DISORDERS OF THE THYROID

GLAND

Presenter: IMCC MIJARES

 THYROID
- Produces two related hormones, thyroxine
(T4) and triiodothyronine (T3)

- Autoimmune disorders of the thyroid gland

can stimulate overproduction of thyroid
hormones (thyrotoxicosis)

- It can cause glandular destruction and

hormone deficiency (hypothyroidism)
 ANATOMY AND DEVELOPMENT
- Greek thyreos, shield, plus eidos, form

- It consists of two lobes connected by an

isthmus

- It is located anterior to the trachea between

the cricoid cartilage and the suprasternal
notch
- It is 12–20 g in size, highly vascular, and soft in
consistency.

- Four parathyroid glands are located posterior

to each pole of the thyroid

- Recurrent laryngeal nerves traverse the lateral

borders of the thyroid gland
- It develops from the floor of the primitive
pharynx during the third week of gestation.

- The developing gland migrates along the

thyroglossal duct

- Thyroid hormone synthesis normally begins at

about 11 weeks’ gestation.
- It consists of numerous spherical follicles
composed of thyroid follicular cells that
surround secreted colloid
REGULATION OF THE THYROID AXIS
- Thyroid hormones act via negative feedback
predominantly through thyroid hormone
receptor β2 (TRβ2) to inhibit TRH and TSH
production

- Hypothalamic TRH stimulates pituitary

production of TSH, in turn, stimulates thyroid
hormone synthesis and secretion
Thyroid stimulating hormone
- Secreted by the thyrotrope cells of the anterior
pituitary

- Pivotal role in control of the thyroid axis

- Serves as the most useful physiologic marker of

thyroid hormone action

- The “set-point” in this axis

- It is released in a pulsatile manner and
exhibits a diurnal rhythm; its highest levels
occur at night.

- Peak TSH secretion occurs ~15 min after

administration of exogenous TRH.

- Dopamine, glucocorticoids, and somatostatin

suppress TSH
 THYROID HORMONE SYNTHESIS, METABOLISM,
AND ACTION

Thyroid hormone synthesis:

- Thyroglobulin (Tg): large iodinated glycoprotein

- After secretion into the thyroid follicle, Tg is

iodinated on tyrosine residues

- Reuptake of Tg into the thyroid follicular cell

allows proteolysis and the release of newly
synthesized T4 and T3.
Iodine Metabolism and Transport:

- Iodide uptake is a critical first step in thyroid

hormone synthesis

- It is mediated by NIS, which is expressed at the

basolateral membrane of thyroid follicular cells

- Pendrin, located on the apical surface of the

thyroid cells, mediates iodines efflux into the
lumen
Organification, Coupling, Storage, and Release:
- After iodide enters the thyroid, it is trapped
and transported to the apical membrane of
thyroid follicular cells

- It involves TPO and hydrogen peroxide

produced by dual oxidase (DUOX) and DUOX
maturation factor (DUOXA)

- The iodotyrosines in Tg are then coupled via an

ether linkage in a reaction that is also catalyzed
by TPO.
- After coupling, Tg is taken back into the thyroid
cell, where it is processed in lysosomes to
release T4 and T3.

- Uncoupled mono- and diiodotyrosines (MIT,

DIT) are deiodinated by the enzyme
dehalogenase, thereby recycling any iodide
that is not converted into thyroid hormones.
 THYROID HORMONE TRANSPORT AND
METABOLISM
Serum Binding Proteins:
- Thyroxine binding protein (TBG) has high
affinity for thyroid hormones (T4 > T3), it
carries about 80% of the bound hormones

- Albumin binds up to 10% of T4 and 30% of T3

-Transthyretin (TTR) carries about 10% of t4 but

little of T3
THYROID HORMONE ACTION
 HYPOTHYROIDISM
- CONGENITAL HYPOTHYROIDSIM

- AUTOIMMUNE HYPOTHYROIDISM

- IATROGENIC HYPOTHYROIDISM

- SECONDARY HYPOTHYROIDISM
 CONGENITAL HYPOTHYROIDISM
• It occurs in about 1 in 4000 newborns

• It may be transient, especially if the mother has TSH-R

blocking antibodies or has received antithyroid drugs,
but permanent hypothyroidism occurs in the majority.

• Thyroid gland dysgenesis in 80–85%

• Inborn errors of thyroid hormone synthesis in 10–15%

• TSH-R antibody-mediated in 5%
• The developmental abnormalities are twice as
common in girls

• Mutations are being increasingly identified,

but most remain idiopathic
 Clinical manifestations
• The majority of infants appear normal at birth
and <10% are diagnosed based on clinical
features:
- Prolonged jaundice, feeding problems,
hypotonia, enlarged tongue, delayed bone
maturation, and umbilical hernia.

• Other congenital malformations, especially

cardiac, are four times more common

• Permanent neurologic damage results if

treatment is delayed.
 Diagnosis and Treatment
• Neonatal screening programs have been
established.

• T4 is instituted at a dose of 10–15 μg/kg per day,

and the dose is adjusted by close monitoring of
TSH levels

• T4 requirements are relatively great during the

first year of life, and a high circulating T4 level is
usually needed to normalize TSH.
 AUTOIMMUNE HYPOTHYROIDISM
• Associated with a goiter (Hashimoto’s, or goitrous
thyroiditis) or, at the later stages of the disease, minimal
residual thyroid tissue (atrophic thyroiditis)

• The mean annual incidence rate is up to 4 per 1000

women and 1 per 1000 men.

• It is more common in certain populations, such as the

Japanese

• The mean age at diagnosis is 60 years

• The prevalence of overt hypothyroidism increases with age

 Pathogenesis
• HLA-DR polymorphisms are the best
documented genetic risk factors for
autoimmune hypothyroidism, especially HLA-
DR3, -DR4, and -DR5 in Caucasians.

• A gene on chromosome 21 may be

responsible for the association between
autoimmune hypothyroidism and Down’s
syndrome.
• The female preponderance is most likely due
to sex steroid effects on the immune response

• Environmental susceptibility factors are poorly

defined at present

• A high iodine intake and decreased exposure

to microorganisms in childhood
• The thyroid lymphocytic infiltrate is composed
of activated CD4+ and CD8+ T cells as well as
B cells

• Local T cell production of cytokines may

render thyroid cells more susceptible to
apoptosis mediated by death receptors
• In Hashimoto’s thyroiditis, there is a marked
lymphocytic infiltration of the thyroid with
germinal center formation, atrophy of the
thyroid follicles accompanied by oxyphil
metaplasia, absence of colloid, and mild to
moderate fibrosis.

• In atrophic thyroiditis, the fibrosis is much

more extensive, lymphocyte infiltration is less
pronounced, and thyroid follicles are almost
completely absent.
 Clinical Manifestations
• Onset is insidious

• Hashimoto’s thyroiditis may present because of

goiter rather than the symptom.

• Goiter may not be large, but it is usually irregular

and firm in consistency

• Rarely associated with pain.

• It may be associated with signs or symptoms
of other autoimmune diseases, particularly
vitiligo, pernicious anemia, Addison’s disease,
alopecia areata, and type 1 diabetes mellitus.
 IATROGENIC HYPOTHYROIDISM
• Common cause of hypothyroidism

• Often detected by screening before symptoms

develop

• In the first 3–4 months after radioiodine

treatment, transient hypothyroidism may
occur due to reversible radiation damage
• Iodine deficiency is responsible for endemic goiter
and cretinism but is an uncommon cause of adult
hypothyroidism

• Mild hypothyroidism after subtotal thyroidectomy

• Chronic iodine excess can also induce goiter and

hypothyroidism

• Iodine excess is responsible for the hypothyroidism

that occurs in up to 13% of patients treated with
amiodarone and lithium
 SECONDARY HYPOTHYROIDISM
• Usually diagnosed in the context of anterior
pituitary hormone deficiencies

• TSH levels may be low, normal, or even slightly

increased

• It due to secretion of immunoactive but

bioinactive forms of TSH
 Treatment
Clinical Hypothyroidism:
• Daily replacement dose of levothyroxine is
usually 1.6 μg/kg body weight (typically 100–
150 μg), ideally taken at least 30 min before
breakfast

• Adult patients under 60 years old without

evidence of heart disease may be started on
50–100 μg levothyroxine (T4) daily.
• TSH responses should be measured about 2
months after instituting treatment or after any
subsequent change in levothyroxine dosage.

• Patients may not experience full relief from

symptoms until 3–6 months after normal TSH
levels are restored.

• Adjustment of levothyroxine dosage is made in

12.5- or 25-μg increments if the TSH is high;
decrements should be made if the TSH is
suppressed.
• Follow-up measurement of TSH is
recommended at annual intervals and may be
extended to every 2–3 years if a normal TSH is
maintained over several years

• In patients of normal body weight who are

taking ≥200 μg of levothyroxine per day, an
elevated TSH level is often a sign of poor
adherence to treatment.
• Such patients often have normal or high
unbound T4 levels despite an elevated TSH

• Patients who miss a dose can be advised to

take two doses of the skipped tablets at once.
Subclinical Hypothyroidism
• It refers to biochemical evidence of thyroid
hormone deficiency in patients who have few
or no apparent clinical features of
hypothyroidism

• No universally accepted recommendations for

the management of subclinical
hypothyroidism
• Levothyroxine is recommended if the patient
is a woman who wishes to conceive or is
pregnant, or when TSH levels are above 10
mIU/L

• When TSH levels are below 10 mIU/L,

treatment should be considered when
patients have suggestive symptoms of
hypothyroidism, positive TPO antibodies, or
any evidence of heart disease
• Treatment is administered by starting with a
low dose of levothyroxine (25–50 μg/d) with
the goal of normalizing TSH.

• If levothyroxine is not given, thyroid function

should be evaluated annually.
 Special treatment considerations
• Women with a history or high risk of
hypothyroidism should ensure that they are
euthyroid prior to conception and during early
pregnancy

• Thyroid function should be evaluated

immediately after pregnancy is confirmed

• Every 4 weeks during the first half of the

pregnancy, with less frequent testing after 20
weeks’ gestation
• The levothyroxine dose may need to be increased
by up to 50% during pregnancy, with a goal TSH
of less than 2.5 mIU/L during the first trimester
and less than 3.0 mIU/L during the second and
third trimesters.

• After delivery, thyroxine doses typically return to

prepregnancy levels.

• Pregnant women should be counseled to

separate ingestion of prenatal vitamins and iron
supplements from levothyroxine by at least 4 h.
• Elderly patients may require 20% less
thyroxine than younger patients

• Starting dose of levothyroxine is 12.5–25 μg/d

with similar increments every 2–3 months
until TSH is normalized.
 Myedema coma
• 20–40% mortality rate

• There may be a history of treated hypothyroidism with poor

compliance, or the patient may be previously undiagnosed.

• Myxedema coma almost always occurs in the elderly

• Precipitated by factors that impair respiration, such as drugs

(especially sedatives, anesthetics, and antidepressants),
pneumonia, congestive heart failure, myocardial infarction,
gastrointestinal bleeding, or cerebrovascular accidents.

• Sepsis should also be suspected.

• Exposure to cold may also be a risk factor.

• Hypoventilation, leading to hypoxia and
hypercapnia, plays a major role in pathogenesis

• Hypoglycemia and Dilutional hyponatremia also

contribute

• Clinical manifestations include reduced level of

consciousness, sometimes associated with
seizures, as well as the other features of
hypothyroidism

• Hypothermia can reach 23°C (74°F)

• Levothyroxine can initially be administered as a single
IV bolus of 500 μg, which serves as a loading dose

• It is usually continued at a dose of 50–100 μg/d.

• If suitable IV preparation is not available, the same

initial dose of levothyroxine can be given by
nasogastric tube (although absorption may be impaired
in myxedema).

• Liothyronine (T3) intravenously or via nasogastric tube,

in doses ranging from 10 to 25 μg every 8–12 h.
• Excess liothyronine has the potential to
provoke arrhythmias

• Combine levothyroxine (200 μg) and

liothyronine (25 μg) as a single, initial IV bolus
followed by daily treatment with
levothyroxine (50–100 μg/d) and liothyronine
(10 μg every 8 h)

• External warming is indicated only if the

temperature is <30°C,
• Parenteral hydrocortisone (50 mg every 6 h) should be
administered

• Any precipitating factors should be treated

• Ventilatory support with regular blood gas analysis is

usually needed during the first 48 h

• Hypertonic saline or IV glucose may be needed if there

is severe hyponatremia or hypoglycemia

• Hypotonic IV fluids should be avoided

• Sedatives should be avoided if possible or used in

reduced doses.
 THYROTOXICOSIS
• State of thyroid hormone excess

• Hyperthyroidism is the result of excessive

thyroid function
 GRAVES’ DISEASE
• It accounts for 60–80% of thyrotoxicosis.

• The prevalence varies among populations, reflecting genetic factors

and iodine intake

• High iodine intake is associated with an increased prevalence

• Occurs in up to 2% of women but is one-tenth as frequent in men.

• Rarely begins before adolescence and typically occurs between 20

and 50 years of age

• It also occurs in the elderly.

 Pathogenesis
• As in autoimmune hypothyroidism, a
combination of environmental and genetic
factors, including polymorphisms in HLA-DR,
the immunoregulatory genes CTLA-4, CD25,
PTPN22, FCRL3, and CD226, as well as the
TSH-R

• Stress is an important environmental factor

• Smoking is a minor risk factor for Graves’ disease
and a major risk factor for the development of
ophthalmopathy

• Sudden increases in iodine intake

• Threefold increase in the occurrence of Graves’

disease in the postpartum period

• During the immune reconstitution phase after

highly active antiretroviral therapy (HAART) or
alemtuzumab treatment.
• The hyperthyroidism of Graves’ disease is
caused by TSI that are synthesized in the
thyroid gland as well as in bone marrow and
lymph nodes.

• TPO antibodies occur in up to 80% of cases

and serve as a readily measurable marker of
autoimmunity.

• Cytokines appear to play a major role in

thyroid-associated ophthalmopathy.
 Clinical Manifestations
• Depends on the severity of thyrotoxicosis, the
duration of disease, individual susceptibility to
excess thyroid hormone, and the patient’s age
• The earliest manifestations of ophthalmopathy
are usually a sensation of grittiness, eye
discomfort, and excess tearing.

• One third of patients have proptosis

• In severe cases, proptosis may cause corneal

exposure and damage

• Periorbital edema, scleral injection, and chemosis

are also frequent
• The most serious manifestation is
compression of the optic nerve at the ape of
the orbit, leading to leading to papilledema
and peripheral field defects

• If left untreated, permanent loss of vision

• The “NO SPECS” scoring system to evaluate

ophthalmopathy
Thyroid dermopathy
• Occurs in <5% of patients

• Presence of moderate or severe ophthalmopathy.

• Most frequent over the anterior and lateral

aspects of the lower leg (pretibial myxedema)

• Skin changes can occur at other sites particularly

after trauma
• It a noninflamed, indurated plaque with a deep
pink or purple color and an “orange skin”
appearance

• Nodular involvement

• Rarely extend over the whole lower leg and foot,

mimicking elephantiasis

Thyroid acropachy
• refers to a form of clubbing found in <1% of
patients with Graves’ disease
 Treatment
• The main antithyroid drugs are the
thionamides, such as propylthiouracil,
carbimazole and the active metabolite of the
latter, methimazole

• All inhibit the function of TPO, reducing

oxidation and organification of iodide
• Propylthiouracil inhibits deiodination of T4 → T3

• Half-life of this drug (90 min)

• Hepatotoxicity

• It has limited indications for its use to the first

trimester of pregnancy, the treatment of thyroid
storm, and patients with minor adverse reactions
to methimazole.

• Monitoring of liver function tests is

recommended
• The initial dose of carbimazole or methimazole is
usually 10–20 mg every 8 or 12 h, but once-daily
dosing is possible after euthyroidism is restored

• Propylthiouracil is given at a dose of 100–200 mg every

6–8 h, and divided doses are usually given throughout
the course

• The starting dose of antithyroid drugs can be gradually

reduced (titration regimen) as thyrotoxicosis improves.

• High doses may be given combined with levothyroxine

supplementation (block-replace regimen) to avoid
drug-induced hypothyroidism
• Thyroid function tests and clinical manifestations
are reviewed 4–6 weeks after starting treatment

• Dose is titrated based on unbound T4 levels

• Most patients do not achieve euthyroidism until

6–8 weeks after treatment is initiated

• The usual daily maintenance doses of antithyroid

drugs in the titration regimen are 2.5–10 mg of
carbimazole or methimazole and 50–100 mg of
propylthiouracil.
• Maximum remission rates (up to 30–60% in some
populations) are achieved by 12–18 months for
the titration regimen and by 6 months for the
block-replace regimen

• Younger patients, males, smokers, and patients

with severe hyperthyroidism and large goiters are
most likely to relapse when treatment stops

• All patients should be followed closely for relapse

during the first year after treatment and at least
annually thereafter
• The common minor side effects of antithyroid
drugs are rash, urticaria, fever, and arthralgia
(1–5% of patients).

• Rare but major side effects include hepatitis

(propylthiouracil; avoid use in children) and
cholestasis (methimazole and carbimazole); an
SLE-like syndrome; and, most important,
agranulocytosis (<1%).
• Propranolol (20–40 mg every 6 h) or longer-
acting selective β1 receptor blockers such as
atenolol may be helpful to control adrenergic
symptoms

• Beta blockers are also useful in patients with

thyrotoxic periodic paralysis

• Anticoagulation with warfarin should be

considered in all patients with atrial fibrillation
who often spontaneously revert to sinus rhythm
with control of hyperthyroidism
• Radioiodine causes progressive destruction of
thyroid cells and can be used as initial treatment
or for relapses after a trial of antithyroid drugs.

• There is a small risk of thyrotoxic crisis after

radioiodine, which can be minimized by
pretreatment with antithyroid drugs for at least a
month before treatment

• Antecedent treatment with antithyroid drugs

should be considered for all elderly patients or
for those with cardiac problems to deplete
thyroid hormone stores before administration of
radioiodine.
• Carbimazole or methimazole must be stopped
3–5 days before radioiodine administration to
achieve optimum iodine uptake

• Propylthiouracil appears to have a prolonged

radioprotective effect and should be stopped
for a longer period before radioiodine is given,
or a larger dose of radioiodine will be
necessary.
• A practical strategy is to give a fixed dose
based on clinical features, such as the severity
of thyrotoxicosis, the size of the goiter
(increases the dose needed), and the level of
radioiodine uptake (decreases the dose
needed).

• 131I dosage generally ranges between 370

MBq (10 mCi) and 555 MBq
• Patients need to avoid close, prolonged contact
with children and pregnant women for 5–7 days

• Rarely, there may be mild pain due to radiation

thyroiditis 1–2 weeks after treatment.

• Hyperthyroidism can persist for 2–3 months

before radioiodine takes full effect.

• β-adrenergic blockers or antithyroid drugs

• Persistent hyperthyroidism can be treated
with a second dose of radioiodine, usually 6
months after the first dose.

• The risk of hypothyroidism after radioiodine

depends on the dosage but is at least 10–20%
in the first year and 5% per year thereafter
• Pregnancy and breast-feeding are absolute
contraindications to radioiodine treatment

• Patients can conceive safely 6 months after

treatment

• Severe ophthalmopathy: use of prednisone,

40 mg/d, at the time of radioiodine treatment,
tapered over 6–12 weeks
• Subtotal or near-total thyroidectomy is an
option for patients who relapse after
antithyroid drugs and prefer this treatment to
radioiodine.

• Some experts recommend surgery in young

individuals, particularly when the goiter is
very large.
• Careful control of thyrotoxicosis with
antithyroid drugs, followed by potassium
iodide (3 drops SSKI orally tid), is needed prior
to surgery to avoid thyrotoxic crisis and to
reduce the vascularity of the gland

• Major complications of surgery: bleeding,

laryngeal edema, hypoparathyroidism, and
damage to the recurrent laryngeal nerves
• Titration regimen of antithyroid drugs should
be used to manage Graves’ disease in
pregnancy

• Propylthiouracil should be used in early

gestation

• Should be limited to the first trimester and

then maternal therapy should be converted to
methimazole (or carbimazole) at a ratio of 15–
20 mg of propylthiouracil to 1 mg of
methimazole
• Antithyroid drugs given to the mother can be
used to treat the fetus and may be needed for 1–
3 months after delivery, until the maternal
antibodies disappear from the baby’s circulation.

• The postpartum period is a time of major risk for

relapse of Graves’disease.

• Breast-feeding is safe with low doses of

antithyroid drugs.
-.
• Graves’ disease in children is usually managed
with methimazole or carbimazole (avoid
propylthiouracil), often given as a prolonged
course of the titration regimen.

• Surgery or radioiodine may be indicated for

severe disease
Thyrotoxic crisis, or thyroid storm
• Rare and lifethreatening exacerbation of
hyperthyroidism, accompanied by fever, delirium,
seizures, coma, vomiting, diarrhea, and jaundice

• mortality rate due to cardiac failure, arrhythmia,

or hyperthermia is as high as 30%, even with
treatment

• Usually precipitated by acute illness (e.g., stroke,

infection, trauma, diabetic ketoacidosis), surgery
(especially on the thyroid), or radioiodine
treatment of a patient with partially treated or
untreated hyperthyroidism.
• Large doses of propylthiouracil (500–1000 mg
loading dose and 250 mg every 4 h) should be
given orally or by nasogastric tube or per rectum

• Methimazole can be used in doses up to 30 mg

every 12 h

• One hour after the first dose of propylthiouracil,

stable iodide is given to block thyroid hormone
synthesis via the Wolff-Chaikoff effect

• Propranolol should also be given to reduce

tachycardia and other adrenergic manifestations
(60–80mg PO every 4 h; or 2 mg IV every 4 h).
• Short-acting IV esmolol can be used to
decrease heart rate while monitoring for signs
of heart failure.

• Additional therapeutic measures include

glucocorticoids (e.g., hydrocortisone 300 mg
IV bolus, then 100 mg every 8 h), antibiotics if
infection is present, cooling, oxygen, and IV
fluids.
OPTHALMOPATHY
• Requires no active treatment when it is mild or
moderate

• General measures include meticulous control of

thyroid hormone levels, cessation of smoking,
and an explanation of the natural history of
ophthalmopathy.

• Discomfort can be relieved with artificial tears

(e.g., 1% methylcellulose), eye ointment, and the
use of dark glasses with side frames
• Periorbital edema may respond to a more upright
sleeping position or a diuretic

• Severe ophthalmopathy, with optic nerve

involvement or chemosis resulting in corneal
damage, is an emergency requiring joint
management with an ophthalmologist

• Pulse therapy with IV methylprednisolone (e.g.,

500 mg of methylprednisolone once weekly for 6
weeks, then 250 mg once weekly for 6 weeks) is
preferable to oral glucocorticoids, which are used
for moderately active disease.
• Orbital decompression can be achieved by removing
bone from any wall of the orbit, thereby allowing
displacement of fat and swollen extraocular muscles.

THYROID DERMOPATHY
• Does not usually require treatment

• Surgicalremoval is not indicated.

• If necessary, treatment consists of topical, high-

potency glucocorticoid ointment under an occlusive
dressing.

• Octreotide may be beneficial in some cases

THYROIDITIS
 Acute Thyroiditis
• Rare

• It is the suppurative infection of the thyroid.

• In children and young adults, the most common

cause is piriform sinus

• A long-standing goiter and degeneration in a

thyroid malignancy are risk factors in the elderly.
 Clinical Manifestations
• Presents with: thyroid pain, often referred to
the throat or ears, and a small, tender goiter
that may be asymmetric.

• Fever, dysphagia, and erythema over the

thyroid are common, as are systemic
symptoms of a febrile illness and
lymphadenopathy.
• The erythrocyte sedimentation rate (ESR) and
white cell count are usually increased, but thyroid
function is normal

• FNA biopsy shows infiltration by

polymorphonuclear leukocytes

• Culture of the sample can identify the organism

• Antibiotic treatment is guided initially by Gram

stain and, subsequently, by cultures of the FNA
biopsy
• Surgery may be needed to drain an abscess

• Tracheal obstruction, septicemia,

retropharyngeal abscess, mediastinitis, and
jugular venous thrombosis may complicate
 Subacute thyroiditis
• also termed de Quervain’s thyroiditis, granulomatous
thyroiditis, or viral thyroiditis

• Mumps, Coxsackie, Influenza, Adenoviruses, and

Echoviruses

• Can mimic pharyngitis

• The peak incidence occurs at 30–50 years

• Women are affected three times more frequently than

men.
• It has a characteristic patchy inflammatory
infiltrate with disruption of the thyroid
follicles and multinucleated giant cells within
some follicles

• The follicular changes progress to granulomas

accompanied by fibrosis.

• Finally, the thyroid returns to normal, usually

several months after onset.
 Clinical manifestations
• The onset is acute, severe, and without
obvious antecedent
• Presents with a painful and enlarged thyroid,
sometimes accompanied by fever
• Malaise and symptoms of an upper
respiratory tract infection may precede the
thyroid-related features by several weeks
 Laboratory evaluation
• Thyrotoxic phase - T4 and T3 levels are increased;
TSH is suppressed

• The white blood cell count may be increased

• Thyroid antibodies are negative

• FNA biopsy is used to distinguish unilateral

involvement from bleeding into a cyst or
neoplasm.
 Treatment
• Large doses of aspirin (e.g., 600 mg every 4–6 h)
or NSAIDs

• Glucocorticoids should be given

• The usual starting dose is 40–60 mg of

prednisone

• Dose is gradually tapered over 6–8 weeks

• Thyroid function should be monitored every
2–4 weeks using TSH and unbound T4 levels.

• Levothyroxine replacement may be needed if

the hypothyroid phase is prolonged, but doses
should be low enough (50–100 μg daily) to
allow TSH mediated recovery.
 Silent Thyroiditis
• Painless thyroiditis

• Occurs in patients with underlying autoimmune

thyroid disease

• Has a clinical course similar to that of subacute

thyroiditis

• Occurs in up to 5% of women 3–6 months after

pregnancy (postpartum Thyroiditis)
• Brief phase of thyrotoxicosis lasting 2–4 weeks,
followed by hypothyroidism for 4–12 weeks, and
then resolution

• Associated with the presence of TPO antibodies

antepartum

• Normal ESR and the presence of TPO antibodies

• Propranolol, 20–40 mg three or four times daily.

• Thyroxine replacement may be needed for the
hypothyroid phase but should be withdrawn
after 6–9 months

• . Annual follow-up

• Recur in subsequent pregnancies.

 Drug induced thyroiditis
• Cytokines such as IFN-α or IL-2

• IFN-α, which is used to treat chronic hepatitis

B or C and hematologic and skin malignancies

• Most common in women with TPO antibodies

prior to treatment.
 Chronic thyroiditis
• Most common clinically apparent cause of
chronic thyroiditis is Hashimoto’s thyroiditis

• Riedel’s thyroiditis is a rare disorder that typically

occurs in middle-aged women

• It presents with an insidious, painless goiter with

local symptoms due to compression of the
esophagus, trachea, neck veins, or recurrent
laryngeal nerves
• Dense fibrosis disrupts normal gland architecture
and can extend outside the thyroid capsule.

• The goiter is hard, nontender, often asymmetric,

and fixed

• Requires open biopsy as FNA biopsy is usually

inadequate.

• Treatment is directed to surgical relief of

compressive symptoms
 SICK EUTHYROID SYNDROME
(NONTHYROIDAL ILLNESS)
• Release of cytokines such as IL-6.

• Decrease in total and unbound T3 levels (low T3

syndrome) with normal levels of T4 and TSH.

• The magnitude of the fall in T3 correlates with

the severity of the illness.

• Very sick patients may exhibit a dramatic fall in

total T4 and T3 levels (low T4 syndrome)
• Another key factor in the fall in T4 levels is altered
binding to TBG

• TSH levels may range from <0.1 mIU/L in very ill

patients, especially with dopamine or
glucocorticoid therapy, to >20 mIU/L during the
recovery phase of SES.

• Any severe illness can induce changes in thyroid

hormone levels, but certain disorders exhibit a
distinctive pattern of abnormalities.
Useful features to consider include
• previous history of thyroid disease and thyroid
function tests,

• evaluation of the severity and time course of the

patient’s acute illness,

• Medications that may affect thyroid function or

thyroid hormone levels,

• Measurements of rT3 together with unbound

thyroid hormones and TSH.
 Treatment
• Monitoring the patient’s thyroid function tests
during recovery, without administering thyroid
hormone, unless there is historic or clinical
evidence suggestive of hypothyroidism
 THYROID FUNCTION IN PREGNANCY
Five factors alter thyroid function in pregnancy:

1. Transient increase in hCG during the first trimester, which

stimulates the TSHR;

2. Estrogen-induced rise in TBG during the first trimester, which is

sustained during pregnancy;

3. Alterations in the immune system, leading to the onset,

exacerbation, or amelioration of an underlying autoimmune
thyroid disease

4. Increased thyroid hormone metabolism by the placenta

5. Increased urinary iodide excretion, which can cause impaired

thyroid hormone production in areas of marginal iodine
sufficiency.
• Women with a precarious iodine intake (<50
μg/d) are most at risk of developing a goiter
during pregnancy or giving birth to an infant
with a goiter and hypothyroidism.

• The WHO recommends a daily iodine intake of

250 μg during pregnancy and prenatal
vitamins should contain 150 μg per tablet.
• The rise in circulating hCG levels during the
first trimester is accompanied by a reciprocal
fall in TSH that persists into the middle of
pregnancy

• hCG-induced changes in thyroid function can

result in transient gestational hyperthyroidism
that may be associated with hyperemesis
gravidarum
• Subclinical hypothyroidism occurs in 2% of
women, but overt hypothyroidism is present
in only 1 in 500

• Targeted TSH testing for hypothyroidism

• Thyroid hormone requirements are increased

by up to 50% during pregnancy in
levothyroxine-treated hypothyroid women
 GOITER AND NODULAR THYROID
DISEASE
• Goiter refers to an enlarged thyroid gland

• Biosynthetic defects and iodine deficiency are

associated with reduced efficiency of thyroid
hormone synthesis, leading to increased TSH

• Nodular disease is characterized by the

disordered growth of thyroid cells, often
combined with the gradual development of
fibrosis.
• It is common, occurring in about 3–7% of
adults when assessed by physical examination.

• Using ultrasound, nodules are present in up to

50% of adults, with the majority being <1 cm
in diameter.

• May be solitary or multiple,

• May be functional or nonfunctional.

 Diffuse Nontoxic (Simple) Goiter
• Diffuse enlargement of the thyroid occurs in
the absence of nodules and hyperthyroidism

• Simple goiter, the absence of nodules, or

• Colloid goiter, presence of uniform follicles

that are filled with colloid
• Most commonly caused by iodine deficiency
(endemic goiter)

• Thyroid enlargement in teenagers (juvenile

goiter)

• More common in women than men

• In iodine-deficient areas, thyroid enlargement

reflects a compensatory effort to trap iodide and
produce sufficient hormone under conditions in
which hormone synthesis is relatively inefficient
• TSH levels are usually normal or only slightly
increased

• Iodide appears to have direct actions on

thyroid vasculature and may indirectly affect
growth through vasoactive substances such as
endothelins and nitric oxide.
 Clinical Manifestations and Diagnosis
• If thyroid function is preserved, most goiters
are asymptomatic

• Symmetrically enlarged, nontender, generally

soft gland without palpable nodules

• Pemberton’s sign refers to symptoms of

faintness with evidence of facial congestion
and external jugular venous obstruction when
the arms are raised above the head,
• Thyroid function tests should be performed in all
patients with goiter to exclude thyrotoxicosis or
hypothyroidism.

• A low TSH with a normal free T3 and free T4,

particularly in older patients, suggests the
possibility of thyroid autonomy or undiagnosed
Graves’ disease, (subclinical thyrotoxicosis)

• TPO antibodies may be useful to identify patients

at increased risk of autoimmune thyroid disease.
 Treatment
• Iodine replacement induces variable regression of
goiter in iodine deficiency,

• Surgery is rarely indicated for diffuse goiter. Exceptions

include documented evidence of tracheal compression
or obstruction of the thoracic inlet

• Surgery should be followed by replacement with

levothyroxine, with the aim of keeping the TSH level at
the lower end of the reference range to prevent
regrowth of the goiter.
 Nontoxic Multinodular Goiter
• Occurs in up to 12% of adults

• More common in women than men and

increases in prevalence with age

• More common in iodine-deficient regions

• Typically wide variation in nodule size

• Histology reveals a spectrum of morphologies
ranging from hypercellular regions to cystic
areas filled with colloid. Fibrosis is often
extensive, and areas of hemorrhage or
lymphocytic infiltration may be seen

• Most nodules within an MNG are polyclonal in

origin, suggesting a hyperplastic response to
locally produced growth factors and cytokines
 Clinical Manifestations
• Asymptomatic and euthyroid

• An individual notices an enlargement in the neck, or as

an incidental finding on imaging.

• Symptomatic MNGs are usually extraordinarily large

and/or develop fibrotic areas that cause compression.

• Sudden pain is usually caused by hemorrhage into a

nodule

• Hoarseness, reflecting laryngeal nerve involvement

 Diagnosis
• Thyroid architecture is distorted, and multiple
nodules of varying size

• Pemberton’s sign

• A TSH level should be measured to exclude

subclinical hyper- or hypothyroidism, but thyroid
function is usually normal.

• Tracheal deviation is common, but compression

must usually exceed 70% of the tracheal diameter
• Pulmonary function testing : inspiratory stridor

• CT or MRI

• Barium swallow (extent of esophageal compression)

• Ultrasonography can be used to identify which nodules

should be biopsied based on sonographic features and
size

• For nodules with more suspicious imaging

characteristics biopsy is recommended when ≥1 cm.
 Treatment
• managed conservatively

• If levothyroxine is used, it should be started at

low doses (50 μg daily) and advanced gradually
while monitoring the TSH level to avoid excessive
suppression.

• Contrast agents and other iodine-containing

substances should be avoided because of the risk
of inducing the Jod-Basedow effect
• When acute compression occurs,
glucocorticoid treatment or surgery may be
needed.

• Surgery remains highly effective

 Toxic Multinodular Goiter
• presence of functional autonomy in toxic MNG

• Subclinical hyperthyroidism or mild

thyrotoxicosis.

• Elderly

• Atrial fibrillation or palpitations, tachycardia,

nervousness, tremor, or weight loss
• Recent exposure to iodine, from contrast dyes or
other sources, may precipitate or exacerbate
thyrotoxicosis.

• TSH level is low.

• Uncombined T4 level may be normal or minimally

increased; T3 is often elevated to a greater
degree than T4

• Thyroid scan: heterogeneous uptake with

multiple regions of increased and decreased
uptake
• Ultrasound imaging should be performed to
assess the presence of discrete nodules
corresponding to areas of decreased uptake
(“cold” nodules).

• If present, FNA may be indicated

• The cytology results, if indeterminate or

suspicious, may direct the therapy to surgery
 Treatment
• Radioiodine is generally the treatment of
choice

• Surgery provides definitive treatment of

underlying thyrotoxicosis as well as goiter.

• Patients should be rendered euthyroid using

an antithyroid drug before operation
 Hyperfunctioning Solitary Nodule
• Toxic adenoma is a solitary, autonomously
functioning thyroid nodule

• acquired somatic, activating mutations in the

TSH-R

• Thyrotoxicosis is usually mild

• subnormal TSH level

• presence of the thyroid nodule

• absence of clinical features suggestive of Graves’

disease or other causes of thyrotoxicosis

• Thyroid scan provides a definitive diagnostic test

• Demonstrating focal uptake in the

hyperfunctioning nodule and diminished uptake
in the remainder of the gland, as activity of the
normal thyroid is suppressed.
• activating mutations in either the TSH-R or the
GSα subunit genes are identified in >90% of
patients with solitary hyperfunctioning
nodules.
 Treatment
• Radioiodine ablation is usually the treatment
of choice

• Relatively large radioiodine doses (e.g., 370–

1110 MBq [10–29.9 mCi] 131I) have been
shown to correct thyrotoxicosis in about 75%
of patients within 3 months
• Surgical resection is also effective and is usually
limited to enucleation of the adenoma or
lobectomy, thereby preserving thyroid function
and minimizing risk of hypoparathyroidism or
damage to the recurrent laryngeal nerves.

• Medical therapy using antithyroid drugs and beta

blockers can normalize thyroid function but is not
an optimal long-term treatment
 BENIGN NEOPLASMS
• common (5–10% adults)

• Many are mixed cystic/solid lesions on ultrasound

and may appear spongiform reflecting the
pathology of macrofollicular structure

• Majority of solid nodules (whether hypo-, iso-, or

hyperechoic) are also benign

• FNA, with ultrasound guidance, is the diagnostic

procedure of choice to evaluate thyroid nodules
• Pure thyroid cysts, <2% of all thyroid growths,
consist of colloid and are benign as well.

• Cysts frequently recur, even after repeated

aspiration, and may require surgical excision if
they are large.

• Ethanol ablation to sclerose the cyst has been

used successfully for patients who are
symptomatic
 THYROID CANCER
• Most common malignancy of the endocrine system

• Derived from the follicular epithelium are classified

according to histologic features

• Differentiated tumors, such as papillary thyroid cancer

(PTC) or follicular thyroid cancer (FTC), are often
curable

• Anaplastic thyroid cancer (ATCis aggressive, responds

poorly to treatment, and is associated with a bleak
prognosis.
 Pathogenesis
RADIATION:
• Increases the risk of benign and malignant
thyroid nodules, is associated with multicentric
cancers, and shifts the incidence of thyroid
cancer to an earlier age group

• Radiation from nuclear fallout

• Children seem more predisposed to the effects of

radiation than adults
TSH and GROWTH FACTORS:

• Higher serum TSH levels, even within normal

range, are associated with increased thyroid
cancer risk in patients with thyroid nodules
 WELL DIFFERENTIATED THYROID CA
PAPILLARY THYROID CA
• Most common type of thyroid cancer

• 70–90% of well-differentiated thyroid malignancies

• 25% of thyroid glands at autopsy

• Characteristic cytologic features include psammoma

bodies, cleaved nuclei with an “orphan-Annie”
appearance caused by large nucleoli, and the
formation of papillary structures.
• Multifocal and to invade locally within the thyroid
gland as well as through the thyroid capsule and into
adjacent structures in the neck.

• Propensity to spread via the lymphatic system but can

metastasize hematogenously as well, particularly to
bone and lung.

• If identified in the early stages (>80% stages I or II) and

have an excellent prognosis

• Mortality is markedly increased in stage IV disease,

especially in the presence of distant metastases (stage
IVC), but this group comprises only about 1% of
patients.
FOLLICULAR THYROID CA
• More common in iodine-deficient regions

• Tends to spread by hematogenous routes leading

to bone, lung, and central nervous system
metastases

• less favorable than for PTC

• Poor prognostic features include distant

metastases, age >50 years, primary tumor size >4
cm, Hurthle cell histology, and the presence of
marked vascular invasion.
 Evaluation of Thyroid Nodule
• Palpable thyroid nodules are found in about
5% of adults

• Nodules are more common in iodine-deficient

areas, in women, and with aging

• >1 cm in diameter
 Treatment
SURGERY
• All well-differentiated thyroid cancers should be surgically excised

• Preoperative sonography

• If cytology is diagnostic for thyroid cancer, bilateral surgery should

be done.

• If malignancy is identified pathologically after lobectomy,

completion surgery is recommended unless the tumor is T1a or is a
minimally invasive follicular cancer

• Near total thyroidectomy is preferable in almost all patients

TSH SUPPRESSION THERAPY
• Most tumors are TSH-responsive

• Levothyroxine suppression of TSH is a mainstay of thyroid

cancer treatment

• The degree of TSH suppression should be individualized

based on a patient’s risk of recurrence.

• For patients at low risk of recurrence, TSH should be

suppressed into the low but detectable range (0.1–0.5
mIU/L).

• If subsequent surveillance testing indicates no evidence of

disease, the TSH target may rise to the lower half of the
normal range
• For patients at high risk of recurrence or with
known metastatic disease, TSH levels should
be kept to <0.1 mIU/L if there are no strong
contraindications to mild thyrotoxicosis.

• In this instance, unbound T4 must also be

monitored to avoid excessive treatment.
RADIOIODINE TREATMENT
• Postsurgical radioablation of the remnant thyroid
eliminates residual normal thyroid, facilitating the use
of Tg determinations and radioiodine scanning for long-
term follow-up.

• Radioiodine uptake is determined primarily by

expression of the NIS and is stimulated by TSH,
requiring expression of the TSHR.

• The retention time for radioactivity is influenced by the

extent to which the tumor retains differentiated
functions such as iodide trapping and organification.
• Not all patients benefit from radioiodine therapy.

• Neither recurrence nor survival rates are

improved in stage I patients with T1 tumors (≤2
cm) confined to the thyroid.

• However, in higher risk patients (larger tumors,

more aggressive variants of papillary cancer,
tumor vascular invasion, presence of large-
volume lymph node metastases), radioiodine
reduces recurrence and may increase survival.
131I THYROID ABLATION AND TREATMENT
• Radioiodine is administered after iodine
depletion (patient follows a low-iodine diet for
1≤2 weeks) and in the presence of elevated
serum TSH levels to stimulate uptake of the
isotope into both the remnant and potentially
any residual tumor.

• A WBS following radioiodine treatment is used

to confirm the 131I uptake in the remnant and
to identify possible metastatic disease.
 Follow-Up Whole-Body Thyroid Scanning
and Thyroglobulin Determinations
• Serum thyroglobulin is a sensitive marker of
residual/ recurrent thyroid cancer after
ablation of the residual postsurgical thyroid
tissue.

• Vast majority of papillary thyroid cancer

recurrences are in cervical lymph nodes

• Neck ultrasound should be performed about 6

months after thyroid ablation
• In low-risk patients who have no clinical
evidence of residual disease after ablation and
a basal Tg <1 ng/mL on levothyroxine, an
rhTSH-stimulated Tg level should be obtained
6–12 months after ablation, without WBS

• If stimulated Tg levels are low (<1 ng/mL) and,

ideally, undetectable, the risk of recurrence is
<5% at 5 years.
• The use of WBS is reserved for patients with
known iodine-avid metastases or those with
elevated serum thyroglobulin levels and
negative imaging with ultrasound, chest CT,
and neck cross sectional imaging who may
require additional 131I therapy.

• External beam radiotherapy is also used to

treat specific metastatic lesions, particularly
when they cause bone pain or threaten
neurologic injury
 ANAPLASTIC AND OTHER FORMS OF
THYROID CANCER
• Poorly differentiated and aggressive cancer

• Prognosis is poor

• Die within 6 months of diagnosis

• Chemotherapy has been attempted with multiple

agents, including anthracyclines and paclitaxel, but it is
usually ineffective

• External beam radiation therapy can be attempted and

continued if tumors are responsive.
THYROID LYMPHOMA
• Lymphoma in the thyroid gland often arises in the
background of Hashimoto’s thyroiditis

• Diffuse large-cell lymphoma is the most common

type in the thyroid

• Often highly sensitive to external radiation

• Surgical resection should be avoided as initial

therapy
MEDULLARY THYROID CARCINOMA
• Sporadic or familial and accounts for about 5% of
thyroid cancers

• Three familial forms of MTC: MEN 2A, MEN 2B,

and familial MTC without other features of MEN

• MTC is more aggressive in MEN 2B than in MEN

2A, and familial MTC is more aggressive than
sporadic MTC

• Elevated serum calcitonin provides a marker of

residual or recurrent disease
• All patients with MTC should be tested for RET
mutations

• The management of MTC is primarily surgical

• These tumors do not take up radioiodine.

• External radiation treatment and

chemotherapy may provide palliation in
patients with advanced disease