THE THYROID GLAND produce measurable amounts of thyroid hormone.
Iodine is an essential component of thyroid
The thyroid gland is responsible for the
production of two hormones: thyroid hormone
and calcitonin. Calcitonin is secreted by
parafollicular C cells and is involved in calcium
homeostasis. Thyroid hormone is critical in
regulating body metabolism, neurologic
development, and numerous other body functions.
Clinically, conditions affecting thyroid hormone
levels are much more common than those
affecting calcitonin and are the major focus of this
chapter.
Thyroid Anatomy and Development
The thyroid gland is positioned in the lower
anterior neck and is shaped like a butterfly. It is
made up of two lobes resting on each side of the
trachea, bridged by the isthmus, with a band of
thyroid tissue running anterior to the trachea.
Posterior to the thyroid gland lie the parathyroid
glands—which regulate serum calcium levels—
and the recurrent laryngeal nerves innervating
the vocal cords. The locations of these structures
become important during thyroid surgery, when
injury could lead to hypocalcemia or permanent
hoarse voice
The fetal thyroid develops from an outpouching
of the foregut at the base of the tongue that
migrates to its final location over the thyroid
cartilage in the first 4 to 8 weeks of gestation. By
week 11 of gestation, the thyroid gland begins to
hormone. In parts of the world where severe
iodine deficiency exists, neither the mother nor
the fetus can produce sufficient amounts of
thyroid hormone and both develop
hypothyroidism. As thyroid hormone is critical to
fetal neurologic development, hypothyroidism
can lead to mental retardation and cretinism.
In areas where iodine deficiency is not an issue,
other problems with thyroid development may
occur, including congenital hypothyroidism,
which occurs in 1 of 4,000 live births. If the
mother has normal thyroid function, small
amounts of maternal thyroid 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
procedures, including computed
tomography (CT) scans and heart
catheterization.
 It is also present in amiodarone, a
medication used to treat certain heart
conditions. The recommended minimum
daily intake of iodine is 150 μg.
 If iodine intake drops below 50 μg daily,
the thyroid gland is unable to
manufacture adequate amounts of thyroid
hormone, and thyroid hormone
deficiency—hypothyroidism—results.
 Thyroid cells are organized into spheres
surrounding a central core of fluid called
colloid. These structures are called
follicles. The major component of
colloid, thyroglobulin, is a glycoprotein
manufactured exclusively by thyroid
follicular cells and rich in the amino
 acid tyrosine. Some of these tyrosyl
residues will be iodinated, producing the
building blocks of thyroid hormone.

 On the outer side of the follicle, iodine is

actively transported into the thyroid cell
by the Na+/I− symporter located on the
basement membrane. Inside the thyroid
cell, iodide diffuses across the cell to the
apical side of the follicle, which abuts the
core of colloid. Here, catalyzed by a
membrane-bound enzyme called thyroid
peroxidase (TPO), concentrated iodide
is oxidized and bound with tyrosyl
residues on thyroglobulin. This results in
production of monoiodothyronine
(MIT) and diiodothyronine (DIT). This
same enzyme also aids in the coupling of
two tyrosyl residues to form
triiodothyronine (T3) (one MIT residue
+ one DIT residue) or thyroxine (T4)
(two DIT residues). These are the two
active forms of thyroid hormone. This
thyroglobulin matrix, with branches
now holding T4 and T3, is stored in the
core of the thyroid follicle.
 Thyroid-stimulating hormone (TSH)
signals the follicular cell to ingest a
microscopic droplet of colloid by
endocytosis. Inside the follicular cell,
these droplets are digested by
intracellular lysosomes into T4, T3, and
other products. T4 and T3 are then
secreted by the thyroid cell into the
circulation
Biosynthesis of thyroid hormone. Thyroid
hormone synthesis includes the following steps:
(1) iodide (I−) trapping by thyroid follicular cells;
(2) diffusion of iodide to the apex of the cell and
transport into the colloid; (3) oxidation of
inorganic iodide to iodine and incorporation of
iodine into tyrosine residues within thyroglobulin
molecules in the colloid; (4) combination of two
diiodotyrosine (DIT) molecules to form
tetraiodothyronine (thyroxine, T4) or of
monoiodotyrosine (MIT) with DIT to form
triiodothyronine (T3); (5) uptake of
thyroglobulin from the colloid into the follicular
cell by endocytosis, fusion of the thyroglobulin
with a lysosome, and proteolysis and release of T4
and T3; and (6) release of T4 and T3 into the
circulation.
METABOLISM OF THYROXINE
  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
There are three forms of iodothyronine 5′-
deiodinase.
1. Type 1 iodothyronine 5′-deiodinase, 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 thyrotropin releasing
hormone (TRH) and thyrotropin (TSH)
control of the hypothalamic– pituitary–
thyroid axis
Protein Binding of Thyroid Hormone
 When released into the circulation, only
0.04% of T4 and 0.4% of T3 are
unbound by proteins and available for
hormonal activity. The three major
binding proteins, in order of significance,
are thyroxine-binding globulin (TBG),
thyroxine-binding prealbumin (TBPA),
and albumin. Alterations to the
concentrations of binding proteins
significantly affect circulating quantities
of T4 and T3. For example, high estrogen
levels during pregnancy lead to increased
TBG production by the liver, which
results in higher levels of bound thyroid
hormones, leading to high levels of total
T3 and total T4. Typically, however,
levels of the unbound active, or free,
thyroid hormones remain in the normal
range and the individual remains
euthyroid. In some instances, however,
measurement of free T4 and free T3 may
be necessary to eliminate any confusion
caused by abnormal binding protein
levels.
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. 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 hypothalamus and pituitary
sense that there is an inadequate amount of
thyroid hormone in circulation, TRH and TSH
secretion increases and stimulates increased
thyroid hormone production.
If thyroid hormone levels are high, TRH and TSH
release will be inhibited, leading to lower levels of
thyroid hormone 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
Thyroid-Stimulating Hormone
Actions of Thyroid Hormone
 Once released from the thyroid gland,
thyroid hormone circulates in the
bloodstream where free T4 and T3 are
available to travel across the cell
membrane. In the cytoplasm, T4 is
deiodinated into T3, the active form of
thyroid hormone. T3 combines with its
nuclear receptor on thyroid hormone
responsive genes, leading to production
of messenger RNA that, in turn, leads to
production of proteins that influence
metabolism and development.
 Effects of thyroid hormone include tissue
growth, brain maturation, increased heat
production, increased oxygen
consumption, and increased expression of
β- adrenergic receptors.
 Clinically, individuals who have excess
thyroid hormone (thyrotoxicosis) will
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.
TESTS FOR THYROID FUNCTION
 The most useful test for assessing thyroid
function is the TSH, currently in its third
generation. All the assays are capable of
diagnosing primary hypothyroidism
(thyroid gland disease leading to low
thyroid hormone production) with
elevated levels of TSH.
 Second-generation TSH immunometric
assays, with detection limits of 0.1
mU/L, effectively screen for
hyperthyroidism, but the third-
generation TSH chemiluminometric
assays, with increased sensitivity to
detection limits of 0.01 mU/L, give fewer
false-negative results and more accurately
distinguish between euthyroidism and
hyperthyroidism. [Euthyroidism is
defined as normal thyroid function that
occurs with normal serum levels of TSH
and T4]
 Although a fourth-generation assay
exists, it is used for research purposes and
 the third-generation TSH assays are the
preferred method for monitoring and
adjusting thyroid hormone replacement
therapy and screening for abnormal
thyroid hormone production in the
clinical setting.
 The sensitivity of the third-generation
TSH assays led to the ability to detect
what is termed subclinical disease—or a
mild degree of thyroid dysfunction—
due to the large reciprocal change in TSH
levels seen for even small changes in free
T4. In subclinical hypothyroidism, the
TSH is minimally increased while the
free T4 stays within the normal range.
Likewise, in subclinical
hyperthyroidism, the TSH is low while
the free T4 is normal
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 measure free T4 and T3, the
biologically active hormone forms, were
developed. At least partially because of
lower processing costs and ease of
interpretation, free T4 kits now replace
total T4 assessment at the clinical level
 Currently available assay kits for
measuring free T4 levels are not error
proof, though, and can still be affected by
some binding protein abnormalities.
When this is suspected, measurement of
free T4 levels is performed by dialysis.
Kits that estimate free T3 levels have
theoretical advantages; however, actual
clinical utility is yet to be clearly defined.
Thyroglobulin
 Thyroglobulin is a protein synthesized
and secreted exclusively by thyroid
follicular cells. This prohormone in the
circulation is proof of the presence of
thyroid tissue. This fact makes
thyroglobulin an ideal tumor marker
thyroid cancer post treatment surveillance
as patients with well-differentiated
thyroid cancer successfully treated with
surgery and radioactive iodine ablation
should have undetectable thyroglobulin
levels.
 Thyroglobulin is currently measured by
double-antibody RIA, enzymelinked
immunoassay (ELISA),
immunoradiometric assay (IRMA), and
immunochemiluminescent assay (ICMA)
methods. The accuracy of the
thyroglobulin assay is primarily
dependent on the specificity of the
antibody used and the absence of
antithyroglobulin autoantibodies. Even
with modern assays, antithyroglobulin
autoantibodies interfere with
measurements and lead to unreliable
thyroglobulin results. For this reason, it is
critically important to screen for
autoantibodies whenever thyroglobulin is
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-
differentiated thyroid cancer and
antithyroglobulin autoantibodies has been
successfully treated with surgery and
radioactive iodine ablation,
autoantibodies should disappear over
time.
Thyroid Autoimmunity
 Many diseases of the thyroid gland are
related to autoimmune processes. In
autoimmune thyroid disease, antibodies
are directed at thyroid tissue with variable
 responses. The most common cause of
hyperthyroidism is an autoimmune
disorder called Graves' disease. The
antibodies in this condition are directed at
the TSH receptor (TSHR), stimulating the
receptor and leading to growth of the
thyroid gland and production of excessive
amounts of thyroid hormone. This
condition can be diagnosed with tests that
detect TSHR stimulating antibodies.
 Two types of assays exist to detect an
autoimmune etiology to hyperthyroidism:
competition-based assays that detect
TSH receptor antibodies (TRAb) based
upon their ability to compete for TSHR
with a known ligand and thyroid-
stimulating immunoglobulin (TSI)
assays detecting cAMP production in
patients' sera. Tests for TSH receptor
antibodies (TRAb, TSHRAb) can detect
antibodies directed against the TSHR
whether they act to stimulate or block the
TSHR. Both stimulating and blocking
antibody assays will be positive in 70%
to 100% of patients with Graves' disease.
 Chronic lymphocytic thyroiditis—
commonly known as Hashimoto's
thyroiditis—is at the other end of the
autoimmune continuum. In this condition,
antibodies lead to decreased thyroid
hormone production by destruction of the
thyroid gland, which is the most common
cause of hypothyroidism in the developed
world. The best test for this condition is
the TPO antibody, which is present in
10% to 15% of the general population
and 80% to 99% of patients with
autoimmune hypothyroidism
allows prompt identification and
treatment of thyroid malignancies and
avoids unnecessary surgery in most
individuals with benign thyroid lesions.
In this procedure, a small-gauge needle is
inserted into the nodule and cells are
aspirated for cytological evaluation. The
procedure can be performed using
palpation if the nodule is palpable, but is
becoming more commonly used with the
assistance of ultrasound imaging. FNA
biopsy results are reported according to
the Bethesda System for Reporting
Thyroid Cytopathology as falling into
one of six categories:
nondiagnostic/unsatisfactory, benign,
atypia/follicular lesion of undetermined
significance, follicular
neoplasm/suspicious for follicular
neoplasm, suspicious for malignancy, and
malignant. These categories dictate
subsequent treatment, ranging from
routine ultrasound monitoring to surgical
excision.

Other Tools for Thyroid Evaluation

Fine-Needle Aspiration
 Thyroid fine-needle aspiration (FNA)
biopsy is often the first step and most
accurate tool in the evaluation of thyroid
nodules in the absence of
hyperthyroidism. The routine use of FNA
  Depression
 Mental retardation (infants), slowed
cognition
 Menorrhagia
 Growth failure (children)
 Pubertal delay
 Dry skin
Disorders of the Thyroid  Edema
 Constipation
Hypothyroidism—  Hoarseness
defined as a low free T4  Dyspnea on exertion
level with a normal or
high TSH—is one of the  Because of the diffuse distribution of
most common disorders thyroid hormone receptors and the many
of the thyroid gland, metabolic effects of thyroid hormone,
occurring in 5% to 15% hypothyroidism can lead to a variety of
of women over the age other abnormalities. Hyponatremia can
of 65. Symptoms of occur from the combination of increased
hypothyroidism vary, urinary sodium excretion and an inability
depending on the degree to maximally dilute urine due to
of hypothyroidism and inappropriate release of antidiuretic
the rapidity of its onset. When thyroid hormone is hormone; significant degrees of
significantly decreased, symptoms of cold hypothyroidism can lead to myopathy
intolerance, fatigue, dry skin, constipation, and elevated levels of creatine kinase
hoarseness, dyspnea on exertion, cognitive (CK); and anemia can also be seen, either
dysfunction, hair loss, and weight gain have as a result of a decreased demand for
been reported. On physical examination, those oxygen carrying capacity or through an
with severe hypothyroidism may have low body associated autoimmune pernicious
temperature, slowed movements, bradycardia, anemia. Fifty percent or more of those
delay in the relaxation phase of deep tendon with uncorrected hypothyroidism will
reflexes, yellow discoloration of the skin (from have hyperlipidemia that improves with
hypercarotenemia), hair loss, diastolic thyroid hormone replacement.
hypertension, pleural and pericardial effusions,  In the presence of these clinical
menstrual irregularities, and periorbital abnormalities (hyponatremia,
edema. unexplained elevation of creatine
phosphokinase [CPK], anemia, or
Signs: hyperlipidemia), evaluation for
 Delayed relaxation phase of deep tendon hypothyroidism as a potential secondary
reflex testing cause should be considered.
 Bradycardia  Hypothyroidism can be divided into
 Diastolic hypertension primary, secondary, or tertiary disease,
 Coarsened skin, yellowing of skin dependent on the location of the defect.
(carotenemia) The most common cause of
hypothyroidism in developed countries is
 Periorbital edema
chronic lymphocytic thyroiditis, or
 Thinning of eyebrows/loss of lateral Hashimoto's thyroiditis. This disorder is
aspect of brows an autoimmune disease targeting the
 Slowed movements/speech thyroid gland, often associated with an
 Pleural/pericardial effusion enlarged gland, or goiter. TPO antibody
 Ascites testing is positive in 80% to 99% of
Symptoms patients with chronic lymphocytic
 Cold intolerance thyroiditis. Other common causes of
 hypothyroidism include iodine
deficiency, thyroid surgery, and
radioactive iodine treatment.
Occasionally, individuals will experience
transient hypothyroidism associated
with inflammation of the thyroid gland.
Examples of transient hypothyroidism
include recovery from nonthyroidal
illness and the hypothyroid phase of any
of the forms of subacute thyroiditis
(painful thyroiditis, postpartum
thyroiditis, and painless thyroiditis).
Primary
Thyroid gland dysfunction
Secondary
Pituitary dysfunction
Tertiary
Hypothalamic dysfunction
treatment of choice. In primary hypothyroidism,
the goal of therapy is to achieve a normal TSH
level. If hypothyroidism is of secondary or tertiary
origin, TSH levels will not be useful in managing
the condition, and a midnormal free T4 level
becomes the treatment target.
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.

Causes of Hypothyroidism

Hypothyroidism is treated with thyroid hormone

replacement therapy. Levothyroxine (T4) is the

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
anxiety, emotional lability, weakness, tremor,
palpitations, heat intolerance, increased
perspiration, and weight loss despite a normal
or increased appetite
Signs
 Tachycardia
 Tremor
 Warm, moist, flushed, smooth skin
 Lid lag, widened palpebral fissures
 Ophthalmopathy (Graves' disease)
 Goiter
 Brisk deep tendon reflexes
 Muscle wasting and weakness
 Dermopathy/pretibial myxedema (Graves'
disease)
 Osteopenia, osteoporosis
Symptoms:
 Nervousness, irritability, anxiety
 Tremor
 Palpitations
 Fatigue, weakness, decreased exercise
tolerance
 Weight loss
 Heat intolerance
 Hyperdefecation
 Menstrual changes (oligomenorrhea)
 Prominence of eyes
Graves ‘disease
Graves' disease is the most common cause of
thyrotoxicosis. It is an autoimmune disease in
which antibodies are produced that activate the
TSHR. Features of Graves' disease include
thyrotoxicosis, goiter, ophthalmopathy (eye
changes associated with inflammation and
infiltration of periorbital tissue), and
dermopathy (skin changes in the lower
extremities that have an orange peel texture).
There is a strong familial disposition to Graves'
disease—15% of patients will have a close
relative with this condition—and women are five
times more likely to develop it than men.
Laboratory testing will usually document a high
free T4 and/or T3 level with a low or undetectable
TSH. TSIs and TSH receptor antibodies are
usually positive in this condition. RAIU will be
elevated, and the thyroid scan will show diffuse
uptake (also known as Toxic Diffuse Goiter)
Disorders Associated with Thyrotoxicosis
RAIU, radioactive iodine uptake; Tg,
thyroglobulin; TSHRAb, TSH receptor
antibodies; TSI, thyroid-stimulating
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
scanning or magnetic resonance
imaging (MRI), most patients with
Graves' hyperthyroidism will be shown to
 have ophthalmopathy. Findings in
Graves' ophthalmopathy include orbital
soft tissue swelling, injection of the
conjunctivae, proptosis (forward
protrusion of the eye secondary to
infiltration of retro-orbital muscles and
fat), double vision (secondary to orbital
muscle involvement and fibrosis), and
corneal disease (often related to trauma
because of difficulty closing the eyelids).
Treatment of Graves' ophthalmopathy
may include noninvasive modalities such
as moisturizing and protecting the cornea
with drops and ointment or more invasive
therapies such as injection of
glucocorticoids retroorbitally
and, less frequently, surgical
decompression of the orbits
to prevent optic nerve injury
and blindness.
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
and symptoms of hyperthyroidism,
possibly with palpable nodule(s).
 On a thyroid scan, the nodules are
“hot”—that is, they avidly take up
radioactive iodine. The RAIU within the
nodule is also inappropriately high for the
suppressed level of TSH. In toxic
multinodular goiter, there are multiple
areas within the thyroid gland that are
autonomously producing thyroid
hormone
 Treatment for these two conditions
involves surgery, radioactive iodine, or
medication (PTU or MMI). Although
the medications can block thyroid
hormone production, they are not
expected to lead to remission in these two
conditions. Often, the toxic nodules
produce so much thyroid hormone that
the rest of the thyroid gland is suppressed
and metabolically inactive. When
radioactive iodine is given, it tends to
destroy only the hyperactive
(autonomous) nodules, leaving normal
(suppressed) thyroid tissue undamaged.
Because the normal thyroid tissue is
hypofunctioning and takes up little of the
radioactive iodine, when treatment is
given, the patient may be left with normal
thyroid function without the need for
thyroid hormone replacement therapy.
DRUG-INDUCED THYROID
DYSFUNCTION
Amiodarone-Induced Thyroid Disease
 Several drugs other than PTU and MMI
can affect thyroid function. Amiodarone,
a drug used to treat cardiac arrhythmias,
is a fat-soluble drug with a long half-life
(50 days) that interferes with normal
thyroid function. The fact that 37% of the
molecular weight of amiodarone is iodine
accounts for a significant part of the
thyroid dysfunction seen. Iodine, when
given in large doses, acutely leads to
inhibition of thyroid hormone production.
This is called the Wolff-Chaikoff effect.
Amiodarone also blocks T4-to-T3
conversion.
 The combination of these two actions
leads to hypothyroidism in 8% to 20% of
patients on chronic amiodarone
therapy. Amiodarone can also lead to
hyperthyroidism in 3% of patients treated
chronically with this medication. Certain
patients develop hyperthyroidism as they
escape the Wolff-Chaikoff effect and use
the excess iodine for thyroid hormone
production. In others, the medication may
induce inflammation of the gland
(subacute thyroiditis) with subsequent
leakage of stored thyroid hormone into
the circulation.
Subacute Thyroiditis
 Several conditions occur that lead to
transient changes in thyroid hormone
levels. These conditions are associated
with inflammation of the thyroid gland,
leakage of stored thyroid hormone,
followed by repair of the gland.
 Although nomenclature varies between
authors, grouping together postpartum
thyroiditis, painless thyroiditis, and
painful thyroiditis as forms of subacute
thyroiditis is one of the simplest
classification schemes. These conditions
are often associated with a thyrotoxic
phase when thyroid hormone is leaking
into the circulation, a hypothyroid phase
when the thyroid gland is repairing itself,
and a euthyroid phase when the gland is
repaired with the duration of these phases
lasting from weeks to months.
 Postpartum thyroiditis is the most
common form of subacute thyroiditis. It
occurs in 3% to 16% of women in the
postpartum period. It is strongly
associated with the presence of TPO
antibodies and chronic lymphocytic
thyroiditis. Patients may experience a
period of thyrotoxicosis followed by
hypothyroidism or simply
hypothyroidism or hyperthyroidism.
Thyroid hormone levels usually return to
normal after several months; however, by
4 years postpartum, 25% to 50% of
patients have persistent hypothyroidism,
goiter, or both. During the thyrotoxic
phase, β-blockers can be used if
treatment is necessary. During the
hypothyroid phase, thyroid hormone
replacement therapy can be given if
symptoms require, usually for three to 6
months, with continuation if permanent
hypothyroidism develops. The thyrotoxic
phase of this condition, as well as other
forms of subacute thyroiditis, can be
distinguished from Graves' disease by a
low RAIU and an absence of TSI or TSH
receptor antibodies. Painless thyroiditis
or subacute lymphocytic thyroiditis
shares many characteristics of postpartum
thyroiditis, except there is no associated
pregnancy.
 Painful thyroiditis, also called subacute
granulomatous, subacute
nonsuppurative thyroiditis, or de
Quervain's thyroiditis, is characterized
by neck pain, low-grade fever, myalgia, a
tender diffuse goiter, and swings in
thyroid function tests (as discussed
earlier). Viral infections are felt to trigger
this condition. TPO antibodies are usually
absent; erythrocyte sedimentation rate
and thyroglobulin levels are often
elevated.
NONTHYROIDAL ILLNESS
 Hospitalized patients, especially
critically ill patients, often have
abnormalities in 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
thyroid hormone replacement therapy is
not indicated.
THYROID NODULES
 Thyroid nodules are common. Clinically
apparent thyroid nodules are present in
6.4% of adult women and 1.5% of adult
men, according to Framingham data.
Autopsy studies, however, suggest 20%
to 76% of women in iodine-replete areas
have thyroid nodules, with rates
correlating with decade of age and
increased use of thyroid ultrasound
supports these estimates, with
unsuspected nodules, or
“incidentalomas” 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 become a routine
practice to help distinguish the nodules
that require surgical removal from those
that do not
 Parathyroid Gland
 It is located on or near the thyroid capsule
(region of the thyroid gland); sometimes
within the thyroid gland.
 It may also be found outside their normal
anatomic site-between the hyoid bone in
the neck and mediastinum.
 Most people have a 4 parathyroid glands
but some have 8 or as few as two.
 Is the smallest endocrine gland in the
body
 It secretes PTH-hypercalcemic hormone.
Role of PTH
 Prime role: to prevent hypocalcemia
(regulates blood calcium)
 It preserves calcium and phosphate
within normal range.
 It promotes bone resorption-release
calcium into the blood stream.
 It increases renal rebasorption of calcium
 It stimulates conversion of inactive
Vitamin D to activated vitamin D3.
 Indirectly stimulates intestinal absorption
of calcium.
 As calcium level increase, PTH secretion
is suppressed allowing urinary loss of
calcium and calcium to remain in bone.
 If calcium levels decreased, PTH is
released.
CLINICAL DISORDERS
I. 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: Inc. 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: Inc. 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.
II. Hypoparathyroidism
 It is due to accidental injury to the
parathyroid glands (neck) during surgery-
postsurgical cause.
 Other cause: auto immune parathyroid
destruction
 Individuals are unable to maintain
calcium concentration in blood without
calcium supplementation.