CHAPTER

NO 1

INTRODUCTION

1
Chapter no 1

Introduction

Thyroid stimulating hormone (TSH) is a hormone secreted and produced

by basophilic cells known as thyrotrophs in the interior pituitary gland in human

and other vertebrates. Thyroid stimulating hormone acts on thyroid gland and

control the thyroid secretion (Mori et al, 1978).

1.1 Thyroid gland

Thyroid gland is a part of the endocrine system in the human body. It is the

largest organ specialized for endocrine function in the human body. Thyroid gland

is butterfly in shape and consist of right and left lobes. This gland is located in the

neck (in the front of the trachea just below the larynx). In the adult the weight of

this gland is 15 to 20g. This gland is consist of thousands of follicles, a spheroidal

sac of epithelial cells called as thyrocytes, a depot of thyroid hormone precursor

and thyroglobulin (Marshall and Bangert, 2008).

The thyroid gland secretes three hormones which are thyroxin (T4),

triiodothyronine (T3), and calcitonin. The T4 and T3 are iodinated derivatives of

thyrosine and produced the follicular cells, which are separates the embryological

origin. Calcitonin is functionally different to the other thyroid hormones. It has a

big role in calcium homeostasis (Beckett and Toft, 2008). The major product of the

thyroid gland T4 (approximately 90%. Most T3 (more than 80%) is derived from

2
T4 by deiodination in peripheral tissues (liver, kidney muscle) (Marshall and

Bangert, 2008).

Thyroid hormones (THs) are essential for normal growth and development

and stimulates metabolism and most tissues. THs increase mitochondrial

oxidative phosphorylation and maintain amino acid and electrolyte transport into

cells. THs increase calorigenesis and oxygen consumption in most tissue. They

stimulates the synthesis of protein that can be structural protein or enzymes. THs

regulates carbohydrates metabolism, accelerating insulin degradation and

increasing gluconeogenesis. THs also increase the sensitivity of the cardiovascular

and nervous system (Beckett and Toft, 2008).

The synthesis of these hormones require the amino acid thyrosine and the

trace mineral iodine. The production of these iodinated amino acids begins with

synthesis of thyroglobulin that is posttranslationally modified in a series of

biochemically unique reactions. Within thyrocytes, iodide is oxidized to iodine.

This reaction is catalyzed by enzyme thyroperoxidase (TPO) in the presence of

hydrogen peroxide (H2O2). Iodine then binds to 3’ position in the tyrosil ring, a

reaction yielding 3-monoiodotyrosine (MIT). A subsequent addition of another

iodine to 5’ position of the tyrosyl residue on MIT creates 3, 5- diidotyrosine (DIT).

T4 is created by the condensation or coupling of two DIT molecules. Smaller

amounts of DIT within the thyroid can also condense with MIT to form either T3

or rT3. All the biosynthetic processes within the thyroid gland are controlled by

3
feedback mechanism within the hypothalamic-pituitary-thyroid axis (Biazhanova

and Kopp, 2009).

Iodine play a central role in thyroid physiology, being both major

constituent of thyroid hormones and a regulator of thyroid gland function.

Thyroid gland concentrates iodine (I-) against an electrochemical gradient by a

carrier-mediated mechanism driven by ATP and is under the control of thyroid-

stimulating hormone (TSH; thyrotropin). All of the subsequent steps in

biosynthesis of thyroid hormones, from oxidation and organification of iodide to

the secretion of T4 and T3 into the circulation, are stimulated by TSH and inhibited

by excess iodine (Cavalieri, 1997).

1.1.1 Effect of thyroid hormones on different body functions

Thyroid hormones effect some specific body function like stimulation of

carbohydrates metabolism, stimulation of fat metabolism, stimulation of protein

metabolism, effect on plasma and liver fats. It increase the requirements for

vitamins and also increase the basal metabolic rate (BMR). It effect the

cardiovascular system and have also excitatory effects on nervous system. It effect

the sleep, other endocrine glands and sexual functions (Guyton and Hall, 2002).

1.2 What is Thyroid Stimulating Hormone?

Thyroid stimulating hormone (TSH) is a hormone that control the thyroid

gland secretion. It is secreted by thyrotrophs in the interior pituitary gland. TSH

4
acts on thyroid gland, adipose tissues, eye etc. TSH increase the release of thyroid

hormone and causes morphological changes in thyroid tissue, and promotes

biosynthesis of the thyroid hormones through enhancement of inorganic iodide

uptake, iodination of thyrosine in thyroglobulin, and change of iodothyrosine to

thyroid hormones. Thyroid stimulating hormone promotes metabolism of

glucose, phospholipids and nucleic acids in the thyroid. In the adipose tissue, TSH

enhances glucose uptake, degradation of lipids, and oxygen consumption (Woeber

and Braverman, 1979).

Thyroid stimulating hormone (TSH) stimulates the production and

secretion of the metabolically active thyroid hormones, thyroxin (T4) and

triiodothyronine (T3), by interacting with a specific receptor on the thyroid cell

surface (Rees et al, 1977). T3 and T4 are responsible for regulating diverse

biochemical processes throughout the body which are essential foe normal

development and metabolic and neural activity (Sterling and Lazarus, 1977).

Thyroid stimulating hormone (TSH) receptors penetrates the cell

membrane 7 times and is coupled with G-protein-PKA system. TSH and TSH

metabolites bind to cell membrane of retro orbital tissue and increase adenylate

cyclase activity, causing exophthalmos (Woeber and Braveman, 1979).

1.2.1 Structure and composition

Thyroid stimulating hormone (TSH) or thyrotropin is a glycoprotein with a

molecular weight of approximately 28,000 Daltons, synthesized by the basophilic

5
cells (thyrotropes) of the anterior pituitary (Pierce, 1971). TSH is composed of two

non-covalently linked subunits designated alpha and beta. Although the alpha

subunits of TSH is common to luteinizing hormone (LH), follicle stimulating

hormone (FSH), and human chorionic gonadotropin (HCG), the beta subunits of

these glycoproteins are hormone specific and confer biological as well as

immunological specificity. Both alpha and beta subunits are required for biological

activity (Pierce, 1971). The synthesis and secretion of TSH is stimulated by

thyroprotein releasing hormone “TRH” (Sterling and Lazarus, 1977).

1.2.2 History

The history of TSH began with the discovery of thyroid-stimulating activity

in the pituitary gland. Edward Uhlenhuth was first demonstrated that the interior

lobe of the pituitary gland secretes a thyroid stimulator using some species of

salamanders (Uhlenhuth, 1927). In 1929 two scientist names Leob and M Aaron

works independently confirmed Uhlenhuth’s results using Guinea pig. These

initial findings were followed in the 1960s by the purification of TSH (Ladenson et

al, 2000). In the early 1970s by the determination of the primary structure of the

TSH subunits. In the 1980s, the cloning of the human δ-subunit gene, were the

important milestones in studding TSH expression, regulation, and action from the

basic science stand point (Magner and Endocr, 1990 and Gurr et al, 1983). Another

major breakthrough occurred in 1994 with the elucidation of the crystal structure

of the closely related Human Chorionic Gonadotropin (HCG) which indicated that

6
the glycoprotein hormones belong to the super family of Cystine-Knot Growth

Factors (Lapthorn et al; 1994 and Lustbader et al; 1994).

Then in 1966 it was found that TSH exerts its biological effects by binding

to a protein on the thyroid cell plasma membrane (Pastan et al; 1966).

1.2.3 Effects of TSH on thyroid gland and human body

TSH effect the thyroid gland secretion such as T3 and T4 by the thyroid

gland. The specific effects of TSH on thyroid gland on are as follow.

. It increase the proteolysis of the thyroglobulin that has already been store

in the follicles, with resultant release of the thyroid hormones into the circulating

blood and the diminishment of the follicular substance itself (Dumont et al; 1992).

. It increase the activity of iodine pump, which increase the rate of iodine

trapping (Dumont et al; 1992).

. It increase the iodination of thyrosine to form the thyroid hormones

(Dumont et al; 1992).

. It increased the size and secretary activity of the thyroid cells (Dumont et

al; 1992).

1.2.4 Diseases causes due to the TSH abnormality / Thyroid disorders

The thyroid disorders is related to either over/excessive or low/inadequate

production of thyroid hormones which regulate TSH that leading to the

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hyperthyroidism and hypothyroidism respectively (Roderick and Whaley, 1994).

The thyroid level can be detected in blood serum. Disease showing low blood TSH

levels are hyperthyroidism, pan hypopituitarism, isolated TSH deficiency,

Sheehan’s syndrome, etc. on other side diseases showing high blood TSH level are

pituitary tumor, ectopic TSH-producing tumor, hypothyroidism etc (Mori and

Wakabayashi, 1978).

1.2.4.1 Hyperthyroidism

Hyperthyroidism also called as Thyrotoxicosis. It is an abnormal condition

of thyroid gland in over secretion of thyroid hormones characterized by an

increased metabolism and weight loss (Roderick and Whaley, 1994). The patient

with hyperthyroidism may present emotional fragility, body weight loss,

excessive perspiration, diarrhea, trembling, hypercholesterolemia, heat

intolerance or menstrual cycle irregulation. Hyperthyroidism is a pathological

syndrome in which tissue is exposed to excessive amounts of circulating thyroid

hormone (Harjai and Licata, 1997). If there is too much thyroid hormone secreted

then every function of the body tends to speed up (Tomer and Davies, 1993).

Hyperthyroidism is caused by elevated free T3 and T4 levels and

characterized by nervousness, hyperactivity, restlessness, tachycardia and cardiac

arrhythmia, and weight loss due to the increase of basal metabolic rate (BMR). The

hyperthyroid persons have different difficulties like tolerating exercise, alteration

in cardiovascular system and thyrotoxic myopathy (muscles weakness and

8
atrophy) which often occur in severe cases. High level of thyroid hormones may

cause the myocardial infarction, increase risk for osteoporosis and may increase

insulin requirements for diabetics (Tomer and Davies, 1993).

The main cause of hyperthyroidism is Graves’s disease. Graves’ disease is

an autoimmune disorder in which antibodies (TS Ab) against the TSH receptor act

to stimulate the thyroid in the absence of TSH. This usually results in goiter

formation due to chronic and uncontrolled thyroid stimulation, with T3 levels

usually increased more than those of T4 (Tomer & Davies, 1993).

Another cause is toxic adenoma which are non-malignant but produce T3

and T4 autonomously. As might be expected, these patients present with high T4,

very high T3, and low TSH (Tomer & Davies, 1993).

Hyperthyroidism is also cause due to the pituitary adenoma. Pituitary

adenomas secrete TSH, resulting in hyperthyroid condition and goiter. The

adenomas usually do not respond to TRH (Tomer & Davies, 1993).

Other causes of hyperthyroidism are excessive T3 and T4 ingestion,

thyrotoxicosis facticia (thyroid hormone ingestion), ectopic thyroid tissue and

thyroid malignancy also called as thyroid cancer which is very markedly

decreased ability to produced thyroid hormone (less than 1% of normal tissue) etc

(Tomer & Davies, 1993).

9
 The symptoms of hyperthyroidism are nervousness, irritability, increased

sweating, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of the

skin, fine brittle hair and weakness in the muscle commonly in the upper arms and

thighs. In hyperthyroidism the patient may have more frequent bowel

movements, but diarrhea is uncommon. The patient may lose weight despite a

good appetite and, for women, menstrual flow may lighten and menstrual periods

may occur less often. Since hyperthyroidism increases the body metabolism, many

individuals initially have a lot of energy. However, as the hyperthyroidism

continues, the body tends to break down, so being tired is very common.

Hyperthyroidism usually begins slowly but in some young patients these changes

can be very abrupt. At first, the symptoms may be mistaken for simple

nervousness due to stress. Hyperthyroidism in Graves’ disease (also known as

Basedow’s Disease), which is the most common form of hyperthyroidism, the eyes

may look enlarged because the upper lids are elevated. Sometimes, one or both

eyes may bulge. Some patients have swelling of the front of the neck from an

enlarged thyroid gland (goiter) (Tomer and Davies, 1993).

Hyperthyroidism can be treated by antithyroid drugs like methimazole or

propylthiouracil. It is also be treated radioactive iodine to destroy the thyroid cells

that make the thyroid hormones (Tomer and Davies, 1993).

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1.2.4.2 Hypothyroidism

Hypothyroidism is an underactive thyroid gland. Hypothyroidism means

that the thyroid gland can’t make enough thyroid hormone to keep the body

running normally. People are hypothyroid if they have too little thyroid hormone

in the blood. Hypothyroidism is a condition in which the thyroid gland is not able

to produce enough thyroid hormone. In this condition people have symptoms

associated with a slow metabolism. Hypothyroidism has been associated with a

reduction in bone density, growth retardation, congestive cardiac insufficiency,

bradycardia, constipation, body weight gain or myxedema. Hypothyroidism, like

hyperthyroidism, probably is initiated by autoimmunity against the thyroid

gland, but immunity that destroys the glands rather than stimulates (Shargel et al;

2013).

Hypothyroidism can be either subclinical or overt. Subclinical

hypothyroidism is characterized by high TSH concentration and normal fT4 and

fT3 concentration in the serum. Such patients will be asymptomatic. In overt

hypothyroidism, the TSH levels will be high and fT4 levels will be low. Patients

with a high serum TSH concentration and a low serum fT4 confirm the diagnosis

of hypothyroidism (James and Groot, 2016 and Wass, Owen and Turner, 2014)

Secondary hypothyroidism can be due to pituitary disorder, Sheehan’s

syndrome, trauma and hypophysitis. Patients with macro adenoma are

11
hypothyroid after surgery or radiation. These patients have other types of

pituitary hormone deficiency (Shargel et al; 2013).

Tertiary hypothyroidism is attributed to deficiency in TRH to stimulate the

pituitary. Most patients with central hypothyroidism have low or normal serum

TSH concentrations (James and Groot, 2016). Secondary and tertiary

hypothyroidism can be suspected in the following situations such as known

pituitary or hypothalamic disease, mass lesion in the pituitary and when

symptoms are related to other hormonal deficiencies. Resistance to thyroid

hormone (RTH), a rare syndrome is characterized by diminished response to

increased circulating levels of fT4 and fT3 and non-suppressed serum TSH. These

patients present with short stature, hyperactivity, goiter, learning disability and

attention deficit (Shargel et al; 2013).

Symptoms of hypothyroidism are fatigue, weakness, cold intolerance,

weight gain, decreased basal metabolic rate, edema, growth failure, dry skin,

decreased hearing etc (Shargel et al; 2013). Hypothyroid status also results in

decreased cardiac function which can lead to congestive heart failure.

Hypothyroidism can lead to both hypertension and hypercholesterolemia, and is

associated with increased risk for development of atherosclerosis (Weetman and

Macgregor, 1994).

The major causes of hypothyroidism is iodine deficiency. It is a big problem

all over the world which lead to the many problems during pregnancy and lead to

12
the goiter. Hypothyroidism may cause due to auto immune diseases,

hyperthyroidism treatment, radiation therapy and hypertension (Shargel et al;

2013).

1.2.4.3 Condition arises due to hypothyroidism

Cretinism:

Hypothyroid conditions during fetal development result in impairment of growth

and brain functioning. The hypothyroidism may be due to iodide deficiency or to

congenital defects, such as lack of TSH receptor. The result is a mentally retarded,

dwarfed newborn (Weetman and Macgregor, 1994).

Goiter:

The thyroid is capable of massive increases in size, resulting in a visually

obvious bulge in the neck. Goiter formation usually results from excessive

stimulation of the thyroid by TSH. In hypothyroid conditions, this is usually due

to low thyroid hormone production, as a result of iodide deficiency. Goiter

formation also occur due to the goitrogens which are usually involved in the

iodine uptake (Weetman and Macgregor, 1994).

Congenital goiter:

Defects in thyroglobulin synthesis or structure, or in iodide incorporation

cause neonatal goiter and hypothyroidism. In some cases increased T3 synthesis

leads to low euthyroid status, allowing essentially normal growth, but not

13
alleviating the mental symptoms. Defects in TG may result in the presence of

proteins iodinated on tyrosine and histidine in urine (in the absence of TG, TPO

uses a variety of other proteins as substrates). In some cases the defect alters the

three-dimensional structure of the TG protein, and therefore although iodination

is normal, coupling is inhibited (Weetman and Macgregor, 1994).

Excess iodide:

Paradoxically, too much dietary iodide can result in decreased thyroid

hormone production, although the thyroid usually compensates. However, the

fetus responds to excess iodide by shutting down thyroid hormone production,

resulting in goiter, hypothyroid disorders, and problems during labor (Weetman

and MacGregor, 1994).

Idiopathic myxedema:

Myxedema, a condition of puffy skin characteristic of hypothyroidism, is

in some cases not associated with any obvious cause. One possible cause is the

presence of antibodies that act as antagonists rather than the agonist-type action

of TS (Weetman and Macgregor, 1994).

Haishmoto’s syndrome:

Hypothyroidism can result from an autoimmune attack on the thyroid. It is

often subclinical, especially in early stages, due to compensating hypertrophy and

hyperplasia of undamaged thyroid tissue, and to increase in secretion of T3.

14
 Autoimmune attack on the thyroid may be associated with other autoimmune

disorders, such as Addison’s disease and diabetes mellitus (Weetman and

Masgregor, 1994).

Hypothyroidism can be treated with levothyroxine based on the TSH value.

The appropriate method of treatment depends on the duration, severity and the

prescence of other associated disorders (Shargel et al; 2013).

Objectives

The present study was design to find out the following objectives

 To find out the thyroid disorders in the population of Dir upper and Lower

 To find out the proportion of hypothyroidism and hyperthyroidism in the study

area.

 To evaluate the hypothyroidism and hyperthyroidism of the study area according

to age, gender and season wise.

15
 CHAPTER

NO 2

Review of

literature

16
Chapter no 2

Review of literature

According to Kalk. (1981) at Johannesburg in 1981, the incidence of Graves’

disease which is mainly cause hyperthyroidism and which is lead to the formation

of Goiter was 5.5 per 100,000 per year, which was lower than the rates of 50 per

100,000 reported in the United Kingdom. A 60% increasing in the incidence in

Graves’ disease was observed over a ten year period between 1974 and 1984.

According to Parl etal. (1991) in iodine –sufficient countries the prevalence

of hypothyroidism ranges from 1% to 2%, rising to 7% in individuals aged between

85 and 89 years. Hypothyroidism is ten time more prevalent in women than man.

In 2002 according to United States National Health and Nutrition

examination Survey (NHANES III), overt hyperthyroidism was detected in 0.5%

of overall population while 0.75 of the general population had subclinical

hyperthyroidism. A population base study from several care homes for aged

people in Cape Town indicated a prevalence of hyperthyroidism 0.6% and

hypothyroidism in 1.7% of the population.

According to Khan et al. (2002), in Pakistan the prevalence of

hyperthyroidism was 5.1 % and hypothyroidism was 4.1 % of the general

17
population. The prevalence of hypothyroidism and hyperthyroidism is higher in

females than males.

In 2005 different TSH cut-off limits have been reported in population-based

studies conducted in various countries. Subsequent findings confirmed that

ethnicity, iodine intake, gender, age, and body mass index can influence the

reference range of serum TSH. In fact the normal TSH upper limit was lower in

African Americans (3.6 mIU/L) than in Mexican Americans or Caucasians (4.2

mIU/L).

According to Teng et al. (2006) over the past decade in China, the

prevalence of subclinical hypothyroidism has increased (16.7%). Similar to the

data from Chinese cohorts, a large cross sectional multicity study in India reported

in 2013 remarkably high rates of hypothyroidism (10%).

Hypothyroidism is one of the commonest chronic disorders in Western

populations. In the United Kingdom, the annual incidence of primary

hypothyroidism in women is 3.5 per 1000 and men 0.6 per 1000. During 2006 12

million prescriptions for levothyroxine (50 μg or 100 μg tablets) were dispensed in

England, equivalent to about 1.6 million people taking long term thyroid

replacement therapy, about 3% of the population. The management of

hypothyroisism is generally considered straightforward and is mostly carried out

in primary care in the UK. Cross sectional surveys of patients taking levothyroxine

18
have, however, shown that between 40% and 48% are either over treated or under-

treated.

Usha et al. (2009) reports have been published from Nepal, where thyroid

dysfunction is found to be more prevalent in Nepali females (42.85%) than in

males (30.04%).

Kardara et al. (2010) conducted a population based study in India and

reported higher prevalence rate of hypothyroidism in female (11.4%) than males

(6.2%).

According to Vanderpump et al. (2011) in Europe, 44% of school-age

children still have insufficient iodine intake, and Italy seems to become mildly

iodine deficient in past decade.

According to Blatt et al. (2012); Mosso et al. (2012); Altomare et al. (2013)

and Larsen et al. (2014) the prevalence of any degree of hypothyroidism in

pregnancy has varied from 12.3% (Finnish), 15.5% (Americans), 35.3% (South

Americans) and 17% (Danish) in these recent studies.

According to Blatt et al. (2012) in the Americans study with samles from

over half a million pregnant women, there were significant differences in the

prevalence of hypothyroid disorders among Asian American women (19.3%) as

compared to African Americans (6.7%) and Caucasians (16.4%).

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 Dhanwal et al. (2013) reported from Delhi in 2013 that a hypothyroidism

prevalence of 14.3% with a cut-off of 4.5 mIU/L as upper limit of normal in a

cohort of 1000 pregnant women.

According to Unnikrishnan et al. (2013) a regional variations were reported in

India, with higher rates of hypothyroidism in inland than in coastal regions.

Among all cities, Kolkata recorded the highest prevalence of hypothyroidism

(21.67%). Cities located in the inland regions of India (Dlhi, Ahmadabad and

Kolkata) reported a significantly higher prevalence of hypothyroidism (11.73%)

than those in the coastal areas (Mumbai, Chennai and Goa) (9.45%).

A Chinese study by Li et al. (2014) showed that the Chinese population

displays 0.5 to 5.08 mU/I as first trimester reference range; as a consequence, using

the suggested 0.1 to 2.5 mU/I as reference range, about 28% of the pregnant

patients in China would suffer from hypothyroidism, versus 4% when using an

ethnically specific reference range. Not all of them will have thyroid disease.

According to Du Y et al. (20140) A Japanese study reported the occurrence

of hypothyroidism ranging between 4 and 8.5% of the population which might be

rise to about 20% in women over 60 years of age.

Goel et al. (2015) conduced a prospective observational study in all the

consecutive first trimester pregnant women attending Santosh Medical College,

Hospital, and Ghaziabad from June 2014 to April 2015. They found serum TSH

20
level normal in 66.2% women, 32.5% women had subclinical hypothyroidism and

1.3% women had overt hypothyroidism.

Deoker et al. (2015) found 22.16% subjects having thyroid dysfunction in

the study population in India. Out of these, 4.24% were overt hypothyroid, 9.44%

were subclinical hypothyroid, 2.5% overt hyperthyroid and 5.97% were found to

be subclinical hyperthyroid. They conducted study in different age of groups

among them the highest TSH concentration was seen in the age group 60—69 years

and lowest TSH was seen in age group 10—19 years.

Tiwari et al. (2016) conducted a cross sectional study on 1000 pregnant

women. Overall prevalence of hypothyroidism was found to be 10.2% with SCH

(6/4%) being commoner than OH (3.8%), 33 hypothyroid women excluded who

were already on treatment. Out of 69 remaining hypothyroid women, 48 had SCH

(69.56%) and 21 had OH (3.43%) and were categorized as group A1 and A2

successively.

According to Ahmad et al. (2016), 200 million individuals worldwide and

42 million people in India have thyroid disorder and 1.6% people at risk.

Yousaf, Shah and Jan. (2017) conducted a cross sectional study in Peshawar city

Pakistan and they found a higher prevalence rate of hyperthyroidism (60%) and

hypothyroidism (73.3%) in female as compared to male in the study population.

21
 According to Schraga. (2018) the overall incidence of hyperthyroidism is

estimated between 0.05% and 1.3%, with the majority consisting of subclinical

disease. A population based study in the United Kingdom and Ireland found an

incidence of 0.9 cases per 100,000 children younger than 15 years, showing that the

disease incidence increases with age. The hyperthyroidism is approximately 5 to

10 times less than hypothyroidism.

22
 CHAPTER

NO 3

Methods and

materials

23
Chapter no 3

Methods and Materials

3.1 Study Area Location.

District Dir is a region in northwestern Pakistan, in the Khyber

Pakhtunkhwa. It is located in foothills of the Himalayas. Before Pakistan was

created, District Dir was a princely state and it remained so until 1969 when it was

abolished by a presidential declaration, with the Dir District being created the

following year. Dir District was 5,280 square kilometers in area and lay along the

disputed border controlled by the Afghan nationalists. The region is situated

between Chitral and Peshawar. In 1996 the District was split into Lower Dir and

Upper Dir. It is bordered by Chitral to the northwest and north, Swat to the east,

Malakand to the south, Bajaur Agency to the southwest and Afghanistan to the

west (Sayed, 2015).

District Dir Upper is the upper part of old District Dir. At the time of

independence, Dir was a state ruled by Nawab Shah Jehan Khan. It was merged

with Pakistan in 1969 and later on declared a District in 1970 and it was bifurcated

into Upper and Lower Dir Districts (Sayed, 2015).

District Dir upper is situated in the northern part of Pakistan. It is bounded

on the North and northwest by the Chitral District and Afghanistan, on the East

by Swat District, and on the South by Lower Dir District. This District is divided

24
into Dir and Wari subdivisions and 5 Tehsils, including Wari, Dir. Barawl, Larjam

and Sheringal. The District is divided into 28 union councils all of which are rural.

The District include 1 National seat and 3 Provincial seats of legislative assemblies.

Fig no: 3.1 (Map of District Dir Upper)

In District Dir Upper the main language is Pashto and majority of the

people (98%) are Pashtuns. A few people are speal Hindko, Gojari and Khowar

25
Chitrali. The majority of the population in this area are Yousafzai, Swati,

Mishwani, Sahibzadgan, Miagan and Roghani. The ruling class is Yousafzai

Pashtuns.

Topography of District Dir Upper

The topography of the District Dir Upper is dominated by high mountains.

The most important mountain range is the Hindu Raj. It runs from Northeast to

Southwest along the northern border with Chitral District. In winter, whole area

remain snow covered. The mountains in Westren part of the District are covered

with forests, while the Eastren mountains range, Dir Kohistan, is barren. Dir

Kohistan is the origin of the main river of Chitral i.e. Panjkora river. District

headquarter Upper Dir is connected with metal led or shingled roads to all Tehsil

headquarters. The District is totally mountainous so there is no railways and

airports (Sayed, 2015).

Climate of District Dir Upper

The summer season is moderate and worm, where June and July are hottest

months. On average, the maximum and minimum temperature in June is about 33

and 16 degree centigrade respectively. Winter season is severely cold and harsh.

Temperature rapidly falls from November onwards. During the month of

December, January and February, temperature normally falls below freezing

point. The mean maximum and minimum temperature in January is 11 and -2

degree centigrade respectively (Sayed, 2015).

26
 District Lower Dir is the lower part of the old District Dir. At the time of

independence Dir Lower is also ruled by Nawab Shah Jehan Khan. It was merged

in Pakistan in 1969 and later on declared a District in 1970. In 996, it was bifurcated

into Upper and Lower Dir Districts. This District is located in North-western part

of KPK Province and is spread over in area of 1583 square kilometers. Apart from

small area in the south-west, the District is mostly a rugged mountainous terrain.

The District border with Swat District on its East, Afghanistan on its West, Upper

Dir and Chitral on its North and North-West respectively and Malakand and

Bajaur Agency on its South. The District is administratively subdivided into two

Tehsil which contain a total of 37 union councils. The District is represented in

provincial assembly by 4 elected MPAs. The short route that links District lower

Dir to the provincial Capital is the one that passes through District Charsada and

Malakand District. For the people coming from down country, however, the more

convenient approach is through the Mardan and Malakand Districts. There is no

railway tract leading to the District.

27
 Fig No: 3.2 (Map of District Dir Lower)

Pashto is the main language of Dir, while Gugru, Kohistani are the language of

Kohistnis and Gugars. Few people speak Hindko and Chitrali. The majority of the

population in this area belong to Isazai and Ismailzia tribes (Sayed, 2015).

Topography of the District Dir Lower

The topography of the District is dominated by the mountains and hills

which are part of the range/branches of the southern Hindukush with the highest

28
peaks in the Northern part of Dir. The majority valleys of lower Dir includes,

Timergara, Jandul, Midan, Samarbagh and Asband.

Climate of the District Dir Lower

The summer season is hot in winter is extremely cold. A steep rise of

temperature occur from May to June, and then very hot during July to the end of

August but during September weather turns normal, especially at nights. A rapid

falls in temperature occur from October onwards. In the coldest months are

December and January. The mean minimum temperature recorded for the month

of January is -8 degree centigrade. Most of the rain fall occur in the month of July,

August, December, January and February. Towards the end of the cold weather,

there are occasional thunderstorm and hailstorms (Sayed, 2015).

3.2 Study Design

The hospital based cross sectional 1 year study was conducted from

September 2018 to august 2019. Blood samples and data were collected from

patients visiting the Qazi clinical laboratory Timergara KPK Pakistan for various

tests. The exclusion criteria were diseases like kidney, bone, heart, diabetes and

liver. All the patients are belonging to different areas of Dir lower and Upper.

Approval of the study was given by the Department of Zoology and for the

conducting tests approval was given by Sahib Zada Fazal Ahad sir ‘head of Qazi

clinical laboratory”. The study subject is divided into three groups hyperthyroid,

hypothyroid and euthyroid. A total of 360 numbers of persons were examined for

29
TSH tests. They are includes gender wise, age wise and season wise, where 231 are

females and 129 are males and their ages are ranging from 30 months to 85 years.

Blood samples (5ml) was collected from each patient and keep in -20 °C. For

the further processing the samples were placed to the Cobas e 411 analyzer to

obtain the resulting value of TSH test. Cobas e 411 is an analyzer using for TSH,

T3 and T4 tests. For these tests the blood serum is kept in the CalSet, 4 x 1.3 mL

and then the CalSet placed in the analyzer machine for about 40 minutes. After 40

the machine gives the result value on screen automatically.

To the reference of American Thyroid Association the international normal TSH

value is 0.4 -- 4.0 mU/L. In Qazi clinical laboratory the normal TSH value for 1

year to 20 years is0.7 -- 6.4 mU/L, for 21 to 50 years is 0.4 -- 4.2 mU/L and for 50

to 85 and above is 0.5 -- 8.9 mU/L ( mU/L stands for milliunits per liter).

30
CHAPTER

NO 4

Results

31
Chapter 4

Results

The current study was carried out for one year to evaluate the prevalence

of thyroid stimulating hormones in District Dir upper and lower, also analyzed

the hypothyroid, hyperthyroid during the study. During the current survey a total

of 360 cases were conducted from the study area in them 64 (17.77%) cases were

found hypothyroid, 111 (30.83%) hyperthyroid and 185 (51.38%) euthyroid (Table

4.1).

Table.4.1 Shows Hypo and Hyperthyroid percentage of Dir Upper and

lower.

S.NO Parameters =n %age Normal Valve

1 Hypothyroid 64 17.77% 0.4 -- 4.0 mU/L

2 Hyperthyroid 111 30.83% 0.4 -- 4.0 mU/L

3 Euthyroid 185 51.38% 0.4 -- 4.0 mU/L

Total 360 100

*** =n represented numbers i.e., 1, 2, 3……. and %age for percent.

Season wise arrangement of hypo and hyperthyroid caused persons at Dir

Upper and Lower, a total of 360 cases were recorded in them 90 cases were

collected per season of the year. Table 4.2 showed that in autumn season the

32
highest of cases 42 (46.66%) euthyroid, followed by Hyperthyroid of 36 (40%) then

12 (13.33%) cases by hypothyroid.

Table. 4.2 shows season wise %age of hypo and hyperthyroidism

Season S.No Parameters =n %age Normal

Valve

1 Hypothyroid 12 13.33% 0.4 -- 4.0

Autumn mU/L

2 Hyperthyroid 36 40% 0.4 -- 4.0

mU/L

3 Euthyroid 42 46.66% 0.4 -- 4.0

mU/L

Total 90 100

1 Hypothyroid 24 26.66% 0.4 -- 4.0

Winter mU/L

2 Hyperthyroid 24 26.66% 0.4 -- 4.0

mU/L

3 Euthyroid 42 46.66% 0.4 -- 4.0

mU/L

Total 90 100

33
 1 Hypothyroid 12 13.33% 0.4 -- 4.0

Spring mU/L

2 Hyperthyroid 23 25.55% 0.4 -- 4.0

mU/L

3 Euthyroid 55 61.11% 0.4 -- 4.0

mU/L

Total 90 100

Summer 1 Hypothyroid 16 17.77% 0.4 -- 4.0

mU/L

2 Hyperthyroid 28 31.11% 0.4 -- 4.0

mU/L

3 Euthyroid 46 51.11% 0.4 -- 4.0

mU/L

Total 90 100

mU/L stands for Milliunits per liter

Age wise the subjects are divided into three groups. Group 1 ranging

from 1 year to 20 years, group 2 ranging from 21 to 50 years and group 3 ranging

from 51 years up to 80 and above aged persons. Fig: 4.1 shows the percentage of

hypo and hyperthyroidism among different age groups in that the young people

that have highest percentage of normal value and healthier than the elders

followed by 72.91% normal value (euthyroid) and also shows the total number of

hypo and hyper thyroid peoples of different ages.

34
 80.00% 72.91%
70.00%
60.00%
47.48% 49.46%
50.00%
38.70%
40.00%
30.59%
30.00% 21.91%
20.00% 16.66%
10.41% 11.82%
10.00%
0.00%

hyper=67

hyper=36
hypo=5

hypo=48

eu104

hypo=11
eu=35

eu=46
hype=8

total=48 total=219 total=93

1 to 20 21 to 50 50+

Fig no: 1 shows the total no and %age Age wise prevalence of hypo and

hyperthyroidism

Fig: 4.2 represents the Gender wise division. The study were

included 129 males and 231 females. Fig no: 4.2 represent the %age and total

number of hypo and hyperthyroidism in males and females. The Fig no: 4.2 shows

that female are more hyperthyroid than the males, ranging 34.05% and 24.80%

respectively.

35
70.00%

60.00% 57.36%

48.05%
50.00%

40.00% 34.19%

30.00% 24.80%
17.82% 17.74%
20.00%

10.00%

0.00%
hypo=23 hyper=32 eu=74 hypo=41 hyper=79 eu=111
total=129 total=231
Males Females

Fig no: 4.2 shows the Gender wise division of hypo and

hyperthyroidism

36
CHAPTER

NO 5

Discussion

37
Chapter no 5

Discussion

Thyroid gland is very important gland in human body. It produced

hormones which are essential for growth, development and metabolism in many

body tissues. These hormones have also a vital role in proteins synthesis,

carbohydrates metabolism, insulin degradation and increase the cardiovascular

activities and nervous system. TSH regulates the secretions of thyroid gland so

TSH regulates the above mentioned functions including growth, metabolism and

development etc. According to Ahmad et al. (2016), 200 million individuals

worldwide and 42 million people in India have thyroid disorder and 1.6% people

at risk.

The current study was conducted to investigate the prevalence of TSH

levels in District Dir upper and lower. District Dir is a rural area and the people’s

lives here have many hurdles and complications especially women’s that they are

housewives and have difficult life span. In the current study 360 patients were

studied (males and females) visiting Qazi clinical laboratory and investigate that

the people of District Dir upper and lower are more hyperthyroid (30.38%) as

compare to hypothyroid (17.77%). According to Khan et al. (2002), in Pakistan the

prevalence of hyperthyroidism was 5.1 % and hypothyroidism was 4.1 % of the

38
general population. The prevalence of hypothyroidism and hyperthyroidism is

higher in females than males.

In gender wise investigation a high prevalence of hyperthyroidism in

females (34.19%) were found as compare to males (24.80%). The study shows that

the prevalence of hypothyroidism is almost same in both sexes (males and

females) which are 17.82% and 17.74% respectively. A Japanese study investigate

the prevalence of hypothyroidism ranging from 4 to 8.5% and which might be

increase about 20% in women with the age of 60. Yousaf, Shah and Jan. (2017)

conducted a cross sectional study in Peshawar city Pakistan and they found a

higher prevalence rate of hyperthyroidism (60%) and hypothyroidism (73.3%) in

female as compared to male in the study population. Kardara et al. (2010)

conducted a population based study in India and reported higher prevalence rate

of hypothyroidism in female (11.4%) than males (6.2%).

Different seasons have a clear impact on TSH secretion. In this study the

subjects were divided season wise and investigate that in the spring season people

are healthier as compare to other seasons. The prevalence of euthyroidism (normal

TSH range) is high in spring season (61.11%). In the current study the high

prevalence of hypothyroidism were found in season winter (26.66%) and high

hyperthyroidism in season autumn (40%). The study shows that the autumn and

winter seasons are least favorable for health and have low prevalence of

euthyroidism (46.66% both).

39
 Just like other factors age have also effects on different body parts and their

functions. The older person’s body parts slowly lose their function and many

complications can developed with aging. There for in the current study the

subjects also divided into age wise groups and found that the young people (group

of 1—20 years people) are healthier (72.91% euthyroid) as compare to aged. The

current study investigate a high prevalence of hypothyroidism (21.91%) in group

21—50 years people and a high prevalence of hyperthyroidism (38.70%) in group

of 50+ people. Deoker et al. (2015) found 22.16% subjects having thyroid

dysfunction in the study population in India. Out of these, 4.24% were overt

hypothyroid, 9.44% were subclinical hypothyroid, 2.5% overt hyperthyroid and

5.97% were found to be subclinical hyperthyroid. They conducted study in

different age of groups among them the highest TSH concentration was seen in

the age group 60—69 years and lowest TSH was seen in age group 10—19 years.

40
 Conclusion

This study suggested that the prevalence of thyroid disorders is high in the

study population and hyperthyroidism is more common than hypothyroidism. In

the study population females are more suffering from thyroid disorders. The high

prevalence of thyroid disorder was found in the age group of 21 to 50 years. The

highest concentration of thyroid stimulating hormone (133.5 mU/L) was found in

the 50 years old man and lowest (<0.005 mU/L) was found in the age between 20

to 60 years. This study suggested that the prevalence of thyroid disorder is more

common in females than males and also more common in cold and dry weather.

41
 Recommendation

 More study are required to investigate the reason of the high prevalence of thyroid

disorder especially for the high prevalence of hyperthyroidism in females.

 It is recommended to find, how to control the high prevalence of thyroid disorders.

 It is recommended to study iodine level in water and food diet in the study area

which play a vital role in thyroid hormones regulation.

 Hyperthyroidism is more common in women in the study population so it is

necessary to investigate the prevalence of TSH level in the pregnancy stage of the

women in the study population and also study the mental level of the school

children’s.

42
 CHAPTER

NO 6

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43
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