It is estimated that approximately 20 million Americans have a thyroid
disorder which means 1 in every 10 people6. Hypothyroidism
is caused from decreased production of thyroid hormone which results in
decreased metabolism6. Hypothyroidism occurs more commonly
in women 1.2-2% as compared to men 0.2 %. Hypothyroidism is also more
common in menopausal women. People at high risk for thyroid dysfunction
include post-partum women, people with high levels of radiation exposure
(< 20mGy), elderly, and people with Down Syndrome4. The
elderly are often undiagnosed because symptoms mimic aging6.
Also as a person ages, the incidence increases.1
The primary cause of hypothyroidism is the failure of the thyroid gland
termed primary hypothyroidism. There are several causes of primary hypothyroidism
such as Hashimoto’s disease (inflammation of the thyroid by an autoimmune
mechanism)6, iatrogenic hypothyroidism such as after radioactive
iodine therapy, iodine deficiency, enzyme defects, underdevelopment of
the thyroid gland, and substances that cause goiters. Another cause of
thyroid disorder is Wilson’s Syndrome. A less common cause of hypothyroidism
is from pituitary or hypothalamic disease called secondary hypothyroidism.
This article will focus primarily on the role of the thyroid hormones,
symptoms, and treatment of hypothyroidism, with additional information
on Wilson’s Syndrome.
The thyroid is a gland in the body which is composed of two lobes on
either side of the trachea2. The thyroid produces hormones
that are involved in almost every part of the body. In adults, the major
role is to maintain metabolic stability. Thyroid hormones are stored in
the thyroid gland and in the blood. The hypothalamic-pituitary-thyroid
axis is designed to monitor levels of the hormones in the body and to
maintain levels in a very specific narrow range.1
The synthesis of thyroid hormone occurs when the thyroid hormones thyroxine
(T4) and triiodothyronine (T3), the more biologically active hormone,
are formed on thyroglobulin. The thyroid cell is the site where the synthesis
of the large glycoprotein thyroglobulin takes place. Iodinated tyrosine,
which is present in the glycoprotein, binds together to make the active
thyroid hormones. Iodine is an important element for the functioning of
the thyroid gland and an adequate supply is needed2.
Three proteins are involved in the transport of T4 and T3: thyroid-binding
globulin (TBG), thyroid-binding prealbumin (TBPA) and albumin. The secretion
of T4 occurs primarily in the thyroid although this is not the case for
T3. T3 is formed from the breakdown of T4 in the peripheral tissues. In
comparing the two hormones, T3 is the more active, therefore T3 plays
the primary role in regulating metabolic activity within the body. The
thyroid’s growth and function is maintained by TSH (thyroid stimulating
hormone). The thyroid is regulated by several mechanisms. First the anterior
pituitary gland secretes TSH which regulates the thyroid hormones. Also
the process of removing iodine from T4 and T3 is regulated by many factors
which include nutrition, drugs, illness, and other non-thyroid hormones.1
In Wilson’s syndrome there is a problem converting T4 to T3. In
normal thyroid function, T4 converts to T3 in the active form and reverse
T3 (RT3) in an inactive form. The enzyme that is used to convert T4 to
T3 is inhibited by stress, acute and chronic illness, fasting and the
stress hormone cortisol. In times of stress, the body produces more T4
to RT3 to conserve energy for stress. A vicious cycle then occurs with
more RT3 than T3 being produced.8
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Wilson's
Syndrome symptoms7 : |
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- hair loss
- weight gain
- cold extremities
- low body temperature
- low blood pressure
- irregular menstrual cycles
- infertility
- premenstrual syndrome
- unexplained & chronic fatigue
- osteoporosis
- hypoglycemia
- constipation
- muscle cramps
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In Wilson’s Syndrome, the thyroid levels appear normal although
the patient is still experiencing symptoms of low thyroid. These symptoms
worsen in periods of physical or emotional stress. Possible stressors
include childbirth, surgery, divorce, death in family, or job and family
stress. The symptoms persist even when the stressors have passed.
Nonpharmacologic treatment includes getting plenty of rest, eliminating
as much emotional stress as possible, moderate exercise for stress control,
and eating a well balanced diet. Pharmacologic treatment includes reducing
T4 by giving T3. In this fashion, the body senses it has enough hormones
and decreases production of T4, which decreases production of RT3. Treatment
only lasts for a couple of weeks or months. Sustained release T3 seems
to be best tolerated in twice daily dosing. Immediate release T3 is marketed
under liothyronine (Cytomel), but does not appear to work as well as sustained
release T3, which a compounding pharmacy would have to prepare. Dessicated
thyroid (Armour thyroid) has also been used since its main constituent
is T3 although it has T4 as well. Levothyroxine (Synthoid) is not as good
of an option because it is only T4.8
Hypothyroid
symptoms6: |
|
- lethargy and decreased energy
- cold intolerance
- muscle cramps
- muscle pain and stiffness
- constipation
- weight gain
- dry skin
- mental slowing
- course hair and skin
- depression
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In hypothyroidism, patients can have a wide variety of symptoms but generally
there is slowing of metabolic processes3. There is a range
of hypothyroidism that consists of subclinical to overt hypothyroidism
to myxedema2. Patient who are older have fewer signs and symptoms
and in both young and old patients there is little correlation between
clinical and biochemical manifestations2.
Decreased levels of thyroid hormone result in swelling around the eyes
and decreased heart rate. A patient’s speech is often slow and the
voice is hoarse. Also decreased reflexes are also common. In the later
stages, there is accumulation of glycoaminoglycans into interstitial tissues
and this accumulation results in edema of skin, muscle, heart, and striated
muscles, which results in symptoms of a round puffy face, loss of hair
and dry skin. Patients also can experience hearing loss, numbness in the
extremities, and day time sleepiness6. There is also a decrease
in the conversion of carotene to vitamin A which causes the skin to have
a yellowish color3. Also hypothyroidism is involved in decreased
conversion of estrogen precursors into estrogen which can result in infertility3.
Lab tests performed in diagnosing and monitoring primary hypothyroidism
are serum TSH and Free Thyroxine Index (FT4I)6. The first step
in evaluation is to measure serum TSH and free T4 index or serum free
T42. Overt primary hypothyroidism reveals a rise in TSH and
free serum T4 level is low2. If the serum free T4 is low and
the TSH is normal or low then diagnosis of central hypothyroidism or nonthyroidal
disease can be made2. Additional tests might include free T4,
thyroid autoantibodies such as antithyroglobulin autoantibodies and anti-thyroid
peroxidase, and in the case of suspicious thyroid structure then a thyroid
scan and/or ultrasonography5. Less common but very important
tests also include total T3 and free T3 as TSH is often normal indicating
euthyroid despite adequate T3 levels which could be indicative of Wilson’s
Syndrome.
Goals of therapy include the restoration
of thyroid
hormone in tissues and to provide relief from symptoms.
Patients should be educated about life long treatment and the need for
follow-up to evaluate the response. Compliance should also be assessed
at each visit2. Thyroid hormone replacement is either natural
or synthetic. Dosing of thyroid medications depends on patient’s
age, the addition of other disorders, and the severity and length of time
of hypothyroidism. T4 replacement (L-thyroxine) is the main stay of treatment2.
In middle-aged and young adults the dose should be 0.075-0.1 mg/day. In
the elderly, the initial dose should be 0.05 mg/day2. There
are many factors that alter the dosage needs of patients. Patient should
be instructed to tell their doctor of all your medical conditions and
medications they are currently taking2. Treatment pace depends
on the severity and length of time the patient has had hypothyroidism
and on other comorbid medical conditions5. If converting T4
to T3 is a problem, then other options include T3/T4 supplementation with
Armour as well as custom compounding of T3/T4 or T3 as extended release.
In an article published in the journal "Endocrine", researchers
looked at the treatment of thyroiditis. Patients were women who had Grave’s
Disease, but who now had hypothyroidism due to thyroidectomy. The authors
compared thyroxine (T4) to thyroxine plus triiodothryonine (T3) treatment.
The author’s substituted 10 mcg of T3 for 50 mcg of T4. There was
a significant decrease in free T4, but there was no significant change
in T3 or TSH concentration. The authors’ concluded that treatment
with T4 plus T3 increased mental functioning, but not on cognitive functioning.
Also symptoms of hypothyroidism and hyperthyroidism decreased on the symptom
scale after combination therapy was used.9 In another journal
article in the "New England Journal of Medicine" in which the
researchers compared thyroxine with thyroxine plus triiodothyronine in
patients with hypothyroidism, the researchers concluded that partial substitution
of the T3 for the T4 may improve mood and neuropsychologic function.10
The measurement of free and total thyroid hormone levels and TSH are
important in monitoring the patient for the correct dose. Signs and symptoms
should resolve within 4-8 weeks, although some symptoms may continue for
4-6 months2. The goal of therapy is euthyroidism. For monitoring,
TSH and T4 levels should check every 4- 6 weeks until euthyroidism occurs2.
The correct maintenance dose should allow TSH to be in the normal range.
For patients who have secondary hypothyroidism monitoring should occur
with the following of T4 levels. For monitoring Wilson’s Syndrome,
T3 and free T3 should be used. Monitoring is very important since over-dosing
can result in heart failure, chest pain, or heart attack. Patients who
are chronically on T4 should have TSH reassessed every 6-12 months to
ensure proper medication dosage2. If hypothyroidism is managed
correctly the symptoms should be reversible3.
References:
- Reasner CA, Ralbert RL. Thyroid disorders. Pharmacotherapy a pathophysiologic
approach. 5th ed. Dipiro JT, Talbert RL, Yee GC, etal., eds. New York:
McGraw-Hill;2002:1359-1378.
- Felig P, Frohman LA. The thyroid: physiology, thyrotoxicosis, hypothyroidism,
and painful thyroid. Endocrinology and metabolism. 4th ed. New York:
McGraw-Hill; 2001:261-329.
- Greenspan FS. The thyroid gland. Basic and clinical endocrinology.
7th ed. Greenspan FS, Gardner DG. New York: Lange Medical Books/McGraw-Hill;
2004:215-251.
- Screening for
thyroid disease: recommendation statement. 2004 National Guideline
Clearinghouse.
- American Association of Clinical Endocrinologists medical guidelines
for clinical practice for the evaluation and treatment of hyperthyroidism
and hypothyroidism. 2002
National Guideline Clearinghouse.
- Armour thyroid
web site. Hypothyroidism.
- Diamonte, M. The new approach to low thyroid conditions. To your
health: the magazine of healing and hope [online]. 1997 Sept/Oct [cited
2004 Sept 22]. Available from : database Alt HealthWatch
- Wilson’s
Syndrome
- Bunevicous R, Jakubonien N, Jurkevivius R, et al. Thyroxine vs thyroxine
plus triiodothyronine in treatment of hypothyroidism after thyroidectomy
for Grave’s Disease. Endocrine. 2002;18:129-33.
- Bunevivius R, Kazanavicius G, Zalinkevicius R, et al. Effects of
thyroxine as compared with thyroxine plus triidothyronine in patients
with hypothyroidism. New England Journal of Medicine. 1999;340 (6):424-70.
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