Download Thyroid Disorders

Thyroid
Disease
Garrett Preston Clark, D.O.
Internal Medicine
What does the Thyroid Do?
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Heart rate
Respiratory rate
Rate of caloric consumption
Skin maintenance
Growth
Fertility
Digestion
Heat regulation
How does it do it?
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The thyroid secretes two hormones:
Thyroxine (T4)  major hormone
produced by the thyroid (aka pre-hormone
of T3)
Triiodothyronine (T3)  is 3 to 8 times
more potent than T4
Most circulating T3 is derived from
deiodination of circulating T4 in the
peripheral tissues
Deiodin…WHAT ? !!!
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Dietary iodine is essential for both T3 and
T4 (about 150 mcg/day).
T4 & T3 are bound to thyroid binding
globulin (TBG), thyroxine-binding
prealbumin, and albumin
70% of T4 is bound to TBG
20% to TBPA
10% to albumin
Deiodin…WHAT ? !!!
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Pretty much ALL of T3 is bound to TBG !
0.04% of T4 is unbound
0.4% of T3 is unbound
Free hormone is taken up by the tissues
Deiodin…WHAT ? !!!
1.
2.
3.
4.
Oxidation of I- by peroxidase
Iodination of thyroglobulin
Proteolytic release of hrmn from follcile
Peripheral conversion of T4 to T3
SO:
Iodine from blood  (in follicle) I- 
thyroglobulin  Diiodtyrosine  T3,T4
bound to thyroglobulin  (out of follicle)
peripheral conversion T4 to T3
SO:
The thyroid gland produces predominantly
the prohormone T4 together with a small
amount of the bioactive hormone T3. Most
T3 is produced by deiodination of T4 in
peripheral tissues. Alternative, inner ring
deiodination (IRD) of T4 yields the
metabolite rT3, the thyroidal secretion of
which is negligible.
Thyroid:
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Many factors effect conversion rate,
including body’s need from moment to
moment and presence or absence of
illness.
Oxidation of I- by peroxidase followed by
iodination of thyroglobulin is inhibited by
propylthiouracil and methimazole
Peripheral conversion is inhibited by
propylthiouracil.
Chemical Structure
Thyroid Hormones continued
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T4 de-iodinated in liver and kidney results
in T3 and reverse T3 (inactive)
Thyroid hormones poorly soluble in water,
so 99% is protein bound
The principle carrier is thyroxine binding
globulin, a glycoprotein synthesized by the
liver
Iodine:
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Essential for thyroid hormone production
Iodine is concentrated from blood via the
Sodium-iodide symporter, so-called “iodine
trap”
Thyroid Stimulating Hormone
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TSH (Thyroid Stimulating Hormone) is
released from anterior pituitary
Controller of TSH secretion is Thyrotropin
Releasing Hormone (TRH) from
hypothalamus
Both inhibited by high blood levels of
thyroid hormones (negative feedback
loop)
TRH-TSH-Thyroid Hormone
Feedback Loop
Hypothalamic-Pituitary-Thyroid Axis
Hyperthyroid: Definition
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Condition results when tissues are
exposed to excess thyroid hrmn
Characterized by increased basal
metabolism, goiter, and disturbances of
the autonomic nervous system
Affects women 3:1 more than men
Hyperthyroid Diseases:
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Graves’ disease
Toxic nodular goiter (Plummer’s disease)
Toxic adenoma
Therapeutic induced hyperthyroid (Lugol’s,
amiodarone, etc.)
Thyroiditis
Primary and/or metastatic follicular
carcinoma
TSH producing tumor of the hypophysis
Hyperthyroid: Common
Symptoms and Signs
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Heat intolerance, excessive sweating, and
moist skin
Hyperactivity and tenseness
Weight loss (unintentional)
Fine tremors, palpitations, and tachycardia
Infiltrative dermopathy
Ocular signs, including lid lag,
exophthalmus, and conjunctival injection
Generalized pruritis
Hyperthyroid: Diagnostic Workup
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History and physical
Blood chemistries, including hormone
levels and specific antibodies
Ultrasound
Thyroid scan
Fine needle biopsy (particularly with
hyperthyroidism associated with
nodularity)
Grave’s Disease
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Autoimmune disease associated with the
production of antibodies that bind to TSH
receptors in the follicular cells of the
thyroid and activate these cells to produce
T4 and T3.
These antibodies therefore simulate TSH TSH has no part in this hyperfunctioning
Graves’ Disease:
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Most common form of adult
hyperthyroidism
Peaks in 3rd and 4th generations
Bilateral exophthalmos occurs in 40-50%
of Graves’ patients- unilateral involvement
is rare
Graves’ Disease
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T3 and T4 concentrations increased
TSH level decreased
Autoimmune antibodies to TSH receptors
RAI and Tc-99m studies are increased
Scans usually show mildly enlarged thyroid
which concentrates isotope evenly and
intensely
Graves’ Disease- Therapy
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Treatment with antithyroid drugs
(Propranolol, propylthiouricil,
methimazole)
Long term remission rate with
conservative treatment is low (30-50%)
Propranolol β-blocker; makes patient
eumetabolic but not euthyroid
Graves’ Disease- Therapy:
Surgery
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Surgery is the treatment of choice if
patient younger than 21 years of age, is
sensitive to iodine, or have very large
goiters
Recurrence rate as low as (2-9%)with a
3% incidence of hypothyroidism
Side effects: vocal cord paralysis and
hypoparathyroidism
Graves’ Disease- Therapy:
Radioactive Iodine-131
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RAI-131 = Therapy of choice for women
past childbearing years and adult males
No proven increase in incidence of
carcinoma, leukemia, etc.
25% of patients will be hypothyroid one
year after treatment; incidence increases
2%/year for the next 20 years
Graves’ Ophthalmopathy
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Most frequent extrathyroidal
manifestationof Graves’ disease
Fortunately, most patients with only minor
involvement, amenable to non-aggressive
treatment
Graves’ Exophthalmos:
Infiltrative Dermopathy of
Graves’ Disease
Toxic Adenoma: Definition
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Autonomous hyperfunctioning nodule
surrounded by normal functioning tissue
Rarely two or more adenomas exist in
normally functioning thyroid
No clear cause; neither antibodies nor TSH
involved
Nodule must be 2.5-3cm in size to
produce hyperthyroidism
Toxic Adenoma: Presentation
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Symptoms and signs of hyperthyroidism.
No exophthalmos.
 No infiltrating dermopathy.
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The thyroid gland may be enlarged, but is
generally of normal size.
On palpation, a non-tender, mildly firm
nodule is palpable.
Toxic Adenoma: Diagnosis
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T3 and T4 levels are elevated.
The TSH concentration is decreased.
Specific antibodies are absent.
On Radioisotope scan, the thyroid gland
is usually of normal size.
One
cool
hot nodule - rest of the gland is
So, What’s a “cold” nodule?
A nonfunctioning thyroid
nodule/lump that does not
concentrate radioactive
isotopes in a thyroid scan
and may be indicative of
cancer
Remember…
Cold = Cancer
Toxic Adenoma: Treatment
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Unless contraindicated, radioactive iodine
(131I) - higher doses are usually
necessary.
Production of hypothyroidism is rare.
Toxic Multinodular Goiter
(Plummer’s Disease)
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Enlarged multinodular goiter found in
areas of iodine deficiency in which
patients with long-standing non-toxic
goiter develop thyrotoxicosis
Range from a single hyperfunctioning
nodule within an enlarged thyroid to
multiple hyperfunctioning nodules
scattered throughout the gland barely
distinguishable from non-functioning
nodules and ordinary thyroid tissue
Plummer’s Diseas:
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A middle-aged person with 10 - 15 years
history of an enlarged gland.
The general symptoms and signs of
hyperthyroidism.
Exophthalmos is absent.
Infiltrative dermopathy is absent.
The gland is enlarged and
multinodular.
Plummer’s Disease: Diagnosis
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The serum T3 and T4 levels are raised.
The TSH concentration is decreased.
No auto-immune antibodies are present
Scan shows an enlarged, multinodular
gland.
One, two or more nodules are hot
(overactive).
Plummer’s Disease: Treatment
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Similar to treatment for Grave’s disease
Plummer’s disease is more resistant to
131I therapy than Graves’ - apparently
because the nodules of low activity
become active as the hyperactive nodules
are destroyed and more TSH is released.
Induction of hypothyroidism is rare
Secondary Hyperthyroidism
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This term refers to hyperthyroidism precipitated
by excess TSH secretion by a pituitary tumour or
by other tumours (e.g. choriocarcinoma, struma
ovarii, etc.)
Clinical signs and symptoms same as other
causes of hyperthyroidism, without
exophthalmos
The T3, T4 and TSH concentrations are raised
The thyroid is enlarged and the isotope uptake is
diffusely increased.
Hyp
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othyroidism
Condition where insufficient thyroid
hormones are produced
Two main types are distinguished,.
primary and secondary hypothyroidism
Primary hypothyroidism by far more
common
Hypothyroidism
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Hashimoto’s Thyroiditis
Idiopathic
Iodine deficiency
Over-irradiation
Hypothyroidism- Characteristics:
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Cold intolerance
Weight gain
Constipation
Lowering of voice
Menorrhagia
Slowed mental and physical function
Hyp
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othyroidism
Primary hypothyroidism is characterized by
a high serum TSH concentration and a low
serum free T4 concentration.
Patients with a high serum TSH
concentration and a normal serum free T4
concentration have subclinical
hypothyroidism
Hyp
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othyroidism
Secondary hypothyroidism is characterized
by a low serum T4 concentration and a
serum TSH concentration that is not
appropriately elevated
Differentiation must be made between
pituitary and hypothalamic disorders.
Hypothyroid: Lab Studies
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Anemia: normo-/micro-/macrocytic.
 Dr. John Pimp Question ! ! ! ! !
T4 and T3 concentrations are low, and
TSH concentration is high in the primary
type.
T4, T3 and TSH are low in the secondary
type.
Thyroiditis
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Inflammation of the thyroid gland
Classified as chronic, subacute, and acute
Can initially present as hyperthyroidism,
ramification may result in hypothyroidism
Shinya Hashimoto
R.I.P.
Hashimoto’s Thyroiditis
(Not the wrestler)
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A chronic inflammation of the thyroid with
lymphocytic infiltration of the gland caused by
autoimmune factors
Most common cause of primary hypothyroidism
in North America
Women to men 8:1
Often, + family history
Also, increased in patients with chromosomal
disorders, including Turner's, Down,Klinefelter's
syndromes.
Hashimoto’s: Signs and
Symptoms
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Painless enlargement of the thyroid gland
Examination reveals a nontender goiter, smooth
or nodular, firm, and more rubbery than the
normal thyroid; many patients have
hypothyroidism when first seen
Other forms of autoimmune disease are
common
There may be an increased incidence of thyroid
neoplasia, particularly papillary carcinoma and
thyroid lymphoma
Hashimoto’s: Diagnosis
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Laboratory findings early in the disease
consist of normal T4 and TSH levels and
high titers of thyroid peroxidase antibodies
and less commonly anti-thyroglobulin
antibodies
The thyroid radioactive iodine uptake may
be increased
Later in the disease, the patient develops
hypothyroidism with decreased T4,
decreased thyroid radioactive iodine
uptake, and increased TSH
Hashimoto’s: Treatment
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Usually requires lifelong replacement
therapy with thyroid hormone to decrease
goiter size and treat the hypothyroidism
Occasionally, the hypothyroidism is
transient
The average oral replacement dose with Lthyroxine is 100-120 µg/day
Subacute Thyroiditis (de
Quervain’s Thyroiditis)
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Acute inflammatory disease of the thyroid,
probably caused by a virus
Frequently a history of mumps
The gland shows giant cell infiltration but
lymphocyte infiltration is absent
Female patients outnumbered male
patients in a ratio of 3-6:1
Although the disease has been described
at all ages, it is rare in children
Subacute Thyroiditis:
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Sudden onset of sore throat, tenderness
of the neck and low grade fever
Gradual onset extends over 1 to 2 weeks
and continues with a fluctuating intensity
for 3 to 6 weeks
Thyroid gland is typically enlarged two or
three times the normal size or larger and
is tender to palpation
Often confused with pharyngitis or otitis
media
Subacute Thyroiditis:
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Approximately one-half of the patients present
during the first weeks of the illness, with
symptoms of thyrotoxicosis, including
nervousness, heat intolerance, palpitations,
tremulousness, and increased sweating
As the disease process subsides, transient
hypothyroidism occurs in about one-quarter of
the patients
Ultimately thyroid function returns to normal and
permanent hypothyroidism occurs in less than
10 percent of the cases
Subacute Thyroiditis: Diagnosis
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History and clinical examination.
An elevated erythrocyte sedimentation
rate.
The T4 level is elevated, the TSH is low.
The 131I-uptake is down in the presence
of elevated T4, and a radioisotope scan
(99mTcO4-) shows a cool thyroid or the
thyroid is not visualized.
Subacute Thyroiditis: Treatment
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In some instances, no treatment is
required
Mainstay of treatment is analgesia
Initial therapy with Aspirin or NSAIDs
May need corticosteroids
Levothyroxine may be useful in situations
where the patient is not already
hyperthyroid due to the release of
thyroidal contents into the circulation
Acute (Infectious) Thyroiditis
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Rare
However occasionally, esp in children, a
persistent fistula from the pyriform sinus
may make the left lobe of the thyroid
particularly susceptible to abscess
formation
Occasionally, acute bacterial supporative
thyroiditis occurs in children receiving
cancer chemotherapy
Acute Thyroiditis: Etiology
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Virtually any bacteria can infect the thyroid
Strep, Staph, pneumococcus, salmonella,
bacteroides, t. pallidum, pasturella, and
mycobacterium all documented
In addition, fungal infections, including
cryptococcus, have been reported
Most commonly, however, especially in children,
infection of the thyroid gland is a result of direct
extension from an internal fistula from the
pyriform sinus
Acute Thyroiditis: Presentation
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Pain in the region of the thyroid gland,hot
and tender
Unable to extend the neck and often sits
with the neck flexed in order to avoid
pressure on the thyroid gland
Swallowing is painful
Pediatric presentation more typical than
adult
In general, no sign of hypo- or
hyperthyroidism
Acute Thyroiditis: Treatment
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Surgical removal of fistulous tract in
pediatric patients with communication
with pyriform sinus
Systemic antibiotics with broad spectrum
coverage needed for some patients
Must add fungal coverage in
immunocompromised patients
Acute Thyroiditis: Prognosis
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Some patients with thyroiditis, the
destruction may be sufficiently severe that
hypothyroidism results
Patients with a particularly diffuse
thyroiditis should have follow-up thyroid
function studies performed to determine
that this has not occurred
Surgical removal of a fistula or branchial
pouch sinus is required to prevent
recurrence when this is present
Cretinism:
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Hypothyroidism of the fetus or child
CAUSES:
Iodine deficient diet in mother or during
early life of child
Thyroid developmental defect
Thyroid relates enzyme deficiency
Failure of decent during development
Transfer of anti-thyroid Abs from mother
with autoimmune disease to fetus
Cretinism – Clinical Features:
 Impaired
physical growth
 Enlarged tongue
 Mental retardation
 Enlarged, distended abdomen
CRETINISM:
Amiodarone and Thyroid
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Amiodarone used to treat cardiac
arrythmias
Structurally similar to thyroid hormone,
comprised of 39% iodine
Patients on amiodarone may become
hypo- or hyperthyroid
If hypothyroid, stop amiodarone and give
T4
Thyroid Nodule:
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Ninety-five percent of solitary thyroid nodules
are benign
Thyroid cancers typically present as a dominant
solitary thyroid nodule, cold nodule on scan
Papillary carcinoma accounts for 60 percent,
follicular carcinoma accounts for 12 percent, and
the follicular variant of papillary carcinoma
accounting for six percent
Fine needle biopsy is a safe, effective, and easy
way to determine if a nodule is cancerous
Features Favoring Benign Nodule
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Family history of Hashimoto's thyroiditis
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Family history of benign thyroid nodule or goiter
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Symptoms of hyperthyroidism or hypothyroidism
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Pain or tenderness associated with a nodule
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Soft, smooth, mobile nodule
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Multinodular goiter without a predominant nodule
(lots of nodules, not one main nodule)
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“Warm" nodule on thyroid scan (produces normal
amount of hormone)
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Simple cyst on ultrasound
Malignant Nodule
Characteristics:
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Age less than 20
Age greater than 70
Male gender
New onset of swallowing difficulties
New onset of hoarseness
History of external neck irradiation during childhood
Firm, irregular and fixed nodule
Presence of cervical lymphadenopathy (swollen hard lymph
nodes in the neck)
Previous history of thyroid cancer
Nodule that is "cold" on scan (shown in picture above,
meaning the nodule does not make hormone)
Solid or complex on ultrasound
Thyroid Disease: Review
Condition
TSH
Free T4
Free T3
Other
Graves’ Disease
↓↓↓
↑
Usually ↑
Thyroid scan with diffuse
isotope uptake
Toxic Adenoma
↓
↑ or Normal
↑ or Normal
thyroid scan shows functioning
nodule and suppression of
other thyroid tissue
Toxic Multinodular Goiter
↓
↑ or Normal
↑ or Normal
thyroid scan shows enlarged
gland with multiple active
nodules
Thyroiditis
↓
Variably ↑
Variably ↑
thyroid scan shows low
radioiodine uptake,
thyroglobulin level markedly
raised.
Factitious Hyperthyroidism
↓
↑
↑ or Normal
low radioiodine uptake on
thyroid scan and absent
thyroglobulin levels
Pregnancy
Normal
↑ total T4
Normal free
T4
↑ total T3
Norma free
T3
positive pregnancy test
THE TESTS:
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Best way to initially test thyroid function is to
measure the TSH
High TSH level indicates that the thyroid
gland is failing because of a problem that is
directly affecting the thyroid (primary
hypothyroidism)
low, usually indicates that the person has an
Overactive thyroid that is producing too much
thyroid hormone (hyperthyroidism)
THE TESTS (RECALL):
Occasionally, a low TSH may result from an
abnormality in the pituitary gland, which
prevents it from making
enough TSH to stimulate the thyroid
(secondary hypothyroidism)
T4 Tests:
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2.
T4 circulates in the blood in two forms:
Bound to proteins that prevent the T4
from entering the various tissues that
need thyroid hormone.
Free T4, which does enter the various
target tissues to exert its effects
T4 Tests:
The free T4 fraction is most important to
determine how the thyroid is functioning,
and tests to measure this
are called the Free T4 and the Free T4
Index.
T4 Tests:
The FTI tells how much T4 is present
compared to the thyroxine-binding
globulin. The FTI can help tell if abnormal
amounts of T4 are present because of
abnormal amounts of thyroxin-binding
globulin.
T3
T3 (No, the other T3):
Triiodothyronine (T3). Most of the T3 in
the blood is attached to the thyroxinebinding globulin. Less than 1% of the T3
is unattached.
T3
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Not used much in these parts
A T3 blood test measures both bound and
free triiodothyronine.
THE END
References
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American Association of Clinical Endocrinologists medical guidelines for
clinical practice for the evaluation and
treatment of
hyperthyroidism and hypothyroidism. Endocr
Pract. 2002 NovDec;8(6):457-69
Bartalena L. Pinchera A, Macocci C. Management of Graves’
ophthalmopathy:
Reality and prespectives. Endocrine Reviews 2000;
21:168-199.
Beers, Mark MD et al. The Merck Manual of Diagnosis and Therapy Seventh
Edition. Merck, New York, 1995
Braunwald, et al. Harrison’s Principals of Internal Medicine, 15th Edition.
McGraw, New York. 2001.
Klopper JF. Diagnosis and management of amiodarone-induced
hyperthyroidism. SA Med J 1999; 89:453-454.
Murray IPC and Ell PJ. (1998) Nuclear Medicine in Clinical Diagnosis and T
reatment. 2nd Ed. Churchill Livingstone,
Edinburgh: 136-142.
O'Reilly DS; Thyroid function tests-time for a reassessment.;BMJ 2000 May
13;320(7245):1332-4.
Student BMJ . Interpreting Thyroid Function Tests.
www.emedicine.com
References:
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http://www.aafp.org/afp/20050815/623_f2.gif
http://bio.kuleuven.be/endo/fotos/HPT.jpg
http://www.thyca.org/images/T3.gif
http://www.peacehealth.org/kbase/topic/medtes
t/hw27377/descrip.htm
http://www.thyroid.org/patients/brochures/Func
tionTests_brochure.pdf
http://www.thyroidmanager.org/Chapter3/3cframe.htm