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What is hypothyroidism?

Hypothyroidism refers to any state in which thyroid hormone production
is below normal. There are many disorders that result in
hypothyroidism. These disorders may directly or indirectly involve the
thyroid gland. Because thyroid hormone affects growth, development,
and many cellular processes, inadequate thyroid hormone has widespread
consequences for the body.

This article will focus specifically on hypothyroidism in adults.

What are thyroid hormones?

Thyroid hormones are produced by the thyroid gland. This gland is
located in the lower part of the neck, below the Adam's apple. The
gland wraps around the windpipe (trachea) and has a shape that is
similar to a butterfly - formed by two wings (lobes) and attached by a
middle part (isthmus).

The thyroid gland uses iodine (mostly available from the diet in foods
such as seafood, bread, and salt) to produce thyroid hormones. The two
most important thyroid hormones are thyroxine (T4) and
triiodothyronine (T3), which account for 99.9% and 0.1% of thyroid
hormones present in the blood respectively. However, the hormone with
the most biological activity is T3. Once released from the thyroid
gland into the blood, a large amount of T4 is converted into T3 - the
active hormone that affects the metabolism of cells.

Thyroid hormone regulation- the chain of command

The thyroid itself is regulated by another gland that is located in
the brain, called the pituitary. In turn, the pituitary is regulated
in part by the thyroid (via a "feedback" effect of thyroid hormone on
the pituitary gland) and by another gland called the hypothalamus.

The hypothalamus releases a hormone called thyrotropin releasing
hormone (TRH), which sends a signal to the pituitary to release
thyroid stimulating hormone (TSH). In turn, TSH sends a signal to the
thyroid to release thyroid hormones. If a disruption occurs at any of
these levels, a defect in thyroid hormone production may result in a
deficiency of thyroid hormone (hypothyroidism).

Hypothalamus - TRH


Pituitary- TSH


Thyroid- T4 and T3

The rate of thyroid hormone production is controlled by the pituitary
gland. If there is an insufficient amount of thyroid hormone
circulating in the body to allow for normal functioning, the release
of TSH is increased by the pituitary gland in an attempt to stimulate
more thyroid hormone production. In contrast, when there is an
excessive amount of circulating thyroid hormone, TSH levels fall as
the pituitary attempts to decrease the production of thyroid hormone.
In persons with hypothyroidism, there is a continuously decreased
level of circulating thyroid hormones.

What causes hypothyroidism?

Hypothyroidism is a very common condition. It is estimated that 3 to
5% of the population has some form of hypothyroidism. The condition is
more common in women than in men, and its incidence increases with
age.

Below is a list of some of the common causes of hypothyroidism in
adults followed by a discussion of these conditions.

Hashimoto's Thyroiditis Lymphocytic Thyroiditis After Hyperthyroidism
Thyroid Destruction (from radioactive iodine or surgery) Pituitary
or Hypothalamic Disease Medications Severe Iodine Deficiency

Hashimoto's Thyroiditis: The most common cause of hypothyroidism in
the United States is an inherited condition called Hashimoto's
thyroiditis. This condition is named after Dr. Hakaru Hashimoto who
first described it in 1912. In this condition, the thyroid gland is
usually enlarged (goiter) and has a decreased ability to make thyroid
hormones. Hashimoto's is an autoimmune disease in which the body's
immune system inappropriately attacks the thyroid tissue. In part,
this condition is believed to have a genetic basis. This means that
the tendency toward developing Hashimoto's thyroiditis can run in
families. Hashimoto's is 5 to 10 times more common in women than in
men. Blood samples drawn from patients with this disease reveal an
increased number of antibodies to the enzyme, thyroid peroxidase
(anti-TPO antibodies). Since the basis for autoimmune diseases may
have a common origin, it is not unusual to find that a patient with
Hashimoto's thyroiditis has one or more other autoimmune diseases such
as diabetes or pernicious anemia ( B12 deficiency). Hashimoto's can be
identified by detecting anti-TPO antibodies in the blood and by
performing a thyroid scan.

Lymphocytic Thyroiditis following hyperthyroidism: Thyroiditis refers
to inflammation of the thyroid gland. When the inflammation is caused
by a particular type of white blood cell known as a lymphocyte, the
condition is referred to as lymphocytic thyroiditis. This condition is
particularly common after pregnancy and can actually affect up to 8%
of women after they deliver. In these cases, there is usually a
hyperthyroid phase (in which excessive amounts of thyroid hormone leak
out of the inflamed gland), which is followed by a hypothyroid phase
that can last for up to 6 months. The majority of affected women
eventually return to a state of normal thyroid function, although
there is a possibility of remaining hypothyroid.

Thyroid destruction secondary to radioactive iodine or surgery:
Patients who have been treated for a hyperthyroid condition (such as
Graves' disease) and received radioactive iodine may be left with
little or no functioning thyroid tissue after treatment. The
likelihood of this depends on a number of factors including the dose
of iodine given, along with the size and the activity of the thyroid
gland. If there is no significant activity of the thyroid gland six
months after the radioactive iodine treatment, it is usually assumed
that the thyroid will no longer function adequately. The result is
hypothyroidism. Similarly, removal of the thyroid gland during surgery
will be followed by hypothyroidism.

Pituitary or Hypothalamic disease: If for some reason the pituitary
gland or the hypothalamus are unable to signal the thyroid and
instruct it to produce thyroid hormones, a decreased level of
circulating T4 and T3 may result, even if the thyroid gland itself is
normal. If this defect is caused by pituitary disease, the condition
is called "secondary hypothyroidism." If the defect is due to
hypothalamic disease, it is called "tertiary hypothyroidism."

A pituitary injury may result after brain surgery or if there has been
a decrease of blood supply to the area. In these cases of pituitary
injury, the TSH that is produced by the pituitary gland is deficient
and blood levels of TSH are low. Because the thyroid gland is no
longer stimulated by the pituitary TSH, hypothyroidism results. This
form of hypothyroidism can, therefore, be distinguished from
hypothyroidism that is caused by thyroid gland disease, in which the
TSH level becomes elevated as the pituitary gland attempts to
encourage thyroid hormone production by stimulating the thyroid gland
with more TSH. Usually, hypothyroidism from pituitary gland injury
occurs in conjunction with other hormone deficiencies, since the
pituitary regulates other processes such as growth, reproduction, and
adrenal function.

Medications: Medications that are used to treat an over-active thyroid
(hyperthyroidism) may actually cause hypothyroidism. These drugs
include methimazole (Tapezole) and propylthiouracil (PTU). The
psychiatric medication, lithium, is also known to alter thyroid
function and cause hypothyroidism. Interestingly, drugs containing a
large amount of iodine such as amiodarone (Cardorone), SSKI, and
Lugol's solution can cause a decrease in thyroid function, thereby
resulting in low blood levels of thyroid hormone.

Severe Iodine Deficiency: In areas of the world where there is an
iodine deficiency in the diet, severe hypothyroidism can be seen in
5 to 15% of the population. Examples of these areas include Zaire,
Ecuador, India, and Chile. Severe iodine deficiency is also seen in
remote mountain areas such as the Andes and the Himalayas. Since the
addition of iodine to table salt and to bread, iodine deficiency is
rarely seen in the United States.

What are the symptoms of hypothyroidism?

The symptoms of hypothyroidism are often subtle. They are not specific
(which means they can mimic the symptoms of many other conditions) and
are often attributed to aging. Patients with mild hypothyroidism may
have no signs or symptoms. The symptoms generally become more obvious
as the condition worsens and the majority of these complaints are
related to a metabolic slowing of the body. Common symptoms are listed
below:

Fatigue Depression Modest weight gain Cold intolerance Excessive
sleepiness Dry, coarse hair Constipation Dry skin Muscle cramps
Increased cholesterol levels Decreased concentration Vague aches and
pains Swelling of the legs

As the disease becomes more severe, there may be puffiness around the
eyes, a slowing of the heart rate, a drop in body temperature, and
heart failure. In its most profound form, severe hypothyroidism may
lead to a life-threatening coma (myxedema coma). In a severely
hypothyroid individual, a myxedema coma tends to be triggered by
severe illness, surgery, stress, or traumatic injury. This condition
requires hospitalization and immediate treatment with thyroid hormones
given by injection.

Properly diagnosed, hypothyroidism can be easily and completely
treated with thyroid hormone replacement. On the other hand, untreated
hypothyroidism can lead to an enlarged heart (cardiomyopathy),
worsening heart failure, and an ac***ulation of fluid around the lungs
(pleural effusion).

How is hypothyroidism diagnosed?

A diagnosis of hypothyroidism can be suspected in patients with
fatigue, cold intolerance, constipation, and dry, flaky skin. A blood
test is needed to confirm the diagnosis.

When hypothyroidism is present, the blood levels of thyroid hormones
can be measured directly and are usually decreased. However, in early
hypothyroidism, the level of thyroid hormones (T3 and T4) may be
normal. Therefore, the main tool for the detection of hyperthyroidism
is the measurement of the TSH, the thyroid stimulating hormone. As
mentioned earlier, TSH is secreted by the pituitary gland. If a
decrease of thyroid hormone occurs, the pituitary gland reacts by
producing more TSH and the blood TSH level increases in an attempt to
encourage thyroid hormone production. This increase in TSH can
actually precede the fall in thyroid hormones by months or years (see
the section on Subclinical Hypothyroidism below). Thus, the
measurement of TSH should be elevated in cases of hypothyroidism.
However, there is one exception. If the decrease in thyroid hormone is
actually due to a defect of the pituitary or hypothalamus, then the
levels of TSH are abnormally low. As noted above, this kind of thyroid
disease is known as "secondary" or "tertiary" hypothyroidism. A
special test, known as the TRH test, can help distinguish if the
disease is caused by a defect in the pituitary or the hypothalamus.
This test requires an injection of the TRH hormone and is performed by
an endocrinologist
(hormone specialist).

The blood work mentioned above confirms the diagnosis of
hypothyroidism, but does not point to an underlying cause. A
combination of the patient's clinical history, antibody screening (as
mentioned above), and a thyroid scan can help diagnose the precise
underlying thyroid problem more clearly. If a pituitary or
hypothalamic cause is suspected, an MRI of the brain and other studies
may be warranted. These investigations should be made on a case by
case basis.


How is hypothyroidism treated?

With the exception of certain conditions, the treatment of
hypothyroidism requires life-long therapy. Before synthetic
levothyroxine (T4) was available, desiccated thyroid tablets were
used. Desiccated thyroid was obtained from animal thyroid glands,
which lacked consistency of potency from batch to batch. Presently, a
pure, synthetic T4 is widely available. Therefore, there is no reason
to use desiccated thyroid extract.

As mentioned earlier, the most active thyroid hormone is actually T3.
So why do physicians choose to treat patients with the T4 form of
thyroid? T3 (Cytomel) is available and there are certain indications
for its use. However, for the majority of patients, a form of T4
(Levoxyl, Synthroid) is the preferred treatment. This is a more stable
form of thyroid hormone and requires once a day dosing, whereas T3 is
much shorter-acting and needs to be taken multiple times a day. In the
overwhelming majority of patients, synthetic T4 is readily and
steadily converted to T3 naturally in the bloodstream, and this
conversion is appropriately regulated by the body's tissues.

The average dose of T4 replacement in adults is approximately 1.6
micrograms per kilogram per day. This translates into approximately
100 to 150 micrograms per day. Children require larger doses. In
young, healthy patients, the full amount of T4 replacement hormone may
be started initially. In patients with preexisting heart disease, this
method of thyroid replacement may aggravate the underlying heart
condition in about 20% of cases. In older patients without known heart
disease, starting with a full dose of thyroid replacement may result
in uncovering heart disease, resulting in chest pain or a heart
attack. For this reason, patients with a history of heart disease or
those suspected of being at high risk are started with 25 micrograms
or less of replacement hormone, with a gradual increase in the dose at
6 week intervals.

Ideally, synthetic T4 replacement should be taken in the morning, 30
minutes before eating. Other medications containing iron or antacids
should be avoided, because they interfere with absorption.

Therapy for hypothyroidism is monitored at approximately 6 week
intervals until stable. During these visits, a blood sample is checked
for TSH to determine if the appropriate amount of thyroid replacement
is being given. The goal is to maintain the TSH within normal limits.
Depending on the lab used, the absolute values may vary, but in
general, a normal TSH range is between 0.5 to 5.0uIU/ml. Once stable,
the TSH can be checked yearly. Over-treating hypothyroidism with
excessive thyroid medication is potentially harmful and can cause
problems with heart palpitations and blood pressure control and can
also contribute to osteoporosis. Every effort should be made to keep
the TSH within the normal range.

What is subclinical hypothyroidism?

Subclinical hypothyroidism refers to a state in which patients do not
exhibit the symptoms of hypothyroidism. These patients also have a
normal amount of circulating thyroid hormone. The only abnormality is
an increased TSH on their blood work. This implies that the pituitary
gland is working extra hard to maintain a normal circulating thyroid
hormone level and that the thyroid gland requires extra stimulation by
the pituitary to produce adequate hormones. The majority of these
patients can be expected to progress to obvious hypothyroidism,
especially if the TSH is above a certain level. While there is some
controversy, many endocrinologists will treat such patients,
especially if they have a high cholesterol blood level. The abnormal
cholesterol profile will likely improve with thyroid hormone
replacement. If the cholesterol levels are normal, it is also
reasonable to follow these patients without treatment and repeat the
blood TSH and thyroid hormone levels in 4 to 6 months to see if more
significant hypothyroidism is apparent. Both of these approaches are
reasonable and patients should be encouraged to speak with their
physicians about specific concerns and preferences.

What's best for you?

If you are concerned that you may have hypothyroidism, you should
mention your symptoms to your physician. A simple blood test is the
first step in the diagnosis. From there, both you and your doctor can
decide what the next steps should be. If treatment is warranted, it is
important for you to let your doctor know of any concerns or questions
you have about the options available. Remember that thyroid disease is
very common and, in good hands, hypothyroidism is easily addressed and
treated.

Hypothyroidism At A Glance

Hypothyroidism refers to any state in which thyroid hormone production
is below normal. There are many disorders that result in
hypothyroidism. The thyroid gland is regulated by another gland that
is located in the brain, the pituitary. Hypothyroidism is a very
common condition. The symptoms of hypothyroidism are often subtle. A
blood test is needed to confirm hypothyroidism. With the exception of
certain conditions, the treatment of hypothyroidism requires life-long
medication.

http://www.medicinenet.com/Hypothyroidism/article.htm