THYROID GLAND d

Diseases Of Thyroid Gland

An

OMC LECTURE
Thyroid gland
 The thyroid gland is one of the
largest endocrine glands.
 The thyroid gland is located
immediately below the larynx
and anterior to the upper part of
the trachea. It weighs about
15- 20g.

 It consists of 2 lateral lobes

connected by a narrow band of
thyroid tissue called the isthmus.

 The isthmus usually overlies the

region from the 2nd to 4th
tracheal cartilage.
 4 tiny parathyroid glands located
posteriorly at each pole of thyroid
gland.
 Hormone secreted-
 Thyroxine(T4)
 Tri iodothyronine (T3)
 Reverse T3
 Calcitonin
HISTOLOGY
 The lobes of the thyroid
contain many hollow,
spherical structure called
follicles, which are the
functional units of the
thyroid gland.

 Between the follicles there

are C cells, which secrete
calcitonin.

 Each follicle is filled with a

thick sticky substance
called colloid.
 The major constituent of colloid is a
large glycoprotein called thyroglobulin.

 Unlike other endocrine glands, which

secretes their hormones once they are
produced, the thyroid gland stores
considerable amount of the thyroid
hormones in the colloid until they are
needed by the body.
Iodine Metabolism
 Raw material, essential for thyroid
synthesis
 Source-
 Sea foods, milk, iodized salt.

 Dailyreq- 100-200
microgram/day
 From the total amount of Iodine entering
the ECF, 20% enters the thyroid
gland and 80% excreted in urine.
 Thyroid contain 95% of total iodine
 Thyroid gland stores enough hormone
to maintain euthyroid state for 3
months.
 Daily secretion-
 93% Thyroxine (3-8 mgm/dl)
 7% T3(0.15 mgm/dl)
 T3 is 4 times more potent than T4
REGULATION OF THYROID
HORMONE SECRETION
 Plasma thyroid hormone binding
proteins
 ~99.97% of plasma T4 and 99.7% of T3
are non-covalently bound to proteins.
 Thyroxine Binding Globulin(TBG) is the
major binding protein for T4 and T3. TBG’s
affinity for T4 is ~10-fold greater than for
T3.
 Transthyretin also carries some T4.
 Albumin carries small amounts of T4 and
T3.
Importance of free versus
protein-bound hormone
 Only free T4 and free T3 are
biologically active and regulated by
feedback loops.
 Therefore conditions that alter TBG
levels alter total T4 and T3, but do not
alter free T4 and free T3.
 Pregnancy
 Acute hepatitis
 Chronic liver failure
 PHYSIOLOGICAL EFFECTS OF
THYROID HORMONES
 Metabolic rate and heat production:
◦ ↑ metabolic activities
◦ ↑ O₂ consumption to most metabolically
active tissues
◦ BMR can ↑ by 60 – 100%
◦ Since ↑ metabolism results in ↑ heat
production → thyroid hormone effects is
calorigenic
 Intermediary metabolism:
◦ Modulates rates of many specific reactions
involved in metabolism
Sympathomimetic effect-
 Sympathomimetic: any action similar to one
produced by the sympathetic nervous system
 Thyroid hormone ↑ target cell
responsiveness to catecholamines

The cardiovascular system:

 ↑ the heart’s responsiveness to circulating
catecholamines.
 ↑ heart rate and force of contraction → ↑
CO
 In response to the heat load → peripheral
vasodilation
Laboratory Evaluation and
Imaging Studies of
Function
Thyroid
 Serum T4
 Serum T3
 TSH
 Anti-thyroid antibodies
 Thyroid stimulating Immunoglobulins
 Thyroid uptake and scan
 Thyroid Ultra sound
Serum Thyroxine (T4)

 Measure free T4, not total T4

 Only free T4 is biologically active
◦ Conditions that alter TBG alter total T4 but
not free T4
◦ Pregnancy raises total T4
◦ Chronic liver failure lowers total T4

•High in hyperthyroidism
 Low in hypothyroidism
Serum Triiodothyronine (T3)

 High in hyperthyroidism
 •Low in hypothyroidism
 But generally not worth measuring in
hypothyroidism because T3 is less
sensitive and less specific than the
decrease in free T4

 •Measurement of free T3 is preferable to

total T3.
Serum Thyrotropin (Thyroid
Stimulating Hormone; TSH)
 TSH is LOW in hyperthyroidism
 TSH is HIGH in hypothyroidism

 TSH is the most sensitive screening

test for hyperthyroidism and
primary hypothyroidism
 TSH within the normal range excludes
these diagnoses
Antithyroid
Antibodies
 Antimicrosomal antibodies (thyroid
peroxidase antibodies)
 •Anti-thyroglobulin antibodies
 •Present in ~95% of Hashimoto’s
and
~60% of Graves’ patients at the time
of diagnosis
 •Usually not very helpful in making a
diagnosis or guiding therapy
Thyroid Stimulating
Immunoglobulins

Is present in Graves’

disease
Imaging studies

 •Thyroid US
 •Neck CT
 Diseases Of Thyroid Gland
 DIVIDED INTO:
HYPOTHYROIDISM (Gland destruction)
 Under-production of thyroid hormones
Myxoedema (Gull Disease)
Cretinism
Thyroiditis
HYPERTHYROIDISM
(thyrotoxicosis)
 Over-production of thyroid
hormone
 Grave’s Disease
 Thyrotoxicosis

GOITER- Diffuse and multi-

nodular
NEOPLASTIC PROCESSES
 Beningn
 Hypothyroidism

Resulting from reduced circulating level of T3 and T4

 Causes of Hypothyroidism
◦ Primary
1. Dietary Iodide deficiency
2. Iodine defficiency
3. Autoimmune (Hashimoto´s Thyroiditis)
4. Drugs: amiodarone, lithium, thiocyanates, phenylbutazone, sulfonylureas
5. Iatrogenic- Surgical removal of the thyroid gland and radiation treatment
6. Congenital (1 in 3000 to 4000)
7. Infiltrative disorders

◦ Secondary
 Pituitary gland destruction
 Isolated TSH deficiency
 Bexarotene(anti cancer drug) treatment
 Hypothalamic disorders
 Hypothyroidism appears in 3 forms-
 1. Myxoedema (Gull Disease)
 2. Cretinism
 3. Thyroiditis
 Myxoedema (Gull Disease)
 hypothyroidism developing in adults,
deposition of excess mucoprotein in skin of forearm,
Leg, feet
 Features-
 Enlargement of thyroid gland (Goiter)
 Lack of interest in daily household chores.
 slowing of physical and mental activity
 generalized fatigue, dull look
 apathy
 overweight
  CO
 - shortness of breath
 -  exercise capacity
  Sympathetic activity
 - constipation
 -  sweating
 Skin-dry, thicken, yellow(carotinemia), cool ( blood flow)
 edema, puffy face, periorbital swelling.
 Ptosis ( drooping of upper eyelid)
 coarse hair
 broadening of facial features
 enlarged tongue
 deepening of voice (telephonic voice)

 Calorigenic action- BMR decreases to 30-40%

 cold-intolerant
 Bone marrow- anemia ( normocytic, normochromic)
 Menstrual irregularities
 Carbohydrate metabolism- Low blood sugar
 Lipid metabolism- Increased serum Cholesterols, TGs, phospholipids

 CNS- Myxedematous madness (psychosis)

 Knee jerk reaction time increased
 Memory loss
Cretinism
 hypothyroidism developing
in infancy/early childhood, due to maternal
iodine deficiency.
 Listless, somnolent, apathetic to play, devoid
of initiatives.

 Features-
 Severe mental retardation (imbeciles-IQ-25-
49)
 Occurs in iodine deficient areas of
world (i.e. Himalayas, China,
Africa)
 Clinical-
Impaired skeletal development
 Impaired CNS development
 Inadequate maternal thyroid hormone prior to fetal thyroid gland
formation  severe mental retardation
 Often deaf and mute
 Dwarfism and stunted growth
 Thick, coars, dry skin
 Protruded abdomen (pot belly-Splanchnomegaly) and enlarged
tongue
 Failure of sexual developments
 Delayed milestones-
 Length of the child fails to increase
 Dentition is delayed
 Delayed sitting up and head holding
 Delayed walking
 Delayed closure of ant fontanels
 Delayed standing up and speech
On the left, a euthyroid 6
year old girl at the
50th height percentile
(105 cm).
On the right, a 17 year old
girl with a height of 100
cm, mental retardation,
myxedema and a TSH of
288 (normal 0.3-5.5).
 (Werner & Ingbar’s The Thyroid, 8th Edition,
page 744.)
Lab Findings-

 IncreasedTSH
 Decreased free T4
 Decreased FT3

 Anti-TPO and anti-Tg Abs (Hashimoto’s)

 Hypothyroidism: Therapy

 L-Thyroxine
(levothyroxine;
T4)
 Goals-
 Alleviate
symptoms
 Normalize TSH
Thyroiditis
Inflammation of thyroid
Types:
 a) Hashimoto thyroiditis

 1) gradual thyroid failure due
to autoimmune destruction of thyroid
 2) 45-65 yrs
 3) 10:1 female
 4) major cause of non endemic goiter in
predominance
children
 5) genetic component- patients with
Turner syndrome have  circulating anti-
thyroid Ab

 Clinical:

 1) progressive depletion of thyroid epithelial cells

 2) replaced with mononuclear cells and fibrosis
 3) comes to clinical attention as painless
enlargement of thyroid with some degree of
hypothyroidism
 4) hypothyroidism progresses slowly
 5) can be preceded by “hashitoxicosis” (transient
hyperthyroidism caused by inflammation
associated with Hashimoto's thyroiditis)
 6) patients at risk in developing
other autoimmune diseases
 7) no cancer risk
 b) Subacute (granulomatous) thyroiditis
 [“ De Quervain thyroiditis”]

 i) occurs less often than Hashimoto

 ii) 30-50 yrs
 iii) female preponderance 5:1
 iv) caused by viral infection (Coxsackie
virus, mumps and adenoviruses)
 v) history of upper respiratory infection just prior
to onset of thyroiditis
 vi) seasonal incidence (summer peak)
 vii) acute or gradual
 viii) painful presentation, radiating to jaw, throat,
ears: especially when swallowing
 ix)inflammation and hyperthyroidism are
transient
x) self limited disease

c) Subacute lymphocytic (painless)

thyroiditis
 i) uncommon
 ii) hyperthyroid presentation
 - may present with any
of signs of hyperthyroidism (no
opthalmopathy, as in Graves disease)
 d) Riedel thyroiditis
 i) fibrosis of thyroid and
neighboring structures
 ii) presents as hard and fixed thyroid
which clinically is similar to CA
Congenital Hypothyroidism
 Prevalence: 1 in 3000 to 4000 newborns

 Cause: Dysgenesis 85%

 Treatment:
◦ Supplemental treatment With Levothyroxine is
“essential” for a normal C.N.S. Development and
prevention of mental retardation
Hyperthyroidism
 Itis a condition resulting from increased level
of circulating FT4 and FT3

 Cause-
 Thyrotoxicosis
 Causes of Thyrotoxicosis:
◦ Primary Hyperthyroidism
1) Grave´s disease( Exopthalmic Goiter)
2) Toxic Multinodular Goiter
3) Toxic adenoma
4) Functioning thyroid carcinoma metastases
5) Activating mutation of TSH receptor
6) Drugs: Iodine excess
Graves disease
Most common cause of
endogenous hyperthyroidism
Characteristics:
 a) hyperthyroidism
 i) diffuse enlargement of thyroid
 ii) lymphocytic infiltration
 b) infiltrative ophthalmopathy
 i) with resultant exophthalmos
 c) localized infiltrative dermopathy
 i) “pretibial myxedema”
 peak incidence 20-40
 female preponderance (7:1)
 familial link

 Pathogenesis:
 a) autoimmune disorder
 b)Thyroid stimulating Ab (Long acting
thyroid stimulator) action like TSH
 c)LATS protectors- prevent inactivation of
LATS
 LATS combine with receptors on thyroid cells plasma
membrane and displace TSH from its binding sites.
 Act via cAMP to cause prolonged action.
 Leads to-
 Increased formation and release of T3,T4
 Increased growth of thyroid gland
 Features
Exopthalmos-
Protrusion of the eye ball with visibility
of sclera between lower lid and cornea.
Due to-
 retro-orbital connective tissue and ocular muscles
are increased
 i)inflammatory edema (cytokines induced)
 ii) T-cell infiltration
 iii) fatty infiltration
 iv)mucopolysaccharide and water
accumulation
 v) these cause eye to bulge
outward
Lid retraction-
Visibility of sclera between
upper lid and cornea
Due to overstimulation of
levator palpebrae superiosis

Calorigenic action-
 BMR ↑ 30%-100%
 Heat intolerance
 Weight loss (thyrotoxic
myopathy)
Lactation ↑
Scanty periods
Vitamine B & C deficiency
CVS- tachycardia, high
output cardiac failure
Thyroid diabetes
CNS- overexcitibility,
tremors,irritability,nervousness
Smooth, moist, warm skin
Flushing of face and hands
 Overgrown nails (acropachy), which may lift off
the nail bed (onycholysis)
Fine soft thinned scalp hair
Generalized itching
(pruritus)
Increased skin
pigmentation
 “Pretibial
Thyrotoxicosis
 Symptoms:
◦ Hyperactivity
◦ Irritability
◦ Dysphoria
◦ Heat intolerance & sweating
◦ Palpitations
◦ Fatigue & weakness
◦ Weight loss with increased appetite
◦ Diarrhea
◦ Polyuria
◦ Sexual dysfunction
 Signs:
◦ Tachycardia
◦ Atrial fibrillation
◦ Tremor
◦ Goiter
◦ Warm, moist skin
◦ Muscle weakness, myopathy
◦ Lid retraction or lag
◦ Gynecomastia
◦ * Exophtalmus
◦ * Pretibial myxedema
Lab findings-

 Suppressed TSH
 Elevated Free T4
 Elevated Free T3
Treatment
: ◦ Reducing thyroid hormone synthesis:
 Antithyroid drugs (Methimazole, Propylthyouracil)
 Radioiodine (131I)
 Subtotal thyroidectomy

◦ Reducing Thyroid hormone effects:

 Propranolol
 Glucocorticoids
 Benzodiazepines

◦ Reducing peripheral conversion of T4 to T3

 Propylthyouracil
 Glucocorticoids
 Iodide
Thyrotoxic crisis or Thyroid storm:
It´s a life-threatening exacerbation of thyrotoxicosis,
acompanied by fever, delirium, seizures, coma,
vomiting, diarrhea, jaundice.
Mortality rate reachs 30% even with treatment

It´s usually precipitated by acute illness, such as:

 Stroke, infection,trauma, diabeic ketoacidosis,

surgery, radioiodine treatment
Thyroid storm
 i) abrupt onset of severe hyperthyroidism

 ii) febrile, tachycardia

 iii) is a medical emergency

- death from cardiac arrhythmias
Goiter
 Diffuse and multinodular
 enlargement of the thyroid
 most common manifestation of thyroid
disease
 most often caused by dietary iodine
deficiency (i.e., impaired synthesis
of thyroid hormone)
 Two types:
 i) endemic
 ii) sporadic

 Endemic goiter (<10% population)

 i) geographic area deficient in iodine
 ii) mountainous areas of world
 - Himalayas, Andes,Alps
 iii) TSH
 iv) can result from ingestion of certain
“goitrogens”- cabbage, cauliflower, Brussels,sprouts, turnips, cassava
 Contain Progoitrin/ Progoitrin activator( anti thyroid agent)
 Prevent incorporation of iodine with
tyrosine.
 Sporadic goiter
 i) less frequent than endemic
 ii) female preponderance
 iii) peak incidence near puberty

• Multinodular goiter
a) recurrent hyperplasia/hypertrophy
b) all simple nontoxic goiters evolve into
multinodular goiters
 c) produce the most extreme thyroid
enlargements, often mistaken for
neoplasm
 d) asymmetrically enlarged thyroid
small % of patients may develop a
hyperfunctioning thyroid (nodule)
resulting in a “toxic multinodular
goiter”
 Plummer syndrome is example without
dermopathy, nor-ophthalmopathy (as in
Graves)

• All goiters may cause “Mass Effects”

◦ a) dysphagia
◦ b) compression of large vessels
◦ c) airway obstruction
Thyroid Neoplasms
 Adenomas
 discrete solitary masses
 derived from follicular epithelium
(i.e., “follicular adenomas”)

NOT transform into malignancy
 Usually present as unilateral painless
mass
 Take up less radioactive iodine compared
to normal thyroid parenchymal cells
 i) “cold” nodules
 ii) ~10% of cold nodules 
malignant
 iii) “hot” nodules rarely 
malignant
 Biopsy is “gold” standard for diagnosis
 Other benign tumors
 a) cysts
 b) lipomas
 c) hemangiomas
 d) dermoid cysts
 e) teratomas (mainly in infants)
•Thyroid Cancer typically appears as a "cold nodule". That is to say, it
appears as a white area or defect in an otherwise black thyroid. A "cold"
area is NOT necessarily cancer. Indeed, most "cold nodules" are benign!
Ultrasound, perhaps followed by biopsy, often plays an important role
in differentiation

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 Thyroid Carcinomas

most appear in adults

papillary CA may present in
childhood
female predominance (early
and middle adult)
 childhood and late adulthood have equal
gender distribution
Most CA are well differentiated:
 a) papillary CA (~80% of cases)
 b) follicular CA ( ~15% of cases)
 c) medullary CA (~5% of cases)
 d) anaplastic CA (< 5% of cases)