Transcript Thyroid gland modified part 2

Thyroid hormones
2
Introduction
• TSH glycoproteins consisting of alpha and beta subunits, the alpha
subunit is similar to that found in three glycoproteins hormones LH,
FSH, HCG is in turn regulated by thyrotropin releasing hormone
TRH from hypothalamus.
•
TRH is a tripeptide which has been synthesized and is available for
exogenous administration. A 200 microgram bolus of TRH given
intravenously produces a rise in TSH with a peak at 20 minutes (425mU/L) which falls but does not reach baseline by 60 minutes after
injection
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The levels of circulating T4 and T3 exert a
feedback effect on the secretion of TSH and
possibly TRH. A fall in T4 and T3 stimulates TSH
release and increase of T4 and T3 suppresses
TSH.
Thyroid hormones
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Hormones (T4, T3, and RT3), once released into the bloodstream, exist
either as protein bound or in a free form.
The T3 and T4 hormones help regulate the body's metabolic rate (the rate
at which the various processes in the body work, such as how quickly
calories are burnt).
An excess of T3 and T4 will make you feel overactive and you may lose
weight. If you don't have enough of these hormones, you'll feel sluggish and
you may gain weight.
• Measurement of total thyroid hormones includes
protein-bound and free fractions.
• Alterations in the concentration of serum proteins
will affect total T4 and total T3 levels. Such
changes in proteins may result in misleading
elevation or reduction of total thyroxine and triiodothyronine.
• This can be recognized either by direct
measurement TBG, to arrive at a T4/TGB ratio, or
by an indirect method of estimating the available
binding sites for thyroid hormone.
• Because over 99% of released thyroid hormone is
attached to proteins in the blood, it is believed that
measuring the amount not attached to proteins (i.e., free
thyroid hormone) is a more accurate measurement of
thyroid hormone levels. Measuring the total hormone
level is generally less reliable.
• Techniques which measure free fractions of T4 or T3 are
not usually influenced by the amount of TBG present.
• Whilst T4 is produced entirely by the thyroid, T3 is also
produced by peripheral conversion from T4 in cells of the
kidney, liver, heart, anterior pituitary and other tissue.
• T4 is deiodinated to the active metabolite T3 or an
inactive metabolite reverse T3(rT3). The mechanism
controlling these conversions is poorly understood
• Note that high levels of estrogens (birth control pills, nonbio-identical hormone replacement, or pregnancy) or
estrogen dominance can increase the amount of the
protein that binds T4.
• This will produce misleading elevated Total T4 and T3
values which can look like ‘hyperthyroidism’ when it is
not. But free T3 or free T4 not affected with these
conditions
• In healthy individuals, T4 is largely
converted to T3 but in severely ill people
suffering from a variety of acute or chronic
illnesses, less T3 and more reverse T3 is
produced.
Triiodothyronine (T3)
• T3 is typically only measured in cases of
hyperthyroidism where the T4 levels are
normal.
RT3: Reflects the level of Reverse T3. It is used to
measure often but found little need for it once. It is
realized the approximate value can be estimated from
knowing T4 and T3 values since we know that T4 will
become either T3 or RT3. For example, if the T4 is
elevated and the T3 is low, we know that RT3 (what the
rest of the T4 becomes) will be relatively elevated.
• Cortisol decreases TSH, lowering thyroid hormone
production.
. Cortisol inhibits the conversion of T4 to active T3, and
increases the conversion of T4 to reverse T3.
Hypothyroidism
• In overt primary hypothyroidism, serum total T4 is low and serum
TSH raised.
• Serum T3 levels are of no diagnostic value as they are frequently in
the normal range even when T4 is low.
• In primary hypothyroidism the ECG may reveal bradycardia, low
voltage complexes, ST segment depression and T wave inversion,
but such changes are not invariably present and are not specific.
• In hypothyroidism secondary to pituitary disease, T4 values and FTI
are low and there is no TSH response to TRH, but with lesser
degrees of pituitary impairment the pattern of the TSH response to
TRH is variable.
• In hypothalamic disease, TSH response to TRH is typically delayed.
Hyperthyroidis
The clinical diagnosis of hyperthyroidism is confirmed by finding an
elevated serum T4.
if T4 is normal but thyrotoxicosis is still suspected, then T3 should be
measured.
T3 is often elevated before T4 in hyperthyroidism (T3 toxicosis), but
other evidence of thyroid autonomy, such as a flat TSH response to
TRH or failure of T3 suppression of radio-iodine uptake, should be
sought.
Misleading high total T4 value are found in pregnancy or oral
contraceptive therapy due to the effect of estrogens on TBG capacity
and in rare condition of familial increased TBG. Such patients are
clinically euthyroid and the high t4 levels can be corrected by direct
measurement of TBG or free thyroxine index, and free T4 levels are
normal.
Antithyroid antibodies
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Antithyroid antibodies are created when the body's immune system attacks
parts of the thyroid with antibodies. There are several different types of
antithyroid antibodies. TSH-R Ab is a TSH receptor antibody, and is present
in most of patients who have Graves' disease. The antibodies stimulate the
TSH-receptor which causes the thyroid to make more thyroid hormone (T4
and T3).
Antithyroglobulin antibodies (Anti-TG Ab) are present in patients with
Hashimoto's thyroiditis. Antibodies against the protein thyroglobulin can
result in destruction of thyroid cells. This destruction can lead to
hypothyroidism.
Antithyroid peroxidase antibodies (Anti-TPO Ab) are similar to
antithyroglobulin antibodies. They are found in high levels in patients with
Hashimoto's thyroiditis, and can lead to destruction of thyroid cells.
• * Antibodies: Autoimmune thyroid disease falls into two main
categories: Hashimoto’s Thyroiditis and Grave’s Disease.
Hashimoto’s Thyroiditis is typically identified by checking antibodies
that attach the thyroid tissue.
• Grave’s Disease is typically diagnosed using Thyroid-Stimulating
Immunoglobulin (TSI), Long Acting Thyroid Stimulator (LATS) and
TSH-Binding Inhibiting Immunoglobulin (TBII). These are different
names for the same test.
Hashimoto’s patient
• Hashimoto’s patient who is taking replacement hormones but still
suffers from hypothyroid symptoms – often in spite of repeated
changes in the dose and type of medication.
• In these patients, inflammation is depressing thyroid receptor site
sensitivity and producing hypothyroid symptoms, even though lab
markers like TSH, T4 and T3 may be normal.
Confounding factor
• When exogenous T4 is ingested, the T4 (or free T4)
measurements can become discordant from the TSH
measurements. For example, suppose a patient has
primary hypothyroidism with a low FT4 level and an
elevated TSH level. With oral administration of thyroxine,
the FT4 can return to the reference interval far more
quickly than can the TSH, which may not return to the
reference interval for several weeks
Tumor in thyroid gland
• The important points to remember are that cancers
arising in thyroid nodules generally do not cause
symptoms, thyroid tests are typically normal even when
cancer is present, and the best way to find a thyroid
nodule is to make sure your doctor checks your neck!
• The primary therapy for all forms of thyroid cancer is
surgery.
• After surgery, patients need to be on thyroid hormone for
the rest of their life.
• If your doctor recommends radioactive iodine therapy,
your TSH will need to be elevated prior to the treatment.
• Thyroid cancer that spreads (metastasizes) to
distant locations in the body occurs rarely but
can be a serious problem.
• Surgery and radioactive iodine remain the best
way to treat such cancers as long as these
treatments continue to work.
• However, for more advanced cancers, or when
radioactive iodine therapy is no longer effective,
other means of treatment are needed
Thyroid tumor
• Example 2:
• * George had a thyroidectomy to remove a cancerous tumor. He
was healthy otherwise. His thyroid hormone replacement of 75mcg
Synthroid is not enough to meet his needs. He is hypothyroid.
* Thyroid lab values show are: TSH = 5 (high), FT4 = 0.7 (low), FT3
= 280 (lower than optimal but relatively higher than T4)
• What does this mean: The pituitary gland is sensing insufficient
thyroid energy and is therefore sending a strong signal to the
(absent) thyroid gland telling it to make more T4. Because there is
insufficient T4, the body can compensate by converting T4 to T3 at a
higher than usual rate, hence we see a T3 that is higher than T4 on
a relative scale.
• All patients who have undergone thyroidectomy require thyroid
hormone replacement with levothyroxine once the thyroid is
removed.
• The dose of levothyroxine prescribed by your doctor will in part be
determined by the extent of your thyroid cancer.
• More extensive cancers require higher doses of levothyroxine to
suppress TSH.
• In cases of minimal or very low risk cancers, it’s safe to keep TSH
in the normal range.
• The TSH level is the most sensitive indicator of whether the
levothyroxine dose is correctly adjusted and should be followed
regularly by your doctor.
Thyroglobulin
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Thyroglobulin is a protein produced by thyroid tissue and most types of
thyroid cancer and is usually checked at least once annually. Following
thyroidectomy and radioactive iodine ablation, thyroglobulin levels should be
undetectable for life. Therefore, a detectable thyroglobulin level should raise
a suspicion for possible cancer recurrence.
Detectable thyroglobulin levels may require additional tests and possible
further treatment with radioactive iodine and surgery.
Thyroglobulin is generally measured either when you’re on thyroid hormone
with a low or normal TSH, or after TSH is elevated either by stopping thyroid
hormone for 3-6 weeks, or after injection of Thyrogen®.
Measurement of thyroglobulin may not be possible in up to 25% of patients
who have interfering thyroglobulin antibodies present in their blood. In these
patients, other means of follow up are often used.
• In addition to routine blood tests, your doctor may want to
periodically repeat a whole-body iodine scan to determine if any
thyroid cells remain.
• Whole body scanning is also done after your TSH level is raised,
either by stopping your thyroid hormone or by administering
Thyrogen® injections.
• Increasingly, these scans are only done for high risk patients and
have been largely replaced by routine neck ultrasound and
thyroglobulin measurements that have a higher diagnostic sensitivity
especially when done together.
Follow up the thyroid cancer
treatment
• People treated for thyroid cancer are typically asked to return to the
doctor’s office every six months to a year. At a follow-up care visit,
the doctor will conduct a physical examination and blood tests to
watch the level of TSH suppression and to test for Tg.
• If the thyroid gland has been removed, there should be little or no Tg
in the blood; an elevated level may indicate the cancer has returned.
• Other blood tests may be done depending on the specific type of
thyroid cancer treated. Blood tests also help the doctor determine
the correct dosage of the patient’s thyroid replacement medication (if
needed), which may be adjusted over time as the patient gets older.
Thyroid cancer
 acromegaly – a rare condition where the body produces too much
growth hormone can be considered as risk factor for thyroid cancer.
 The thyroid gland is the only organ which makes Tg. Therefore, Tg
is a good test to tell if there are thyroid cells in the body. Once the
whole thyroid is taken out, the thyroglobulin level should go down to
close to zero.
• Thyroglobulin levels can then be measured, by a simple blood test,
after thyroidectomy.
• Thyroglobulin is used as a tumor marker (i.e. test to see how much
cancer is in the body) for thyroid cancer.
• If thyroglobulin levels go up after removing the whole thyroid, there
is concern that the cancer may have come back (i.e. recurred) or
spread (i.e. metastasized).
Calcitionin
• Calcitonin helps control blood calcium levels. Calcium is
a mineral that performs a number of important functions,
such as building strong bones.
• Calcitonin isn't essential for maintaining good health
because your body also has other ways of controlling
calcium.
• Calcitonin is produced by the parafollicular, or C
cells, found in the thyroid gland.
• This test is used as a tumor marker for a rare
type of thyroid cancer known as medullary
thyroid cancer.
Appropriate use of thyroid tests
Test
comment
Screening
serum TSH
FT4
Most sensitive test for primary
hypothyroidism and hyperthyroidism
Excellent test
For hypothyroidism
Serum TSH
High in primary and low in secondary
hypothyroidism
For hyperthyroidism
Anti-thyroglobulin and
anti-thyroperoxidase
antibodies
Elevated in Hashimoto thyroiditis
Serum TSH
T3 or FT3
I123 uptake and scan
Antithyroperoxidase and
antithyroglobulin
antibodies
TSI , TSH-R-Ab (stim)
Suppressed except in TSH-secrting pitutary
tumor or pituitary hyperplasia(rare)
Elevated
Increase uptake; diffuse versus (hot) foci
on scan
Elevated in Graves disease
Ususally (65%) positive in Graves disease
For thyroid nodules
Fine-needle aspiration biopsy
I123 uptake and scan
99mTC scan
ultrasonography
Best diagnostic method for
thyroid cancer.
Cancer is usually (cold); less
reliable than FNA biopsy
Vascular versus avascular
Useful to assist FNA biopsy.
Useful in assessing the risk of
malignancy(multinodular
goiter or pure cysts are less
likey to be malignant). Useful
to mointor nodules and
patients after thyroid surgery
for carcinoma
Note:
• In states of thyroid hormone resistance,
the concentrations of the thyroid hormones
and thyroid-stimulating hormone TSH are
typically elevated, but the affected patients
are usually euthyroid or even possibly
hypothyroid.