COMPnREHENSIVE REVIEW ON HYPOTHYROID

PATHOPHYSIOLOGY ETIOLOGY MANAGEMENT

ABSTRACT:
Hypothyroidism is a condition that results from thyroid hormone deficiency that can range from
an asymptomatic condition to a life-threatening disease. The prevalence of hypothyroidism
varies according to the population, from up to 3 to 4% in some populations and in the case of
subclinical hypothyroidism up to 5–10%. Clinical symptoms of hypothyroidism are diverse,
broad, and non-specific and can be related to many systems, reflecting the systemic effects of
thyroid hormones. The severity of the symptoms is usually related to the severity of the thyroid
hormone deficit. The most common form of hypothyroidism, primary hypothyroidism, is
diagnosed when there is elevation of TSH and decrease in the level of free T4 and Subclinical
hypothyroidism is diagnosed when there is an elevation of TSH with normal levels of free T4.
The treatment of choice for hypothyroidism is thyroxine (T4), which has shown efficacy in
multiple studies to restore the euthyroid state and improve the symptoms of hypothyroidism. In
subclinical hypothyroidism, the treatment depends on the age, functionality, and comorbidities of
the patients. Pulmonary hypertension (PH) is a classic pathophysiological consequence of
left-sided valvular heart disease (VHD). However, as opposed to other forms of PH, there are
relatively few published data on the prevalence, impact on outcome, and management of PH with
VHD. The objective of this paper is to present a systematic review of PH in patients with VHD.
PH is found in 15% to 60% of patients with VHD and is more frequent among symptomatic
patients. PH is associated with higher risk of cardiac events under conservative management,
during valve replacement or repair procedures, and even following successful corrective
procedures. The first description of the disease was given in as early as 1859. Since then a
number of theories have been proposed by various researchers to explain the pathogenesis of the
disease. Treatment options for coccydynia include ergonomic adaptation, manual therapy,
injections and surgery. Despite being identified as a disease as early as 18th century, several
uncertainties with respect to the origin of pain, predisposing factors and treatment outcomes of a
wide range of treatment options persist till date. The current narrative review presents various
aspects of the disease including pathoanatomic, clinical presentation, radiological features and
management options for the disease.

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KEYWORDS: Hypothyroid, Pathophysiology, Etiology.

INTRODUCTION:

Thyroid hormone is essential for the normal development of many human tissues and regulates
the metabolism of virtually all cells and organs of the human body throughout life.
Hypothyroidism, the clinical condition of thyroid hormone deficiency, is a common disorder in
the general population. Overt hypothyroidism is defined by thyroid-stimulating hormone (TSH)
levels above the upper limit of the reference range while levels of free thyroxine (fT4) are below
the lower limit of the reference range. The reference range is typically statistically defined by the
2.5th and 97.5th percentiles of the measured circulating thyroid hormone values in populations
defined as healthy. In subclinical hypothyroidism, TSH levels are elevated but fT4 levels are still
within the reference range. Untreated hypothyroidism, especially overt hypothyroidism, can lead
to serious adverse effects on multiple organ systems, both in the short and long term. Most adult
patients with hypothyroidism have acquired hypothyroidism, which originates either in the
thyroid (primary hypothyroidism) or in the pituitary or hypothalamus (central hypothyroidism).
Hypothyroidism can also result from severe iodine deficiency because the synthesis of thyroid
hormone requires the trace element iodine. Chronic autoimmune thyroid disease, Hashimoto
thyroiditis, is the most common cause of primary hypothyroidism in iodine-replete areas.
Because thyroid hormone is also essential for multiple aspects of normal development in
childhood, most developed countries have established neonatal screening programmes to detect
congenital hypothyroidism (prevalence of 1 in 500–3,000 newborns, depending on ethnicity)1,2
as well as programmes to prevent severe iodine deficiency (for example, universal salt
iodization). The onset of hypothyroidism is insidious in most cases and symptoms may present
late in the disease process. Symptoms are generally non-specific and the most common include
fatigue, cold intolerance and constipation. As a consequence, there is a large variation in clinical
presentation and the presence of symptoms has a low sensitivity and positive predictive value
(that is, symptoms are not specific to hypothyroidism) for diagnosis.

HYPOTHYROID:

Hypothyroidism is a disorder that occurs when the thyroid gland does not make enough thyroid
hormone to meet the body’s needs. Thyroid hormone regulates metabolism—the way the body

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uses energy— and affects nearly every organ in the body. Without enough thyroid hormone,
many of the body’s functions slow down. About 4.6 percent of the U.S. population age 12 and
older has hypothyroidism. The thyroid is a 2-inch-long, butterfly-shaped gland weighing less
than 1 ounce. Located in the front of the neck below the larynx, or voice box, it has two lobes,
one on each side of the windpipe. The thyroid is one of the glands that make up the endocrine
system. The glands of the endocrine system produce and store hormones and release them into
the bloodstream. The hormones then travel through the body and direct the activity of the body’s
cells. The thyroid gland makes two thyroid hormones, triiodothyronine (T3) and thyroxine (T4).
T3 is made from T4 and is the more active hormone, directly affecting the tissues. Thyroid
hormones affect metabolism, brain development, breathing, heart and nervous system functions,
body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol
levels. Thyroid hormone production is regulated by thyroid-stimulating hormone (TSH), which
is made by the pituitary gland in the brain. When thyroid hormone levels in the blood are low,
the pituitary releases more TSH. When thyroid hormone levels are high, the pituitary responds
by dropping TSH production.

CAUSES OF HYOTHYROID:

Hypothyroidism has several causes, including

. Hashimoto’s disease

. thyroiditis, or inflammation of the thyroid

. congenital hypothyroidism, or hypothyroidism that is present at birth

. surgical removal of part or all of the thyroid

. radiation treatment of the thyroid

. some medications

Less commonly, hypothyroidism is caused by too much or too little iodine in the diet or by
abnormalities of the pituitary gland.

Hashimoto’s Disease:

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Hashimoto’s disease, also called chronic lymphocytic thyroiditis, is the most common cause of
hypothyroidism in the United States.1 Hashimoto’s disease is a form of chronic inflammation of
the thyroid gland. Hashimoto’s disease is also an autoimmune disorder. Normally, the immune
system protects the body against foreign invaders—such as viruses and bacteria—that can cause
illness. But in autoimmune diseases, the immune system attacks the body’s own cells and organs.
With Hashimoto’s disease, the immune system attacks the thyroid, causing inflammation and
interfering with its ability to produce thyroid hormones. More information about Hashimoto’s
disease can be found in the National Endocrine and Metabolic Diseases Information Service
(NEMDIS) fact sheet Hashimoto’s Disease.

Thyroiditis:

Thyroiditis causes stored thyroid hormone to leak out of the thyroid gland. At first, the leakage raises
hormone levels in the blood, leading to hyperthyroidism—when thyroid hormone levels are too
high––that lasts for 1 to 2 months. Most people then develop hypothyroidism before the thyroid is
completely healed.

Several types of thyroiditis can cause hyperthyroidism followed by hypothyroidism:

. Subacute thyroiditis:

This condition involves painful inflammation and enlargement of the thyroid. Experts are not
sure what causes subacute thyroiditis, but it may be related to a viral or bacterial infection. The
condition usually goes away on its own in a few months.

. Postpartum thyroiditis:

This type of thyroiditis develops after a woman gives birth. For more information, see the section
titled “What happens with pregnancy and thyroid conditions”.

. Silent thyroiditis :

This type of thyroiditis is called “silent” because it is painless, as is postpartum thyroiditis, even
though the thyroid may be enlarged. Like postpartum thyroiditis, silent thyroiditis is probably an
autoimmune condition and sometimes develops into permanent hypothyroidism.

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Congenital Hypothyroidism:

Some babies are born with a thyroid that is not fully developed or does not function properly. If
untreated, congenital hypothyroidism can lead to mental retardation and growth failure. Early
treatment can prevent these complications, so most newborns in the United States are screened
for hypothyroidism.

Surgical Removal of the Thyroid :

When part of the thyroid is removed, the remaining part may produce normal amounts of
thyroid hormone, but some people who have this surgery develop hypothyroidism. Removal of
the entire thyroid always results in hypothyroidism.

Part or all of the thyroid may be surgically removed as a treatment for:

. hyperthyroidism

. a large goiter, which is an enlarged thyroid that may cause the neck to appear swollen and can
interfere with normal breathing and swallowing

. thyroid nodules, which are noncancerous tumors, called adenomas, or lumps in the thyroid that
can produce excess thyroid hormone

. thyroid cancer

Radiation Treatment of the Thyroid :

Radioactive iodine, a common treatment for hyperthyroidism, gradually destroys the cells of the
thyroid. Most people who receive radioactive iodine treatment eventually develop
hypothyroidism. People with Hodgkin’s disease, other lymphomas, and head or neck cancers are
treated with radiation, which can also damage the thyroid.

Medications :

Some drugs can interfere with thyroid hormone production and lead to hypothyroidism,
including

. amiodarone, a heart medication

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. interferon alpha, a cancer medication

. lithium, a bipolar disorder medication

. interleukin-2, a kidney cancer medication

symptoms of hypothyroidism:

Hypothyroidism has many symptoms that can vary from person to person. Some common symptoms of
hypothyroidism are

. fatigue . weight gain . a puffy face . cold intolerance . joint and muscle pain .constipation .
dry skin . dry, thinning hair . decreased sweating . heavy or irregular .menstrual periods and
impaired fertility . depression . slowed heart rate

However, hypothyroidism develops slowly, so many people don’t notice symptoms of the
disease.

Symptoms more specific to Hashimoto’s disease are a goiter and a feeling of fullness in the
throat.

Hypothyroidism can contribute to high cholesterol, so people with high cholesterol should be
tested for hypothyroidism. Rarely, severe, untreated hypothyroidism may lead to myxedema
coma, an extreme form of hypothyroidism in which the body’s functions slow to the point that it
becomes life threatening. Myxedema requires immediate medical treatment.

develop hypothyroidism :

Women are much more likely than men to develop hypothyroidism. The disease is also more
common among people older than age 60.1 Certain factors can increase the chances of
developing thyroid disorders.

People may need more regular testing if they

. have had a thyroid problem before, such as a goiter

. have had surgery to correct a thyroid problem

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. have received radiation to the thyroid, neck, or chest

. have a family history of thyroid disease

. have Turner syndrome, a genetic disorder that affects females

. are older than age 60

. have been pregnant or delivered a baby within the past 6 months People should get tested
regularly to help uncover thyroid problems—especially subclinical problems. Subclinical means
a person has no apparent symptoms.

pregnancy and thyroid conditions :

Hypothyroidism :

During pregnancy, hypothyroidism is usually caused by Hashimoto’s disease and occurs in three
to five out of every 1,000 pregnancies.

Uncontrolled hypothyroidism raises the chance of miscarriage, preterm delivery, and

preeclampsia—a dangerous rise in blood pressure during late pregnancy.

Untreated hypothyroidism during pregnancy may also affect the baby’s growth and brain
development. Thyroid medications can help prevent these problems and are safe to take during
pregnancy. Women with hypothyroidism should discuss their condition with their health care
provider before becoming pregnant.

Postpartum thyroiditis :

This inflammation of the thyroid gland affects about 4 to 9 percent of women in the first year
after giving birth.2 Postpartum thyroiditis is believed to be an autoimmune condition and causes
hyperthyroidism that usually lasts for 1 to 2 months. Women with postpartum thyroiditis often
develop hypothyroidism before the thyroid gland is completely healed. The condition is likely to
recur with future pregnancies. Postpartum thyroiditis sometimes goes undiagnosed because the
symptoms are mistaken for postpartum blues—the exhaustion and moodiness that sometimes

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follow delivery. If symptoms of fatigue and lethargy do not go away within a few months or if a
woman develops postpartum depression, she should talk with her health care provide

Hypothyroidism diagnosed :

Many symptoms of hypothyroidism are the same as those of other diseases, so hypothyroidism
usually cannot be diagnosed based on symptoms alone. With suspected hypothyroidism, health
care providers take a medical history and perform a thorough physical examination. Health care
providers may then use several blood tests to confirm a diagnosis of hypothyroidism and find its
cause:

TSH test:

The ultrasensitive TSH test is usually the first test a health care provider performs. This test
detects even tiny amounts of TSH in the blood and is the most accurate measure of thyroid
activity available. Generally, a TSH reading above normal means a person has hypothyroidism
and a reading below normal means a person has hyperthyroidism. Mildly elevated TSH without
symptoms indicates subclinical hypothyroidism. Some health care providers treat subclinical
hypothyroidism immediately. Others prefer to leave it untreated but monitor their patients for
signs that the condition is worsening. Health care providers may conduct additional tests to help
confirm the diagnosis or determine the cause of hypothyroidism.

Thyroid autoantibody test :

This test looks for the presence of thyroid autoantibodies. Most people with Hashimoto’s disease
have these antibodies, but people whose hypothyroidism is caused by other conditions do not.
More information about testing for thyroid problems can be found in the NEMDIS fact sheet
Thyroid Function Tests.

Hypothyroid treated :

Health care providers treat hypothyroidism with synthetic thyroxine, a medication that is
identical to the hormone T4. The exact dose will depend on the patient’s age and weight, the
severity of the hypothyroidism, the presence of other health problems, and whether the person is
taking other drugs that might interfere with how well the body uses thyroid hormone. Health care

8
providers test TSH levels about 6 to 8 weeks after a patient begins taking thyroid hormone and
make any necessary adjustments to the dose. Each time the dose is adjusted, the blood is tested
again. Once a stable dose is reached, blood tests are normally repeated in 6 months and then once
a year. Hypothyroidism can almost always be completely controlled with synthetic thyroxine, as
long as the recommended dose is taken every day as instructed.

Mechanism of Hypothyroid :

In primary hypothyroidism, decreased production of thyroid hormones by the thyroid gland

causes a compensatory increase of TSH. Secondary hypothyroidism is caused by pituitary
disorders causing decreased TSH release and decreased T3/T4 levels.

Management of Hypothyroid:

Treatment for hypothyroidism usually includes taking the thyroid hormone medicine
levothyroxine (Levo-T, Synthroid, others) every day. This medicine is taken by mouth. It returns
hormone levels to a healthy range, eliminating symptoms of hypothyroidism.

Diagnosis of Hypothyroid :

The first blood test typically done to diagnose hypothyroidism measures the level of
thyroid-stimulating hormone (TSH) in the blood. If it's high, the test is done again, along with a
blood test for the thyroid hormone T-4 . If the results show that TSH is high and T-4 is low, then
the diagnosis is hypothyroidism.

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Treatment of Hypothyroid :

An underactive thyroid (hypothyroidism) is usually treated by taking daily hormone replacement

tablets called levothyroxine. Levothyroxine replaces the thyroxine hormone, which your thyroid
does not make enough of. You'll initially have regular blood tests until the correct dose of
levothyroxine is reached.

Antithyroid Drug :

Antithyroid drugs (also called thionamides) are most often used to treat an overactive thyroid
(hyperthyroidism) caused by Graves' disease. These drugs block the formation of thyroid
hormone by the thyroid gland .

Radioactive Iodine:

Radioactive iodine (RAI) is treatment for overactive thyroid (hyperthyroidism) and certain types
of thyroid cancer. The term “radioactive” may sound frightening, but it is a safe, generally
well-tolerated, and reliable treatment that targets thyroid cells so there is little exposure to the
rest of your body's cells.

Pathophysiology:

Pathophysiology (consisting of the Greek origin words “pathos” = suffering; “physis” = nature,
origin; and “logos” = “the study of”) refers to the study of abnormal changes in body functions
that are the causes, consequences, or concomitants of disease processes. Studies of
pathophysiology are concerned with the investigation of biological processes that are directly
related to disease processes of physical, mental, or psychophysiological conditions and
disorders (e.g., alterations in the endocrine system, in certain neurotransmitters, or
inflammatory parameters related to the activity of the immune system). Thus,
pathophysiological research aims at identifying biological markers and mechanisms for

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predicting and explaining disease processes in terms of etiology and pathogenesis.
Pathophysiology is formally considered as a subdiscipline within physiology.

Causes of Pathophysiology :

Pathophysiology is the study of the disturbance of normal mechanical, physical, and

biochemical functions, either caused by a disease, or resulting from a disease or abnormal
syndrome or condition that may not qualify to be called a disease.

Symptoms of Pathophysiology :

Infection is defined as the instance in which a bacterium or virus invades the body.
The five stages of infection include:

Incubation:

The period occurring between initial exposure and the onset of symptoms. During
this time, bacterial particles replicate.

Prodromal:

Bacterial particles continue to replicate, and infected individuals are at risk of

transmitting their infection. The prodromal period occurs after incubation but
before the main symptoms of infection occur.

Illness:

During the illness phase, the infected will begin to exhibit characteristic symptoms
of their infection. Symptoms may include anything from fever and fatigue to
vomiting and stomach pain, depending on the type of infection.

Decline:

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The stage in which the immune system creates a defense, resulting in a decline in
symptoms. However, the virus is still transmissible, and secondary infections are
still possible.

Convalescence:

This is the final stage of infection. The individual returns to feeling normal, and
their symptoms fully diminish.

Develop Pathophysiology :

Etiology :

Etiology, in its most general definition, is the study of the causes or reasons for
phenomena. A description of etiologic process includes the identification of those
causal factors that, acting in concert, provoke a particular disease or injury. When
the cause is unknown, a condition is said to be idiopathic. If the cause is the result
of an unintended or unwanted medical treatment, the resulting condition is said to
be iatrogenic. Most disorders are multifactorial, having several different etiologic
factors that contribute to their development. For example, coronary heart disease is
a result of the interaction of genetic predisposition, diet, exposure to cigarette
smoke, elevated blood pressure, and perhaps numerous other lifestyle and
hormonal factors acting in concert. None of these individual factors can be said to
cause the disease. When the link between an etiologic factor and development of a
disease is less than certain, but the probability is increased when the factor is
present, it is termed a risk factor. The identification of risk factors is important for
disease prevention and various levels of prevention provide focus for the
epidemiology section at the end of this chapter.

Some diseases are closely linked with etiologic factors, such that they are said
to be the causative agents in the disease. For example, microbial pathogens are

12
considered to be causative agents for infectious diseases: human
immunodeficiency virus causes HIV disease, influenza viruses cause the flu, and
Mycobacterium tuberculosis causes pulmonary tuberculosis. These diseases do not
occur unless the pathogen is present in the body; however, this does not mean that
the infection will have the same consequences in each case, because many host
factors affect the clinical course. Even when the link between disease and etiologic
agent is strong, only a portion of the population exposed to the factor may develop
the disease. For example, in persons who consume large quantities of alcohol and
develop liver cirrhosis, it is the alcohol consumption that is considered to be the
cause, yet only a portion of persons who drink heavily will develop cirrhosis.

Pathogenesis :

Pathogenesis refers to the development or evolution of a disease, from the initial

stimulus to the ultimate expression of the manifestations of the disease.3 The
sequence of physiologic events that occurs in response to an etiologic agent is a
dynamic interplay of changes in cell, tissue, organ, and systemic function. As the
ways in which intricate intercellular communication networks control physiologic
function are discovered, pathogenesis is being increasingly understood on the
cellular level. One of the best examples of this communication network is the
immune system and its interactions with essentially every other cell in the body. A
disruption in the delicate system of checks and balances between immune tolerance
of normal cells and immune surveillance for abnormal cells and foreign antigens is
at the root of a large number of degenerative and inflammatory diseases.

Pathologic disruptions in cellular behavior lead, in turn, to changes in

organ and system function that may be detected by clinical or laboratory
examination. Most pathophysiology texts take a systems approach to presenting
information. This approach builds on the way in which students learn anatomy and

13
physiology and has its roots in medical specialization. Usually the clinical
examination of a patient is also conceptualized by a systems approach. Although
the division into systems is useful for dividing the content into conceptual pieces, it
is important to remember that the organism functions as an integrated whole and
the intercellular communication networks are not confined within single systems.

Clinical Manifestations :

Manifestations of disease that are observed are termed signs of disease. Such
objective data may be gathered by clinical examination or by biochemical analysis,
diagnostic imaging, and other laboratory tests. The subjective feelings of an
abnormality in the body are termed symptoms. By definition, symptoms are
subjective and can only be reported by the affected individual to an observer. For
example, the feeling of nausea is a symptom, whereas vomiting is objectively
observed and is a sign. Some signs and symptoms, such as fever and headache, are
nonspecific and, although they designate that something is amiss, they do not
indicate a specific cause. The clinical manifestations of some diseases may change
significantly over time, resulting in a completely different clinical presentation at
different stages. Knowledge of the possible stages of a disease is helpful in making
an appropriate diagnosis and anticipating the clinical course.

Stages and Clinical Course :

Early in the development of a disease, the etiologic agent or agents may provoke a
number of changes in biological processes that can be detected by laboratory
analysis, although no recognition of these changes by the patient has occurred. The
interval between exposure of a tissue to an injurious agent and the first appearance
of signs and symptoms may be called a latent period or, in the case of infectious
diseases, an incubation period. The prodromal period, or prodrome, refers to the

14
appearance of the first signs and symptoms indicating the onset of a disease.
Prodromal symptoms often are nonspecific, such as headache, malaise, anorexia,
and nausea. During the stage of manifest illness, or the acute phase, the disease
reaches its full intensity, and signs and symptoms attain their greatest severity.
Sometimes during the course of a disease, the signs and symptoms may become
mild or even disappear for a time. This interval may be called a silent period or
latent period. For example, in the total-body irradiation syndrome, a latent period
may occur between the prodrome and the stage of manifest illness. Another
example is syphilis, which may have two latent periods: one occurring between the
primary and secondary clinical stages and another occurring between the secondary
and tertiary stages.

A number of diseases have a subclinical stage, during which the patient functions
normally, although the disease processes are well established. It is important to
understand that the structure and function of many organs provide a large reserve
or safety margin, so that functional impairment may become evident only when
organ damage has become advanced. For example, chronic renal disease can
completely destroy one kidney and partly destroy the other before any symptoms
related to a decrease in renal function are perceived.

The clinical course of a disease is often classified as acute or chronic. An acute

condition has relatively severe manifestations but runs a short course measured in
hours, days, or a few weeks. A chronic condition lasts for months to years.
Sometimes chronic disease processes begin with an acute phase and become
prolonged when the body’s defenses are insufficient to overcome the causative
agent or stressor. In other cases, chronic conditions develop insidiously and never
have an acute phase.

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Convalescence is the stage of recovery after a disease, injury, or surgical operation.
Occasionally a disease produces a subsequent pathologic condition called a sequela
(plural: sequelae). For example, the sequela of an inflammatory process might be
scarring. The sequelae of acute rheumatic inflammation of the heart might be
scarring and deformation of cardiac valves. In contrast, a complication of a disease
is a new or separate process that may arise secondarily because of some change
produced by the original problem. For example, bacterial pneumonia may be a
complication of viral infection of the respiratory tract.

Treatment Implications :

An understanding of the etiology, pathogenesis, and clinical consequences of a

particular disorder may suggest, or “imply,” that certain treatments could be
helpful. For example, understanding that a person with septic shock has excessive
dilation of blood vessels that contributes to hypotension implies that fluid
administration would likely be helpful. In contrast, most patients with cardiogenic
shock have fluid overload, and hypotension in this case is unlikely to improve with
fluid administration. The treatment implications discussed in pathophysiology
texts usually are general statements rather than specific prescriptions. For example,
the pathophysiology of heart failure is characterized by fluid overload, which
implies that diuretic therapy would be useful; however, the exact selection of a
drug and the dosing schedule would depend on a number of factors particular to the
individual patient. Specific treatment recommendations are beyond the scope of a
pathophysiology text and can be found in pharmacology and clinical practice
textbooks.

Mechanisms Of pathophysiology :
Physiological aspects. Thyroid hormone production and release are regulated by a
very sensitive feedback loop, the hypothalamus–pituitary–thyroid axis .

16
Thyrotropin-releasing hormone (TRH) produced in the hypothalamus controls
production of TSH by the ante-rior pituitary gland. TSH in turn regulates the
production and secretion of the two forms of thyroid hormone by the thyroid gland:
T4 and the more bioactive hormone triiodothyronine (T3)24. Serum TSH levels
follow a circa-dian rhythm: levels are highest between 9pm and 5am and lowest
between 4pm and 7pm .The fundamental aim of the domain of pathophysiology is
to unravel the altered biological (i.e., physical and chemical) processes in our
organism that precede, accompany, or follow certain disorders or diseases

Management of Pathophysiology

Management of Pathophysiology presents a comprehensive overview on the

various therapeutic practices and ongoing research relating to the development of
more potent and novel formulations for managing high altitude pathophysiology. It
provides a detailed application of both herbal and non-herbal therapeutic agents,
including their nanoformulations. This important reference provides benefits to the
medical and herbal scientific communities, doctors treating patients with high
altitude complications, individuals travelling to high altitudes for recreation or
work, and scientists working on future drug development.

Diagnosis of Pathophysiology:

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Deranged function in an individual or an organ due to a disease. For example, a
pathophysiologic alteration is a change in function as distinguished from a
structural defect.

Etiology:

The etiology of a disease is its cause or origin. Etiology is also the name for the study of the
causes of diseases. It can also refer to the study of the cause of things in other fields, such as
philosophy and physics.

Causes of Etiology :

The term “etiology” means the science of causes; from a scientific perspective, all diseases must
have causes. A cause is something that produces an effect; in epidemiology it is customary to
distinguish necessary cause, sufficient cause, proximal cause, and distal cause.

Symptoms of Etiology :

. Generalized Body pain

. Weight loss

. Lack of interest in food

. Chills

Mechanism of Etiology

Different etiological mechanisms may be involved, and there forms two major hypotheses:
biological hypothesis and psychological hypothesis. Biological hypothesis included four
mechanisms: lesion location mechanism, neurotransmitters mechanism, inflammatory cytokines
mechanism and gene polymorphism mechanism.

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Management of Etiology :

Chronic rhinosinusitis (CRS) is a common health care problem, yet many aspects of this
diagnosis remain poorly understood. Its etiology is often debated and remains a significant area
of research. The diagnosis of CRS is based on subjective symptoms, duration of symptoms and
objective evidence of inflammation. Each of these criteria must be met to make a diagnosis of
CRS. Management of CRS often involves a combination of systemic and topical therapies with
surgery reserved for patients who fail medical therapy. This review provides a comprehensive
view of the etiology, diagnosis and management of CRS.

Daignosis of Etiology :

It is an evidence-based approach to diagnosing and managing diseases of unknown cause or

origin. This method uses data from multiple sources to better understand why a person is
experiencing certain symptoms and how to appropriately treat them.

Treatment of Etiology :

From this etiological perspective, treatments should aim at solving health problems by
addressing behavior options, such as stress reduction or a dietary change. Biomedical causes, in
contrast, would include genetic components or viral and bacterial diseases.

Conclusion:

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Although the causes and consequences of hypothyroidism were initially described over a century
ago90, essential information regarding prevalence, genetic causes, environmental factors, and
thresholds for diagnosis, treatment and management optimization for hypothyroidism are still
limited.Prevalence and incidence data for primary hypo thyroidism are lacking for many regions
around the world. Furthermore, despite the importance of new-born screening programmes for
the early detection and treatment of congenital hypothyroidism, over 70% of the world
population is not screened at birth, hampering estimates of congenital hypothyroidism
occurrence176and, more importantly, hampering timely treatment. With ever-changing risk
factors for thyroid disease (for example, iodine nutrition status and ageing populations),
researchers, clinicians and policymakers require available and up-to-date statistics.The
heritability of TSH levels has been estimated at 65% while, in the largest GWAS to date all 42
significant associations together accounted for 33% of the genetic variance in TSH levels,
displaying clear polygenicity13. While increasing the sample size in future GWAS will
contribute to the search for the missing heritability, improved techniques (such as whole-genome
sequencing) are expected to have a substantial impact as well. In addition to genetic and inherent
factors (for example, sex), environmental risk factors, including smoking and BMI, are known to
influence thyroid function. However, the variability explained by age, sex, smoking, BMI,
TPOAb levels and alcohol use combined only accounts for ~7% of TSH and 5% fT4 variation16.
Therefore, study of other risk factors, including endocrine-disrupting chemicals, is needed to
determine their contribution to thyroid dysfunction, perhaps starting at pre-conception or
conception.

Reference :

1. Mehran, L. et al. Evaluation of the congenital hypothyroidism screening programme in Iran: a

3-year retrospective cohort study. Arch. Dis. Child. Fetal Neonatal Ed. 104, F176–F181 (2019).
2. Deladoey, J., Ruel, J., Giguere, Y. & Van Vliet, G. Is the incidence of congenital
hypothyroidism really increasing? A 20-year retrospective population-based study in Quebec. J.
Clin. Endocrinol. Metab. 96, 2422–2429 (2011).
3. Canaris, G. J., Steiner, J. F. & Ridgway, E. C. Do traditional symptoms of hypothyroidism
correlate with biochemical disease? J. Gen. Intern. Med. 12, 544–550 (1997).
4. Kantor, E. D., Rehm, C. D., Haas, J. S., Chan, A. T. & Giovannucci, E. L. Trends in

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prescription drug use among adults in the United States from 1999-2012. JAMA 314, 1818–1831
(2015).
5. ClinCalc DrugStats Database. Levothyroxine: Drug Usage Statistics, U. S., 2013–2019.
ClinCalc.comhttps://clincalc.com/DrugStats/Drugs/Levothyroxine(2021).
6. Brito, J. P. et al. Levothyroxine use in the United States, 2008-2018. JAMA Intern. Med. 181,
1402–1405 (2021).
7. Jonklaas, J. et al. Guidelines for the treatment of hypothyroidism: prepared by the american
thyroid association task force on thyroid hormone replacement. Thyroid 24, 1670–1751 (2014).
8. Hollowell, J. G. et al. Serum TSH, T(4), and thyroid antibodies in the United States population
(1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin.
Endocrinol. Metab. 87, 489–499 (2002).
9. Canaris, G. J., Manowitz, N. R., Mayor, G. & Ridgway, E. C. The Colorado Thyroid Disease
Prevalence study. Arch. Intern. Med. 160, 526–534 (2000).

10. Garmendia Madariaga, A., Santos Palacios, S., Guillen-Grima, F. & Galofre, J. C. The
incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J. Clin. Endocrinol.
Metab. 99, 923–931 (2014).
11. Zimmermann, M. B. & Boelaert, K. Iodine deficiency and thyroid disorders. Lancet Diabetes
Endocrinol. 3, 286–295 (2015).
12. Pedersen, I. B. et al. A cautious iodization programme bringing iodine intake to a low
recommended level is associated with an increase in the prevalence of thyroid autoantibodies in
the population. Clin. Endocrinol. 75, 120–126 (2011).
13. Teumer, A. et al. Genome-wide analyses identify a role for SLC17A4 and AADAT thyroid
hormone regulation. Nat. Commun. 9, 4455 (2018).
14. Vanderpump, M. P. The epidemiology of thyroid disease. Br. Med. Bull. 99, 39–51 (2011).

15. Belin, R. M., Astor, B. C., Powe, N. R. & Ladenson, P. W. Smoke exposure is associated
with a lower prevalence of serum thyroid autoantibodies and thyrotropin concentration elevation
and a higher prevalence of mild thyrotropin concentration suppression in the third National
Health and Nutrition Examination Survey.

16. Chaker, L. et al. Thyroid function characteristics and determinants: the rotterdam study.
Thyroid 26, 1195–1204 (2016).

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17. Kus, A. et al. Variation in normal range thyroid function affects serum cholesterol levels,
blood pressure, and type 2 diabetes risk: a mendelian randomization study. Thyroid 31, 721–731
(2021).
18. Wang, X. et al. Causal association between serum thyrotropin and obesity: a bidirectional,
mendelian randomization study. J. Clin. Endocrinol. Metab. 106, e4251–e4259 (2021).
19. Liu, C. et al. Small for gestational age is a risk factor for thyroid dysfunction in preterm
newborns. BMC Pediatr. 20, 179 (2020).
20. Asakura, Y., Tachibana, K., Adachi, M., Suwa, S. & Yamagami, Y. Hypothalamo-pituitary
hypothyroidism detected by neonatal screening for congenital hypothyroidism using
measurement of thyroidstimulating hormone and thyroxine.

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