TABLE OF CONTENTS
- Hypothyroidism
- Hyperthyroidism
- Postpartum thyroiditis
Hypothyroidism can be classified into different groups
based on the organ responsible for the abnormality and the severity
of disease, including
- * "primary hypothyroidism" (hypothyroidism
due to a thyroid gland abnormality) in which there is a decreased
concentration of free T4 and an elevated concentration of TSH.
- * "secondary hypothyroidism" (hypothyroidism
due to a pituitary gland abnormality) in which there is a decreased
concentration of both free T4 and TSH (the T4 is low since there
is inadequate stimulation of the thyroid gland by TSH). When the
TSH and free T4 are both low then a structural lesion in or around
the pituitary gland should be ruled out with a radiologic test.
- * "tertiary hypothyroidism" (hypothyroidism
due to a hypothalamic or CNS abnormality)
- * "subclinical hypothyroidism" in which there
is an elevated TSH concentration but the free T4 level is normal.
Many of these women become hypothyroid eventually, and many physicians
use the presence of abnormally high levels of anti-thyroid antibodies
to direct their treatment. If there are elevated anti-thyroid
antibodies then the patient most likely will become hypothyroid,
she may develop a goiter if untreated so treatment should be considered.
If there is a minimal elevation in TSH and the patient is asymptomatic
with normal anti-thyroid antibody levels then annual TSH levels
to monitor the progression of disease could be considered.
Thyroid abnormalities are more common in women than in men. Hypothyroidism
increases with aging. Up to 45% of women have evidence of thyroiditis,
which is inflammation of the thyroid gland, usually secondary
to an auto immune process. 15-20% (about 1 in 6) of women over
60 years of age have evidence of hypothyroidism.
Thyroid hormone is formed in the thyroid gland, which is present
in the neck. Circulating iodide absorbed from the diet (by the
small intestine) enters the thyroid gland (under the influence
of thyroid stimulating hormone, TSH) where it is oxidized to iodine
and is bound to tyrosine. Thyroxine (T4) and triiodothyronine
(T3) are the two thyroid hormones that are stored in the thyroid
gland within a colloid called thyroglobulin. TSH stimulates an
enzyme that releases active thyroid hormone (T4 and T3) from the
thyroglobulin storage compartment and enhances their secretion
into the circulating blood. T4 is secreted from the thyroid gland
at a rate 20 times greater than T3, but the bioactivity of T4
results predominantly from its conversion to the more active form
T3 in the tissues of the body (mostly the liver and kidney). Circulating
T4 and T3 are predominantly bound to proteins, with about 80%
bound to TBG (thyroxine binding globulin) and about 20% bound
to either thyroxine binding prealbumin and albumin. These binding
proteins limit the bioactivity of the hormone, with the "free
T4" and "free T3" fractions of the total T4 and
total T3 reflecting the bioactive component.
Thyroid hormones secreted by the thyroid gland communicate with
the hypothalamus and the pituitary gland of the brain to help
maintain the circulating thyroid hormone concentration within
a normal range (similar in principle to the ovarian feedback system).
Circulating thyroid hormones suppress TRH secretion from the hypothalamus
and decrease the pituitary sensitivity to available TRH, both
of which reduce pituitary TSH secretion. The TSH secreted from
the pituitary gland is very sensitive to circulating thyroid hormone
levels so that a small change in free T4 in the circulation results
in a large change in TSH.
Therefore, circulating free T4 and TSH concentrations are the
best initial screening tests for thyroid disease. In the cost
effective world of modern medicine, a single sensitive TSH concentration
is initially all that is required. If the TSH is abnormal, then
the free T4 should be checked.
The clinical appearance of hypothyroidism involves a spectrum
of abnormalities from "unrecognized" to "overwhelming."
The symptoms are often mild and go unnoticed, but may include
- menstrual irregularity or amenorrhea (due to an ovulatory
dysfunction),
- cold intolerance (person always feels colder than others and
cannot tolerate cold environments),
- decreased energy and exercise tolerance with easy fatiguability,
- constipation,
- mental slowness with poor memory,
- depression,
- delayed reflexes, and
- water retention with periorbital (around the eyes) edema (swelling)
Lab abnormalities associated with hypothyroidism may include:
- anemia
- elevated cholesterol (as well as elevated LDL-cholesterol
fraction),
- hyponatriemia (decreased sodium due to water retention), and
- elevated liver enzymes
Hyperthyroidism is diagnosed when the free T4 is elevated.
If TSH is low and the free T4 is normal, the free T3 should be
checked since there is an uncommon form of hyperthyroidism called
"T3 thyrotoxicosis" that is due to a selective increase
in T3.
Causes for hyperthyroidism include:
- * Graves' disease (diffuse goiter),
- * Plummer's disease (nodular goiter, generally seen
in postmenopausal women), and
- * a pituitary TSH secreting tumor, which is a rare
cause of hyperthyroidism (both the TSH and free T4 are elevated)
Graves' disease appears to be caused by TSH like antibodies produced
by an autoimmune disorder. These TSH like antibodies bind the
TSH receptors to continuously activate them. These auto antibodies
have been referred to by a number of names including TSI (thyroid
stimulating immunoglobulin) and LATS (long acting thyroid stimulator).
The diagnosis of Graves' disease or Plummer's disease is made
by finding a suppressed TSH, an elevated free T4 or free T3, and
a radioactive iodine uptake scan to indicate the presence of a
diffuse goiter (Graves'), a solitary hot nodule (Plummer's) or
a hot nodule in a multinodular goiter (Plummer's).
The radioactive iodine uptake scan is important to rule out a
"cold" nodule. If a "cold" solitary nodule
is identified (does not take up radioactive iodine on scan) there
is a 10-15% chance of malignancy (cancer) and further evaluation
is required.
A thyroid nodule in a multinodular goiter without a history of
high risk factors for cancer is not usually an indication for
further evaluation since it has the same risk of cancer as a normal
thyroid gland. High risk factors for thyroid cancer are
- * a history of irradiation to the head and neck (1
out of 9 with this history develop thyroid cancer),
- * a rapidly growing or hard nodule,
- * palpable regional lymph nodes, or
- * vocal cord paralysis.
The clinical appearance of hyperthyroidism includes
- exophthalmos (bulging of the eyes) and pretibial myxedema
(in Graves')
- nervousness and tremor
- heat intolerance (always feeling hotter than those around
you and intolerant of heated environments)
- sweating with moist warm skin
- diarrhea
- palpitations and possible tachycardia
- goiter
Postpartum thyroiditis is a common disorder involving anti-microsomal
anti-thyroid antibodies (a destructive thyroiditis) that is underreported
and underdetected. The actual incidence is believed to be about
5-10%, occurs about 3-6 months after delivery (pregnancy) transiently
for about 6 months, usually starts with hyperthyroidism that is
followed by hypothyroidism, and is often mistaken for depression
or anxiety. The disorder tends to recur in subsequent pregnancies
and usually the woman will develop hypothyroidism secondary to
the destructive thyroiditis. Antithyroid medication does not treat
the hyperthyroid stage because the outpouring of thyroid hormone
is due to destruction of the microsomal compartments of the thyroid
cells (thyroiditis is not affected by the antithyroid medicines).
Thyroid replacement medication is effective for the hypothyroid
state but since there usually is a spontaneous remission treatment
is usually not initiated. If treatment is initiated, the patient
is generally weaned off treatment (slowly) after about 1 year
and reassessed.
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