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A CROSS SECTIONAL STUDY ON PREVALENCE OF THYROID ABNORMALITIES IN PEOPLE WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS AND PEOPLE

WITHOUT DIABETES MELLITUS A DISSERTATION SUBMITTED TO

THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY In partial fulfillment of the regulations for the award of the degree of

M.D. GENERAL MEDICINE – BRANCH I

DEPARTMENT OF GENERAL MEDICINE

GOVERNMENT VELLORE MEDICAL COLLEGE AND HOSPITAL

THE TAMILNADU DR.M.G.R MEDICAL UNIVERSITY CHENNAI

APRIL 2016

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CERTIFICATE

This is to certify that the dissertation titled

“A CROSSSECTIONAL STUDY ON PREVALENCE OF THYROID ABNORMALITIES IN PEOPLE WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS AND PEOPLE WITHOUT DIABETES MELLITUS” is a genuine work done by Dr. VIJAYAKUMAR N, Post Graduate student (2013–2016) in the Department of General Medicine, Government Vellore Medical College, Vellore under the guidance of Prof.Dr.D.Anbarasu MD.

Date: Prof. Dr. D. Anbarasu, M.D., Guide and Chief, Medical Unit- II, Department of General Medicine, Govt. Vellore Medical College.

Date: Prof. Dr. J. Philomena, M.D., Head of the Department,

Department of General Medicine, Govt. Vellore Medical College.

Date: Prof.Dr.G.Selvarajan, M.S.,DLO., The Dean,

Government Vellore Medical College.

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DECLARATION

I, DR. VIJAYAKUMAR N solemnly declare that this dissertation titled “A CROSS SECTIONAL STUDY ON PREVALENCE OF THYROID ABNORMALITIES IN PEOPLE WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS AND PEOPLE WITHOUT DIABETES MELLITUS” is a bonafide work done by me in Department of General Medicine, Government Vellore Medical College and Hospital, Vellore under the guidance and supervision of Prof. Dr.D.Anbarasu M.D.,Guide and Chief, Medical Unit- II.

This dissertation is submitted to The Tamilnadu Dr. M.G.R.

Medical University, Chennai in partial fulfillment of the university regulations for the award of M.D., Degree in General Medicine (Branch – I)

Place : Vellore DR.VIJAYAKUMAR N

Date :

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ACKNOWLEDGEMENT

It gives immense pleasure for me to thank everyone who has helped me during the course of my study and in preparing this dissertation.

My sincere thanks to Prof.Dr.G.Selvarajan, M.S., DLO., the Dean, Govt. Vellore Medical College for permitting me to conduct the study and use the resources of the College.

I am very thankful to the chairman of Ethical Committee and members of Ethical Committee, Government Vellore Medical College and hospital for their guidance and help in getting the ethical clearance for this work.

I am deeply indebted to my esteemed teacher, Chief and guide Prof.Dr.D.Anbarasu MD, for his active involvement at all times. I feel it was my good fortune to have had Prof.Dr.D.Anbarasu MD as my guide and teacher. He has been a source of constant inspiration and encouragement to accomplish this work. With a deep sense of gratitude I acknowledge the guidance rendered to me by him.

I express my sincere thanks to Prof.Dr.J.Philomena MD, Professor and Head, Department of General medicine for her timely advice and valuable suggestions in preparing this dissertation.

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I express my sincere gratitude to Prof. Dr.S.P.Kumaresan M.D., for his valuable inputs and support.

I express my deepest sense of thankfulness to my Assistant Professors Dr.M.Rangaswamy MD, Dr.P.S.Ramesh MD,

Dr.C.Govindaraju MD, for their valuable inputs and constant encouragement without which this dissertation could not have been completed.

I am particularly thankful to my fellow postgraduate colleagues Dr. Arun Natesh R, Dr. Chandru J and Dr. Magudeeswaran R for

their valuable support in the time of need throughout the study.

I thank my junior Post Graduate Dr. Aravind C S who supported me in completing the dissertation.

It is my earnest duty to thank my parents and wife without whom accomplishing this task would have been impossible.

I am extremely thankful to my patients who consented and participated to make this study possible.

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LIST OF ABBREVIATIONS

ADA - American Diabetes Association BMI - Body Mass Index

CAD - Coronary Artery Disease DIT - Diiodotyrosine

DM - Diabetes Mellitus FBS - Fasting Blood Sugar

FNAC - Fine Needle Aspiration Cytology HbA1c - Glycated Hemoglobin

HCG - Human Chorionic Gonadotrophin HDL - High Density Lipoprotein

LDL - Low Density Lipoprotein MIT - Mono Iodo Tyrosine NIS - Sodium Iodide Symporter PPBS - Post Prandial Blood Sugar T3 - Triiodothyronine

T4 - Thyroxine

TBG - Thyroxine Binding Globulin TBPA - Thyroxine Binding Pre Albumin TPO - Thyroperoxidase

TTR - Transthyretin

TRH - Thyrotrophin Releasing Hormone VLDL - Very Low Density Lipoprotein

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ABSTRACT

Background

Thyroid function abnormalities are commonly seen in type 2 diabetes mellitus. The prevalence of thyroid abnormalities in diabetes mellitus varies from 10% to 30% in different parts of the world.

Recognition and early intervention of thyroid dysfunction may significantly reduce the risk of adverse cardiovascular and cerebrovascular events in people with diabetes mellitus.

Aims and objectives

To compare the prevalence and distribution of thyroid function abnormalities in people with newly diagnosed type 2 diabetes mellitus and people without diabetes mellitus.

Methods

In this cross sectional study 194 subjects with newly diagnosed type 2 diabetes mellitus and 190 subjects without diabetes mellitus were investigated for fasting and postprandial blood sugar, free T3,free T4,TSH, total cholesterol and triglyceride levels.Statistical analysis was done using SPSS 16 software.The difference between various parameters was considered statistically significant when the p value was < 0.05 Results

The prevalence of thyroid dysfunction was significantly higher in people with newly diagnosed type 2 diabetes mellitus (23.7%) than

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people without diabetes mellitus(6.3%) ( p value < 0.001).Prevalence of thyroid dysfunction among males is 9.94% and among females is 20.20%( p value 0.004). Among people with newly diagnosed type 2 diabetes mellitus the prevalence of subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, overt hyperthyroidism are 16.5%, 4.6%,2.1%,0.5% respectively. Among non diabetic subjects the prevalence of subclinical hypothyroidism, overt hypothyroidism and subclinical hyperthyroidism are 4.7%,1.1%,0.5% respectively. Mean age of people with thyroid dysfunction is 51.29% + 9.74years and in people without thyroid dysfunction is 50.77+10.08years (p value > 0.05).

Conclusion:

Thyroid function abnormalities are more common in people with newly diagnosed type 2 diabetes mellitus than non-diabetic subjects and the prevalence is higher in females than males. Subclinical hypothyroidism is the most common thyroid abnormality both in diabetic and non diabetic subjects. Our study emphasis the need to check thyroid function status in people with diabetes mellitus.

Keywords: type 2 diabetes mellitus, thyroid dysfunction, TSH, free T3, free T4.

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TABLE OF CONTENTS

S.NO TITLE PAGE NO

1 INTRODUCTION 1

2 AIM OF THE STUDY 3

3 REVIEW OF LITERATURE 4

4 MATERIALS AND METHODS 40

5 RESULTS AND ANALYSIS 45

6 DISCUSSION 73

7 SUMMARY OF RESULTS 81

8 CONCLUSION 83

9 BIBLIOGRAPHY

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ANNEXURES PROFORMA MASTER CHART CONSENT FORM

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INTRODUCTION

Diabetes mellitus is a common endocrine disorder that involves multiple organs of the body leading to significant morbidity and mortality due to its accompanying complications. It is characterised by high blood sugar due to abnormality in the carbohydrate, protein and fat metabolism. The basic pathology in diabetes mellitus is defective insulin secretion or action. The burden of diabetes mellitus in India as estimated by World Health Organisation was 31.7 million in the year 2000 and 50.8 million in the year 20101. This number is expected to rise to 87 million in the year 20301.The Indian Council of Medical Research estimated that India has a prevalence of 77.2 million people with prediabetes and 62.4 million people with diabetes in the year 20112.

Thyroid disorders are the second common endocrine disorders occurring next to diabetes mellitus7. The prevalence of thyroid diseases are higher in people with diabetes mellitus than those without diabetes mellitus3,4.Insulin and thyroid hormones play vital role in maintenance of cellular metabolism.

Abnormality in one hormone level may alter the functional state of other hormone. Of all the thyroid dysfunctions subclinical hypothyroidism is the most common abnormality as per previous studies5,6,7

Autoimmunity is the main reason explaining the association between type 1 diabetes mellitus and thyroid dysfunction. Though the mechanism behind association between type 2 diabetes mellitus and thyroid dysfunction is

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not clear it could be due to abnormal TSH response to TRH, absence of nocturnal TSH peak and a low T3 state3.

Recognition and management of thyroid dysfunction in diabetes mellitus helps to achieve a good glycemic control, decrease the cardiovascular risk and improve the general wellbeing. This study aims to estimate the prevalence of thyroid function abnormalities in people with newly detected diabetes mellitus and to compare it with the non diabetic population attending the outpatient department of Government Vellore medical college Hospital during the period between august 2014 and July 2015.

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AIM OF THE STUDY

1. To compare the prevalence of thyroid function disorders in people with newly diagnosed type 2 diabetes mellitus and those without diabetes mellitus

2. To study the distribution of thyroid function disorders in people with newly detected type 2 diabetes mellitus and those without diabetes mellitus.

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REVIEW OF LITERATURE

HISTORICAL REVIEW

The term diabetes was coined by Aretaeus of cappadocia during second century9. The word diabetes is derived from greek work dia(through) and bianeon (to go) meaning a siphon “because fluid does not remain in body but uses man’s body as a ladder whereby to leave it as if patient was a siphon”

which described polyuria8. He described the disease as “melting down of flesh into urine, thirst unquenchable, kidneys never stop making water”8,9,10. Charaka, sushrutha and vaghbatha described the sweet taste of urine in patients with polyuria during 5th and 6th century BC and the disease is named

‘madhumeha’ in Sanskrit literature. They described that the urine of these patients were sticky to touch, tasted like honey and ants were strongly attracted to it. They described two forms of disease where one form affects thin individual who has a lesser survival and the other form affects obese and elderly people. This observation is parallel to the two types of diabetes, type 1 and type 2. They also described the relation of diabetes to sedentary life style, obesity, diet and hereditary factors11.

Endemic goitre was known to doctors of antiquity in China, India and Greece. Wharton gave the name thyroid which means ‘shield’ and he considered that this is a structure especially in females that gives rotundity and beauty to the neck.

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In the 16th century Andrecos vesslius described thyroid gland as two glands situated on the root of the larynx which are large fungus like flesh coloured and covered with blood vessels.

Eustachius (1520-74 AD) discovered the isthmus of thyroid gland.

Albercht von haller(1708-1777) was the first person to classify thyroid gland among the ductless glands.

Dendall of Mayo clinic in 1915 was the first to isolate the thyroid hormone, thyroxine.

Charles Robert Harington first described the exact chemical structure of thyroxine in the year 1926 and he was the first to synthesis the hormone artificially in laboratory12.

ANATOMY OF THYROID GLAND:

Development of thyroid gland commences in the third week of intrauterine life from the primitive pharynx. From there it descends along thyroglossal duct to the anterior aspect of neck. Because of this feature ectopic thyroid locations are at the base of the tongue (lingual thyroid) or along the pathway of the descent of thyroglossal duct. From 11weeks of intrauterine life the metabolic activity of thyroid gland begins and it secretes the thyoid hormones13.The thyroid medullary C cells are derived from the neural crest derivatives of the ultimobranchial body. These C cells are present dispersed throughout the thyroid gland . Factors having vital role in thyroid

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organogenesis are TTF 1,TTF 2,PAX 8. These factors also contribute to the induction of genes of thyroglobulin, thyroid peroxidase(TPO) & TSH- Receptor13. Mutation in these genes or their transcription factors can cause thyroid dyshormonogenesis or thyroid agenesis.

The word thyroid is derived from Greek in which ‘thyreos means shield’ and ‘eidos means form’. The thyroid gland is situated anerior to trachea between the cricoid cartilage and suprasternal notch. It has two lobes connected by an isthumus. The thyroid is a highly vascular gland with arterial supply from the superior and inferior thyroid arteries and from the artery thyroidea ima14.The normal thyroid blood flow is between 4 and 6mL/minute per gram.

In hyperthyroid states resulting from Graves’ disease, blood flow may exceed 1 L/minute and may be associated with an audible bruit or even a palpable thrill.

The venous drainage of thyroid gland is via the thyroid veins into internal jugular and innominate vein. The thyroid gland consists of numerous follicles that lie surrounding the colloid. The colloid is a proteinaceous fluid which contains thyroglobulin. The thyroid follicular cells has a basolateral surface and an apical surface. The basolateral surface faces the blood vessel and the apical surface is apposed to the colloid. The TSH-Receptor which is situated on the basolateral surface on stimulation by TSH stimulates the reabsorption of thyroglobulin from the colloid which undergoes proteolysis at the cytoplasm of the follicular cell and finally releases the thyroid hormone into the bloodstream.

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PHYSIOLOGY OF THYROID GLAND

The principal hormones secreted by the thyroid are thyroxine (T4) (3,5,3’,5’-Tetraiodothyronine), triiodothyronine (T3)

(3,5,3’-triiodothyronine), and calcitonin. T3 is also formed by 5’deiodination of T4 at the level of pheripheral tissues. Both T4 and T3 are iodine-containing aminoacids. Small amounts of reverse triiodothyronine ( RT3)(3,3’,5’- triiodothyronine) is also formed. RT3 is an inactive hormone. T3 is metabolically more active than T415.T4 normally occurs as levo isomers. T3 and T4 shares the same functions, but their potency and rapidity of action differs.T3 is more potent than T4.The half life of T3 is much lesser than T4.

CHEMICAL STRUCTURE OF THYROID HORMONES (figure 1)

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Iodine metabolism and transport:

Iodide after absorption from the intestine enters the systemic circulation.

These ions enter the thyroid follicles along the basolateral membrane through the sodium iodide symporter (NIS). This process enabling entry of iodides into the thyroid follicles is termed as iodide trapping. The trapped iodide is transported to apical membrane where it undergoes oxidation which is mediated by thyroid peroxidise and hydrogen peroxide. The NIS levels are regulated by blood iodine levels. Low iodine levels in the blood stimulate NIS expression and high iodine levels suppresses NIS expression. NIS gene mutations are one of the rare causes of congenital hypothyroidism. Pendrin an iodine transporter is located at the apical surface of the cell. This transporter mediates the efflux of iodine into the cell lumen. Pendrin gene mutations result in pendred syndrome a disease characterised by goitre and sensorineural deafness. The recommended average daily intake of iodine is13

150-250microgram for adults 90-120 microgram for children

250microgram for pregnant and lactating mothers

The normal urine iodine levels is more than 10microgram/dL in iodine sufficient areas.

Thyroglobulin synthesis:

Thyroglobulin is a glycoprotein secreted into the thyroid follicles. Every single molecule of thyroglobulin contains about 2769 aminoacids which includes 70 tyrosine amino acids which form the major substrates to form the

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thyroid hormones. Thus, the thyroid hormones form within the thyroglobulin molecule.

Synthesis of Thyroid Hormones:

After the initial step of oxidation is completed iodine combines with thyroglobulin molecule .This process is called as organification. Iodine combines with tyrosine residues to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). By coupling reactions MIT and DIT combines to form T3 and DIT and DIT combine to from T4. After coupling the Thyroglobulin molecule is taken up by the thyroid cells where the lysosomes act to release T3 and T4 from the thyroglobulin. MIT and DIT that are uncoupled during this process undergoes dehalogenation to release iodides that goes for recycling.

Storage of Thyroglobulin:

After synthesis and secretion, the thyroid hormones are stored in ample quantity within the follicles. This storage pool acts as a reservoir and delivers the hormones to meet the needs of the body and maintain the blood levels in normal range for a period of few months when the synthesis of thyroid hormones are lowered due to thyroid diseases.

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Table 1: CHARACTERISTICS OF THYROID HORMONES13 Hormone Property Thyroxine (T4) Triiodothyronine (T3)

Total hormone Concentration 8 μg/dL 0.14 μg/dL Fraction of total hormone in the

free form

0.02% 0.3%

Unbound hormone 21 x 10-12 M 6 x 10-12 M

Serum half-life 7 days 0.75 days

Fraction directly from the thyroid

100% 20%

Rate of production 90 μg/d 32 μg/d

Intracellular hormone fraction 20% 70%

Relative metabolic Potency 0.3 1

Factors regulating hormone synthesis and release:

TSH acts on TSH Receptor (TSH-R) located on the basolateral surface of the thyroid follicular cell which is coupled to the Gs alpha which in turn activates adenylyl cyclase that increases cyclic AMP production which ultimately leads to release of thyroglobulin.

THYROID HORMONE TRANSPORT AND METABOLISM:

Major fraction of thyroid hormones are bound to the plasma proteins thyroid binding globulin, transthyretin (thyroid binding prealbumin), albumin.

Since the unbound hormone is the biological active form, the homeostatic

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mechanisms regulates the hypothalamo pituitary thyroid axis in such a way to maintain the normal concentration of these hormones16. A number of abnormalities of the thyroid hormone binding proteins result in abnormal levels of total T3 and T4 with normal levels of unbound hormones. This makes free T3 and T4 a better tool to detect the thyroid function abnormalities than the total T3 and T4 levels17.

THYROID HORMONE SYNTHESIS (figure 2)

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Table 2: PHYSIOLOGICAL EFFECTS OF THYROID HORMONES18

TARGET TISSUE EFFECT MECHANISM

Heart Chronotropic

Increase the number and affinity of beta adrenergic

receptors

Heart Inotropic

Enhances responses to circulating catecholamines Increases proportion of alpha

myosin heavy chain Adipose tissue Metabolic Stimulate lipolysis

Muscle Metabolic Increase protein breakdown

Bone Developmental

Promote normal growth and skeletal development.

Increases bone turnover Central Nervous system Developmental Promotes normal brain

development

Gut Metabolic Augments rate of

carbohydrate absorption Lipoprotein Metabolic Potentiates formation of LDL

receptors

Other Calorigenic

Increases cellular oxygen consumption

Increases metabolic rate

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REGULATION OF THYROID HORMONES (figure 3)

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The spectrum of thyroid function abnormalities include 1. Overt hypothyroidism

Low free T3& free T4 levels High TSH levels

2. Subclinical hypothyroidism Normal free T3& free T4 levels High TSH levels

3. Overt hyperthyroidism High free T3& free T4 levels Low TSH levels

4. Subclinical hyperthyroidism Normal free T3& free T4 levels Low TSH levels

HYPOTHYROIDISM

Iodine deficiency remains the common cause of hypothyroidism worldwide13.

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Epidemiology:

Primary hypothyroidism is common. Large Population based surveys had estimated the prevalence of hypothyroidism around 5% with higher incidences in women and older age although it occurs in men and younger individuals19. The prevalence of hypothyroidism is 3.9% among the adult population in India20.

The causes of hypothyroidism are :

1. PRIMARY HYPOTHYROIDISM Autoimmune hypothyroidism

Hashimoto's thyroiditis, atrophic thyroiditis Iatrogenic

Radioiodine, thyroidectomy, external irradiation Drugs

Iodine excess, lithium, antithyroid drugs, p-aminosalicyclic acid, interferon-α, aminoglutethimide

Iodine deficiency

Congenital hypothyroidism

Agenesis of thyroid gland, ectopia of thyroid gland, abnormal thyroid hormone synthesis

Infiltrative disorders

Amyloidosis, sarcoidosis, hemochromatosis, scleroderma, cystinosis, Riedel's thyroiditis

Overexpression of type 3 deoiodinase in infantile hemangioma

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2. SECONDARY HYPOTHYROIDISM Hypopituitarism

Tumors, surgery, radiation, trauma, Sheehan's syndrome, genetic forms of combined pituitary hormone deficiencies, infiltrative disorders Isolated TSH deficiency or inactivity

Bexarotene treatment Hypothalamic disease

Tumors, trauma, infiltrative disorders, idiopathic 3. TRANSIENT HYPOTHYROIDISM:

Silent thyroiditis Subacute thyroiditis

Withdrawal of thyroxine therapy in patients with intact thyroid gland After I131 treatment or thyroidectomy in Graves disease

Clinical features of hypothyroidism:

Symptoms Tiredness, weakness

Dryness of skin Feeling cold Hair loss

Difficulty concentrating and poor memory Constipation

Weight gain with poor appetite Dyspnea

Hoarse voice

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Menorrhagia (later oligomenorrhea or amenorrhea) Paresthesia

Impaired hearing

Signs

Dry coarse skin; cool peripheral extremities Puffy face, hands, and feet (myxedema) Diffuse alopecia

Bradycardia Peripheral edema

Delayed tendon reflex relaxation Carpal tunnel syndrome

Serous cavity effusions Screening for hypothyroidism:

Screening for hypothyroidism is indicated in21 All neonates

Trisomy 21

Antenatal mother

Thyroid disorder in family Associated autoimmune diseases

Patients taking drugs that alter thyroid function Mental Depression

Dyslipidemia

People with thyroid nodule

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Laboratory evaluation of hypothyroidism:

TSH is elevated with low T4 in clinical hypothyroidism. In secondary hypothyroidism the TSH levels are low in addition to T4, T3. In subclinical hypothyroidism the TSH alone is elevated but not more than 10uIU/ml with normal T4 and T3 levels. Anti TPO antibodies are seen in nearly ninety percent of autoimmune hypothyroidism.

Creatine kinase, serum cholesterol and triglycerides may be elevated.

FNAC of the goitre is done to look for the presence of autoimmune thyroiditis.

Treatment:

The dosage of thyroxine replacement therapy in general is 1.6 μg per kg

per day13. Orally administered L-thyroxine is well absorbed in the fasted than fed state. Since the half life of L-Thyroxine is longer(7days), it can be given as once daily dose. The dose is titrated based on the TSH responses checked ideally after 8weeks of initiation of thyroxine. The dosages of L-thyroxine is adjusted in 12.5-25ug increments or decrements based on the TSH response.

The dose is maintained in a concentration targeting a serum TSH level between 2-3mIU/L21. Once the TSH levels are stablilised periodic measurement of TSH is done annually.

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SUBCLINICAL HYPOTHYROIDISM:

Subclinical hypothyroidism is an entity where there is a biochemical evidence of hypothyroidism with no appartent clinical features of hypothyroidism. These patients have an elevated TSH level but with a normal Free T4 value. Subclinical hypothyroidism most commonly precedes overt hypothyroidism21. The elevation in TSH will be modest and values more than 10mIU/L are often associated with hypothyroid symptoms13. Subclinical hypothyroidism may be self resolving in certain individuals or it may be persisting .In others the condition may progress further to a state of clinical hypothyroidism. The risk of progression of subclinical to overt hypothyroidism is high in patients with high initial values of TSH and presence of antiTPO antibodies21.The prevalence of subclinical hypothyroidism among males is 3%

and 6-8% among females in the general population13. The rate of progression from subclinical to overt hypothyroidism is higher in individuals with initial TSH concentrations greater than 10 mU/L and in those with positive TPO-Ab, presence of goitre13,24. Subclinical hypothyroidism is an asymptomatic stage of hypothyroidism where certain features like endothelial dysfunction and capillary basement membrane thickening are often observed. A metaanalysis done by Gao et al showed evidence of carotid intimal thickness in patients with subclinical hypothyroidism that may be attributed to elevated TSH level, dyslipidemia and hypertension. The association of subclinical hypothyroidism with dyslipidemia is more strongly found in females, elderly individuals and those with TSH levels more than 12mIU/L22.Adverse cardio vascular risk

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factors that have been associated with subclinical hypothyroidism are increased serum lipids, diastolic hypertension, impaired endothelial function, increased arterial stiffness, elevated C-reactive protein levels and abnormal coagulation parameters. Therefore thyroxine replacement therapy is adviced in people with persistingly high levels of TSH .The rate of progression from subclinical to overt hypothyroidism is nearly 20 percent per year21.It is recommended to confirm the presence of sustained elevation of TSH for a period of more than 3months before initiating thyroxine replacement therapy. Thyroxine therapy is the treatment of choice and replacement is initiated at a low dose of 25-50ug per day and adjusted on the basis of TSH response. In pregnancy and infertility with subclinical hypothyroidism full replacement dose of thyroxine is suggested. Till now there are no prospective randomised control trials to see the impact of treatment of subclinical hypothyroidism on cardiovascular events.

In summary, subclinical hypothyroidsm a frequently encountered condition has many recommendations which are based on weak evidences rather than prospective randomised control trials which are urgently needed to back the current recommendations.

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FACTORS FAVOURING LEVOTHYROXINE THERAPY IN

PATIENTS WITH A TSH LEVEL OF 5-10mIU/L:

Antenatal mother Anxious to conceive Thyromegaly

Therapeutic trial for possible hypothyroid symptoms Children

Persistent Thyroid stimulating hormone levels more than 8mIU/L Mood disorder

Infertility

Anti-thyroid antibody positivity Increasing trend of TSH levels Menstrual irregularities

Dyslipidemia?

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EVALUATION OF HYPOTHYROIDISM(figure 4)

HYPERTHYROIDISM

Hyperthyroidism is a state of excess thyroid function and thyrotoxicosis is a state of excess thyroid hormone levels13. Thyrotoxicosis is a common condition often encountered by medical practitioners of all disciples as it presents in myriad ways.

Causes :

Grave’s disease

Toxic multinodular goitre Toxic adenoma

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Thyroiditis

Subacute thyroiditis Silent thyroiditis Postpartum thyroiditis Drugs

Iodine excess (Jod-Basedow phenomenon ) Levothyroxine/triiodothyronine

Amiodarone Lithium

Interferon alpha Antiretroviral therapy Tyrosine kinase inhibitors Beta HCG mediated hyperthyroidism

Choriocarcinoma Hydatiform mole

Gestational thyrotoxicosis

Familial gestational hyperthyroidism due to TSH receptor mutations Struma ovarii

TSH secreting pituitary adenoma

Most common cause for thyrotoxicosis is Grave’s disease which accounts for 75% of cases25. Grave’s disease typically affects women of age between 30 and 50years but can occur at any age in both sexes25

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Pathophysiology:

Autoimmunity is the basic pathophysiological mechanism in Grave’s disease where autoantibodies stimulate the thyroid stimulating hormone receptor leading to increased production and secretion of thyroid hormones and hyperplasia of thyroid follicular cells as well. Genetic and environmental factors like smoking, dietary iodine and stress contribute to the pathogenesis of Grave’s disease.

Over secretion of thyroid hormones is the pathophysiological process in hyperthyroidism due to toxic multinodular goitre and solitary toxic nodule.

Histologically these nodules are benign follicular adenomas.

Relesase of preformed thyroid hormone into the circulation occurs in thyroiditis due to the inflammatory destruction of thyroid follicles.

Thyrotoxicosis in thyroiditis is usually transient.

Gestational hyperthyroidism is usually seen in the first trimester of pregnancy because of the increased secretion of Beta HCG by the placenta which is structurally similar to thyroid stimulating hormone. Gestational hyperthyroidism is more commonly observed in patients with hyperemesis gravidarum due to associated high levels of beta HCG.

Clinical features:

Symptoms:

Hyperactivity Irritability

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Intolerance to heat Excessive sweating Palpitations

Fatiguability Muscle weakness

Weight loss with increased appetite Diarrhea

Polyuria

Oligomenorrhea Loss of libido Signs:

Tachycardia

Atrial fibrillation in the elderly Tremor

Goiter

Warm and moist skin

Muscle weakness, proximal myopathy Lid retraction or lag

Gynecomastia

Graves ophthalmopathy Thyroid dermopathy Thyroid acropachy Onycholysis

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Systolic hypertension Wide pulse pressure Thyroid bruit

Signs of heart failure

Of all the clinical features, heat intolerance, palpitation, tremor, anxiety, tiredness and weight loss are the common symptoms of thyrotoxicosis. The severity of symptoms may vary in different age groups with older patients tend to have fewer symptoms. In a large cross sectional study of over 3000 population with thyrotoxicosis more than 50% of patients of age more than 61years had fewer than three classic symptoms of thyrotoxicosis26 .

In Grave’s disease there may be a diffuse thyromegaly with thrill or bruit because of hypervascularity. Staring gaze in hyperthyroidism is due to retraction of eyelids that occurs as a result of hyperactivity of the sympathetic system. The onset of Graves' ophthalmopathy occurs within the year before or after the diagnosis of thyrotoxicosis in 75% of patients. Smokers are more prone for ophtalmopathy.

Elderly individuals with thyrotoxicosis are more prone for atrial fibrillation. In a large population cohort study by selmer et al, of the 50000 adults studied the cumulative incidence of atrial fibrillation over eight years was 13% among people with age more than 65years27.

In thyrotoxic periodic paralysis patients present with acute muscle paralysis and it is commonly seen in asian men. Factors that trigger thyrotoxic

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paralysis are infection, strenuous physical activity, alcohol, high carbohydrate diet.

Thyroid storm is a rare presentation of thyrotoxicosis precipitated by poor compliance to treatment, surgery, childbirth, infection and trauma. It is a life threatening condition manifested by tachycardia, fever, agitation, altered sensorium, cardiac failure and abnormal liver function.

Thyroid dermopathy is strongly assosciated with thyroid ophthalmopathy and it is seen in <5% of patients with Grave’s disease. It is characterised by non inflamed indurated plaque typically over the anterolateral aspect of leg (pretibial myxedema).

Thyroid acropachy is a form of clubbing which is seen in patients with Grave’s disease. This condition is strongly associated with thyroid dermopathy.

Laboratory evaluation:

TSH level is low with unbound and total levels of thyroid hormones being elevated. T3 thyroxicosis is diagnosed when the patient presents with isolated elevation of T3 level and low TSH. Low TSH levels with normal Free T3 and T4 levels is called subclinical hyperthyroidism.

Graves’ disease is characterised by the presence of TSH receptor antibodies with a sensitivity of 98% and specificity of 99%. Thyroid peroxidise antibodies are positive in 75% of patients with Graves disease.

Radionuclide utake studies are done with radioactive iodide or technetium. Diffusely increased radionuclide uptake is seen in Graves’disease.

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Patchy uptake is seen in toxic nodule and toxic multinodular goitre. No uptake of radionuclide material is seen in thyroiditis.

Treatment:

The treatment modalities are thionamide antithyroid drugs, radio iodine therapy, thyroidectomy.

Available antithyroid drugs include propylthiouracil, carbimazole and methimazole. These drugs act by inhibiting thyroid peroxidise and thus decreasing oxidation and organification of iodide. Propylthiouracil acts by inhibiting the peripheral conversion of T4 to T3. The dose of carbimazole is 20-40mg daily . Methimazole is usually 15-30 mg given twice or thrice daily.

Propylthiouracil use is restricted by its serious side effect of liver injury seen in about 1 in 10000 adults.

Remission of hyperthyroidism is obtained in 4-8weeks of antithyroid drugs after which euthyroidism is maintained either by a block and replace regimen or a titrated regimen.

In block and replace regimen a fixed dose of antithyroid drug is given to block the thyroid hormone production. Replacement therapy with thyroxine is done appropriately to achieve a normal thyroid functional state. In titrated regimen the dose of antithyroid drug is periodically adjusted thereby permitting intrinsic production of thyroid hormones to occur in a regulated manner.

Pruritic rash and agranulocytosis are the reported side effects of antithyroid drugs. Antithyroid drugs given to pregnancy can cause congenital abnormalities like cutis aplasia, choanal atresia, trachea esophageal fistula,

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29

omphalocele, urinary tract and cardiac malformations. A Danish nationwide study showed birth defects in 9.1% of children born to mothers treated with carbimazole or methimazole and 8% of children born to mothers treated with propylthiouracil compared to 5.4% of children born to mothers who were left untreated with a previous diagnosis of hyperthyroidism28

Current guidelines recommend the usage of propylthiouracil for pregnant mothers with hyperthyroidism during the first trimester of pregnancy29

Propanolol can be used to reduce the symptoms of sympathetic overactivity.

Radioablation therapy with radioiodine (iodine131) is another treatment option for hyperthyroidism. This can be tried either as a first line treatment in naïve hyperthyroid patients or for those who relapse after antithyroid drugs.

The dangerous adverse effect with radioiodine therapy is its propensity to precipitate thyrotoxic crisis. This occurs due to the release of preformed thyroid hormones from the gland. Risk of such an adverse effect can be lowered by giving antithyroid drugs for a period of four weeks prior to radioiodine therapy.

The beta radiation has a 2mm radius of activity and it produces death of thyroid cells by inducing DNA damage. Current UK guidance recommends 370- 550Mbq of radio iodine for Graves’disease. Radioiodine is preferred in young males of age less than 40 years and those with a large goitre and patients who are unlikely to achieve long term remission with thionamide drugs. Lifelong necessity of levothyroxine replacement has to be informed before starting

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30

radioablation. Pregnancy and lactation are absolute contraindications for radioiodine therapy. Radioiodine should not be used in patients with active Graves’ophthalmopathy.

Subtotal or near-total thyroidectomy is considered in patients who develop recurrence of the disease following drug therapy, those with a large goitre or those with active Graves’ ophthalmology.Complications following thyroidectomy include hypocalcemia due to hypoparathyroidism, vocal cord paralysis due to recurrent laryngeal nerve injury.

SUBCLINICAL HYPERTHYROIDISM:

Subclinical hyperthyroidism is a condition in which the TSH levels are suppressed below normal in the context of normal free thyroid hormone levels and without clinical symptoms and signs. The prevalence of subclinical hyperthyroidism in the general population is estimated to be around 0.7%(NHANESIII). Suppression of TSH levels may be caused by drugs like opiates, levodopa, metformin, steroids and levothyroxine. Epidemiological studies show evidences that the risk of atrial fibrillation is increased in patients with low TSH30. Annual checkups for thyroid function tests has to be carried out in patients with subclinical hyperthyroidism to detect progression to overt thyrotoxicosis.

Indications for Treatment of Persistent Subclinical Hyperthyroidism31: Osteoporosis in postmenopausal women

Rheumatic heart disease with left atrial enlargement or atrial fibrillation New-onset atrial fibrillation or recurrent cardiac arrhythmias

Congestive cardiac failure

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31

Angina pectoris

Infertility or menstrual abnormalities

Nonspecific symptoms such as fatiguability, nervousness,mental depression, or gastrointestinal disorders especially in patients of age more than 60 years.

EVALUATION OF HYPERTHYROIDISM (figure 5)

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THYROID AND DIABETES

Diabetes mellitus is characterised by high blood sugar as a result of complex interplay between environmental and hereditary factors.

Hyperglycemia in diabetes mellitus is due to lack of or defective secretion of insulin. The thyroid hormones elevates blood glucose level by stimulating hepatic gluconeogenesis and glycogenolysis thereby opposing insulin action.

They also up-regulate the expression of genes such as GLUT-4 involved in glucose transport and phosphoglycerate kinase, involved in glycolysis respectively, thus acting as an insulin agonist in facilitating glucose disposal and utilisation in peripheral tissues32.Thyroid hormones upregulates GLUT 2 expression there by facilitating increased hepatic glucose output33. This shows that the interaction between thyroid hormones and insulin is complex and thus there is an intersecting underlying pathology between diabetes mellitus and thyroid dysfunction.

The prevalence of thyroid disorders is higher in diabetic populations compared with the normal non diabetic population3,4,6,7. Among the various thyroid dysfunctions subclinical hypothyroidism is the most common abnormality noted in diabetic subjects5,36,37.

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THYROID HORMONE AND GLUCOSE INTERACTION

A population based study conducted among general population in cochin, India showed the prevalence of subclinical and overt hypothyroidism is 9.4% and 3.9% respectively and subclinical and overt hyperthyroidism is 1.6%

and 1.3% 20.

The first publication on association between diabetes mellitus and thyroid dysfunction was made in the year 197938 .After that a number of studies on thyroid function abnormalities in diabetic patients have been

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34

reported with varied percentage of prevalence ranging from 2.2 to 17%38,39. However there are a few studies that estimated the prevalence of thyroid abnormalities in diabetes as close as 31% 40.

EFFECTS OF THYROID DYSFUNCTION ON DIABETES:

1.Hyperthyroidism and diabetes

Presence of hyperthyroidism affects the diabetic status. Hyperthyroidism leads to accelerated turnover of insulin by increasing the insulin clearance thereby worsening the glycemic status. Excess thyroid hormones increase the absorption of glucose from the intestines and hepatic glucose output as well contributing to hyperglycemia.

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Thus hyperthyroidism in diabetic population may worsen their glycemic control and lead on to precipitation of diabetic ketoacidosis41,42. Indeed Thyrotoxicosis may unmask latent diabetes. Thus in patients with hyperthyroidism the diagnosis of glucose intolerance needs to be considered cautiously, since treatment of thyrotoxicosis may result in improvement of hyperglycemia. In diabetic patients with unexplained worsening of hyperglycemia, underlying hyperthyroidism should be considered. Insulin resistance is also seen in subclinical hyperthyroidism as evidenced by many studies45,46. Correction of hyperthyroidism may lower the hyperglycaemic status to euglycemia43.

Increased beta oxidation in liver and lipolysis are the possible mechanisms explaining ketoacidosis in patients with hyperthyroidism43,44.

2.Hypothyroidism and diabetes:

In hypothyroidism there is a state of reduced disposition of glucose to skeletal muscles and adipose tissue because of the reduced levels of GLUT 4 transporters whose expression is upregulated by normal levels of thyroid hormones47.On the contrary hepatic glucose production is decreased in hypothyroidism48.In patients with diabetes mellitus and hypothyroidism the clearance of insulin is lowered and the sensitivity to exogenously administered insulin is increased. Thus all these effects shows that the requirement of insulin may be decreased in a patient with diabetes mellitus who develops hypothyroidism31.The most important facet that connects diabetes mellitus and

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36

thyroid dysfunction is insulin resistance and it occurs in both hypothyroidism and hyperthyroidism49.In hypothyroidism there is a reduced rate of insulin stimulated glucose transport due to the perturbed expression of GLUT2 translocation and this leads to insulin resistance50.

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37

EFFECTS OF DIABETES MELLITUS ON THYROID FUNCTION

Alteration in thyroid hormone levels is noted in diabetic patients particularly when they have an uncontrolled hyperglycemia. In a normal healthy individual the TSH levels peak during night. This peaking of TSH is lost in diabetes mellitus along with abnormal response to thyrotropin releasing hormone3,51. Hyperglycemia in diabetes mellitus retards the conversion of T4 to T3 that normally happens in peripheral tissues. Diabetes mellitus alters the functional state of thyroid by acting either at the level of hypothalamus or at the level of peripheral tissues where in the conversion of thyroxine to triiodothyronine is reduced. As a result the levels of reverse T3 is elevated and T3 lowered. The level of T4 could be low or high or normal52.Hyperglycemia in diabetes mellitus can affect the cellular metabolism which may be further worsened by coexixting thyroid disease52.Uncontrolled thyroid function abnormalities in diabetic population may alter glycemic control in such a way that hyperthyroid patients are prone for hyperglycaemic emergencies and hypothyroid patients are prone for recurrent hypoglycaemic episodes. The duration of diabetes mellitus has no significant impact on thyroid dysfunction60,61.

Thyroid hormone replacement therapy may be inadequate in hypothyroidism when there is coexisting diabetes mellitus. Thus the efficacy of thyroxine therapy is affected by diabetes mellitus. Such an association is not seen in other diseases7.Thyroid hormone levels may be altered by the drugs that diabetic patients are taking. The biguanide oral hypoglycaemic agent,

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38

metformin can lower the TSH levels in diabetic patients on thyroxine therapy5. Insulin inhibits the conversion of thyroxine to triiodothyronine in liver thereby the levels of FT4 is increased and FT3 decreased53. Diabetes mellitus by itself is a major risk factor for cardiovascular diseases. The presence of thyroid dysfunction in diabetes mellitus may accelerate the risk of cardiovascular diseases through their relationship with dyslipidemia, insulin resistance and abnormality in vascular endothelial function3. Adequate thyroxine replacement in such patients will reverse the lipid abnormalities31,34.Hypothyroidism not only decreases the degradation of lipids but also their synthesis. However degradation of lipids is reduced to a greater extent than the synthesis with the net effect of accumulation of LDL and triglycerides54.

An elevation in serum LDL-cholesterol has been associated in most studies, with overt and subclinical hypothyroidism55,56. Other parameters in lipid profile like serum HDL and triglycerides levels are not influenced by hypothyroidism54,55. The reduction in LDL levels following levothyroxine therapy is generally in proportion to the original magnitude of LDL and TSH elevation. Higher the initial levels, greater the observed reduction in LDL55.A typical reduction in LDL is 5% to10% from the pretreatment level31. Unrecognised thyroid function abnormalities left untreated can lead on to negative impacts on diabetes mellitus and its complications. The incidence of diabetic complications like nephropathy and retinopathy are high when there is an associated subclinical hypothyroidism57,58,59. Therefore, treatment of subclinical hypothyroidism in diabetic patients will be beneficial. Earlier

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recognition and addressing thyroid dysfunction and diabetes mellitus alters the treatment strategy especially with regards to dyslipidemia and blood pressure control thereby preserving a better cardiovascular function and ultimately resulting in reduction of mortality32,34.

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MATERIALS AND METHODS

This cross sectional study on prevalence of thyroid function abnormalities in people with newly diagnosed type 2 diabetes mellitus and People without diabetes mellitus was done in Government Vellore Medical College Hospital, Vellore.

Study design:

Cross sectional study Sample size:

384 Study period:

August 2014 - July 2015 Study tool:

Self structured questionnaire Inclusion criteria:

People with newly diagnosed type 2 diabetes mellitus of age more than 30 years.

Healthy subjects of age more than 30years without diabetes mellitus.

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Exclusion criteria:

Pregnant women

People with known thyroid disorder Acute illness/infection

People taking drugs that alter thyroid function People not willing to participate in the study Methodology:

People with newly diagnosed type 2 diabetes mellitus who attended the outpatient department of Government vellore medical college hospital were included in one group and healthy people accompanying the patients coming to outpatient department were included in other group. After obtaining written and informed consent from the study population detailed history was elicited and physical examination was performed.

Venous blood was drawn from the subjects and sample was sent for blood sugar, free T3,free T4,TSH,Total cholesterol and triglyceride levels.

Patient details regarding the general information, clinical findings and investigation results are all filled in specially designed proforma.

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Ethical clearance:

This study was approved by the ethical committee of Government Vellore Medical College, Vellore.

Statistical analysis:

Statistical analysis was done by using SPSS 16 software.

Quantitative data was expressed in mean, median, mode and standard deviation. Qualitative data was expressed by Chisquare test . The difference was considered statistically significant when p value < 0.05

Operational guidelines:

Diagnosis of diabetes mellitus was based on ADA criteria:

HbA1C > 6.5%

or

Fasting blood sugar > 126mg/dl or

2 hour plasma glucose > 200mg/dl during an oral glucose tolerance test or

Symptoms of hyperglycemia and a casual plasma glucose > 200mg/dl

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Spectrum of thyroid disorders:

Subclinical hypothyroidism

Normal free T3 and free T4 Elevated TSH

Overt hypothyroidism

Low free T3/free T4 Elevated TSH

Subclinical hyperthyroidism

Normal free T3 and free T4 Decreased TSH

Overt hyperthyroidism

High free T3/ free T4 decreased TSH Dyslipidemia:

Total cholesterol > 200mg/dl Triglycerides > 150mg/dl

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44

Body mass index:

BMI was calculated using the formula, BMI = weight in kg/ height in m2

The BMI values were interpreted based on the Indian standards62 BMI 18-22.9kg/m2 = normal

BMI 23-24.9 kg/m2 = overweight BMI > 25kg/m2 = obesity

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45

193 191 MALES

FEMALES

RESULTS AND ANALYSIS

This study conducted in Government Vellore medical college hospital, Vellore included a total sample of 384 subjects of which 191 were males and 193 were females. The observations found in the study are described below.

Table 3: GENDER DISTRIBUTION OF THE STUDY POPULATION

Sex No. of patients Percentage of patients

Male 191 49.7 %

Female 193 50.3 %

Total 384 100%

CHART 1: GENDER DISTRIBUTION OF THE STUDY POPULATION

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Table 4: DISTRIBUTION OF THE STUDY POPULATION BASED ON THE DIABETIC STATUS

GROUP MALES FEMALES TOTAL

Diabetic subjects 90(46.39%) 104(53.60%) 194 Non diabetic subjects 101(53.15%) 89(46.84%) 190

Total 191 193 384

The term diabetic subjects refer to those who were newly diagnosed to have type 2 diabetes mellitus .Of the total sample of 384 subjects, 194(50.52%) were diabetics and 190(49.47%) were non diabetics . Of the diabetic subjects 90(46.39%) were males and 104(53.60%) were females. Of the non diabetic subjects 101(53.15%) were males and 89 (46.84%) were females.

In the study population 46.6 % were in the age group 30 to 49 years, 47.1% were in the age group 50-69years and 6.2 % were in the age of 70 years and above.

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47

46.60%

47.10%

6.20%

30-49yrs 50-69yrs

70yrs and above

Table 5 : AGE DISTRIBUTION OF THE STUDY POPULATION

AGE IN YEARS NUMBER PERCENTAGE

30-49 179 46.6%

50-69 181 47.1%

70 AND ABOVE 24 6.2%

TOTAL 384 100%

Chart 2: AGE DISTRIBUTION OF THE STUDY POPULATION

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Table 6: AGE DISTRIBUTION OF THE STUDY POPULATION WITH RESPECT TO DIABETIC STATUS

AGE IN YEARS DIABETIC SUBJECTS

NON DIABETIC SUBJECTS

30-49 95(49%) 84(44.2%)

50-69 87(44.8%) 94(49.5%)

70 AND ABOVE 12(6.2%) 12(6.3%)

TOTAL 194(100%) 190(100%)

Mean age of the study population in people with newly diagnosed diabetes mellitus is 50.67+ 10.07years. Mean age of the study population in non diabetic subjects is 51.03+ 9.99years.

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49 30-49YRS

50-69YRS

70YEARS &ABOVE 0

10 20 30 40 50 60 70 80 90 100

DM* NON DM

95

84 87

94

12 12

30-49YRS 50-69YRS

70YEARS &ABOVE

Chart 3: AGE DISTRIBUTION OF STUDY POPULATION WITH RESPECT TO DIABETIC STATUS

DM*: people with newly diagnosed type 2 DM

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Table 7: THYROID FUNCTION STATUS IN DIABETIC AND NON DIABETIC PATIENTS

Out of 194 subjects with newly diagnosed type 2 diabetes mellitus 23.7% had thyroid dysfunction and 76.3 % had normal thyroid function.

Among the non diabetic subjects 6.3 % had thyroid dysfunction and 93.7

% had normal thyroid function.

The percentage of thyroid function abnormalities is higher in people with newly diagnosed type 2 diabetes mellitus (23.7%) than people without diabetes mellitus (6.3%). Using chi-square tests this difference in the prevalence of thyroid dysfunction is statistically significant (p value < 0.001)

Group Euthyroid Thyroid dysfunction Total Diabetic

subjects 148(76.3%) 46(23.7%) 194

Non diabetic

subjects 178(93.7%) 12(6.3%) 190

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51 0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

newly diagnosed DM non DM 76.30%

93.70%

23.70%

6.30%

thyroid dysfunction euthyroid

CHART 4: THYROID FUNCTION STATUS IN DIABETIC AND NON DIABETIC SUBJECTS

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TABLE 8: DISTRIBUTION OF INDIVIDUAL THYROID DYSFUNCTION IN PEOPLE WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS

THYROID STATUS NUMBER OF PATIENTS

PERCENTAGE OF PATIENTS

Normal 148 76.3

Subclinical

hypothyroidism 32 16.5

Overt hypothyroidism 9 4.6

Subclinical

hyperthyroidism 4 2.1

Overt hyperthyroidism 1 0.5

Total 194 100

Among people with newly diagnosed type 2 diabetes mellitus the prevalence of subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, overt hyperthyroidism are 16.5%, 4.6%, 2.1%,0.5% respectively.

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76.30%

16.50%

4.60% 2.10% 0.50%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

CHART 5: PERCENTAGE DISTRIBUTION OF THYROID DYSFUNCTION IN PEOPLE WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS

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TABLE 9: DISTRIBUTION OF THYROID DYSFUNCTION IN NONDIABETIC SUBJECTS

THYROID STATUS NUMBER OF SUBJECTS PERCENTAGE

Euthyroid 178 93.7

Subclinical hypothyroid 9 4.7

Overt hypothyroid 2 1.1

Subclinical hyperthyroid 1 0.5

Overt hyperthyroid 0 0

Total 190 100

In our study among the 190 non diabetic subjects, the most common thyroid dysfunction was subclinical hypothyroidism and the least common abnormality was subclinical hyperthyroidism.

Among non diabetic subjects the prevalence of subclinical hypothyroidism, overt hypothyroidism and subclinical hyperthyroidism is 4.7%, 1.1%, 0.5% respectively.

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93.70%

4.70%

1.10% 0.50% 0 0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

70.00%

80.00%

90.00%

100.00%

CHART 6: PERCENTAGE DISTRIBUTION OF THYROID DYSFUNCTION IN NON DIABETIC POPULATION

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TABLE 10: DISTRIBUTION OF THYROID FUNCTION BASED ON GENDER

SEX EUTHYROID ABNORMAL

HYROID FUNCTION TOTAL

Male 172 (90.05%) 19(9.94%) 191

Female 154(79.79%) 39(20.20%) 193

384

Among the total study population of 384 subjects, 58 subjects (15.10%) had thyroid dysfunction. Of these 58 subjects with thyroid dysfunction, 39 subjects were females and 19 were males.

In the study population 20.20% of females and 9.94% of males had thyroid dysfunction. This difference in gender distribution of thyroid dysfunction is statistically significant (p value = 0.004)

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57 90.05%

79.79%

9.94%

20.20%

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

120.00%

male female

thyroid dysfunction euthyroid

CHART 7: GENDER WISE DISTRIBUTION OF THYROID FUNCTION STATUS

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TABLE 11: GENDER WISE DISTRIBUTION OF INDIVIDUAL THYROID DYSFUNCTION

Sex Euthyroid

Subclinical hypo- thyroid

Overt hypo- thyroid

Subclinical hyper- thyroid

Overt hyper- thyroid

Total

male 172 (90.05%)

15 (7.85%)

3 (1.57%)

1 (0.52%)

0 191

female 154 (79.79%)

26 (13.47%)

8 (4.14%)

4 (2.09)

1

(0.51) 193

Total 326 41 11 5 1 384

Subclinical hypothyroidism is the most common thyroid function abnormality seen in both sexes. The prevalence of subclinical hypothyroidism in males is 7.85% and in females is 13.47%.

Overt hyperthyroidism is the least common abnormality in both sexes. Among females the prevalence of overt hyperthyroidism is 0.51%

and in males no case of overt hyperthyroidism was seen.

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male female 0

20 40 60 80 100 120 140 160

180 172

15

3 1

0 154

26

8 4

1

male female

CHART 8: GENDER WISE DISTRIBUTION OF INDIVIDUAL THYROID DYSFUNCTION

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TABLE 12: DISTRIBUTION OF THYROID FUNCTION ABNORMALITIES IN SUBJECTS WITH NEWLY DETECTED DIABETES

Sex Euthyroid

Subclinical hypo- thyroid

Overt hypo- thyroid

Subclinical hyper- thyroid

Overt hyper- thyroid Male 75(83.3%) 12(13.3%) 2(2.2%) 1(1.1) 0 Female 73(70.2%) 20(19.2%) 7(6.7%) 3(2.9%) 1(1%)

Among the diabetic subjects the common thyroid abnormalities are subclinical hypothyroidism followed by overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism in that order in both sexes.

TABLE 13: DISTRIBUTION OF THYROID FUNCTION ABNORMALITIES IN NON DIABETIC SUBJECTS

Sex Euthyroid

Subclinical hypo- thyroid

Overt hypo- thyroid

Subclinical hyper- thyroid

Overt hyper- thyroid

Male 97(96%) 3(3%) 1(1%) 0 0

Female 81(91%) 6(6.7%) 1(1.1%) 1(1.1%) 0

Among the non diabetic subjects subclinical hypothyroisdism is the most common thyroid dysfunction in both sexes.

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Table 14: AGE WISE DISTRIBUTION OF THYROID DYSFUNCTION

Age No of patients with thyroid dysfunction

Percentage of patients

30-49yrs 24 41.4%

50-69 yrs 30 51.7%

70 yrs & above 4 6.9%

Total 58 100%

The prevalence of thyroid dysfunction is 51.7% in age group 50- 69years age group, 41.1% in 30-49years age group and 6.9% in people of age 70 years and above.

Mean age of people with thyroid dysfunction is 51.29+9.74years.

Mean age of people without thyroid dysfunction is 50.77+10.08 years.

This difference is statistically insignificant (p value > 0.05)

References

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