HYPERTHYROIDISM AND

HYPOTHYROIDISM
- JOSE D. AMARO JR.

Thyroid Pathophysiology
Hypothalamic-Pituitary-Thyroid Axis
This is a negative feedback system.
TRH
produced in the paraventricular nuclei of the
hypothalamus stimulates release of TSH from the
pituitary.
TSH stimulates thyrocytes to pump in iodine.
Then there is organification of iodine by thyroid
peroxidase. This forms T3 and T4, which is
stored as colloid. T4 secretion >> T3 secretion.

 Most T3 is formed peripherally, by deiodination

of T4.
T3 is far more active, T4 is a
prohormone.
Conversion of T4 to T3 is
inhibited
by
starvation,
illness,
drugs
(amiodarone, contrast dyes).
More than 99% of T3 and T4 in blood is bound
to Thyroid Binding Globulin (TBG) and albumin.
T3 acts at nuclear receptors to stimulate
CHO/fat
metabolism,
glycogenolysis,
thermogenesis, protein synthesis, myocardial
contractility, oxygen delivery, digestion, and
sympathetic activity. It is critical for normal
growth and metabolism.

Assessing Thyroid Function

The most common hormone measurements
are free T4 and TSH.
These
have
an
inverse
log-linear
relationship,
in
which
TSH
varies
logarithmically with T4.
**Therefore, the TSH level is the most
sensitive index of thyroid function.
**Low TSH suggests hyperthyroidism.
High
TSH
suggests
primary
hypothyroidism.

Hyperthyroidism
presents as a constellation of symptoms
due to elevated levels of circulating thyroid
hormones. Because of the many actions of
thyroid hormone on various organ systems
in the body, the spectrum of clinical signs
produced by the condition is broad. The
presenting symptoms can be subtle and
nonspecific,
making
hyperthyroidism
difficult to diagnose in its early stages
without the aid of laboratory data.

 The term hyperthyroidism refers to

inappropriately elevated thyroid function.
Though often used interchangeably, the
term thyrotoxicosis, which is an excessive
amount of circulating thyroid hormone, is
not synonymous with hyperthyroidism.
Increased levels of hormone can occur
despite normal thyroid function, such as in
instances of inappropriate exogenous
thyroid hormone or excessive release of
stored hormone from an inflamed thyroid
gland.

Graves disease
(diffuse toxic goiter), the most common form of overt
hyperthyroidism, is an autoimmune condition in which
autoantibodies are directed against the thyroidstimulating hormone (TSH) receptor.
As a result, the thyroid gland is inappropriately
stimulated with ensuing gland enlargement and
increase of thyroid hormone production.
Risk factors for Graves disease include family history of
hyperthyroidism or various other autoimmune disorders,
high iodine intake, stress, use of sex steroids, and
smoking.
The disease is classically characterized by the triad of
goiter, exophthalmos, and pretibial myxedema.

Thyroid storm
is a rare and potentially fatal complication of
hyperthyroidism. It typically occurs in patients
with untreated or partially treated thyrotoxicosis
who experience a precipitating event such as
surgery, infection, or trauma.
Thyroid storm must be recognized and treated on
clinical grounds alone, as laboratory confirmation
often cannot be obtained in a timely manner.
Patients
typically
appear
markedly
hypermetabolic with high fevers, tachycardia,
nausea and vomiting, tremulousness, agitation,
and psychosis.
Late in the progression of disease, patients may
become stuporous or comatose with hypotension.

Pathophysiology
In healthy patients, the hypothalamus produces
thyrotropin-releasing hormone (TRH), which
stimulates the anterior pituitary gland to secrete
thyroid-stimulating hormone (TSH); this in turn
triggers the thyroid gland to release thyroid
hormone.
Thyroid hormone concentration is regulated by
negative feedback by circulating free hormone
primarily on the anterior pituitary gland and to a
lesser extent on the hypothalamus. The secretion
of TRH is also partially regulated by higher
cortical centers.

 The thyroid gland produces the prohormone

thyroxine (T4), which is deiodinated primarily by
the liver and kidneys to its active form,
triiodothyronine (T3). The thyroid gland also
produces a small amount of T3 directly. T4 and
T3 exist in 2 forms: a free, unbound portion that
is biologically active and a portion that is protein
bound to thyroid-binding globulin (TBG). Despite
consisting of less than 0.5% of total circulating
hormone, free or unbound T4 and T3 levels best
correlate with the patient's clinical status.

 Mortality/Morbidity
Thyroid storm, if unrecognized and
untreated, is often fatal.
Adult mortality rate from thyroid storm is
approximately 10-20%, but it has been
reported to be as high as 75% in
hospitalized
populations.
Underlying
precipitating illness may contribute to
high mortality.
Sex
A slight predominance of hyperthyroidism
exists among females.

 Age
Thyroid storm may occur at any age but
is most common in those in their third
through sixth decades of life.
Graves disease predominantly affects
those aged 20-40 years.
The prevalence of toxic multinodular
goiter increases with age and becomes
the primary cause of hyperthyroidism in
elderly persons.

CLINICAL
History
The
clinical
presentation
of
hyperthyroidism ranges from an array of
nonspecific historical features to an
acute life-threatening event. Historical
features common to hyperthyroidism
and thyroid storm are numerous and
represent a hypermetabolic state with
increased beta-adrenergic activity.

 Weight loss
Patients typically report an average loss of approximately 15% of their
prior weight.
Basal metabolic rate is increased with a stimulation of lipolysis and
lipogenesis.
Palpitations
Chest pain - Often occurs in the absence of cardiovascular disease
Psychosis
Menstrual irregularity
Disorientation
Tremor
Nervousness, anxiety, or emotional lability
Heat intolerance
Increased perspiration
Fatigue
Weakness - Typically affects proximal muscle groups
Edema
Dyspnea
Frequent bowel movements

Physical
Fever

Thyromegaly

Tachycardia (often out of

proportion to the fever)

Exophthalmos

Diaphoresis (often profuse)

Atrial fibrillation

Dehydration secondary to GI
losses and diaphoresis

Myopathy

Warm, moist skin

Thyroid bruit - Relatively specific

for thyrotoxicosis

Widened pulse pressure

Fine, resting tremor

Congestive heart failure (may be

a high output failure)

Weight loss

Causes
Hyperthyroidism
results
from
numerous
etiologies,
including
autoimmune,
drug-induced,
infectious, idiopathic, iatrogenic, and
malignancy.

 Autoimmune
Graves disease
Chronic thyroiditis (Hashimoto thyroiditis) Although the primary cause of hypothyroidism,
the disease process occasionally presents
initially with thyrotoxicosis
Subacute thyroiditis (de Quervain thyroiditis) Diffuse, painful inflammation of the thyroid
producing a transient state leakage of stored
hormone
Postpartum thyroiditis - Presents similarly to
subacute thyroiditis 2-6 months postpartum but
typically painless with mild symptoms

 Drug-induced
Iodine-induced
Occurs
after
administration of either supplemental
iodine to those with prior iodine
deficiency or pharmacologic doses of
iodine (contrast media, medications) in
those with underlying nodular goiter
Amiodarone - Its high iodine content is
primarily responsible for producing a
hyperthyroid
state,
though
the
medication
may
itself
induce
autoimmune thyroid disease.

 Infectious
Suppurative thyroiditis - Often bacterial,
results in a painful gland commonly in
those with underlying thyroid disease or
in immunocompromised individuals
Postviral thyroiditis

 Idiopathic
Toxic multinodular goiter - The second
most common cause of hyperthyroidism,
characterized
by
functionally
autonomous nodules, typically after age
50 years

 Iatrogenic
Thyrotoxicosis factitia - A psychiatric
condition in which high quantities of
exogenous thyroid hormone are consumed
Surgery - Now uncommon secondary to
preventative measures, manipulation of
the thyroid gland during thyroidectomy
historically caused a flood of hormone
release, often resulting in highly toxic
blood levels

 Malignancy
Toxic
adenoma
A
single,
hyperfunctioning
nodule
within
a
normally functioning thyroid gland
commonly among patients in their 30s
and 40s
Thyrotropin-producing pituitary tumors
Struma ovarii - Ovarian teratoma with
ectopic thyroid tissue

 Thyroid storm can be triggered by many different

events, classically in patients with underlying
Graves disease or toxic multinodular goiter.

Infection
Surgery
Cardiovascular events
Toxemia of pregnancy
Diabetic ketoacidosis, hyperosmolar coma, and
insulin-induced hypoglycemia
Thyroidectomy
Discontinuation of antithyroid medication
Radioactive iodine
Vigorous palpation of the thyroid gland in hyperthyroid
patients

TREATMENTS
The
large
and
generally
accepted
modalities
for
treatment
of
hyperthyroidism in humans involve initial
temporary use of suppressive thyrostatics
medication
(antithyroid
drugs),
and
possibly later use of permanent surgical or
radioisotope therapy. All approaches may
cause under active thyroid function
(hypothyroidism) which is easily managed
with levothyroxine supplementation.

Temporary medical therapy

Thyrostatics (Antithyroid drugs)
Thyrostatics are drugs that inhibit the
production of thyroid hormones, such as
carbimazole and methimazole, and
propylthiouracil.
Thyrostatics
are
believed to work by inhibiting the
iodination
of
thyroglobulin
by
thyroperoxidase, and thus, the formation
of tetra-iodothyronine (T4).

Propylthiouracil also works outside the

thyroid gland, preventing conversion of
(mostly inactive) T4 to the active form T3.
Because thyroid tissue usually contains a
substantial reserve of thyroid hormone,
thyrostatics can take weeks to become
effective, and the dose often needs to be
carefully titrated over a period of months,
with regular doctor visits and blood tests
to monitor results.

 Beta-blockers
Many of the common symptoms of
hyperthyroidism such as palpitations,
trembling, and anxiety are mediated by
increases in beta adrenergic receptors
on cell surfaces. Beta blockers, typically
used to treat high blood pressure, are a
class of drug which offset this effect,
reducing rapid pulse associated with the
sensation
of
palpitations,
and
decreasing tremor and anxiety.

 Thus,
a
patient
suffering
from
hyperthyroidism
can
often
obtain
immediate temporary relief until the
hyperthyroidism can be characterized with
the Radioiodine test noted above and
more permanent treatment take place.
Note that these drugs do not treat
hyperthyroidism or any of its long term
effects if left untreated, but, rather, they
treat or reduce only symptoms of the
condition.

Permanent treatments
Surgery as an option predates the use of the
less invasive radioisotope therapy (radioiodine
131 thyroid ablation), but is still required in
cases where the thyroid gland is enlarged and
causing compression to the neck structures,
or
the
underlying
cause
of
the
hyperthyroidism may be cancerous in origin.
Some patients suffering from the related
condition of thyroid eye disease leading to
diplopia because this condition can be
worsened by radiotherapy treatment.

 Surgery
Surgery (to remove the whole thyroid or
a part of it) is not extensively used
because most common forms of
hyperthyroidism are quite effectively
treated by the radioactive iodine
method, and because there is a risk of
also removing the parathyroid glands,
and of cutting the recurrent laryngeal
nerve, making swallowing difficult, and
even simply generalized staph infection
as with any major surgery.

 Some Graves' disease patients, however,

who cannot tolerate medicines for one
reason or another, patients who are
allergic to iodine, or patients who refuse
radioiodine
may
opt
for
surgical
intervention. Also, some surgeons believe
that radioiodine treatment is unsafe in
patients with unusually large gland, or
those whose eyes have begun to bulge
from their sockets, fearing that the
massive dose of radioiodine 131 needed
will
only
exacerbate
the
patient's
symptoms.

 Radioiodine
In iodine-131 (radioiodine) radioisotope
therapy, radioactive iodine-131 is given orally
(either by pill or liquid) on a one-time basis, to
severely restrict, or altogether destroy the
function of a hyperactive thyroid gland.
This isotope of radioactive iodine used for
ablative treatment is more potent than
diagnostic radioiodine (iodine-123) which has
a biological half life from 813 hours. Iodine131, which also emits beta particles which are
far more damaging to tissues at short range,
has a half-life of approximately 8 days.

 Patients who do not respond sufficiently to

the first dose are sometimes given an
additional radioiodine treatment, at a larger
dose.
Iodine-131 in this treatment is picked up by
the active cells in the thyroid and destroys
them, rendering the thyroid gland mostly or
completely inactive. Since iodine is picked
more readily (though not exclusively) by
thyroid cells, and (more importantly) is picked
up even more readily by over-active thyroid
cells, the destruction is local, and there are no
widespread side effects with this therapy.

 Radioiodine ablation has been used for over 50

years, and the only major reasons for not using it
are pregnancy and breast-feeding (breast tissue
also picks up and concentrates iodine). Once the
thyroid function is reduced, replacement hormone
therapy taken orally each day may easily provide
the required amount of thyroid hormone the body
needs. There is, however, a contrasting study
noting
increased
cancer
incidence
after
radioiodine treatment for hyperthyroidism.
The principal advantage of radioiodine treatment
for hyperthyroidism is that it tends to have a
much higher success rate than medications.

Hypothyroidism
Hypothyroidism is a common endocrine disorder
resulting from deficiency of thyroid hormone. It
usually is a primary process in which the thyroid
gland produces insufficient amounts of thyroid
hormone.
It can also be secondarythat is, lack of thyroid
hormone secretion due to inadequate secretion of
either thyrotropin (ie, thyroid-stimulating hormone
[TSH]) from the pituitary gland or thyrotropinreleasing hormone (TRH) from the hypothalamus
(secondary or tertiary hypothyroidism).

 The patient's presentation may vary from

asymptomatic to, rarely, coma with
multisystem organ failure (myxedema
coma).
Cretinism
refers
to
congenital
hypothyroidism, which affects 1 per 4000
newborns.
Subclinical hypothyroidism, also referred
to as mild hypothyroidism, is defined as
normal serum free T4 levels with slightly
high serum TSH concentration.

Pathophysiology
Localized disease of the thyroid gland that results in
decreased thyroid hormone production is the most
common cause of hypothyroidism.
Under normal circumstances, the thyroid releases 100125 nmol of thyroxine (T4) daily and only small amounts
of triiodothyronine (T3). The half-life of T4 is
approximately 7-10 days.
T4, a prohormone, is converted to T3, the active form of
thyroid hormone, in the peripheral tissues by 5deiodination.
Early in the disease process, compensatory mechanisms
maintain T3 levels. Decreased production of T4 causes an
increase in the secretion of TSH by the pituitary gland.

 TSH
stimulates
hypertrophy
and
hyperplasia of the thyroid gland and thyroid
T4-5'-deiodinase activity. This, in turn,
causes the thyroid to release more T3.
Because all metabolically active cells
require thyroid hormone, deficiency of the
hormone has a wide range of effects.
Systemic effects are due to either
derangements in metabolic processes or
direct effects by myxedematous infiltration
(ie, accumulation of glucosaminoglycans in
the tissues).

 The myxedematous changes in the heart

result in decreased contractility, cardiac
enlargement,
pericardial
effusion,
decreased pulse, and decreased cardiac
output. In the GI tract, achlorhydria and
decreased intestinal transit with gastric
stasis can occur. Delayed puberty,
anovulation, menstrual irregularities, and
infertility are common.

 Decreased thyroid hormone effect

can cause increased levels of total
cholesterol
and
low-density
lipoprotein (LDL) cholesterol and a
possible change in high-density
lipoprotein (HDL) cholesterol due to a
change in metabolic clearance. In
addition, hypothyroidism may result
in an increase in insulin resistance.

 Frequency
Iodine deficiency as a cause of
hypothyroidism
is
more
common
internationally.
The
prevalence
is
reported as 2-5% depending on the
study, increasing to 15% by age 75
years.

Mortality/Morbidity
In developed countries, death caused by
hypothyroidism is uncommon.

 Sex
Community studies use slightly different criteria for
determining hypothyroidism; therefore, female-tomale ratios vary. Generally, thyroid disease is much
more common in females than in males, with reports
of prevalence 2-8 times higher in females.

Age
The frequency of hypothyroidism, goiters, and thyroid
nodules increases with age. Hypothyroidism is most
prevalent in elderly populations, with 2% to as much
as 20% of older age groups having some form of
hypothyroidism, the odds of having hypothyroidism
were 5 times greater in persons aged 80 years and
older than in individuals aged 12-49 years.

CLINICAL
History
Hypothyroidism commonly manifests as a slowing
in physical and mental activity but may be
asymptomatic. Symptoms and signs of this
disease are often subtle and neither sensitive nor
specific.
Many of the more common symptoms are
nonspecific and difficult to attribute to a specific
cause.
Consequently, the diagnosis of hypothyroidism is
based on clinical suspicion and confirmed by
laboratory testing.

Myxedema coma is a severe form of

hypothyroidism that results in an altered
mental status, hypothermia, bradycardia,
hypercarbia,
and
hyponatremia.
Cardiomegaly, pericardial effusion, cardiogenic
shock, and ascites may be present.
Myxedema coma most commonly occurs in
individuals with undiagnosed or untreated
hypothyroidism who are subjected to an
external stress, such as low temperature,
infection, or medical intervention (eg, surgery
or hypnotic drugs).

SYMPTOMS
Fatigue, loss of energy, lethargy

Emotional lability, mental

impairment

Weight gain

Forgetfulness, impaired memory,

inability to concentrate

Decreased appetite

Constipation

Cold intolerance

Menstrual disturbances, impaired

fertility

Dry skin

Decreased perspiration

Hair loss

Paresthesia and nerve

entrapment syndromes

Sleepiness

Blurred vision

Muscle pain, joint pain, weakness Decreased hearing

in the extremities
Depression

Fullness in the throat,

hoarseness

 The following are symptoms more specific to

Hashimoto thyroiditis:

Feeling of fullness in the throat

Painless thyroid enlargement
Exhaustion
Neck pain, sore throat, or both
Low-grade fever

 OTHER PHYSICAL SIGNS INCLUDE:

Hypothermia

Pallor

Slowed speech and movements

Jaundice

Loss of scalp hair, axillary hair,

pubic hair, or a combination

Coarse, brittle, strawlike hair

Periorbital puffiness

Dull facial expression

Macroglossia

Decreased systolic blood pressure

and increased diastolic blood
pressure

Pericardial effusion
Goiter
Bradycardia
Abdominal distension, ascites (uncommon)
Hyporeflexia with delayed relaxation, ataxia, or
both
Nonpitting edema (myxedema)
Pitting edema of lower extremities
Metabolic
abnormalities
associated
with
hypothyroidism
include
anemia,
dilutional
hyponatremia, hyperlipidemia, and reversible
increase in creatinine.

Causes
Worldwide, iodine deficiency remains
the foremost cause of hypothyroidism.
Autoimmune:
The most frequent cause of acquired
hypothyroidism is autoimmune thyroiditis
(Hashimoto thyroiditis). The body recognizes
the thyroid antigens as foreign, and a
chronic immune reaction ensues, resulting
in lymphocytic infiltration of the gland and
progressive destruction of functional thyroid
tissue.

 Postpartum thyroiditis:
Up to 10% of postpartum women may
develop lymphocytic thyroiditis in the 210 months after delivery.
The frequency may be as high as 25% in
women with type 1 diabetes mellitus.
The condition is usually transient (2-4
mo) and can require a short course of
treatment with levothyroxine (LT4), but
postpartum patients with lymphocytic
thyroiditis are at increased risk of
permanent hypothyroidism

 Subacute
thyroiditis:

granulomatous

Inflammatory
conditions
or
viral
syndromes may be associated with
transient hyperthyroidism followed by
transient hypothyroidism (de Quervain
or
painful
thyroiditis,
subacute
thyroiditis).
These are often associated with fever,
malaise, and a painful and tender gland.

 Drugs:
Medications
such
as
amiodarone,
interferon alpha, thalidomide, lithium,
and
stavudine
have
also
been
associated with primary hypothyroidism.

 Iatrogenic
Use of radioactive iodine for treatment of Graves
disease
generally
results
in
permanent
hypothyroidism within 1 year after therapy. The
frequency is much lower in patients with toxic
nodular goiters and those with autonomously
functioning thyroid nodules. Patients treated with
radioiodine should be monitored for clinical and
biochemical evidence of hypothyroidism.
Thyroidectomy
External neck irradiation (for head and neck
neoplasms, breast cancer, or Hodgkin disease) may
result in hypothyroidism; patients who have
received these treatments require monitoring of
thyroid function.

 Rare:
Rare causes include inborn errors of thyroid hormone
synthesis.

Iodine deficiency or excess:

Worldwide, iodine deficiency is the most common
cause of hypothyroidism.
Excess iodine, as in radiocontrast dyes, amiodarone,
health
tonics,
and
seaweed,
inhibits
iodide
organification and thyroid hormone synthesis.
Most healthy individuals have a physiologic escape
from this effect; however those with abnormal thyroid
glands may not. These include patients with
autoimmune thyroiditis, surgically treated Graves
hyperthyroidism (subtotal thyroidectomy) and prior
radioiodine therapy.

 Central hypothyroidism
Central hypothyroidism (secondary or
tertiary) results when the hypothalamicpituitary axis is damaged. Various
causes should be considered:
Pituitary adenoma
Tumors impinging on the hypothalamus
History of brain irradiation
Drugs (eg, dopamine, lithium)
Sheehan syndrome
Genetic disorders

TREATMENT
Hypothyroidism is treated with the levorotatory forms of thyroxine (LT4) and triiodothyronine (L-T3). Both synthetic and animal-derived
thyroid tablets are available and can be prescribed for patients in need
of additional thyroid hormone. Thyroid hormone is taken daily, and
doctors can monitor blood levels to help assure proper dosing. There
are several different treatment protocols in thyroid replacement
therapy:
T4 Only

This treatment involves supplementation of levothyroxine alone, in a synthetic

form. It is currently the standard treatment in mainstream medicine.

T4 and T3 in Combination

This treatment protocol involves administering both synthetic L-T4 and L-T3
simultaneously in combination.

Desiccated Thyroid Extract

Desiccated thyroid extract is an animal based thyroid extract, most commonly

from a porcine source. It is also a combination therapy, containing natural forms
of L-T4 and L-T3.

HYPOTHYROIDISM
Fatigue, loss of energy,
lethargy

Emotional lability, mental

impairment

Weight gain

Forgetfulness, impaired
memory, inability to
concentrate

Decreased appetite

Constipation

Cold intolerance

Menstrual disturbances,
impaired fertility

Dry skin

Decreased perspiration

Hair loss

Paresthesia and nerve

entrapment syndromes

Sleepiness

Blurred vision

Muscle pain, joint pain,

weakness in the extremities

Decreased hearing

Depression

Fullness in the throat,

hoarseness

HYPERTHYROIDISM
Fever

Thyromegaly

Tachycardia (often out of

proportion to the fever)

Exophthalmos

Diaphoresis (often profuse)

Atrial fibrillation

Dehydration secondary to GI
losses and diaphoresis

Myopathy

Warm, moist skin

Thyroid bruit - Relatively specific

for thyrotoxicosis

Widened pulse pressure

Fine, resting tremor

Congestive heart failure (may be

a high output failure)

Weight loss

Disorientation,
Nervousness, anxiety

Psychosis, Heat intolerance

GOOD DAY

JUNAMARO1946@YAHOO.COM