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THYROID GLAND
LABORATORY
THE THYROID GLAND of gestation. By week 11 of gestation, the
thyroid gland begins to produce measurable
The thyroid gland is responsible for the amounts of thyroid hormone.
production of two hormones:
Iodine is an essential component of
1. thyroid hormone thyroid hormone. In parts of the world where
2. and calcitonin. severe iodine deficiency exists, neither the
Calcitonin is secreted by parafollicular C mother nor the fetus can produce sufficient
cells and is involved in calcium homeostasis. amounts of thyroid hormone and both develop
hypothyroidism. As thyroid hormone is
Thyroid hormone is critical in regulating critical to fetal neurologic development,
body metabolism, neurologic development, hypothyroidism can lead to mental
and numerous other body functions. retardation and cretinism.
Clinically, conditions affecting thyroid In areas where iodine deficiency is not an
hormone levels are much more common than issue, other problems with thyroid
those affecting calcitonin and are the major development may occur, including congenital
focus of this chapter. hypothyroidism, which occurs in 1 of 4,000
live births. If the mother has normal thyroid
function, small amounts of maternal thyroid
THYROID ANATOMY AND DEVELOPMENT hormone crossing the placenta protect the
fetus during development. Immediately
postpartum, however, these newborns require
initiation of thyroid hormone or their further
neurologic development will be significantly
impaired. In much of the developed world,
screening tests are performed on newborns to
detect congenital hypothyroidism.

THYROID HORMONE SYNTHESIS

➢ Thyroid hormone is made primarily of the
trace element iodine, making iodine
metabolism a key determinant in thyroid
function. Iodine is found in seafood, dairy
products, iodine-enriched breads, and
vitamins. Significantly, iodine is used in
high concentrations in the contrast
medium used in many radiologic
The thyroid gland is positioned in the lower procedures, including computed
anterior neck and is shaped like a butterfly. It tomography (CT) scans and heart
is made up of two lobes resting on each side of catheterization.
the trachea, bridged by the isthmus, with a ➢ It is also present in amiodarone, a
band of thyroid tissue running anterior to the medication used to treat certain heart
trachea. conditions. The recommended minimum
daily intake of iodine is 150 μg.
Posterior to the thyroid gland lie the ➢ If iodine intake drops below 50 μg daily,
parathyroid glands—which regulate serum the thyroid gland is unable to manufacture
calcium levels—and the recurrent laryngeal adequate amounts of thyroid hormone,
nerves innervating the vocal cords. The and thyroid hormone deficiency—
locations of these structures become hypothyroidism—results.
important during thyroid surgery, when injury ➢ Thyroid cells are organized into spheres
could lead to hypocalcemia or permanent surrounding a central core of fluid called
hoarse voice. colloid. These structures are called
The fetal thyroid develops from an follicles. The major component of colloid,
outpouching of the foregut at the base of the thyroglobulin, is a glycoprotein
tongue that migrates to its final location over manufactured exclusively by thyroid
the thyroid cartilage in the first 4 to 8 weeks follicular cells and rich in the amino acid

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endocytosis. Inside the follicular cell, these

tyrosine. Some of these tyrosyl residues will be
droplets are digested by intracellular
iodinated, producing the building blocks of
lysosomes into T4, T3, and other products.
thyroid hormone.
T4 and T3 are then secreted by the thyroid
cell into the circulation.

➢ On the outer side of the follicle, iodine is

actively transported into the thyroid cell
➢ Biosynthesis of thyroid hormone. Thyroid
by the Na+/I− symporter located on the hormone synthesis includes the following
basement membrane. Inside the thyroid steps:
cell, iodide diffuses across the cell to the 1. iodide (I−) trapping by thyroid follicular
apical side of the follicle, which abuts the cells;
core of colloid. Here, catalyzed by a 2. diffusion of iodide to the apex of the cell
and transport into the colloid;
membrane-bound enzyme called thyroid
3. oxidation of inorganic iodide to iodine
peroxidase (TPO), concentrated iodide is and incorporation of iodine into tyrosine
oxidized and bound with tyrosyl residues residues within thyroglobulin molecules
on thyroglobulin. This results in in the colloid;
production of monoiodothyronine (MIT) 4. combination of two diiodotyrosine (DIT)
and diiodothyronine (DIT). This same molecules to form tetraiodothyronine
(thyroxine, T4) or of monoiodotyrosine
enzyme also aids in the coupling of two (MIT) with DIT to form triiodothyronine
tyrosyl residues to form (T3);
triiodothyronine (T3) (one MIT residue 5. uptake of thyroglobulin from the colloid
+ one DIT residue) or thyroxine (T4) into the follicular cell by endocytosis,
(two DIT residues). These are the two fusion of the thyroglobulin with a
lysosome, and proteolysis and release
active forms of thyroid hormone. This
of T4 and T3; and
thyroglobulin matrix, with branches now
6. release of T4 and T3 into the circulation.
holding T4 and T3, is stored in the core of
the thyroid follicle.
➢ Activity of thyroid hormone depends on
the location and number of iodine atoms.
Approximately 80% of T4 is metabolized
into either T3 (35%) or reverse T3 (rT3)
(45%).
➢ Outer-ring deiodination of T4 (5′-
deiodination) leads to production of 3,5,3′-
triiodothyronine (T3). T3 is three to eight
times more metabolically active than is T4
and often considered to be the active form
of thyroid hormone, with T4 considered
the “pre”-hormone (with thyroglobulin
being the “prohormone”). In addition to its
“pre”-hormone activity, however, inner-
ring deiodination of T4 results in the
production of metabolically inactive rT3.

➢ Thyroid-stimulating hormone (TSH)

signals the follicular cell to ingest a
microscopic droplet of colloid by

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Metabolism of
Thyroxine: • TRH is synthesized by neurons in the
supraoptic and supraventricular nuclei of
the hypothalamus and stored in the
median eminence of the hypothalamus.
When secreted, this hormone stimulates
cells in the anterior pituitary gland to
manufacture and release TSH.
• TSH, in turn, circulates to the thyroid gland
and leads to increased production and
release of thyroid hormone. When the
PROTEIN BINDING OF THYROID HORMONE
hypothalamus and pituitary sense that
There are two forms of iodothyronine 5′- there is an inadequate amount of thyroid
deiodinase. hormone in circulation, TRH and TSH
secretion increases and stimulates
1. Type 1 iodothyronine 5′-deiodinase, increased thyroid hormone production.
the most abundant form, found mostly in
the liver and kidney, is the largest
contributor to the circulating T3 pool.
Certain drugs (e.g., propylthiouracil,
glucocorticoids, and propranolol) slow the
activity of this deiodinase and are used in
the treatment of severe thyroid hormone
excess, or hyperthyroidism.
2. Type 2 iodothyronine 5′-deiodinase,
found in the brain and pituitary gland,
functions to maintain constant levels of T3
in the central nervous system. Its activity
is decreased when levels of circulating T4
are high and increased when levels are
low. Activity of the deiodination enzymes
gives another level of control of thyroid
hormone activity beyond the • If thyroid hormone levels are high, TRH
thyrotropinreleasing hormone (TRH) and TSH release will be inhibited, leading
and thyrotropin (TSH) control of the to lower levels of thyroid hormone
hypothalamic– pituitary–thyroid axis production. This feedback loop requires a
normally functioning hypothalamus,
pituitary, and thyroid gland, as well as an
absence of any interfering agents or agents
that mimic TSH action.

CONTROL OF THYROID FUNCTION

• Understanding of the hypothalamic–
pituitary–thyroid axis is essential for
correctly interpreting thyroid function
testing. This axis is central to the
regulation of thyroid hormone production.

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but the third-generation TSH

ACTIONS OF THYROID HORMONE chemiluminometric assays, with increased
• Once released from the thyroid gland, sensitivity to detection limits of 0.01
thyroid hormone circulates in the mU/L, give fewer false-negative results
bloodstream where free T4 and T3 are and more accurately distinguish between
available to travel across the cell euthyroidism and hyperthyroidism.
membrane. In the cytoplasm, T4 is • Although a fourth-generation assay exists,
deiodinated into T3, the active form of it is used for research purposes and the
thyroid hormone. T3 combines with its third-generation TSH assays are the
nuclear receptor on thyroid preferred method for monitoring and
hormoneresponsive genes, leading to adjusting thyroid hormone replacement
production of messenger RNA that, in turn, therapy and screening for abnormal
leads to production of proteins that thyroid hormone production in the clinical
influence metabolism and development. setting.
• The sensitivity of the third-generation TSH
Effects of thyroid hormone include: assays led to the ability to detect what is
1. tissue growth, termed subclinical disease—or a mild
2. brain maturation, degree of thyroid dysfunction— due to the
3. increased heat production, large reciprocal change in TSH levels seen
4. increased oxygen consumption, for even small changes in free T4. In
5. and increased expression of β- subclinical hypothyroidism, the TSH is
adrenergic receptors. minimally increased while the free T4
stays within the normal range. Likewise, in
• Clinically, individuals who have excess
subclinical hyperthyroidism, the TSH is
thyroid hormone (thyrotoxicosis) will
low while the free T4 is normal
have symptoms of increased metabolic
activity such as tachycardia and tremor,
while individuals with hypothyroidism
note symptoms of lowered metabolic
activity like edema and constipation.

Serum T4 and T3

• Serum total T4 and T3 levels are usually

measured by radioimmunoassay (RIA),
chemiluminometric assay, or similar
immunometric technique. As previously
mentioned, because more than 99.9% of
thyroid hormone is protein bound,
alteration in thyroid hormone–binding
proteins frequently leads to total T4 and
T3 levels outside of the normal range
without representing true clinical thyroid
dysfunction. Because of this, assays to
TESTS FOR THYROID FUNCTION measure free T4 and T3, the biologically
active hormone forms, were developed. At
Thyroid-Stimulating Hormone
least partially because of lower processing
• The most useful test for assessing thyroid costs and ease of interpretation, free T4
function is the TSH, currently in its third kits now replace total T4 assessment at the
generation. All the assays are capable of clinical level.
diagnosing primary hypothyroidism • Currently available assay kits for
(thyroid gland disease leading to low measuring free T4 levels are not error
thyroid hormone production) with proof, though, and can still be affected by
elevated levels of TSH. some binding protein abnormalities.9
• Second-generation TSH immunometric When this is suspected, measurement of
assays, with detection limits of 0.1 mU/L, free T4 levels is performed by dialysis.
effectively screen for hyperthyroidism,

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• Kits that estimate free T3 levels have

the receptor and leading to growth of the
theoretical advantages; however, actual
thyroid gland and production of excessive
clinical utility is yet to be clearly defined.
amounts of thyroid hormone. This
THYROGLOBULIN condition can be diagnosed with tests that
detect TSHRstimulating antibodies.
• Thyroglobulin is a protein synthesized • Two types of assays exist to detect an
and secreted exclusively by thyroid autoimmune etiology to hyperthyroidism:
follicular cells. This prohormone in the competition-based assays that detect
circulation is proof of the presence of TSH receptor antibodies (TRAb) based
thyroid tissue. This fact makes upon their ability to compete for TSHR
thyroglobulin an ideal tumor marker with a known ligand and thyroid-
thyroid cancer posttreatment surveillance stimulating immunoglobulin (TSI)
as patients with well-differentiated assays detecting cAMP production in
thyroid cancer successfully treated with patients' sera. Tests for TSH receptor
surgery and radioactive iodine ablation antibodies (TRAb, TSHRAb) can detect
should have undetectable thyroglobulin antibodies directed against the TSHR
levels. whether they act to stimulate or block the
• Thyroglobulin is currently measured by TSHR. Both stimulating and blocking
double-antibody RIA, enzymelinked antibody assays will be positive in 70% to
immunoassay (ELISA), 100% of patients with Graves' disease.
immunoradiometric assay (IRMA), and • Chronic lymphocytic thyroiditis—
immunochemiluminescent assay (ICMA) commonly known as Hashimoto's
methods. The accuracy of the thyroiditis—is at the other end of the
thyroglobulin assay is primarily autoimmune continuum. In this condition,
dependent on the specificity of the antibodies lead to decreased thyroid
antibody used and the absence of hormone production by destruction of the
antithyroglobulin autoantibodies. Even thyroid gland, which is the most common
with modern assays, antithyroglobulin cause of hypothyroidism in the developed
autoantibodies interfere with world. The best test for this condition is
measurements and lead to unreliable the TPO antibody, which is present in 10%
thyroglobulin results. For this reason, it is to 15% of the general population and 80%
critically important to screen for to 99% of patients with autoimmune
autoantibodies whenever thyroglobulin is hypothyroidism
measured. If antibodies are present, the
value of the thyroglobulin assay is
marginal.
• Approximately 25% of patients with well-
differentiated thyroid cancer have
antithyroglobulin autoantibodies,
compared to 10% of the general
population. If a patient with well- OTHER TOOLS FOR THYROID EVALUATION
differentiated thyroid cancer and
antithyroglobulin autoantibodies has been Fine-Needle Aspiration
successfully treated with surgery and
• Thyroid fine-needle aspiration (FNA)
radioactive iodine ablation,
biopsy is often the first step and most
autoantibodies should disappear over
accurate tool in the evaluation of thyroid
time.
nodules in the absence of
THYROID AUTOIMMUNITY hyperthyroidism. The routine use of FNA
allows prompt identification and
• Many diseases of the thyroid gland are treatment of thyroid malignancies and
related to autoimmune processes. In avoids unnecessary surgery in most
autoimmune thyroid disease, antibodies individuals with benign thyroid lesions. In
are directed at thyroid tissue with variable this procedure, a small-gauge needle is
responses. inserted into the nodule and cells are
• The most common cause of aspirated for cytologic evaluation. The
hyperthyroidism is an autoimmune procedure can be performed using
disorder called Graves' disease. The palpation if the nodule is palpable, but is
antibodies in this condition are directed at becoming more commonly used with the
the TSH receptor (TSHR), stimulating assistance of ultrasound imaging.

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• FNA biopsy results are reported according

to the Bethesda System for Reporting
Thyroid Cytopathology as falling into one
of six categories:
1. nondiagnostic/unsatisfactory,
2. benign,
3. atypia/follicular lesion of
undetermined significance,
4. follicular neoplasm/suspicious for
follicular neoplasm,
5. suspicious for malignancy,
6. and malignant.
• These categories dictate subsequent
treatment, ranging from routine
ultrasound monitoring to surgical
excision.

• Hypothyroidism—defined as a low free T4

level with a normal or high TSH—is one of
the most common disorders of the thyroid
gland, occurring in 5% to 15% of women
over the age of 65.
• Symptoms of hypothyroidism vary,
depending on the degree of
hypothyroidism and the rapidity of its
onset. When thyroid hormone is
significantly decreased, symptoms of cold
intolerance, fatigue, dry skin, constipation,
hoarseness, dyspnea on exertion,
cognitive dysfunction, hair loss, and
weight gain have been reported. On
physical examination, those with severe
hypothyroidism may have low body
temperature, slowed movements,
bradycardia, delay in the relaxation phase
of deep tendon reflexes, yellow
discoloration of the skin (from
hypercarotenemia), hair loss, diastolic
hypertension, pleural and pericardial
effusions, menstrual irregularities, and
periorbital edema.
Signs:
1. Delayed relaxation phase of deep
tendon reflex testing
2. Bradycardia
3. Diastolic hypertension
4. Coarsened skin, yellowing of skin
(carotenemia)
5. Periorbital edema
6. Thinning of eyebrows/loss of lateral
aspect of brows
7. Slowed movements/speech
8. Pleural/pericardial effusion
9. Ascites

Disorders of the Thyroid

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Symptoms
• Examples of transient hypothyroidism
1. Cold intolerance include recovery from nonthyroidal illness
2. Depression and the hypothyroid phase of any of the
3. Mental retardation (infants), slowed forms of subacute thyroiditis (painful
cognition thyroiditis, postpartum thyroiditis, and
4. Menorrhagia painless thyroiditis).
5. Growth failure (children)
Primary - Thyroid gland dysfunction
6. Pubertal delay
7. Dry skin Secondary - Pituitary dysfunction
8. Edema
Tertiary - Hypothalamic dysfunction
9. Constipation
10. Hoarseness CAUSES OF HYPOTHYROIDISM
11. Dyspnea on exertion
• Because of the diffuse distribution of
thyroid hormone receptors and the many
metabolic effects of thyroid hormone,
hypothyroidism can lead to a variety of
other abnormalities. Hyponatremia can
occur from the combination of increased
urinary sodium excretion and an inability
to maximally dilute urine due to
inappropriate release of antidiuretic
hormone; significant degrees of
hypothyroidism can lead to myopathy and
elevated levels of creatine kinase (CK); and
anemia can also be seen, either as a result
of a decreased demand for oxygen
carrying capacity or through an associated
autoimmune pernicious anemia. Fifty
percent or more of those with uncorrected
hypothyroidism will have hyperlipidemia
that improves with thyroid hormone
replacement.
• In the presence of these clinical
abnormalities (hyponatremia,
unexplained elevation of creatine
phosphokinase [CPK], anemia, or
hyperlipidemia), evaluation for
hypothyroidism as a potential secondary
cause should be considered.
• Hypothyroidism can be divided into
primary, secondary, or tertiary disease,
dependent on the location of the defect.
The most common cause of
hypothyroidism in developed countries is
chronic lymphocytic thyroiditis, or
Hashimoto's thyroiditis. This disorder is
an autoimmune disease targeting the • Hypothyroidism is treated with thyroid
thyroid gland, often associated with an hormone replacement therapy.
enlarged gland, or goiter. TPO antibody Levothyroxine (T4) is the treatment of
testing is positive in 80% to 99% of choice. In primary hypothyroidism, the
patients with chronic lymphocytic goal of therapy is to achieve a normal TSH
thyroiditis. level. If hypothyroidism is of secondary or
• Other common causes of hypothyroidism tertiary origin, TSH levels will not be
include iodine deficiency, thyroid surgery, useful in managing the condition, and a
and radioactive iodine treatment. midnormal free T4 level becomes the
Occasionally, individuals will experience treatment target.
transient hypothyroidism associated with
inflammation of the thyroid gland.

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• Levothyroxine has a half-life of

approximately 7 days. When doses of
thyroid hormone are changed, it is
important to wait at least five half-lives
before rechecking thyroid function tests in
order to achieve a new steady state.

THYROTOXICOSIS

• Thyrotoxicosis is a constellation of
findings that result when peripheral
tissues are presented with, and respond to,
an excess of thyroid hormone.
Thyrotoxicosis can be the result of
excessive thyroid hormone ingestion,
leakage of stored thyroid hormone from
storage in the thyroid follicles, or
excessive thyroid gland production of
thyroid hormone. The manifestations of
thyrotoxicosis vary, depending on the
degree of thyroid hormone elevation and
the status of the affected individual.
Symptoms often include:
1. anxiety,
2. emotional lability,
3. weakness, tremor,
4. palpitations,
5. heat intolerance,
6. increased perspiration,
7. and weight loss despite a normal or
increased appetite
Signs
1. Tachycardia
2. Tremor
3. Warm, moist, flushed, smooth skin
4. Lid lag, widened palpebral fissures
5. Ophthalmopathy (Graves' disease)
6. Goiter
7. Brisk deep tendon reflexes
8. Muscle wasting and weakness
9. Dermopathy/pretibial myxedema
(Graves' disease)
10. Osteopenia, osteoporosis
Symptoms:
1. Nervousness, irritability, anxiety
2. Tremor
3. Palpitations
4. Fatigue, weakness, decreased exercise
tolerance
5. Weight loss
6. Heat intolerance
7. Hyperdefecation

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8. Menstrual changes (oligomenorrhea) RAIU, radioactive iodine uptake; Tg,

9. Prominence of eyes thyroglobulin; TSHRAb, TSH receptor
antibodies; TSI, thyroid-stimulating
GRAVES' DISEASE
immunoglobulin; TPOAb, thyroid peroxidase
antibodies.
Approximately 20% to 25% of patients with
Graves' hyperthyroidism develop clinically
obvious Graves' ophthalmopathy, a
particularly concerning manifestation. With
more sensitive testing, such as orbital CT
• Graves' disease is the most common scanning or magnetic resonance imaging
cause of thyrotoxicosis. It is an (MRI), most patients with Graves'
autoimmune disease in which antibodies hyperthyroidism will be shown to have
are produced that activate the TSHR. ophthalmopathy.
Features of Graves' disease include Findings in Graves' ophthalmopathy
thyrotoxicosis, goiter, ophthalmopathy include:
(eye changes associated with
inflammation and infiltration of 1. orbital soft tissue swelling,
periorbital tissue), and dermopathy (skin 2. injection of the conjunctivae,
changes in the lower extremities that have 3. proptosis (forward protrusion of the
an orange peel texture). There is a strong eye secondary to infiltration of retro-
familial disposition to Graves' disease— orbital muscles and fat),
15% of patients will have a close relative 4. double vision (secondary to orbital
with this condition—and women are five muscle involvement and fibrosis),
times more likely to develop it than men. 5. and corneal disease (often related to
Laboratory testing will usually document a trauma because of difficulty closing
high free T4 and/or T3 level with a low or the eyelids).
undetectable TSH. TSIs and TSH receptor
Treatment of Graves' ophthalmopathy may
antibodies are usually positive in this
include:
condition. RAIU will be elevated, and the
thyroid scan will show diffuse uptake (also 1. noninvasive modalities such as
known as Toxic Diffuse Goiter) moisturizing
2. and protecting the cornea with drops
and ointment
3. or more invasive therapies such as
injection of glucocorticoids
retroorbitally
4. and, less frequently, surgical
decompression of the orbits to prevent
optic nerve injury and blindness.

DISORDERS ASSOCIATED WITH THYROTOXICOSIS TOXIC ADENOMA AND MULTINODULAR GOITER

• Toxic adenomas and multinodular goiter
are two relatively common causes of
hyperthyroidism. These conditions are
caused by autonomously functioning
thyroid tissue. In these instances, neither
TSH nor TSHR-stimulating
immunoglobulin is required to stimulate
thyroid hormone production. In some
toxic nodules, receptor mutations have
been identified. These mutations have the
same effect as chronic stimulation of the
TSHR on thyroid hormone production.
Clinically, toxic adenomas present signs

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and symptoms of hyperthyroidism, escape the Wolff-Chaikoff effect and use

possibly with palpable nodule(s). the excess iodine for thyroid hormone
• On a thyroid scan, the nodules are “hot”— production. In others, the medication may
that is, they avidly take up radioactive induce inflammation of the gland
iodine. The RAIU within the nodule is also (subacute thyroiditis) with subsequent
inappropriately high for the suppressed leakage of stored thyroid hormone into the
level of TSH. In toxic multinodular goiter, circulation.
there are multiple areas within the thyroid
gland that are autonomously producing SUBACUTE THYROIDITIS
thyroid hormone. • Several conditions occur that lead to
Treatment for these two conditions transient changes in thyroid hormone
involves: levels. These conditions are associated
with inflammation of the thyroid gland,
1. surgery, leakage of stored thyroid hormone,
2. radioactive iodine, followed by repair of the gland. Although
3. or medication (PTU or MMI). nomenclature varies between authors,
• Although the medications can block grouping together postpartum thyroiditis,
thyroid hormone production, they are not painless thyroiditis, and painful thyroiditis
expected to lead to remission in these two as forms of subacute thyroiditis is one of
conditions. Often, the toxic nodules the simplest classification schemes. These
produce so much thyroid hormone that conditions are often associated with a
the rest of the thyroid gland is suppressed thyrotoxic phase when thyroid hormone is
and metabolically inactive. When leaking into the circulation, a hypothyroid
radioactive iodine is given, it tends to phase when the thyroid gland is repairing
destroy only the hyperactive itself, and a euthyroid phase when the
(autonomous) nodules, leaving normal gland is repaired with the duration of
(suppressed) thyroid tissue undamaged. these phases lasting from weeks to
Because the normal thyroid tissue is months.
hypofunctioning and takes up little of the • Postpartum thyroiditis is the most
radioactive iodine, when treatment is common form of subacute thyroiditis. It
given, the patient may be left with normal occurs in 3% to 16% of women in the
thyroid function without the need for postpartum period. It is strongly
thyroid hormone replacement therapy. associated with the presence of TPO
antibodies and chronic lymphocytic
DRUG-INDUCED THYROID DYSFUNCTION thyroiditis. Patients may experience a
Amiodarone-Induced Thyroid Disease period of thyrotoxicosis followed by
hypothyroidism or simply
• Several drugs other than PTU and MMI can hypothyroidism or hyperthyroidism.
affect thyroid function. Amiodarone, a Thyroid hormone levels usually return to
drug used to treat cardiac arrhythmias, is normal after several months; however, by
a fat-soluble drug with a long half-life (50 4 years postpartum, 25% to 50% of
days) that interferes with normal thyroid patients have persistent hypothyroidism,
function. The fact that 37% of the goiter, or both. During the thyrotoxic
molecular weight of amiodarone is iodine phase, β-blockers can be used if treatment
accounts for a significant part of the is necessary. During the hypothyroid
thyroid dysfunction seen. Iodine, when phase, thyroid hormone replacement
given in large doses, acutely leads to therapy can be given if symptoms require,
inhibition of thyroid hormone production. usually for three to 6 months, with
This is called the Wolff-Chaikoff effect. continuation if permanent
Amiodarone also blocks T4-to-T3 hypothyroidism develops. The thyrotoxic
conversion. phase of this condition, as well as other
• The combination of these two actions forms of subacute thyroiditis, can be
leads to hypothyroidism in 8% to 20% of distinguished from Graves' disease by a
patients on chronic amiodarone therapy. low RAIU and an absence of TSI or TSH
Amiodarone can also lead to receptor antibodies. Painless thyroiditis or
hyperthyroidism in 3% of patients treated subacute lymphocytic thyroiditis shares
chronically with this medication. Certain many characteristics of postpartum
patients develop hyperthyroidism as they thyroiditis, except there is no associated
• pregnancy.

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• Painful thyroiditis, also called subacute

• become a routine practice to help
granulomatous, subacute
distinguish the nodules that require
nonsuppurative thyroiditis, or de
surgical removal from those that do not.
• Quervain's thyroiditis, is characterized
by neck pain, low-grade fever, myalgia, a PARATHYROID GLAND
tender diffuse goiter, and swings in
thyroid function tests (as discussed • It is located on or near the thyroid capsule
earlier). Viral infections are felt to trigger (region of the thyroid gland); sometimes
this condition. TPO antibodies are usually within the thyroid gland. It may also be
absent; erythrocyte sedimentation rate found outside their normal anatomic site-
and thyroglobulin levels are often between the hyoid bone in the neck and
elevated. mediastinum.
• Most people have a 4 parathyroid glands
NONTHYROIDAL ILLNESS but some have 8 or as few as two.
• Is the smallest endocrine gland in the
• Hospitalized patients, especially critically
body. It secretes PTH-hypercalcemic
ill patients, often have abnormalities in
hormone.
their thyroid function tests without
thyroid dysfunction, a condition known as
nonthyroidal illness or euthyroid sick
syndrome. Typically, the laboratory
pattern is one of normal or low TSH, low
T3, and low free T4. Because illness
decreases 5′-monodeiodinase activity, less
T4 is converted to active T3. This leads to
decreased levels of T3 and higher levels of
reverse T3. There also seems to be an
element of central hypothyroidism and
thyroid hormone–binding changes
associated with severe illness. It is
believed that many of these changes are an
appropriate adaptation to illness and ROLE OF PTH
thyroid hormone replacement therapy is
not indicated. • Prime role: to prevent hypocalcemia
(regulates blood calcium)
THYROID NODULES • It preserves calcium and phosphate within
normal range. It promotes bone
• Thyroid nodules are common. Clinically
resorption-release calcium into the blood
apparent thyroid nodules are present in
stream.
6.4% of adult women and 1.5% of adult
• It increases renal rebasorption of calcium.
men, according to Framingham data.
It stimulates conversion of inactive
Autopsy studies, however, suggest 20% to
Vitamin D to activated vitamin D3.
76% of women in iodine-replete areas
Indirectly stimulates intestinal absorption
have thyroid nodules, with rates
of calcium.
correlating with decade of age and
increased use of thyroid ultrasound • As calcium level increase, PTH secretion is
supports these estimates, with suppressed allowing urinary loss of
calcium and calcium to remain in bone. If
unsuspected nodules, or “incidentalomas”
calcium levels decreased, PTH is released.
found in 20% to 45% of women and 17%
to 25% of men. Despite the frequency of
thyroid nodules, only 5% to 9% of
nonpalpable nodules prove to be thyroid
cancer. FNA of these nodules, with
cytologic examination of the aspirate, has

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 CLINICAL MEDTECH LEC
CHEMISTRY II TERM 02

CLINICAL DISORDERS
Hyperparathyroidism
A. Primary hyperparathyroidism (physiologic
defect lies with the PT Gland). It is due to the
presence of a functioning parathyroid
adenoma. It is accompanied with
phosphaturia. If it goes undetected, severe
demineralization may occur (osteitis fibrosa
cystica)

Lab Results: PTH or high normal range, Inc

ionized calcium, hypercalciuria,
hypophosphatenemia (fasting state)

B. SECONDARY HYPERPARATHYROIDISM

• It develops in response to decrease serum

calcium. There is diffuse hyperplasia of all
4 glands. The patient develops severe bone
disease.
Causes: Vitamin D deficiency and chronic
renal failure.

Lab Results: PTH, Dec. Ionized Calcium

C. TERTIARY HYPERPARATHYROIDISM

• It occurs with secondary

hyperparathyroidism. The phosphate
levels are normal to high calcium
phosphates precipitates in soft tissues.

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