Significance of Hypercholesterolemia in Hypothyroid Patients

1. Abdul Qavi 2. Ghulam Nabi Khokhar 3. Amjad Zahoor 4. Israr Ahmed Akhund
5. Muhammad Ishaq
1. Assoc. Prof. of Pathology 2. Prof. of Pharmacology 3. Assoc. Prof. of Pediatrics 4. Prof. of Physiology
5. Prof. of Surgery,
Jinnah Medical College, Peshawar

ABSTRACT

Introduction: Lipid and lipoprotein is influenced by thyroid hormone. Global distribution thyroid disease is very common in Indo- Pak. Hypercholesterolemia is common finding in hypothyroid patients.

Objective: This study was conducted to know the prevalence of thyroid dysfunction and its relationship with dyslipidemia.

Study Design: Cross Sectional Study

Place & Duration of Study:  This study was conducted at the Department of Pathology Jinnah Medical College Warsak Road Peshawar for the period from December 2012 to May 2013.

Materials and Methods: 300 patients suspicious of thyroid element were included in study group. 100 healthy control subjects with no history of any thyroid and other chronic illness were included in control group, serum FT4, TSH and total cholesterol was estimated by Elisa and colorimetric method respectively and Results were analyzed by applying “student T test” and “Chi- square”.

Result: Out of 300 sera tested 78 (260) had thyroid dysfunction Hypothyroid patients serum showed significantly raised cholesterol level, however no significant association between total cholesterol and raised thyroxin level observed.

Conclusion: Hypercholesterolemia was noted significantly in hypothyroid patients indicating need for monitoring the cholesterol level in thyroid dysfunction to avoid the risk of development of cardiovascular disease.

Key Words: Hypercholesterolemia, Hypothyroidism


INTRODUCTION

Global distribution thyroid disease is very common in Indo- Pak1. Hypercholesterolemia is common finding in hypothyroid patients. Dyslipidemia is essential risk factor in the development of hypertension epithelial dysfunction and cardiovascular diseases7-9. High serum cholesterol level in hypothyroidism is resulted from decrease fractional clearance of LDL by a reduced number of LDL receptor in liver 2,5,10. Present study was planned to observe the association of hypothyroidism and high cholesterol level. Hypothyroidism affects 0.5-2.4% of the population. In the first stages it may go unnoticed as the symptoms may proceed insidiously. Before overt hypothyroidism is established, the only abnormality which may be detected is elevated serum thyrotropin (TSH) 15. At this stage, when thyroid hormones are still in the normal range, the diagnosis of subclinical hypothyroidism is made. Several studies have shown that this disorder is quite common (10% in an elderly population). It is still a matter of controversy whether this disorder should be screened and treated 16. Subclinical Hypothyroidism (SCH) has been detected with increasing frequency in recent years and is causing major controversies concerning management and treatment17. This syndrome is characterized by the finding of elevated TSH levels in the presence of normal circulating thyroid hormones, T4 and T3. In a classical epidemiological study the prevalence of SCH was 7.5% in women and 2.8% in men 18. The highest prevalence (up to 16%) was found in elderly women over 60 year of age). It is to be expected that an increasing number of patients with SCH will be detected by the widespread use of TSH measurements, as TSH screening has been shown to be cost-effective19. Patients with SCH may present with variable clinical manifestations, showing signs and symptoms of hypothyroidism. SCH has been linked with abnormalities of lipid metabolism increased serum total cholesterol and low density lipoprotein cholesterol (LDL-C) 3. Associated with increased with risk for coronary heart disease, and depression (7, 8). In addition, several target tissues were shown to be affected (e.g. ankle reflex time (9, 10) systolic time intervals (11-15), and PRL levels (10, 13). The hypercholesterolemia of hypothyroidism and hypercholesterolemia of hyperthyroidism are long recognized and well-accepted clinical finding. The mechanisms of hypercholesterolemia in hypothyroidism of hypercholesterolemia in hypothyroidism have been ascribed variously to decreased clearance of cholesterol from plasma, reduced conversion of cholesterol to bile acids in the liver and delayed removal of low density lipoprotein from the plasma. The reverse actions have been suggested as being responsible for the low cholesterol concentrations in hyperthyroidism 20. The hypocholesterolemic action of thyroid hormones is well known, and hypothyroid patients commonly is well known, and hypothyroid patients commonly have elevated plasma cholesterol while those with hyperthyroidism have the reverse. A wealth of clinical and human experimental observation indicates a potent influence of the thyroid gland on the metabolism of cholesterol and other lipids. Blood cholesterol, serum phosphatides, and fatty acids are increased in myxedema. In cretinous children, a high ratio of free to total serum cholesterol has been described 22. In adults with myxedema, however, normal or increased ester :total cholesterol ratio occurs. The rise in serum cholesterol is greater than that of phospholipid, and the Cholesterol : Phospholipid ratio is increased. An increase of low density (beta) lipoproteins, both in spontaneous and in induced myxedema, is largely in the SF 0-12 moiety but is found also in fractions SF 12-400; all of the abnormalities are reversed by the administration of desiccated thyroid. The lipoprotein abnormalitymay be reversed with very small doses of desiccated thyroid (15 to 30 mg.) 23 - Similar findings are reported in most animal studies: hypercholesteremia accompanies decreased thyroid function whether this results from surgical extirpation, I131 radiation, or thiourea administration. The domestic pig is a notable exception. The mechanism of the hypercholesteremia has been explained by studies in animals and man. In hyperthyroidism, the serum cholesterol falls in the face of increased cholesterol synthesis, due to increased bile acid excretion (particularly chenodesoxycholic acid). Conversely, in hypothyroidism, cholesterol synthesis is depressed, but bile acid excretion is also decreased; there is a slow turnover of the serum cholesterol, which is elevated apparently because excretion is depressed more than synthesis. Despite the changes in serum cholesterol, available evidence indicates that there is no change in the total body pool of cholesterol in myxedema 24.

MATERIALS AND METHODS

A cross sectional study was undertaken in the department of Pathology Jinnah Medical College Warsak Road Peshawar for the period from December 2012 to May 2013. Three hundred patients suspicious of thyroid disorder were selected. 100 healthy control with normal thyroid profile and no history of other chronic illness ere included in normal control group. Detailed information of patients was collected after informed consent with the help of pretest Performa that include age, sex, family and personal history of chronic disorder. After 12 hours overnight fast 5 ml blood was aseptically collected from medical cubical vein by using disposable syringe for each patient aseptic measures were followed strictly. The serum was separated in properly labeled sterilized vials, stored, A+ T -20Co till analyzed.FT4 and FT3 and TSH were estimated quantitatively by using commercially available Elisa kit (International immune diagnostic Junalane Foster City Canada). The method is base on the principle of competitive solid phase enzyme immunoassay. The total cholesterol was estimated by colorimetric method using kit and standard protocol of RANDOX UK. The data was represented as mean plus minus SD value and significance was determined by using “student T test” and “chi square test”

RESULTS

Among 300 patient suspected of thyroid disorder 78(26%) showed thyroid dysfunction. Subclinical hypothyroidism was 16.1% (48 subjects) Positive correlation between TSH and total cholesterol
(p= 0.454) in overt hypothyroidism.

Table No.1: Comparison of mean total cholesterol and overt hypothyroid patients (Total cholesterol mg/dl)

Overt hypothyroid patient(study group)

Normal control group

218.1+ 69

P= 0.001

163+ 41

Table No.2: Total cholesterol with various TSH values

TSH uv/ml

Total cholesterol regular (mean+-SD)

0.0 to 0.3

15502+31.1

0.3 to 0.3

158.5+ 29.1

6.8 to 10.0

196.2+49.2

16.2 to 20.0

208.1+ 35.1

P value

0.000

Table No.3: Pearson correlation coefficient between FT3, FT4, TSH and total cholesterol in overt hypothyroid patient.

 

FT3

FT4

TSH

Total Cholesterol

-0.051

-0.361

0.429

Correlation is significant at 0.05 levels (1- tailed)

DISCUSSION

The association between hypothyroidism and raised cholesterol level was observed11. Hypercholesterolemia was noted in 46% of hypothyroid patients where as percentage was 4.1% in control group. P-Value was 0.000 highly significant. Cabral et al reported 50% present hypercholesterolemia in hypothyroid patient. It is reported over hypothyroidism is always been associated. Hypercholesterolemia with statistical significant difference3, 4, 12. Increase of total cholesterol can be attributed to the effect of thyroid hormones on expression of LDL receptors and CYP7A, a rate limiting enzyme in bile acid synthesis5, 10. Canorisetal reported the rise of total cholesterol level, with significant trend across grades of thyroid function13. In this study raised mean total cholesterol with modest elevation of TSH was observed as compared to that of euthyroid group14. Hypercholetmaolemia is linked with cardiovascular morbidity as observed with moralizing of hyppthpodism14. Study done by Georgic et al. concluded that subjects with high normal TSH levels combined with positive ThAab may, in fact, have subclinical hypothyroidism due to autoimmune thyroiditis presenting with elevated cholesterol levels20.

CONCLUSION

Hypothyroidism is associated with abnormal total cholesterol which can lead to cardiovascular morbidity. It has been noticed that treatment with thyroxin totally reverses the total cholesterol level. So monitoring of hypercholesterolemia with thyroxin replacement therapy is necessary to overcome the cardiovascular morbidity in hypothyroid patients.

REFERENCES

1.       Ganainazargarah, scenario of endocrinology in south Asia. Indian Endocrinol 2007; 11 1-2

2.       Puccie, chioretol, pinchera A. thyroid and lipid metabolism. Int J obesrelatmetabdisord 2000;24 suppl 2:s109-12.

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4.       Deschapjelerien, lxyebx FH scheen AJ. Thyroid disorder and dysplidemia. Reversed liege 1999;54 (9):746- 50.

5.       Duntas LH. Thyroid disease and lipids. Thyroid 2002;12(4):2807-93.

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9.       The lipid research Clinics Coronary primary preventation trial results. The relationship of reduction in coronary heart disease JAMA 1984; 251(3):351-64.

10.    Tuskra J, limavova Z antosovam. Thyroid disease, days and cardiovascular rishvnitzleh 2007;54(4): 382-5.

11.    Tankcsjoiswkangaw. Plasma cholestrylester transfer protein activity inhyper and hypothyroidism. J Clim Endocrinol 1998; 83(1):140-3.

12.    Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endoer Rev 2008; 29(1):76-131.

13.    Cararis GI, Manonitznayor G, Ridgway EC. The colorodo thyroid disease prevelance study. Arch Inter Med 2000;160(4):256-34.

14.    Aviran M, SuboshitzkyRbrook JG. Cipid and lyrofrotein pattern in thyroid dysfunction and effect of therapy. Clicbiochem 1982;15(1):62-6.

15.    Vanderpump MPJ, Tunbridge WNG, French JM, Appleton D, Bates D, Clark F, et al. The incidence of thyroid disorders in the community: a twenty year follow up of the Wickham survey. Clin Endocrinol 1995;43:55-68.

16.    Weetman AP. Hypothyroidism: screening and subclinical disease. Bri Med J 1997;134:
1175-1178.

17.    Haggerty JJ, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry 1993;150:508-510.

18.    Ross DS. Subclinical hypothyroidism. In: Braverman LE, Utiger RU, editors. Werner and lngbar’s the thyroid. 8th ed. New York: Lipincott-Williams & Wilkins; 2000.p.1001-1006.

19.    Monzani F, Di bello V, Caraccio N, et al. effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab 2001;86:1110-1115.

20.    Georgic M, Maria A, Gregory Pard Demetrious IV: High Serum Cholesterol levels in persons with high normal TSH levels should one extend the definition of subclinical hypothyroidism. Eup J Endo 1998; (138):141-45.

21.    Strand O. influence of Propylthioracil D- and L-triidothyronine on excretion of bile acids in bile fistula rats. Bile acids and steroids 118. Proc Soc Exp Biol Med 1962;109:68-672.

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23.    Rosenman RH, Byers SO, FriedMan M. The mechanisms responsible for the latered blood cholesterol content in deranged thyroid states. J Clin Endocrinol 1952;12:1287.

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3: 242.

 

Address for Corresponding Author:

Prof. Dr. Muhammad Ishaq
Chairman & Founder
Jinnah Medical College, Peshawar
Cell: +92-333-9152060

le �+n-8��0�pt'>Normal

 

Tumor

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Table 1 showing the frequency distribution of bronchogenic carcinoma with hemoptysis with respect to age. Twelve n=12 patients (92.3%) were between (61-70) years of age and one patients (7.6%) between (51-60%) years of age. Among these thirteen patients, who were found to the having bronchogenic carcinoma on biopsy.

NSCLC was found in 84.6% and SCLC was found in 15.3% of cases as shown in Table 2. Among NSCLC squamous eco carcinoma and adenocarcinoma were most frequent histopathology.

Bronchoscopic findings in patients of bronchogenic carcinoma are discussed in Table 3. Seven patients (53.84%) were found to have bronchogenic carcinoma on right side and six patients (46.15%) were found to have carcinoma on left side. Figure showing the side of lung involvement with bronchogenic carcinoma.

DISCUSSION

Smoking is responsible for majority of bronchogenic carcinoma, not only in the west13,14 but retrospective studies in Pakistan showed that smoking history was positive in 79-83% of patients with bronchogenic carcinoma15.

 Hemoptysis occurs as a presenting symptoms in 6-31% of patients with lung cancer16. Since massive bleeding is caused by erosion of the tumor into a major vessel such as pulmonary artery, it was reported that approximately 50% of patients with massive hemoptysis due to lung cancer death as compared to 28% from other causes.

FIBEROPTIC BRONCHOSCOPY plays an important role in managing hemoptysis for diagnosis and treatment17,18.

In our study bronchogenic carcinoma was found in smokers with 40 or more than 40 of smoking and almost all of them except one was in the age range of 61-70 years. This is in consistent with some western studies19. Ekim et. al 20 found that patients with hemoptysis has normal x-ray he found two patients had endobronchial lesion obvious at FIBEROPTIC BRONCHOSCOPY, one turned out to be lung cancer and other pulmonary tuberculosis, further evaluation of hemoptysis requires CT scan of chest and FIBEROPTIC BRONCHOSCOPY. Although the frequency of lung cancer in patients with normal CT chest is rear, all possible effects should be made to ensure that no lung cancer should be missed, for this reasons it is suggested that FIBEROPTIC BRONCHOSCOPY must be included in the initial evaluation of smokers, who represent high risk for lung cancer.

CONCLUSION

As the cigarette smoking is a major risk factor for bronchogenic carcinoma, come out to be the leading cause of hemoptysis, 40 or more than forty pack years of smoking should be evaluated with fiberoptic bronchoscopy which results is reduce cost compared with CT Scan of chest and many other histologic diagnosis tests.

 

REFERENCES

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9.       Suliman IM, Jibran R, Majeed ZM, Demographics of Bronchogenic Carcinoma patients and frequency of cell types. Gomal J Med Sci 2006; 4:2-6.

10.    Amanullah S, Zaidi S HM, Malik Al. Clinic-o-pathological features of lung cancer and incidence of familial malignancies a study of population in Karachi 2006; 12:23-32.

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12.    Genel Colice. Detecting lung cancer as a cause of hemoptysis in patients with normal radiograph : Bronchoscopy vs CT. Chest 1997; 111:877-884.

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14.    Alonso-Fernanadez MA, Farcia-Calmete M, Escoundero-Beuno C, Grupo-Asturpur. Characteristics of lung cancer in a region in northern Spain. Arch Bronchopulmonol 2005; 41: 478-83.

15.    Iqbal ZH, Javed M. Bronchogenic carcinoma: Endobronchial presentation and extent at the time of diagnosis. Pak J Chest Med 2001; 7:11-20.

16.    Keith Rl. Bronchogenic carcinoma and solitary pulmonary nodules. In: Hanely NH, Welsh CH, editors. Current diagnosis and treatment in pulmonary medicine. Boston: McGraw Hill; 2004.p.429-9.

17.    Taher MA, Kamash FA, Almomani JA. End tidal carbon dioxide monitoring during flexible fiber optic bronchoscopy. Pak J Med Sci 2006;22:
149-53.

18.    Sawy MS, Jayakrishnan B, Behbehani N, Abal AT, El-Shamy A, Nair MG. Flexible fiberoptic bronchoscopy. Diagnostic yield. Saudi Med J 2004; 25:1459-63.

19.    Domoua K, N’Dhatz M, Coulibaly G. Hemoptysis: Main etiologies observed in a pneumology Department in Africa. Rev Pneumol Clin 1994; 50:59-62.

20.    Ekim H, Sanisoglu IH. Hemoptysis: Bronchoscopic-computed tomographic correlation in ninety eight cases. East J Med 2000;5:2-25.

 

Address for Corresponding Author:

Prof. Dr. Muhammad Ishaq
Chairman & Founder
Jinnah Medical College Peshawar
Warsak Road, Peshawar
Cell: +92-333-9152060