Tiroid Disorder

dr M. Arman nasution SpPD

Thyroid gland
One of largest pure endocrine glands in the
body ( 20gms).

Its size depends on:

1. age age size.

2. sex female > male.
3. physiological condition (pregnancy,
lactation)
Site:
Located in the neck just below the larynx, on
either
side of & anterior to the trachea.

The Thyroid Gland

130-201 Galen
1543
Vesalius
1656 Wharton Oblong Shield
1873 Gull Adult Cretinism
1889 Murray Liquor Thyroidei
1909 Kocher Nobel Prize
1915
Kendall Isolation of thyroxine
1951
Pitt-Rivers-isolation of T3

Histology of the Thyroid Gland

The thyroid gland contains numerous follicles,
composed of epithelial follicle cells and colloid.
Also, between follicles are clear parafollicular cells,
which produce calcitonin (see coming lecture on
calcium balance).

Thyroid
Hormonal gland
Below Adams Apple
Produces T3, T4, and Calcitonin
Heart rate, metabolism, growth,
blood pressure
Feedback Mechanism

Thyroid gland

(Continued)

The Thyroid Gland

Thyroid gland

(Continued)

Thyroid gland is well vascularized (rich in

blood
supply).
Embryologically:
Originates from an envagination of the
floor of the pharynx.

Thyroid gland

(Continued)

Formed of 2 lobes (Rt & Lt), that are

connected by
band of tissue called isthmus.

Not visible under normal conditions, but can

be felt
during swallowing.

Thyroid Follicles

Thyroid Follicles

Thyroid Hormone Synthesis

Thyroid gland structure - Euthyroid (normal

thyroid)

1. Multiple Follicles (Acini):

Are the functional unit.

Thousands in no.
100 to 300 meters in diameter.
Each follicle is spherical in structure.
Follicular wall is lined with a single layer of
cuboidal
epithelioid cells that secrete into the interior of
the
follicles.

Structure of thyroid follicle

Euthyroid follicle

Each follicle is filled with pink-staining

proteinaceous
material called colloid.
When the gland is INACTIVE:
colloid is abundant, follicles are large, & lining
cells
are flat.
When the gland is ACTIVE:
follicles are small, lining cells are cuboid or
columnar,

Structure of thyroid follicle Euthyroid follicle

Colloid
(glycoprotei
n)

Basal membrane of epithelial

cells
Apical membrane of epithelial
cells
Thyroid Ccell

Capillary
(Rich blood
supply)

Basemen
t
membran
e

Cuboidal epithelial
cells

Thyroid gland secretions

2 important thyroid
hormones:
Thyroxine (T4) or
tetraiodothyronine
- Secreted by Follicular cells.
Triiodothyronine (T3)

- Can be stored in thyroid gland for couple of

months
(2-3 months).
- Having significant effect on metabolic rate of

the body.
Calcitonin
- Secreted by Parafollicular cells.
cells
- Important hormone for Ca2+ metabolism &
homeostasis.

Thyroid hormones
Amount secreted:
- Thyroxine (T4) or tetraiodothyronine 93%
- Triiodothyronine (T3) 7%
Almost all T4 is converted to T3 in

tissues.
T3

T4

T4
Capillary

T4
Reverse T3

(Rich blood
supply)

Target
cell

Thyroid hormones

(continued)

T3 is the active form of T4.

T3 4 times > potent (active/important) than
T4 in
tissue, but it present in much smaller
quantities in
blood, & persists for a much shorter time
than
does T4.

T3 has great affinity to nuclear receptors than

T4.

Transfer of thyroid hormones in blood

Almost all THs are carried in the blood, mostly in
an
inactive form, bound to 3 different types of
proteins:
a. Thyroxine binding globulin 80%
b. Thyroxine binding pre-albumin 10%
c. Plasma albumin (serum albumin) 10%

N.B. T4 has greater affinity to bind proteins than

T3.
Only very little T3 (0.25-0.3%) & T4 (0.03%) are

THYROID HORMONES IN THE

BLOOD

Approximately 99.98% of T4 is bound to

3 serum proteins: Thyroid binding
globulin (TBG) ~75%; Thyroid binding
prealbumin (TBPA or transthyretin) 1520%; albumin ~5-10%
Only ~0.02% of the total T4 in blood is
unbound or free.
Only ~0.4% of total T3 in blood is free.

SPECIFIC ACTIONS OF
THYROID HORMONE:
METABOLIC
Regulates of Basal Metabolic Rate (BMR).
Increases oxygen consumption in most
target tissues.
Permissive actions: TH increases
sensitivity of target tissues to
catecholamines, thereby elevating
lipolysis, glycogenolysis, and
gluconeogenesis.

SPECIFIC ACTIONS OF THYROID

HORMONE: DEVELOPMENT
TH is critical for normal development of

the skeletal system and musculature.

TH is also essential for normal brain
development and regulates
synaptogenesis, neuronal integration,
myelination and cell migration.
Cretinism is the term for the constellation
of defects resulting from untreated
neonatal hypothyroidism.

How thyroid hormones are

synthesized?

T3 & T4 are synthesized in the colloid

by:
1.
2.
3.
4.
5.

Iodine formation.
Thyroglobulin formatiom.
Iodination.
Condensation (coupling).
Thyroid hormones secretion.

6. Deiodination.

How thyroid hormones are synthesized?

1. Iodine formation:
Iodine (Io) is a raw material essential for THs synthesis.
Found in food, e.g. salt, & sea food, in the form of iodide
(I-).

120-150 g of I- is needed daily to maintain normal thyroid

fx in adults (or 1mg/wk).

Iodide (I-) actively transported (trap) into the follicle (90

95%).

(I-) will be 30X in thyroid cells > blood concentration.

(I-) secreted into colloid along concentration gradient.

Peroxidase enzyme found near apex of follicular cells.

How thyroid hormones are synthesized?

2. Thyroglobulin formatiom:

Thyroglobulin is a glycoprotein, made up of 2

subunits, & has a MW of 660,000.

Synthesized in the thyroid cells following entry aa

from ECF.

Secreted into colloid by exocytosis of granules that

also contain thyroid Peroxidase.

How thyroid hormones are synthesized?

3. Iodination:

Iodine attach to tyrosine within thyroglobulin

chain.
Iodinase enzyme is found in the apical
membrane Colloid start iodination process.
1 Iodine + 1 tyrosine
2 Iodine + 1 tyrosine

Mono-iodo-tyrosine (MIT)
iodinase

Di-iodo-tyrosine

Colloid

(DIT)

How thyroid hormones are synthesized?

4. Condensation (coupling):

MIT & DIT or 2 DIT molecules coupled

together.
MIT + DIT = T3
DIT + DIT = T4
N.B.
- Not all DIT & MIT thyroid hormones.
- Only 25% of DIT & MIT give rise to thyroid
hormones.
- T3 can also be formed by de-iodination

How thyroid hormones are synthesized?

5. Thyroid hormones secretion:

After formation of THs, they remain bound to

thyroglobulin in the colloid until secreted.

Hormones are surrounded in colloid by acid pool,

then
converted into colloid droplet.

TSH stimulates pinocytosis of thyroglobulin into the

follicular cell.

Lysozome enzymes hydrolyze peptide bonds &

release T3 & T4 from thyroglobulin.

T3 & T4 will be discharged freely & secreted into

How thyroid hormones are synthesized?

6. Deiodination:

Inside follicular cells, DIT & MIT forms are NOT

secreted into the blood.

DIT & MIT will be deiodinized to (Io) &

tyrosine.

Deiodized tyrosine will recycled back to

synthesize
New MIT & DIT.

How thyroid hormones are synthesized?

Control of thyroid hormones secretions

Hypothalamus (TRH) Anterior pituitary gland (TSH)
(+) thyroid gland (+) THs via cAMP dependent
mechanism.
THs -ve feed back mechanism to Hypothalamus
inorder to inhibit (TRH) secretion to anterior
pituitary gland.

Control of thyroid hormones secretions

THs also -ve feed back mechanism to Anterior pituitary
gland in order to inhibit responsiveness to
Hypothalamus (TRH).

Functions of thyroid hormones

Generally, THs:
1. Increases metabolic rate.

Stimulates increased consumption of

glucose, fatty acids and other molecules.

2. Increases metabolic heat, by

mitochondrial no & activity ATP,

3. Stimulates rate of cellular respiration by:

Production of uncoupling proteins.

Increase active transport by Na+/K+ pumps.
Stimulates O2 consumption of most of cells
in the body.

Functions of thyroid hormones

4. Necessary for normal growth & maturation.
5. Promotes maturation of nervous system.
6. Stimulates protein synthesis.
7. Help regulating lipid & CHO metabolism.

Thyroid Hormone Synthesis

Iodine sequestered in the thyroid glane by a Na-I pump,
whose activitiy is controlled by TSH

thyroid
peroxidase
tyrosine

T4

thyroid
peroxidase

diiodothyronine

de-iodination
by tissue

tetraiodothyronine
(thyroxine, T4)

T3

Tetra-iodothyronine (Thyroxine [T4]

De-iodinated by
target tissue
Tri-iodothyronine (T3)

Cellular effects
Gene transcription/translation
Cellular metabolism

THYROID HORMONES
OH

OH

O
NH2

I
O

Thyroxine (T4)

OH

NH2

I
O

OH

3,5,3-Triiodothyronine (T3)

FEEDBACK REGULATION
THE HYPOTHALAMIC-PITUITARY-THYROID AXIS
Hormones derived from the pituitary that regulate
the synthesis and/or secretion of other hormones are
known as trophic hormones.

Key players for the thyroid include:

TRH - Thyrophin Releasing Hormone
TSH - Thyroid Stimulating Hormone
T4/T3 - Thyroid hormones

PITUITARY-THYROID AXIS

HM Goodman, BASIC MEDICAL ENDOCRINOLOGY 3rd E

THYROID HORMONES
Iodine & tyrosine form both T3 & T4 under
TSH stimulation. However, 10% of T4
production is autonomous and is present
in patients with central hypothyroidism.
When released into circulation T4 binds
to:
Globulin TBG
75%
Prealbumin TBPA
20%
Albumin TBA
5%

THYROID HORMONES (2)

Less than 1% of T4 & T3 is free in

plasma.
T4 is deiodinated in the tissues to
either T3 (active) or reverse T3
(inactive).
At birth T4 level approximates
maternal level but increases rapidly
during the first week of life.
High TSH in the first 5 days of life can
give false positive neonatal screening

TSH
Is a Glico-protein with Molecular

Wt of 28000
Secreted by the anterior pituitary
under influence of TRH
It stimulates iodine trapping,
oxidation, organification, coupling
and proteolysis of T4 & T3
It also has trophic effect on thyroid
gland

TSH (2)
T4 & T3 are feed-back regulators of
TSH
TSH is stimulated by a-adrenergic
agonists
TSH secretion is inhibited by:
Dopamine
Bromocreptine
Somatostatin
Corticosteroids

THYROID HORMONES (3)

Conversion of T4 to T3 is decreased by:
Acute & chronic illnesses
b-adrenergic receptor blockers
Starvation & severe PEM
Corticosteroids
Propylthiouracil
High iodine intake (Wolff-Chaikoff effect)

THYROXINE (T4)
Total T4 level is decreased in:
Premature infants
Hypopituitarism
Nephrotic syndrome
Liver cirrhosis
PEM
Protein losing entropathy

THYROXINE (2)
Total T4 is decreased when the
following drugs are used:
Steroids
Phenytoin
Salicylates
Sulfonamides
Testosterone
Maternal TBII

THYROXINE (3)
Total T4 is increased with:
Acute thyroiditis
Acute hepatitis
Estrogen therapy
Clofibrate
iodides
Pregnancy
Maternal TSI

Introduction
Thyroid disorders:
Hypothyroidism
Hyperthyroidism and
thyrotoxicosis

Graves disease
Thyroiditis
Toxic adenoma
Toxic multinodular goitre
Thyrotoxicosis factitia
Struma ovarii
Hydatidiform mole
TSH-secreting pituitary
adenoma

Nontoxic goitre
Thyroid nodules & thyroid
cancer

Benign thyroid nodules

Thyroid cancer

Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
Lymphoma
Cancer metastatic to the
thyroid

Hyperthyroidism Symptoms
Hyperactivity/ irritability/ dysphoria
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increase of appetite
Diarrhoea
Polyuria
Oligomenorrhoea, loss of libido

Hyperthyroidism Signs
Tachycardia (AF)
Tremor
Goiter
Warm moist skin
Proximal muscle
weakness
Lid retraction or
lag
Gynecomastia

Causes of Hyperthyroidism
Most common
causes
Graves disease
Toxic multinodular
goiter
Autonomously
functioning nodule

Rarer causes
Thyroiditis or other
causes of destruction
Thyrotoxicosis factitia
Iodine excess (JodBasedow phenomenon)
Struma ovarii
Secondary causes (TSH
or HCG)

Graves Disease
Autoimmune disorder
Abs directed against TSH receptor
with intrinsic activity. Thyroid and
fibroblasts
Responsible for 60-80% of
Thyrotoxicosis
More common in women

Graves Disease Eye Signs

N - no signs or symptoms
O only signs (lid retraction or
lag) no symptoms
S soft tissue involvement (periorbital oedema)
P proptosis (>22 mm)(Hertls
test)
E extra ocular muscle
involvement (diplopia)
C corneal involvement
(keratitis)
S sight loss (compression of
the optic nerve)

Graves Disease Other

Manifestations
Pretibial mixoedema
Thyroid acropachy
Onycholysis
Thyroid enlargement
with a bruit
frequently audible
over the thyroid

Diagnosis of Graves Disease

TSH , free T4
Thyroid auto

antibodies
Nuclear thyroid
scintigraphy (I123,
Te99)

Treatment of Graves
Disease
Reduce thyroid hormone production or
reduce the amount of thyroid tissue

Antithyroid drugs: propyl-thiouracil,

carbimazole
Radioiodine
Subtotal thyroidectomy relapse after
antithyroid therapy, pregnancy, young people?

Smptomatic treatment
Propranolol

Hypothyroidism Symptoms
Tiredness and

weakness
Dry skin
Feeling cold
Hair loss
Difficulty in
concentrating and
poor memory
Constipation

Weight gain with

poor appetite
Hoarse voice
Menorrhagia, later
oligo and
amenorrhoea
Paresthesias
Impaired hearing

Hypothyroidism Signs
Dry skin, cool extremities
Puffy face, hands and feet
Delayed tendon reflex
relaxation
Carpal tunnel syndrome
Bradycardia
Diffuse alopecia
Serous cavity effusions

Causes of Hypothyroidism
Autoimmune

Drugs: iodine excess,

hypothyroidism
(Hashimotos,
atrophic thyroiditis)
Iatrogenic
(I123treatment,
thyroidectomy,
external irradiation of
the neck)

lithium, antithyroid
drugs, etc
Iodine deficiency
Infiltrative disorders
of the thyroid:
amyloidosis,
sarcoidosis,haemochr
omatosis,
scleroderma

Lab Investigations of
Hypothyroidism
TSH , free T4
Ultrasound of thyroid little value
Thyroid scintigraphy little value
Anti thyroid antibodies anti-TPO
S-CK , s-Chol , s-Trigliseride
Normochromic or macrocytic anemia
ECG: Bradycardia with small QRS
complexes

Treatment of
Hypothyroidism
Levothyroxine
If no residual thyroid function 1.5 g/kg/day
Patients under age 60, without cardiac disease
can be started on 50 100 g/day. Dose
adjusted according to TSH levels
In elderly especially those with CAD the
starting dose should be much less (12.5 25
g/day)

Thyroiditis

Thyroiditis
Acute: rare and due to suppurative

infection of the thyroid

Sub acute: also termed de Quervains
thyroiditis/ granulomatous thyroiditis
mostly viral origin
Chronic thyroiditis: mostly
autoimmune (Hashimotos)

Acute Thyroiditis
Bacterial Staph, Strep
Fungal Aspergillus, Candida,

Histoplasma, Pneumocystis
Radiation thyroiditis
Amiodarone (acute/ sub acute)
Painful thyroid, ESR usually elevated,
thyroid function normal

Sub Acute Thyroiditis

Viral (granulomatous) Mumps,
coxsackie, influenza, adeno and
echoviruses
Mostly affects middle aged women,
Three phases, painful enlarged
thyroid, usually complete resolution
Rx: NSAIDS and glucocorticoids if
necessary

Sub Acute Thyroiditis (cont)

Silent thyroiditis
No tenderness of thyroid
Occur mostly 3 6 months after
pregnancy
3 phases: hyperhyporesolution, last
12 to 20 weeks
ESR normal, TPO Abs present
Usually no treatment necessary

Clinical Course of Sub Acute

Thyroiditis

Chronic Thyroiditis
Hashimotos
Autoimmune
Initially goiter later very
little thyroid tissue
Rarely associated with
pain
Insidious onset and
progression
Most common cause of
hypothyroidism
TPO abs present (90
95%)

Chronic Thyroiditis
Reidels

Rare
Middle aged women
Insidious painless
Symptoms due to compression
Dense fibrosis develop
Usually no thyroid function impairment

Thyroiditis
The most common form of thyroiditis

is Hashimoto thyroiditis, this is also

the most common cause of long term
hypothyroidism
The outcome of all other types of
thyroiditis is good with eventual
return to normal thyroid function

EXAMPLES OF THYROID DISEASES

1 Hypothyroidism

Hyperthyroidism

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

EXAMPLES OF THYROID DISEASES

Juvenile Hypothyroidism

Congenital Hypothyroidism

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

HYPOTHYROIDISMEPIDEMIOLOGY
Neonatal screening reveals incidence

that varies between 1-5/1000 live

births
The most common cause of preventable
mental retardation in children
Both acquired & congenital forms are
linked to iodine deficiency
Diagnosis is easy & early treatment is
beneficial

ETIOLOGY
CONGENITAL
Hypoplasia & mal-descent
Familial enzyme defects
Iodine deficiency (endemic cretinism)
Intake of goitrogens during
pregnancy
Pituitary defects
Idiopathic

ETIOLOGY /2

ACQUIRED
Iodine deficiency
Auto-immune thyroiditis
Thyroidectomy or RAI therapy
TSH or TRH deficiency
Medications (iodide & Cobalt)
Idiopathic

KILPATRIK GRADING OF
GOITRE

Grade 0: Not visible neck

extended &
Not palpable
Grade 1: Not visible, but palpable
Grade 2: Visible only when neck
is
extended & on swallowing,
Grade 3: Visible in all positions
Grade 4: Large goiter

THYROID GLAND
Derived from pharyngeal

endoderm at 4/40
Migrate from base of the tongue to
cover the 2&3 tracheal rings.
Blood supply from ext. carotid &
subclavian and blood flow is twice
renal blood flow/g tissue.
Starts producing thyroxin at 14/40.

OVERVIEW (2)

Maternal & fetal glands are independent

with little transplacental transfer of T4.
TSH doesnt cross the placenta.
Fetal brain converts T4 to T3 efficiently.
Average intake of iodine is 500 mg/day.
70% of this is trapped by the gland
against a concentration gradient up to
600:1

FUNCTIONS OF
THYROXINE

Thyroid hormones are essential for:

Linear growth & pubertal
development
Normal brain development & function
Energy production
Calcium mobilization from bone
Increasing sensitivity of b-adrenergic
receptors to catecholeamines

CLINICAL FEATURES
Gestational age > 42 weeks
Birth weight > 4 kg
Open posterior fontanel
Nasal stuffiness & discharge
Macroglossia
Constipation & abdominal

distension
Feeding problems & vomiting

CLINICAL FEATURES (2)

Non pitting edema of lower limbs &

feet
Coarse features
Umbilical hernia
Hoarseness of voice
Anemia
Decreased physical activity
Prolonged (>2/52) neonatal jaundice

CLINICAL FEATURES (3)

Dry, pale & mottled skin
Low hair line & dry, scanty hair
Hypothermia & peripheral
cyanosis
Hypercarotenemia
Growth failure
Retarded bone age
Stumpy fingers & broad hands

CLINICAL FEATURES (5)

Skeletal abnormalities:
Infantile proportions
Hip & knee flexion
Exaggerated lumbar lordosis
Delayed teeth eruption
Under developed mandible
Delayed closure of anterior fontanel

OCCASIONAL FEATURES
Overt obesity
Myopathy & rheumatic pains
Speech disorder
Impaired night vision
Sleep apnea (central &

obstructive)
Anasarca
Achlorhydria & low intrinsic factor

OCCASIONAL FEATURES (2)

Decreased bone turnover
Decreased VIII, IX & platelets

adhesion
Decreased GFR & hyponatremia
Hypertension
Increased levels of CK, LDH & AST
Abnormal EEG & high CSF protein
Psychiatric manifestations

ASSOCIATIONS
Autoimmune diseases (Diabetes
Mellitus)
Cardiomyopathy & CHD
Galactorrhoea
Muscular dystrophy +
pseudohypertrophy (KocherDebre-Semelaigne)

GOITROGENS
DRUGS
Anti-thyroid
Cough medicines
Sulfonamides
Lithium
Phenylbutazone
PAS
Oral hypoglycemic agents

GOITROGENS

FOOD
Soybeans
Millet
Cassava
Cabbage

CLINICAL FEATURES (4)

Neurological manifestations
Hypotonia & later spasticity
Lethargy
Ataxia
Deafness + Mutism
Mental retardation
Slow relaxation of deep tendon
jerks

CONGENITAL HYPOTHYRODISM
Primary thyroid defect: usually

associated with goiter.

Secondary to hypothalamic or
pituitary lesions: not associated
with goiter.
2 distinct types of presentation:
Neurological with MR-deafness & ataxia
Myxodematous with dwarfism &
dysmorphism

I: Hyperthyroidism
(thyrotoxicosis)
Hyperthyoidism THs.
Could be:
1ry hyperthyroidism
gland),

(diseases is in the

e.g. Graves disease

Exerts TSH-like effects on thyroid.

Not affected by negative feedback.

T3 & T4 reflex TSH.

2ry hyperthyroidism

(disease is higher

up)

TRH TSH T3 & T4.

Females
Follicular>cells
become
males
(4:1). overactive.

I: Hyperthyroidism Graves disease

90% of hyperthyoidism is due to Graves disease.

GD is an autoimmune disease thyroid stimulating

antibodies IgG

Symptoms of GD:
Exophthalmous,
due to of
retro-orbital
oedema
(irreversible).
-- Lid
lag, due to weakness
extraoccular
muscles
(reversible).

Anxiety & restlessness.

Sleeplessness.
appetite, weight & diarrhea.
Intolerence to heat.

Treatment:

- drugs to iodination process, such as PTU

Propylthiouracil; MMI
methylmercaptoimidazole.

Hyperthyroidism
A.Typical Symptoms caused by thyroid hormone
excess in order of frequency
1.
Nervousness
2.
Palpitations
3.
Rapid pulse
4.
Fatigability
5.
Muscle weakness
6.
Weight loss
7.
Diarrhea
8.
Heat intolerance
9.
Warm skin
10.
Sweating
11.
Tremor
12.
Eye changes (Graves Disease)
13.
Variable gland enlargement

Hyperthyroidism
Diagnostic Tests
By definition secondary hyperthyroidism
means what? (where is the problem
what is causing the problem?)
Pituitary gland TSH T3/T4
Primary
Hyperthyroidism

Secondary
Hyperthyroidism

T3/T4

TSH

Directional Changes in Thyroid

Function Tests
Clinical
State
Euthyroid

Total T4

T3RU

FT4I
N

Free T4
N

TSH
N

Hyperthyroid
Hypothyroid
High TBG

Low TBG

N or

N or

Nonthyroid
Illness

N or

N or
(N = Normal)

Hyperthyroidism
Medical Treatment
Meds first
Goal
T3/T4 levels

Meds alone

sometimes work if not

Surgery

Hyperthyroidism
Medical Treatment
Anti-thyroid therapy
Propylthioracil /
PTU
Methimazole /
Tapazole
Action
Inhibits synthesis
of T3/T4

Hyperthyroidism
Medical Treatment
Propranolol
hydrochloride / Inderal
Beta-blocker
sympathetic nervous
system
No smoking

Hyperthyroidism
Medical Treatment
Meds alone not
Surgery

If Ca Thyroid
Surgery

Euthyroid state

before surgery!
How?
Anti-thyroid meds

Hyperthyroidism
Medical Treatment
Iodine before
surgery

Potassium iodine
saturated
solution (SSKI)
vascularity of
the thyroid
risk of post-op
bleeding

Hyperthyroidism
Medical Treatment
Radioactive Iodine
I131
Used instead of
radiation tx
Stop anti-thyroid
meds x 7 days
Single dose
S&S in @ 3wks
full effect in 3
months

Hyperthyroidism
Medical Treatment
Radioactive Iodine
Safety
No PG nurses
Watch body fluids
Avoid kids x 7
days

Hyperthyroidism
Medical Treatment
Diet (When hyperthyroid)
Calories

4,000-5,000 cal/day
Fluids

Na

Fiber

Caffeine

Hyperthyroidism
Severe
Thyrotoxicosis
AKA: Thyroid Storm
Definition
Sever hyperthyroid
state

Etiology
Stress
Post thyroid
surgery
Undiagnosed

Hyperthyroidism Severe
Thyrotoxicosis
S&S
TH adrenergic

activity epinephrine
Pulse

Temperature

BP

Depression
Activity
Restlessness

Delirium
SOB
Coma

Hyperthyroidism Severe
Thyrotoxicosis
Death
<2hr
Cardiac Failure

Hyperthyroidism Severe
Thyrotoxicosis
Treatment
Fever

Tylenol/
acetaminophen
Not aspirin

For pulse & BP

Propranolol / Inderal
Beta-adrenergic
blocker

If SOB

O2
HOB

Indications for
Thyroidectomy
- Hyperthyroidism (Graves) not
-

responsive to medical therapy with

ophthalmic symptoms
Malignancy (confirmed or high
suspicion based on history and/or
FNA)
Goiter with compressive symptoms
Large thyroid nodule (>2cm) that is
unable to be adequately sampled by
FNA (sampling error due to large area
of nodule and risk of combination of
benign and malignant cells)

Complications of
thyroidectomy
- Intraoperative
- Bleeding
- Damage to arteries/veins of neck

- Postoperative presentation
- Injury to recurrent laryngeal nerve
- Unilateral: hoarseness
- Bilateral: respiratory distress

- Bleeding
- Expanding hematoma causes compression, shortness of breath

- Hypocalcemia
- Removal or injury to parathyroid glands or their blood supply

- Scar

II: Hypothyroidism
Adult (Myxedema)
Hypothyroidism in adults THs.

Could be:
1ry hypothyroidism (diseases is in the
gland)
- autoimmune disease such as Hashimotos
throiditis.
- lack of iodine.
- absence of deiodination enzyme.

T3 & T4 reflex TSH.

2ry hypothyroidism (disease is higher up)
TRH TSH T3 & T4.

II: Hypothyroidism (myxedema) cont.

Symptoms of Hypothyroidism:
- Decreased metabolic rate.
- Slow heart rate & pulse.
- Slow muscle contractions
- appetite, weight gain, & constipation.
- Prolonged sleep, & dizziness.
- Coarse skin.
- Slow thinking, lethargy, & mask face.
- Intolerence to cold ( ability to adapt cold).
- Myxoedema swollen & puffy appearance of
body,
due to deposition of protein-carbohydrate
complexes

II: Hypothyroidism
Children (Cretinism)
Hypothyroidism in children THs.
Hypothyroid from end of 1st trimester to 6

months
postnatally, or in the 1st few years of life.
T3 & T4 reflex TSH.

&

Additional Signs & Symptoms:

- Severe mental retardation.
- Short stature (due to growth of bones, muscle,
brain).

35 years old, China

15-20 years old,

Congo-Kinshasa

Hypothyroidism
Etiology:
Primary:

Hashimotos thyroiditis with or without goitre

Radioactive iodine therapy for Graves disease
Subtotal thyroidectomy for Graves disease or nodular goitre
Excessive iodine intake
Subacute thyroiditis
Rare causes

Iodide deficiency
Goitrogens such as lithium; antithyroid drug therapy
Inborn errors of thyroid hormone synthesis

Secondary: Hypopituitarism
Tertiary: Hypothalamic dysfunction (rare)
Peripheral resistance to the action of thyroid hormone

Causes of Hypothyroidism
1. Dietary deficiency (iodine)
2. Pituitary defect
3. Enzyme deficiency
4. Thyroid autoimmunity
5. Exposure to 131I

Hypothyroidism
Clinical features
Cardiovascular signs:
Bradycardia
Low voltage ECG
Pericardial effusion
Cardiomegaly
Hyperlipidemia
Constipation, ascites
Weight gain
Cold intolerance
Rough, dry skin
Puffy face and hands
Hoarse, husky voice
Yellowish color of skin due to reduced
conversion of carotene to vitamin A
Respiratory failure
Menorrhagia, infertility, hyperprolactinemia

Renal function:

Impaired ability to excrete a water load

Anemia:
Impaired Hb synthesis
Fe deficiency due to:

Menorrhagia
Reduced intestinal absorption

Folate def. due to impaired intestinal

absorption
Pernicious anemia

Neuromuscular system:
Muscle cramps, myotonia
Slow reflexes
Carpal tunnel syndrome
CNS symptoms:
Fatigue, lethargy, depression
Inability to concentrate

Hypothyroidism
Diagnosis:
A FT4 and TSH is diagnostic of primary hypothyroidism
Serum T3 levels are variable (maybe in normal range)
+ve test for thyroid autoantibodies (Tg Ab & TPO Ab) PLUS an enlarged
thyroid gland suggest Hashimotos thyroiditis
With pituitary myxedema FT4 will be but serum TSH will be
inappropriately normal or low
TRH test may be done to differentiate pituitary from hypothalamic
disease. Absence of TSH response to TRH indicates pituitary deficiency
MRI of brain is indicated if pituitary or hypothalamic disease is
suspected. Need to look for other pituitary deficiencies.
If TSH is & FT4 & FT3 are normal we call this condition subclinical
hypothyroidism

Hashimotos Thyroiditis
Hashimotos thyroiditis is a commom cause of hypothyroidism and

goitre especially in children and young adults.

It is an autoimmune disease that involves heavy infiltration of
lymphocytes that totally destroys normal thyroidal architecture
Three different autoantibodies are present: Tg Ab, TPO Ab, and
TSH-R Ab (block)
It is familial and may be associated with other autoimmune diseases
such as pernicious anemia, adrenocortical insufficiency, idiopathic
hypoparathyroidism, and vitiligo.
Shmidts syndrome consists of Hashimotos thyroiditis, adrenal
insufficiency, hypoparathyroidism, DM, ovarian failure, and (rarely)
candidal infections.

Hashimotos Thyroiditis
Symptoms & Signs:

Usually presents with goitre in a patient who is euthyroid or has mild hypothyroidism
Sex distribution: four females to one male
The process is painless
Older patients may present with severe hypothyroidism with only a small, firm
atrophic thyroid gland
Transient symptoms of thyrotoxicosis can occur during periods of hashitoxicosis
(spontaneously resolving hyperthyroidism)

Lab:
Normal or low thyroid hormone levels, and if low, TSH is elevated
High Tg Ab and/or TPO Ab titres
FNA bx reveals a large infiltration of lymphocytes PLUS Hurthle cells

Complications:
Permanent hypothyroidism (occurs in 10-15% of young pts)
Rarely, thyroid lymphoma

Management of Hypothyroidism
Start patient on L-thyroxine 0.05-0.1mg PO OD. L-thyroxine treats

the hypothyroidism and leads to regression of goitre.

If patient is elderly or has IHD start 0.025mg PO OD.
Check TSH level after 4-6 weeks to adjust the dose of L-thyroxine.
In case of secondary hypothyroidism monitor FT4 instead of TSH.
Hypothyroidism during pregnancy:
Check TFT every month. L-thyroxine dose requirement tends to go up
as the pregnancy progresses.

If patient has concommitant hyperprolactinemia and

hypercholesterolemia, treat if not normalized after adequate thyroid

replacement.

DIAGNOSIS
Early detection by neonatal
screening

High index of suspicion in all

infants with increased risk

Overt clinical presentation

Confirm diagnosis by appropriate
lab and radiological tests

LABROTARY FINDINGS
Low (T4, RI uptake & T3 resin uptake)
High TSH in primary hypothyroidism
High serum cholesterol & carotene

levels
Anaemia (normo, micro or macrocytic)
High urinary creatinine/hydroxyproline
ratio
CXR: cardiomegaly
ECG: low voltage & bradycardia

IMAGING TESTS
X-ray films can show:
Delayed bone age or epiphyseal
dysgenesis
Anterior peaking of vertebrae
Coxavara & coxa plana

Thyroid radio-isotope scan

Thyroid ultrasound
CT or MRI

TREATMENT (2)

L-Thyroxin is the drug of choice. Start

with small dose to avoid cardiac strain.

Dose is 10 g/kg/day in infancy. In older

children start with 25 g/day and increase

by 25 g every 2 weeks till required dose.

Monitor clinical progress & hormones

level

TREATMENT
Life-long replacement therapy
5 types of preparations are available:
L-thyroxin (T4)
Triiodothyronine (T3)
Synthetic mixture T4/T3 in 4:1 ratio
Desiccated thyroid (38mg T4 & 9mg
T3/grain)
Thyroglobulin (36mg T4 & 12mg T3/grain)

THYROID FUNCTION
TESTS

1. Peripheral effects:
BMR
Deep Tendon Reflex

Cardiovascular indices (pulse, BP, LV

function tests)
Serum parameters (high cholesterol,
CK, AST, LDH & carcino-embryonic
antigen)

THYROID FUNCTION TESTS

(2)
2. Thyroid gland economy:
Radio iodine uptake
Perchlorate discharge test (+ve in
Pendred syndrome & autoimmune
thyroiditis)
TSH level
TRH stimulation tests
Thyroid scan

THYROID FUNCTION TESTS

(3)
3. Tests for thyroid hormone:
Total & free T4 & T3
Reverse T3 level
T3 Resin Uptake
T3RU x total T4= Thyroid Hormone
Binding Index (formerly Free
Thyroxin Index)

THYROID FUNCTION TESTS

(4)

Special Tests:

Thyroglobulin level
Thyroid Stimulating Immunoglobulin
Thyroid antibodies
Thyroid radio-isotope scan
Thyroid ultrasound
CT & MRI
Thyroid biopsy

Myxedema Coma
Medical emergency, end stage of untreated hypothyroidism
Characterized by progressive weakness, stupor, hypothermia,

hypoventilation, hypoglycemia, hyponatremia, shock, and death

The patient (or a family member) may recall previous thyroid disease,
radioiodine therapy, or thyroidectomy
Hx is of gradual onset of lethargy progressing to stupor or coma. A hx of
amenorrhea or impotence with pituitary myxedema
PE reveals HR and marked hypothermia (as low as 24C)
The pt is usually an obese elderly woman with yellowish skin, a hoarse
voice, a large tongue, thin hair, puffy eyes, ileus, and slow reflexes. An
anterior neck scar may be present. Scanty pubic or axillary hair with
pituitary myxedema
Lab: low FT4, TSH high, normal, or low, cholesterol high or N, serum
Na low
ECG: bradycardia and low voltage
May be ppt by HF, pneumonia, excessive fluid administration, narcotics

Management of Myxedema Coma

Initiate therapy if presumptive clinical diagnosis after TSH, FT3
FT4 drawn. Also draw serum cortisol, ACTH, glucose.
General measures:

Patient should be in ICU setting

Support ventilation as respiratory failure is the major cause of death
in myxedema coma
monitors ABG`s
support blood pressure; hypotension may respond poorly to pressor
agents until thyroid hormone is replaced
hypothermia will respond to thyroxin therapy ; in interim use passive
warming only
hyponatremia will also be corrected by thyroxine therapy in majority
of cases
hypoglycemia requires IV glucose
avoid fluid overload

PROGNOSIS
Depends on:
Early diagnosis
Proper diabetes education
Strict diabetic control
Careful monitoring
Compliance

MYXOEDMATOUS COMA
Impaired sensorium,

hypoventilation bradycardia,
hypotension & hypothermia
Precipitated by:
Infections
Trauma (including surgery)
Exposure to cold
Cardio-vascular problems
Drugs

PROGNOSIS
Is good for linear growth & physical
features even if treatment is delayed,
but for mental and intellectual
development early treatment is
crucial.

Sometimes early treatment may fail

to prevent mental subnormality due
to severe intra-uterine deficiency of
thyroid hormones

Management of Myxedema Coma

Specific measure:
L-thyroxine 0.2-0.5 mg IV bolus, followed by 0.1 mg IV OD until oral
therapy is tolerated
Results in clinical response in hours

Adrenal insufficiency may be precipitated by administration of

thyroid hormone therefore hydrocortisone 100 mg IV q 8h is usually

given until the results of the initial plasma cortisol is known.
Identify and treat the underlying precipitant cause

Graves Disease

Most common form of thyrotoxicosis

May occur at any age but mostly from 20-40
5 times more common in females than in males
Syndrome consists of one or more of the following:

Thyrotoxicosis
Goitre
Opthalmopathy (exopthalmos) and
Dermopathy (pretibial myxedema)

It is an autoimmune disease of unknown cause

15% of pts with Graves have a close relative with the
same disorder

Graves Disease
Pathogenesis:
T lymphocytes become sensitized to Ag within the thyroid gland and
stimulate B lymphocytes to synthesize Ab to these Ag
One such Ab is the TSH-R Ab(stim), which stimulates thyroid cell growth
and function
Graves may be ppt by pregnancy, iodide excess, viral or bacterial
infections, lithium therapy, glucocorticoid withdrawal
The opthalmopathy and dermopathy associated with Graves may
involve lymphocyte cytokine stimulation of fibroblasts in these locations
causing an inflammatory response that leads to edema, lymphocytic
infiltration, and glycosaminoglycans deposition
The tachycardia, tremor, sweating, lid lag, and stare in Graves is due to
hyperreactivity to catecholamines and not due to increased levels of
circulating catecholamines

Graves Disease
Clinical features:
I Eye features: Classes 0-6, mnemonic NO SPECS

Class 0: No signs or symptoms

Class 1: Only signs (lid retraction, stare, lid lag), no symptoms
Class 2: Soft tissue involvement (periorbital edema, congestion

or redness of the conjunctiva, and chemosis)

Class 3: Proptosis (measured with Hertel exopthalmometer)
Class 4: Extraocular muscle involvement
Class 5: Corneal involvement
Class 6: Sight loss (optic nerve involvement)

Graves Disease
Clinical features:
II Goitre:

Diffuse enlargement of thyroid

Bruit may be present
III Thyroid dermopathy (pretibial myxedema):

Thickening of the skin especially over the lower tibia

The dermopathy may involve the entire leg and may extend onto the

feet
Skin cannot be picked up between the fingers
Rare, occurs in 2-3% of patients
Usually associated with opthalmopathy and very TSH-R Ab

Graves Disease
Clinical features:
IV Heat intolerance
V Cardiovascular:

Palpitation, Atrial fibrillation

CHF, dyspnea, angina

VI Gastrointestinal:

Weight loss, appetite

Diarrhea

VII Reproductive:

amenorrhea, oligo-

menorrhea, infertility
Gynecomastia

VIII Bone:

Osteoporosis
Thyroid acropachy

IX Neuromuscular:

Nervousness, tremor
Emotional lability
Proximal myopathy
Myasthenia gravis
Hyper-reflexia, clonus
Periodic hypokalemic
paralysis

X Skin:

Pruritus
Onycholysis
Vitiligo, hair thinning
Palmar erythema
Spider nevi

Graves Disease
Diagnosis:
Low TSH, High FT4 and/or FT3
If eye signs are present, the diagnosis of Graves disease can be made
without further tests
If eye signs are absent and the patient is hyperthyroid with or without a
goitre, a radioiodine uptake test should be done.
Radioiodine uptake and scan:

Scan shows diffuse uptake

Uptake is increased
TSH-R Ab (stim) is specific for Graves disease. May be a useful
diagnostic test in the apathetic hyperthyroid patient or in the pt who
presents with unilateral exopthalmos without obvious signs or laboratory
manifestations of Graves disease

Treatment of Graves Disease

There are 3 treatment options:

Medical therapy
Surgical therapy
Radioactive iodine therapy

Treatment of Graves Disease

A. Medical therapy:
Antithyroid drug therapy:

Most useful in patients with small glands and mild disease

Treatment is usually continued for 12-18 months
Relapse occurs in 50% of cases
There are 2 drugs:
Neomercazole (methimazole or carbimazole): start 30-40mg/D for 1-2m
then reduce to 5-20mg/D.
Propylthiouracil (PTU): start 100-150mg every 6hrs for 1-2m then
reduce to 50-200 once or twice a day
Monitor therapy with fT4 and TSH
S.E.: 5%rash, 0.5%agranulocytosis (fever, sore throat), rare:
cholestatic jaundice, hepatocellular toxicity, angioneurotic edema, acute
arthralgia

Management of Graves disease

A. Medical therapy:
Propranolol 10-40mg q6hrs to control tachycardia, hypertension
and atrial fibrillation during acute phase of thyrotoxicosis. It is
withdrawn gradually as thyroxine levels return to normal
Other drugs:

Ipodate sodium (1g OD): inhibits thyroid hormone synthesis and

release and prevents conversion of T4 to T3

Cholestyramine 4g TID lowers serum T4 by binding it in the gut

Management of Graves disease

B. Surgical therapy:
Subtotal thyroidectomy is the treatment of choice for patients
with very large glands
The patient is prepared with antithyroid drugs until euthyroid
(about 6 weeks). In addition 2 weeks before the operation
patient is given SSKI 5 drops BID to diminish vascularity of
thyroid gland
Complications (1%):

Hypoparathyroidism
Recurrent laryngeal nerve injury

Management of Graves Disease

C. Radioactive iodine therapy:
Preferred treatment in most patients
Can be administered immediately except in:

Elderly patients
Patients with IHD or other medical problems
Severe thyrotoxicosis
Large glands >100g
In above cases it is desirable to achieve euthyroid state first

Hypothyroidism occurs in over 80% of cases.

Female should not get pregnant for 6-12m after RAI.

Management of Graves Disease

Management of opthalmopathy:
Management involves cooperation between the endocrinologist
and the opthalmologist
A course of prednisone immediately after RAI therapy 100mg
daily in divided doses for 7-14 days then on alternate days in
gradually diminishing dosage for 6-12 weeks.
Keep head elevated at night to diminish periorbital edema
If steroid therapy is not effective external x-ray therapy to the
retrobulbar area may be helpful
If vision is threatened orbital decompression can be used

Management of Graves Disease

Management during pregnancy:

RAI is contraindicated
PTU is preferred over neomercazole
FT4 is maintained in the upper limit of normal
PTU can be taken throughout pregnancy or if surgery is
contemplated then subtotal thyroidectomy can be performed
safely in second trimester
Breastfeeding is allowed with PTU as it is not concentrated in
the milk

Toxic Adenoma
(Plummers Disease)
This is a functioning thyroid adenoma
Typical pt is an older person (usually > 40) who has noted

recent growth of a long-standing thyroid nodule

Thyrotoxic symptoms are present but no infiltrative
opthalmopathy. PE reveals a nodule on one side
Lab: low TSH, high T3, slightly high T4
Thyroid scan reveals hot nodule with suppressed uptake
in contralateral lobe
Toxic adenomas are almost always follicular adenomas
and almost never malignant
Treatment: same as for Graves disease

Toxic Multinodular Goitre

Usually occurs in older pts with long-standing MNG
PE reveals a MNG that may be small or quite large

and may even extend substernally

RAI scan reveals multiple functioning nodules in the
gland or patchy distribution of RAI
Hyperthyroidism in pts with MNG can often be ppt by
iodide intake jodbasedow phenomenon.
Amiodarone can also ppt hyperthyroidism in pts with
MNG
Treatment: Same as for Graves disease. Surgery is
preferred.

Subacute Thyroiditis
Acute inflammatory disorder of the thyroid gland most likely due to viral

infection. Usually resolves over weeks or months.

Symptoms & Signs:
Fever, malaise, and soreness in the neck
Initially, the patient may have symptoms of hyperthyroidism with palpitations,
agitation, and sweat
PE: No opthalmopathy, Thyroid gland is exquisitely tender with no signs of local
redness or heat suggestive of abscess formation
Signs of thyrotoxicosis like tachycardia and tremor may be present

Lab:
Initially, T4 & T3 are elevated and TSH is low, but as the disease progresses T4
& T3 will drop and TSH will rise
RAI uptake initially is low but as the pt recovers the uptake increases
ESR may be as high as 100. Thyroid Ab are usually not detectable in serum

Subacute Thyroiditis
Management:
In most cases only symptomatic Rx is necessary e.g.
acetaminophen 0.5g four times daily
If pain, fever, and malaise are disabling a short course of NSAID
or a glucocorticoid such as prednisone 20mg three times daily
for 7-10 days may be necessary to reduce the inflammation
L-thyroxine is indicated during the hypothyroid phase of the
illness. 10% of the patients will require L-thyroxine long term

Other Forms of Thyrotoxicosis

Thyrotoxicosis Factitia:
Due to ingestion of excessive amounts of thyroxine
RAI uptake is nil and serum thyroglobulin is low

Struma Ovarii:
Teratoma of the ovary with thyroid tissue that becomes hyperactive
No goitre or eye signs. RAI uptake in neck is nil but body scan
reveals uptake of RAI in the pelvis.

Hydatidiform mole:
Chorionic gonadotropin is produced which has intrinsic TSH-like
activity.

TSH-secreting pituitary adenoma:

FT4 & FT3 is elevated but TSH is normal or elevated

Visual field examination may reveal temporal defects, and CT or
MRI of the sella usually reveals a pituitary tumour.

Thyroid storm (Thyrotoxic crisis)

Usually occurs in a severely hyperthyroid patient caused by a
precipitating event such as:

Infection
Surgical stress
Stopping antithyroid medication in Graves disease

Clinical clues

fever hyperthermia
marked anxiety or agitation coma
Anorexia
tachycardia tachyarrhythmias
pulmonary edema/cardiac failure
hypotension shock
confusion

Thyroid storm (Thyrotoxic crisis)

Initiate prompt therapy after free T4, free T3, and TSH drawn without
waiting for laboratory confirmation.
Therapy

1. General measures:
Fluids, electrolytes and vasopressor agents should be used as

indicated
A cooling blanket and acetaminophen can be used to treat the pyrexia
Propranolol for betaadrenergic blockade and in addition
causesdecreased peripheral conversion of T4T3 but watch for CHF.
The IV dose is 1 mg/min until adequate beta-blockade has been
achieved. Concurrently, propranolol is given orally or via NG tube at a
dose of 60 to 80 mg q4h

Thyroid storm (Thyrotoxic crisis)

Therapy
2. Specific Measures:
PTU is the anti-thyroid drug of choice and is used in high doses: 1000
mg of PTU should be given p.o. or be crushed and given via nasogastric
tube, followed by PTU 250mg p.o. q 6h. If PTU unavailable can give
methimazole 30mg p.o. every 6 hours.
One hour after the loading dose of PTU is given give iodide which
acutely inhibits release of thyroid hormone, i.e. Lugols solution 2-3
drops q 8h OR potassium iodide (SSKI) 5 drops q 8h.
Dexamethasone 2 mg IV q 6h for the first 24-48 hours lowers body
temperature and inhibits peripheral conversion of T4-T3
With these measures the patient should improve dramatically in the first
24 hours.

3. Identify and treat precipitating factor.

Nontoxic Goitre
Enlargement of the thyroid gland from TSH stimulation which in turn

results from inadequate thyroid hormone synthesis

Etiology:

Iodine deficiency
Goitrogen in the diet
Hashimotos thyroiditis
Subacute thyroiditis
Inadequate hormone synthesis due to inherited defect in thyroidal
enzymes necessary for T4 and T3 biosynthesis
Generalized resistance to thyroid hormone (rare)
Neoplasm, benign or malignant

Nontoxic Goitre
Symptoms and Signs:
Thyroid enlargement, diffuse or multinodular
Huge goitres may produce a positive Pemberton sign (facial flushing
and dilation of cervical veins on lifting the arms over the head)
especially when they extend inferiorly retrosternally
Pressure symptoms in the neck with upward or downward movement of
the head
Difficulty swallowing, rarely vocal cord paralysis
Most pts are euthyroid but some are mildly hypothyroid

RAI uptake and scan:

Uptake may be normal, low, or high depending on the iodide pool

Scan reveals patchy uptake with focal areas of increased and
decreased uptake corresponding to hot and cold nodules
respectively

Management of Nontoxic Goitre

L-thyroxine suppressive therapy:
Doses of 0.1 to 0.2mg daily is required
Aim is to suppress TSH to 0.1-0.4 microU/L (N 0.5-5)

Suppression therapy works in 50% of cases if continued

for 1 year
If suppression does not work or if there are obstructive
symptoms from the start then surgery is necessary

Benign Thyroid Nodules

Thyroid nodules are common especially among older women
Etiology:

Focal thyroiditis
Dominant portion of multinodular goitre
Thyroid, parathyroid, or thyroglossal cysts
Agenesis of a thyroid lobe
Postsurgical remnant hyperplasia or scarring
Postradioiodine remnant hyperplasia
Benign adenomas:

Follicular
Colloid or macrofollicular
Hurthle cell
Embryonal

Rare: Teratoma, lipoma, hemangioma

Thyroid Scans
Purpose
Determine function of the gland and/or a
nodule within the gland

Hot nodules - usually independently

functioning nodules

Rarely, rarely malignant

Cold nodules - either adenoma or

maligancy

15% chance of malignancy in adults.

Thyroid Ultrasound
Can identify

presence of
nodules.
May be able to
characterize
follicular vs. solid.
Not able to rule our
malignant nodule
Aid in biopsy.

Thyroid

Imaging

- Ultrasound
- CT Neck for surgical
planning

CT scan demonstrating large Right

thyroid mass causing tracheal
deviation to left

Thyroid ULTRASOUND

Normal thyroid and surrounding neck anatomy

Fine-Needle Aspiration

Best tool for determining pathology other

than surgical excision.

Can be as high as 80 % sensitive and 95%
specific.
Operator dependent in obtaining adequate
amount of tissue. 25 gauge needle is optimal.
Should not be relied on if negative in patient
with previous neck irradiation.
Multifocal tumors common.

Interpreting the Biopsy

What you get:
Report

benign
indeterminate
suspicious
inadequate specimen

What it means:

benign - 90-95% likelihood it is benign

indeterminate- who knows?
suspicious- its malignant.
inadequate specimen - do it again (and again)

Modified from: Castro, MR, Gharib, H. Endocr Pract 2003; 9:128.

Solitary Nodule Evaluation

TSH if low scan if hot nodule, then observe.
Normal TSH - Do I scan first or FNA first? high risk - scan and FNA
Is the nodule cold or hot?
Cold - FNA biopsy
low risk - FNA
if indeterminate- scan and re-FNA or
excisional biopsy.

Anti-perioxidase Antibody helpful if low- TSH to

diagnose thyroiditis.

Never assume a solitary

thyroid nodule is benign.
Prove it.

Treatment

Medical Management
Involve endocrinology early to assist in management
Thyroid hormone replacement (Levothyroxine) for
hypothyroidism
Thyroid suppression for hyperthyroidism
I-131 for medical thyroid ablation
Observation for benign nodules

Surgery

Failure of medical management

Malignancy or concern for malignant potential
Symptom management

Treatment
- Post-surgical therapy
I-131 : Radioactive iodine ablation may be indicated
postoperatively for any residual malignancy
Thyroid hormone replacement after total
thyroidectomy
Calcium replacement
Surgery to thyroid/parathyroid bed

- Ensure patient has endocrinology follow up

Titrate levothyroxine and help manage long term
iatrogenic hypothyroidism

Thyroid Storm
Definitions
"Exaggerated or florid state of thyrotoxicosis"
"Life threatening, sudden onset of thyroid
hyperactivity"
May represent end stage of a continuum :
Thyroid hyperactivity to thyrotoxicosis to
thyrotoxic crisis to thyroid storm
"Probably reflects the addition of adrenergic
hyperactivity, induced by a nonspecific stress,
into the setting of untreated or undertreated
hyperthyroidism"

Thyroid Storm
Background Etiology
Most cases secondary to Graves' disease
Some due to toxic multinodular goiter
Rare causes :
Acute thyroiditis
Factitious
Malignancies (most do not efficiently
produce thyroid hormones)

Very rare in children

Thyroid Storm
Prognosis
Old references quote almost 100 %
mortality untreated, and 20 % treated (but
these reports were before use of beta
blockers)
Current mortality ? should be < 5%
(although not well studied or reported
due to rarity of cases)

Thyroid Storm
Clinical Presentation
2 most important defining features :
High fever (usually over 40 degrees C)
Significantly abnormal mental status
Agitation, confusion, psychosis, coma

May also exhibit :

Marked tachycardia
Vomiting, diarrhea
Jaundice (in 20 %)
Associated signs of Graves' disease

Thyroid Storm
Precipitating Factors
Infection, especially pneumonia
Cerebrovascular accident
Acute coronary syndrome, Congestive heart failure
Pulmonary embolus
Diabetic ketoacidosis
Parturition / toxemia
Major trauma
Surgery
Iodine 131 Rx or iodine contrast agents
Rapid withdrawl of antithyroid medications

Thyroid Storm
Differential Diagnosis
Environmental heatstroke
Cocaine, amphetamine, or phencyclidine
toxicity
Neuroleptic malignant syndrome
Meningitis or encephalitis
Intracranial hemorrhage
Malignant hyperthermia
Falciparum cerebral malaria

Progression of Neurologic
Findings in Thyroid Storm
Emotional lability
Restlessness
Hyperkinesis
Confusion
Psychosis
Lethargy
Somnolence
Obtundation
Coma

Cardiovascular Findings in
Thyroid Storm
Marked tachycardia
Sinus tach or atrial fibrillation

Increased myocardial irritability

PVC's, PAC's, first degree AV block

Wide pulse pressure

Apical systolic murmur
Loud S1 and S2 valve sounds
Some have high output CHF

Case Reports of Unusual

Presentations of Thyroid Storm
Coma without prominent cardiovascular
findings
Status epilepticus
Nonembolic cerebral infarction
Abdominal pain and fever
Acute renal failure / rhabdomyolysis

Usual Indicated Initial Lab

Studies for Thyroid Storm
Glucose (stat fingerstick because of
altered mental status)
Pulse oximetry (+/- ABG)
CBC, electrolytes, BUN, creatinine
T4RIA, T3RU, TSH, +/- T3RIA
Urinalysis
Liver function tests
Serum cortisol

Thyroid Storm
Usual Lab Results
Lab studies do NOT distinguish
thyrotoxicosis from thyroid storm
Usually T4 and T3 are elevated, but may
only be elevated T3
Usually plasma cortisol is low for degree
of stress present
Hyperglycemia common

Thyroid Storm
Emergent Rx
High flow O2
Rapid cooling if markedly hyperthermic
Ice packs, cooling blanket, mist / fans,
nasogastric tube lavage, acetominophen
(Salicylates contraindicated because cause
peripheral deiodination to T3)
IV fluid bolus if dehydrated
May need inotropes instead if in CHF
Propranolol 1 mg doses or labetolol 10 to 20
mg doses IV & repeat doses as needed

Thyroid Storm
Further Rx
IV diltiazem +/- digoxin for rate control for
atrial fib
IV diuretics if in CHF
IV hydrocortisone (or equivalent) 100 mg
Propylthiouracil (PTU) 600 to 1200 mg PO or
by NG
Sodium iodide 1 gram IV one hour after the
PTU
Find and treat the precipitating cause

Thyroid Storm
Additional Optional Meds
Lithium carbonate 600 mg PO
Follow-on dose 300 mg PO tid

Colestipol (resin which binds T4 in the

gut) 10 grams PO
Follow-on dose 10 grams PO tid

Consider sedatives such as

benzodiazepines (but beta blockers are
the mainstay of therapy)

Actions of Antithyroid Meds for

Thyroid Storm Rx
PTU inhibits hormone synthesis by the thyroid
gland & also inhibits T4 to T3 conversion
peripherally (this is why it is preferred over
methimizole which just acts at the thyroid)
Iodine inhibits secretion of T4 & T3 from the
thyroid (it must be given AFTER synthesis block
from PTU or else it may provide more substrate
for gland hormone synthesis)
Lithium can be used in patients alergic to iodine
but can cause relapse when stopped

Follow-on Doses of Meds for

Thyroid Storm
PTU 100 to 300 mg PO tid
Monitor for later agranulocytosis or liver
dysfunction
Or Methimizole 20 mg PO tid to qid

Sodium iodide 500 mg IV q 12 hours

Or SSKI 5 to 20 gtts PO tid

50 to 100 mg hydrocortisone IV daily till

stable, then wean as appropriate
Propranolol or labetolol or metoprolol (same
daily doses as for hypertension)

Additional Rx for Thyroid Storm

Not Responding to Initial Rx
Plasma exchange or plasmapheresis
Peritoneal dialysis or charcoal
hemoperfusion
Emergency surgery for partial or total
thyroidectomy

Myxedema Coma : The Other

Thyroid Emergency
Represents end stage of improperly treated,
neglected, or undiagnosed primary hypothyroidism
Occurs in 0.1 % or less of cases of
hypothyroidism
Very rare under age 50
50 % of cases become evident after hospital
admission
Mortality is 100 % untreated, 50 % even if treated
Most cases present in winter (cold exposure)

General Causes of Thyroid

Failure
Diseases of the :
Thyroid (primary hypothyroidism) : 95 %
Pituitary (secondary hypothyroidism) : 4 %
Hypothalamus (tertiary hypothyroidism) : < 1%

Can be associated with the multiple

endocrine failure syndromes

Etiologies of Primary
Hypothyroidism
Autoimmune : most common
Some have lymphocytic infiltration variant

Post surgical thyroidectomy

External radiation
Iodine 131 Rx for hyperthyroidism
Severe prolonged iodine deficiency
Antithyroid meds (such as lithium)
Inherited enzymatic defects
True idiopathic

Symptoms of Hypothyroidism
Cold intolerance
Dyspnea
Anorexia
Constipation
Menorrhagia or amenorrhea
Arthralgias, myalgias
Fatigue
Depression
Irritability
Decreased attention & memory
Paresthesias

Signs Related to
Hypothyroidism
Dry, yellow (carotenemic ) skin
Weight gain (41 % of cases)
Thinning, coarse hair
Myxedema signs (mucopolysaccharide deposition in
tissues) :
Puffy eyelids
Hoarse voice
Dependent edema
Carpal tunnel syndrome

Anemia

Hypothyroidism and Myxedema

Coma : Cardiac Signs
Hypotension
Bradycardia
Pericardial effusion
Low voltage EKG
Prolonged QT interval
Inverted / flattened T waves

EKG of 52 year old

female presenting with
fatigue and weight gain
; her T4 was 2.7 and her
TSH was 40

EKG of same patient

on prior slide after
treatment with T4

Precipitants of Myxedema Coma

Cold exposure
Infection
Pneumonia
Urinary tract infection

Trauma
CNS depressants
Narcotics
Barbiturates, Tranquilizers
General anesthetics

Cerebrovascular accident
Congestive heart failure

Myxedema Coma
Typical Presentation
Usual symptoms & signs of
hypothyroidism, plus :
Hypothermia (80 % of cases)
If temp. is normal, consider infection
present
Hypotension / bradycardia
Hypoventilation / respiratory failure
Ileus
Depressed mental status / coma

Patient with
myxedema coma

Contributing Factors to Coma in

Myxedema Coma
Hypothyroidism itself
Hypercapnia
Hypoxia
Hypothermia
Hypotension
Hypoglycemia
Hyponatremia
Drug (sedative) side effect
+/- sepsis

Lab Studies to Order for

Suspected Myxedema Coma
Stat glucose (because of altered mental status)
Pulse oximetry (ABG usually indicated)
CBC, Lytes, BUN, creat., calcium
T4RAI, T3RU, TSH
Serum cortisol
Liver function tests
Relevant drug / alcohol levels

Emergency Treatment of
Myxedema Coma
O2 +/- intubation / ventilation if resp. failure
Rapid blood glucose check +/- IV D50 +/- naloxone
Hydrocortisone 100 to 250 mg IV
Cautious slow rewarming (warm O2, scalp, groin, &
axilla warm packs, +/- NG lavage)
Thyroxine (T4) 500 mcg IV, then 50 mcg IV q day
Add 25 mcg T3 PO or by NG q 12 h (if T4 to T3
peripheral conversion possibly impaired)
Careful IV fluid rehydration (watch for CHF)

Other Aspects of Treatment for

Myxedema Coma
Search for and treat precipitating cause
Use lower doses of most other meds
(drug metabolism is impaired &
decreased until T4 physiology is
restored)
Follow TSH levels
Should decrease in 24 hours and normalize
by day 7 of Rx

"Mechanical " Symptoms

Associated with Goiter
Frequent :
Dyspnea, dysphagia
Fullness, choking or pressure sensation in neck
Less common :
Acute respiratory failure
Superior vena cava syndrome
Esophageal varices
Uncommon but reported :
New onset asthma, phrenic nerve paralysis, Horner's
syndrome, chylothorax, neck abscess, sleep apnea

70 year old male with a substernal goiter causing tracheal compression

Causes of Airway Distress Due

to Thyroid Disease
Preoperative :
Direct tracheal deviation & compression
Intrathyroid bleeding causing tracheal compression
Tracheal invasion by anaplastic cancer
Bleeding into trachea
Resp. failure from pulmonary metastases of thyroid cancer
Postoperative :
Wound hematoma
Laryngeal edema
Bilateral vocal cord paralysis
Tracheomalacia

Thyroid Emergencies
Summary
Important to remember interpretation of
thyroid function tests to avoid overdiagnosis
Keep high index of suspicion for "apathetic
thyrotoxicosis" in the elderly
Usual "ABC" care & correction of temperature
are important aspects of emergency care for
both thyroid storm & myxedema coma
Consider thyroid disease in differential Dx for
upper airway symptoms

Thyroid disease in
Pregnancy

Hypothyroidism in pregnancy may be difficult to

diagnose
Signs and symptoms overlap with common
pregnancy complaints
Among pregnant hypothyroid patients
33% have few or no symptoms
33% have moderate symptoms
33% have classical presentation of hypothyroidism

Maternal thyroid deficiency has been linked to

reduced fetal neuropsychological development

Hypothyroidism: Maternal
and Fetal Risks
Maternal
Fetal
Miscarriages
SGA
PIH
IUGR
Preterm delivery
Prematurity
Postpartum hemorrhage Transient
Hypothyroidism

Thyroid Disease in
Pregnancy
US Endocrine Society recommends

thyroid function screening for all

pregnant women
Clinical studies demonstrated mental
defects in children of mothers with
untreated hypothyroidism during
pregnancy
Haddow et al NEJM. August, 1999

Thyroid disease in the

Neonate
A. Atypical maturation of newborn
thyroid function
retarded development of HPT axis
delayed maturation of thyroid gland
and hormone synthesis
thyroid hormone biosynthetic defects
abnormal thyroid binding proteins

NACB Guideline 2.3

Thyroid Testing of Pregnant
Patients

Both TSH and free T4 estimate test should

be used to assess thyroid status and

monitor L-T4 therapy in pregnant patients
Trimester-specific reference intervals
should be used when reporting thyroid test
values for pregnant patients
The reference intervals should be
appropriate for the iodine intake of the
population in question

TSH & hCG Changes during Pregnancy

From: Glinoer et al. JCEM 71 : 276 (1990)

20
.

50

hCG

40

TSH

15
.

TSH Norm a l
mU /L Range

30

hCG
IU /Lx10

10
.

20

05
.
00
.1

10
0

10

15

20

25

W eeks Gestation

30

35

40

T T 4 & F T 4 C hanges during G estation

From: Glinoer et al. JCEM 71 : 276 (1990)

1.6

14

TBG

3.5
3.0

1.4 12
Total
T4

FT4
ng/dl

T BG

2.5

Free
T4

1.0

2.0

0.8

1.5
40

10

15
20
25
W eeks G estation

30

35

Reference Ranges for

Thyroid tests in Pregnancy
T4 FT4 TSH
(ug/dl) (ng/dl) (mU/L)
0.7 - 2.0 0.3
1st trimester 8.0 - 17.1
- 4.5
2nd trimester 8.0 - 17.8 0.5 - 1.6 0.5 - 4.6
3rd trimester 8.0 - 20.1 0.5 - 1.6 0.8 - 5.2
Quest Laboratories

Clinical Guideline for treating

hypothyroidism before and during
pregnancy
Encourage adherence with L-T4 replacement

therapy before conception

Monitor TSH before conception and during 1st
trimester
Increase L-T4 dosage in athyreotic patients by
25 -50% when pregnancy is confirmed
Monitor TSH every 6-8 weeks during pregnancy
Reinstate pre-pregnancy L-T4 dosage
immediately following delivery

Thyroid Cancer
Approximate frequency of malignant thyroid tumours
Papillary carcinoma (including mixed papillary 75%
and follicular
Follicular carcinoma

16%

Medullary Carcinoma

5%

Undifferentiated carcinomas

3%

Miscellaneous (e.g. lymphoma, fibrosarcoma, 1%

squamous cell ca, teratoma, & metastatic ca)

Discovery
William Stewart Halsted
Late 19th Century
Prominent American Surgeon

Cancer Incidence and Deaths

Estimated- U.S. 2005
Organ System
Lung
Colon
Rectum
Pancreas
Breast
Stomach
Thyroid
Prostate
30,050

New CasesDeaths
172,570
163,510
104,95056,290
42,0007,000
32,18031,800
212,93040,870
24,00014,000
25,6901,490
232,090

Types
Papillary Carcinoma
80%

Follicular Carcinoma
15%

Medullary Carcinoma
3%

Anaplastic Carcinoma

Risk Factors
Radiation

High dose x-rays or radioactive fallout

Family History

Goiters or Colon Growths

Mutated RET gene

Gender

Females

Iodine Levels
Seafood/Shellfish Consumption

Molecular Level
Medullary Carcinoma
Mutation in RET gene

Papillary Carcinoma
Mutated RET, RAS, or BRAF gene
BRAF when not radiation caused
RET when no radiation

Anaplastic Carcinoma
RhoB tumor suppresor

Papillary Carcinoma
Usually presents as a nodule that is firm, solitary, cold on isotope

scan, and usually solid on thyroid US

In MNG, the cancer is usually a dominant nodule that is larger,
firmer and different from the rest of the gland
10% of papillary ca present with enlarged cervical nodes
Grows very slowly and remains confined to the thyroid gland and
local lymph nodes for many years.
In later stages they can spread to the lung
Death usually from local disease or lung metastases
May convert to undifferentiated carcinoma
Many of these tumours secrete thyroglobulin which can be used as
a marker for recurrence or metastasis of the cancer

Follicular Carcinoma
Differs from follicular adenoma by the presence of capsular or

vascular invasion
More aggressive than papillary ca and can spread either by local
invasion of lymph nodes or by blood vessel invasion with distant
metastases to bone or lung
Death is due to local extension or to distant bloodstream metastasis
with extensive involvement of bone, lungs & viscera
These tumours often retain the ability to concentrate RAI
A variant of follicular carcinoma is the Hurthle cell carcinoma.
These tumours behave like follicular cancer except that they rarely
take up RAI
Thyroglobulin secretion by follicular carcinoma can be used to follow
the course of the disease

Management of Papillary and

Follicular Carcinoma
Patients are classified into low risk and high risk groups
The low risk group includes patients under age 45 with primary

lesions under 1cm and no evidence of intra- or extraglandular

spread. Lobectomy is adequate therapy for these patients.
All other patients are considered high risk and require total
thyroidectomy. Modified neck dissection is indicated if there is
lymphatic spread.
Surgery is usually followed by RAI ablation therapy
Patient is placed on L-thyroxine suppressive therapy
Regular F/U with thyroglobulin level, thyroid US, whole body scan
etc.

Medullary Carcinoma
A disease of the C cells (parafollicular cells)
More aggressive than papillary or follicular carcinoma but not as aggressive as

undifferentiated thyroid cancer

It extends locally, and may invade lymphatics and blood vessels
Calcitonin and CEA are clinically useful markers for DX and F/U
80% of medullary ca are sporadic and the rest are familial. There are 4 familial
patterns:

FMTC without endocrine disease

MEN 2A: medullary ca + pheochromocytoma + hyperparathyroidism
MEN 2B: medullary ca + pheochromocytoma + multiple mucosal neuromas
MEN 2 with cutaneous lichen amyloidosis

The familial syndromes are associated with mutations in the ret proto-oncogene (a

receptor protein kinase gene on chrom. 10)

Dx is by FNA bx. Pt needs to be screened for other endocrine abnormalities found in
MEN 2. Family members need to be screened for medullary ca and MEN 2 as well.

Undifferentiated (Anaplastic)
Carcinoma
This tumour usually occurs in older patients with a long history of

goitre in whom the gland suddenlyover weeks or monthsbegins

to enlarge and produce pressure symptoms, dysphagia, or vocal
cord paralysis.
Death from massive local extension usually occurs within 6-36
months
These tumours are very resistant to therapy

Treatment
Surgery
Chemotherapy
Radioactive Iodine Therapy
Thyroid Hormone Therapy
External Radiation Therapy
RS5444

Stats
1% of all cancers
Very high survival rates
Many treatment options

(Not
actually)

1 in 111 (.9%) lifetime risk

Terima kasih
ASS WR WB