to the second tube and 10 μl of serum was added to the third tube then gentle mixing was performed and incubation for at least 5 minutes at 20-25oC. Then alkaline reagent (R4) was added to the blank, standard and sample followed by mixing and incubation for 10 minutes at 20-25oC. The absorbance of the sample and the standard was measured at 580 nm. (21)

Calculations:

The urea concentration can be calculated by the following equation:

Urea concentration = (A sample / A standard) x n = mg/dl

Where n = 50.0 mg/dl

Determination of serum uric acid:

Serum uric acid was determined by enzymatic method according to the principle of Fossati, et al (1980). The kits were supplied by Diamond diagnostic co.

Principle:

Uric acid present in the sample was determined according to the following reaction:

Uric acid + O2 + H2 Uricase Allantoin + H2O2 + CO2

H2O2 + p- hydroxybenzoic acid + 4-aminoantipyrine Peroxidase quinoneimine + HCl + 4 H2O

The increase of quinoneimine concentration was proportional to the uric acid concentration in the sample.

Reagents:

R1

Uric acid standard

6.0 mg/dl

R2

Buffer reagent:

 

 

3,5 Dichloro-2-hydroxybenzene

4.00mmol/l

 

Tris buffer

50 mmol/l

 

Detergent

0.20%

 

Sulfonic acid

R3

Enzymatic reagent:

 

 

Lipapse / Esterase

≥ 100 KU/l

 

Uricase

≥ 300 U/l

 

Peroxidase

≥ 4000 U/l

 

4-aminoantipyrine

0.45 mmol/l

Method:

The working solution was prepared by dissolving the vial of enzymatic reagent (R3) in 30 ml of buffer regent (R2) and mixing well. The working solution was ready to be used after 10 minutes of preparation. 1 ml of working solution was added to each of three tubes, the first for reagent blank, second for standard and third for sample. 20 μl of standard was added to the second tube and 20 μl of serum was added to the third tube then gentle mixing was performed and incubation for 10 minutes at 20-25oC. The absorbance of the sample and the standard was measured at 546 nm. (22)

Calculations:

Uric acid concentration can be calculated by the following equation:

Uric acid concentration = (A sample / A standard) x 6 = mg/dl

Determination of serum TT3:

Priniple:

In the T3 ELISA, a certain quantity of anti-T3 antibody was coated on microtiter wells. A measured quantity of patient serum, and a constant quantity of T3 conjugated with enzyme (horseradish peroxidase) were added to the microtiter wells. During incubation, T3 and conjugated T3 competed for the limited binding sites on the anti-T3 antibody. After incubation for 60 minutes at room temperature, the wells were washed 5 times by water to eliminate unbound T3 conjugate. A solution of TMB reagent was then added and incubated for 20 minutes, leading to the development of blue color. The development of the blue color was stopped with addition of stop solution, and the absorbance was measured spectrophotometrically at 450 nm. The intensity of the color formed was directly proportional to the concentration of enzyme present and was inversely related to the concentration of unlabeled T3 in the sample. By reference to different concentrations of T3 standard assayed in the same way, the concentration of T3 in the unknown sample was quantified.

Reagents:

Sheep anti- T3 coated microtiter wells.

T3 reference standards: 0, 0.5, 1, 2.5, 5 and 7.5 ng/ml.

Enzyme conjugate reagent: 13 ml.

TMB reagent: 11 ml.

Stop solution (1N HCl): 11ml.

Procedure:

The desired number of coated wells was secured in the holder. 25 μl of standard, specimens, and controls was pipetted into appropriate wells. 100 μl of working conjugate reagent was dispensed into each well and mixed for 30 minutes and then incubated at room temperature (18-25oC) for 60 minutes. The incubated mixture was removed by flicking plate content into waste container. The microtiter wells were rinsed and flicked 5 times with distilled or deionized water. All residual water droplets were removed by striking the wells sharply onto absorbent paper or paper towels. 100 μl of TMB Reagent was dispensed into each well and mixed gently for 10 seconds and incubated at room temperature in the dark for 20 minutes. The reaction was stopped by adding 100 μl of stop solution to each well and mixed gently for 30 seconds. The absorbance was read at 450 nm with a microtiter well reader. (23)

Determination of serum TT4

Priniple:

In the T4 ELISA, a certain quantity of anti-T4 antibody was coated on microtiter wells. A measured quantity of patient serum, and a constant quantity of T4 conjugated with enzyme (horseradish peroxidase) were added to the microtiter wells. During incubation, T4 and conjugated T4 competed for the limited binding sites on the anti-T4 antibody. After incubation for 60 minutes at room temperature, the wells were washed 5 times by water to eliminate unbound T4 conjugate. A solution of TMB reagent was then added and incubated for 20 minutes, leading to the development of blue color. The development of the blue color was stopped with addition of stop solution, and the absorbance was measured spectrophotometrically at 450 nm. The intensity of the color formed was directly proportional to the concentration of enzyme present and was inversely related to the concentration of unlabeled T4 in the sample. By reference to different concentrations of T4 standard assayed in the same way, the concentration of T4 in the unknown sample was quantified.

Reagents:

Sheep anti- T4 coated microtiter wells.

T4 reference standards: 0, 2, 5, 10, 15 and 25 μg/dl.

Enzyme conjugate reagent: 13 ml.

TMB reagent: 11 ml.

Stop solution (1N HCl): 11ml.

Procedure:

The desired number of coated wells was secured in the holder. 25 μl of standard, specimens, and controls was pipetted into appropriate wells. 100 μl of working conjugate reagent was dispensed into each well and mixed for 30 minutes and then incubated at room temperature (18-25oC) for 60 minutes. The incubated mixture was removed by flicking plate content into waste container. The microtiter wells were rinsed and flicked 5 times with distilled or deionized water. All residual water droplets were removed by striking the wells sharply onto absorbent paper or paper towels. 100 μl of TMB Reagent was dispensed into each well and mixed gently for 10 seconds and incubated at room temperature in the dark for 20 minutes. The reaction was stopped by adding 100 μl of stop solution to each well and mixed gently for 30 seconds. The absorbance was read at 450 nm with a microtiter well reader. (24)

Determination of serum TSH:

Principle:

The TSH ELISA test was derived from the principle of a solid phase enzyme-linked immunosorbent assay. The assay system used a certain monoclonal antibody directed against a distinct antigenic determinant on the intact TSH molecule. Mouse monoclonal anti TSH antibody was used for solid phase immobilization (on the microtiter wells). A goat anti-TSH antibody was in the antibody-enzyme (horseradish peroxidase) conjugate solution. The test sample was allowed to react concurrently with the two antibodies, leading to the TSH molecules were sandwiched between the solid phase and enzyme-linked antibodies. After incubation for 60-minute at room temperature, the wells were washed with water to eliminate unbound labeled antibodies. A solution of TMB reagent was added and incubated for 20 minutes, leading to the development of a blue color. The development of the blue color was stopped by addition of stop solution, and the color was changed to yellow. The concentration of TSH was directly proportional to the intensity of the yellow color and the absorbance was measured by spectrophotometric method at 450 nm.

Reagents:

Murine Monoclonal Anti-TSH-coated microtiter wells.

Set of reference standards: 0, 0.5, 2, 5, 10 and 25 μIU/ml.

Enzyme conjugate concentrate (x11): 1.3 ml.

Enzyme conjugate diluent: 13 ml

TMB reagent: 11 ml.

Stop solution (1N HCl): 11ml.

Procedure:

The desired number of coated wells was secured in the holder. 25 μl of standards, specimens, and controls were dispensed into appropriate wells. 100 μl of enzyme conjugate reagent was dispensed into each well and mixed for 30 minutes and then incubated at room temperature (18-25oC) for 60 minutes. The incubated mixture was removed by flicking plate content into waste container. The microtiter wells were rinsed and flicked 5 times with distilled or deionized water. All residual water droplets were removed by striking the wells sharply onto absorbent paper or paper towels. 100 μl of TMB Reagent was dispensed into each well and was mixed gently for 10 seconds and incubated at room temperature in the dark for 20 minutes. The reaction was stopped by adding 100 μl of stop solution to each well and mixed gently for 30 seconds. The absorbance was read at 450 nm with a microtiter well reader. (25)

Results

Table (1): Serum creatinine, urea, uric acid, total T3, total T4 and TSH in renal failure group

No.

Creatinine (mg/dl)

Urea (mg/dl)

Uric acid (mg/dl)

TT3 (ng/dl)

TT4 (μg/dl)

TSH (μIU/ml)

1

17

155

6.4

20

6

5.1

2

8.4

157

8.7

100

5.6

7.3

3

20.5

215

11.4

64

2

6.2

4

13.1

186

11

68

4.8

3.2

5

6.6

123

7.5

48

4.5

6.6

6

8.3

224

7.9

60

4

1.2

7

6.1

105

7.6

40

5.2

4.7

8

10.6

155

9.1

32

4.8

4.8

9

7

158

9.8

68

5.6

6.4

10

8.4

146

10

44

2.8

5.6

11

7.6

117

10.2

48

3.6

6.6

12

9.2

120

8.6

52

6.4

4.9

13

13.5

98

7

12

6.8

2.5

14

11.9

148

9.9

64

4.8

2.6

15

12.7

183

8.9

32

4.4

4.2

16

15.5

192

9

160

5.6

0.8

17

9.9

104

7.2

88

4

4.8

18

9.5

165

8.3

40

3.2

6

19

11

173

9

36

1.6

7.4

20

13

220

9.8

48

1.6

6.5

21

13.1

205

9.7

64

6.8

3.7

22

8.4

163

7.9

36

5.2

7.7

23

14.1

213

8.9

80

5.6

5.4

24

16.1

197

10.2

72

1.6

6.6

25

11.5

159

8.9

100

4.4

1.2

26

8.9

137

7.9

80

1.2

5.9

27

6.2

105

7.7

104

4.8

3.9

28

7.3

97

8.9

80

7.6

3.9

29

12.9

146

9.8

84

6.4

3

30

11.4

150

9.2

90

5.4

7

31

15.1

223

8

60

3.2

2.1

32

8.9

150

8

40

4.4

2.8

33

15.4

260

6

112

7.6

3.5

34

13.1

143

7.8

80

2.4

5.5

35

8

158

6.7

52

3.6

3

36

11

199

8.5

76

7.6

1.5

37

9.6

211

8.4

92

6.4

2.1

38

8.6

178

4.9

116

7.2

4.2

39

14

310

7

152

4

6.2

40

11.8

208

6.9

108

6.4

2.7

No.

Creatinine (mg/dl)

Urea (mg/dl)

Uric acid (mg/dl)

TT3 (ng/dl)

TT4 (μg/dl)

TSH (μIU/ml)

41

11

211

6.4

112

6

2.1

42

15.1

208

7.1

96

5.6

2.3

43

8.4

163

6.9

75

7.6

2.2

44

11.1

199

8.3

92

4.8

4.2

45

16.4

254

7.9

46

5.6

6.5

46

11.2

144

6.8

176

6

7.8

47

8.9

136

7.8

88

4

5.9

48

9.2

109

7.5

184

5.5

5.7

49

9.5

123

7.7

120

7.2

5.7

50

10

177

9.1

144

6.4

4.2

51

13.5

153

8.9

46

4.4

2.9

52

8.6

214

7.2

80

1.6

6

53

15.9

265

8.5

40

6.4

5

54

12

162

9.4

96

5.2

6.4

Mean

11.2

171.74

8.3

77.7

4.9

4.56

SD

3.15

46.16

1.3

38

1.73

1.9

SEM

0.43

6.28

0.18

5.2

0.23

0.26

Table (2): Serum creatinine, urea, uric acid, total T3, total T4 and TSH in control group

No.

Creatinine (mg/dl)

Urea (mg/dl)

Uric acid (mg/dl)

TT3 (ng/dl)

TT4 (μg/dl)

TSH (μIU/ml)

55

0.8

41

3.5

48

6.8

3.9

56

1

23

2.5

192

8

3.2

57

0.8

20

2.7

124

7.6

5.2

58

0.6

43

2.5

148

7.6

2.8

59

1

25

2.7

156

6.8

2.1

60

0.8

34

3

172

7.6

2.4

61

0.8

20

4

180

7.2

4.3

62

1.2

20

4

120

7.6

2

63

1.6

34

3.5

140

8.8

5.4

64

1.2

42

2.7

56

7.2

2.2

65

0.6

28

2.5

144

9.6

1.5

Mean

0.95

30

3.05

134.5

7.7

3.18

SD

0.29

9.19

0.59

46

0.84

1.34

SEM

0.09

2.77

0.18

14

0.25

0.66

1. Serum creatinine:

The results of serum creatinine are illustrated in Table (3) and Figure (5). These results show a highly significant increase in the mean level of serum creatinine in the renal failure group as compared with the control group.

Table (3): Serum creatinine in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

0.6 - 1.6

6.1 - 20.5

Mean ± SEM

0.95 ± 0.09 mg/dl

11.2 ± 0.43 mg/dl *

* Significant different from control (p < 0.0001)

Figure (5): Serum creatinine in control group and renal failure group

2. Serum urea:

The results of serum urea are illustrated in Table (4) and Figure (6). These results show a highly significant increase in the mean level of serum urea in the renal failure group as compared with the control group.

Table (4): Serum urea in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

20 - 43

97 - 310

Mean ± SEM

30 ± 2.77 mg/dl

171.74 ± 6.28 mg/dl *

* Significant different from control (p < 0.0001)

Figure (6): Serum urea in control group and renal failure group

3. Serum uric acid:

The results of serum uric acid are illustrated in Table (5) and Figure (7). These results show a highly significant increase in the mean level of serum uric acid in the renal failure group as compared with the control group.

Table 5: Serum uric acid in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

2.5 - 4

4.9 - 11.4

Mean ± SEM

3.05 ± 0.18 mg/dl

8.3 ± 0.18 mg/dl *

* Significant different from control (p < 0.0001)

Figure (7): Serum uric acid in control group and renal failure group

4. Serum total T3:

The results of serum total T3 are illustrated in Table (6) and Figure (8). These results show a highly significant increase in the mean level of serum total T3 in the renal failure group as compared with the control group.

Table 6: Serum total T3 in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

48 - 192

12 - 184

Mean ± SEM

135 ± 14 ng/dl

78 ± 5 ng/dl *

* Significant different from control (p < 0.001)

Figure (8): Serum total T3 in control group and renal failure group

The correlation between serum total T3 and serum creatinine is illustrated in figure (9). This correlation shows that the serum total T3 decreases by increasing the serum creatinine. The slope of the regression line = -3.687 ± 1.07 and R2 = 0.158

Figure (9): Correlation between serum total T3 and serum creatinine

5. Serum total T4:

The results of serum total T4 are illustrated in Table (7) and Figure (10). These results show a highly significant increase in the mean level of serum total T4 in the renal failure group as compared with the control group.

Table (7): Serum total T4 in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

6.8 - 9.6

1.2 - 7.6

Mean ± SEM

7.7 ± 0.25 μg/dl

4.9 ± 0.23 μg/dl *

* Significant different from control (p < 0.001)

Figure (10): Serum total T4 in control group and renal failure group

The correlation between serum total T4 and serum creatinine is illustrated in figure (11). This correlation shows that the serum total T4 decreases by increasing the serum creatinine. The slope of the regression line = - 0.187 ± 0.044 and R2 = 0.22

Figure (11): Correlation between serum total T4 and serum creatinine

6. Serum TSH:

The results of serum TSH are illustrated in Table (8) and Figure (12). These results show a highly significant increase in the mean level of serum TSH in the renal failure group as compared with the control group.

Table (8): Serum TSH in control group and renal failure group

Mean ± SEM

 

Control group

Renal failure group

No. of samples

11

54

Range

1.5 - 5.4

0.8 - 7.8

Mean ± SEM

3.18 ± 0.66 μIU/ml

4.56 ± 0.26 μIU/ml

* Significant different from control (p < 0.05)

Figure (12): Serum TSH in control group and renal failure group

The correlation between serum TSH and serum creatinine is illustrated in figure (13). This correlation shows that the serum TSH increases by increasing the serum creatinine. The slope of the regression line ranging from 0.028 and 0.16 and R2 = 0.03

Figure (13): Correlation between serum TSH and serum creatinine

Discussion

There is an interaction between thyroid gland and kidney. Thyroid hormones are necessary for a good growth and maturation of the kidney. On the other hand, the kidney is not the only organ for elimination and metabolism of pituitary-thyroid axis hormones, but also it is a target organ of actions of some iodothyronines. Thyroid disorders cause significant changes in tubular and glomerular functions and in water and electrolyte homeostasis. Usually hypothyroidism is associated with a decrease in glomerular filtration, hyponatremia, and a modification of the capability of water excretion. Also patients with renal failure often have signs and symptoms of thyroid dysfunction. (26)

In this study serum total T3 levels are showing a highly significant decrease (P < 0.001) in the patients with end stage renal disease as compared with the normal control group as shown in table (6) and figure (8). In addition to that serum total T4 levels also are showing a highly significant decrease (P < 0.001) in the patients with end stage renal disease as compared with the normal control group as shown in table (7) and figure (10). On the other hand serum TSH levels are showing a significant increase (P < 0.05) in the patients with end stage renal disease as compared with the normal control group as shown in table (8) and figure (12).

These results are in agreement with Wartofsky (1994) and Kaptein (1996) who reported that the mean values of serum total T3 and total T4 were significantly decreased in patients with end stage renal disease and this may be due to impaired secretion of the two hormones from the thyroid gland. (27,28) On the other hand Lim (2001) reported that this decrease in the serum total T3 levels may be due to impaired conversion of T4 to T3 by deiodinase enzyme. (29) In this study the serum TSH level was significantly increased in patients with end stage renal disease and this result is against Mehta, et al (1991) who reported that the serum TSH level in patients with end stage renal disease was not increased. (30)

In this study, although the serum TSH level is significantly increased in patients with end stage renal disease, it does not exceed the normal level. This result means that the sensitivity of pituitary gland is affected by the uremic condition as the difference between patients with end stage renal disease and normal controls in serum TSH level (P < 0.05) is less than the difference in serum total T3 (P < 0.001) and the difference in total T4 levels (P < 0.001). These results are in agreement with Lebkowska, et al (2003) who reported that although all patients with end stage renal disease were clinically euthyroid, the biochemical features suggest hypothyroidism. (31)

Lim, et al (1984) reported that the sensitivity of pituitary gland was affected by uremic condition may be due to a central defect in TRH secretion. (32) On the other hand Bianco, et al (2002) reported that the pituitary T3 was found to be normal in uremic rats and the liver T3 was significantly decreased. The difference between the liver and the pituitary is most likely due to the presence of different deiodinases in the two tissues, D1 in the liver and D2 in the pituitary; the latter is less susceptible to inhibition during illnesses. (33)

This study also makes a correlation between the serum creatinine and serum total T3, total T4 and TSH. These correlations helps to understand how much renal damage will affect the serum total T3, total T4 and TSH levels. These correlations illustrate that serum total T3 and total T4 are inversely proportional to the serum creatinine as shown in figure (9) and figure (11). However serum TSH is directly proportional to the serum creatinine as shown in figure (13).

Conclusion

It is important to understand the relationship between the kidney and body hormones. It helps to understand the real mechanism in which these hormones affect the human body. It helps also to manage patients with chronic kidney diseases and improve their quality of life. Finally this study conclude that although the uremic patients regarded to be clinically euthyroid, the disturbances in thyroid hormones level in uremic patients may suggest the existence of some disturbances in the pituitary-thyroid axis hormones and this needs more attention in these patients.

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