LECTURE 8

THYROIDITIS
THYROID CANCER

THYROIDITIS

DEFINITION
Inflammatory disorders of the
thyroid gland

Classification
American Thyroid Association :
1. Acute/subacute thyroiditis:
A. Suppurative
B. Subacute (non-supurative)
a) Granulomatous thyroiditis (De Quervains)
b) Limphocytic subacute thyroiditis (painless )

2. Chronic thyroiditis:
A. Chronic lymphocytic thyroiditis (Hashimotos)
B. Fibroinvasive thyroiditis (Riedels)
C. Chronic suppurative thyroiditis
(tuberculosis,siphillis)
D. Chronic non-suppurative thyroiditis

SUBACUTE GRANULOMATOUS
THYROIDITIS
(DE QUERVAINS)

Etiopathogenesis

most likely due to viral infection

Viral particles NOT identified within the thyroid
episodes often follow upper respiratory infections
associated with falling postconvalescent viral titers of
various viruses (influenza, adenovirus, mumps, and
coxsackievirus)
Histologic features:
Destruction of the thyroid parenchyma
Large phagocytic cells
Giant cells

CLINICAL FEATURES

Fever
Malaise
Soreness in the neck (which may extend up to the
angle of the jaw, or toward the ear lobes)
Simptoms of hyperthyroidism may occur:

Palpitations
Agitation
Sweat

On physical examination
the gland is tender (the patient objects to pressure upon
it)
No evidence of abscesses formation (no redness, no
local heat)
Clinical signs of toxicity (Tachycardia, tremor)

LABORATORY FINDINGS
ESR is markedly elevated (as high as

100mm/1h);
Initially: Thyrotoxicosis profile (elevated T3, T4,
low TSH, low RAIU)
Thyroid autoantibodies usually not detectable
As the disease progresses: T3, T4 will drop,
TSH rises, symptoms of hypothyroidism occur
RAIU will rise later, reflecting recovery of the
gland after the insult

DIFFERENTIAL DIAGNOSIS
Pain:
Acute hemorrhage into a thyroid cyst, nodule, or neoplasm
Infectious thyroiditis
Radiation-induced thyroiditis
Trauma-induced thyroiditis
Thyrotoxicosis:
Graves disease
Toxic adenoma
Toxic multinodular goiter

TREATMENT
Most cases: symptomatic treatment (acetaminophen
500mg every 6 hours)
If pain and fever are disabling short course of
NSAID or glucocorticoid therapy (Prednisone, 2030mg initially, with gradually diminishing dosage for 34 weeks) may be necessary
Levothyroxine is indicated during hypothyroid phase
In 5-10% of cases permanent hypothyroidism may
occur and long-life thyroxine therapy is required

COURSE & PROGNOSIS

Subacute thyroiditis usualy resolves
completely and spontaneously over
weeks/months.
Occasionally: the disease starts to
resolve, then suddenly get worse;
Rarely: the course may extend over
several years, with repeated episodes of
inflammatory disease and remission.

CHRONIC THYROIDITIS

Hashimotos thyroiditis
The most common cause of hypothyroidism and
goiter in the USA
The major cause of goiter in children and young
adults
The major cause of idiopathic myxedema (the
end stage of Hashimotos thyroiditis)
Riedels thyroiditis is considered a variant of
Hashimotos thyroiditis, characterized by
extensive fibrosis outside the gland; the thyroid
body is enlarged, with a stony consistence

ETIOLOGY & PATHOGENESIS

autoimmune disease
Tg-Ab
TPO-Ab
TSH-receptor-blocking Ab (TRAb-block) found in patients with atrophic thyroiditis

1-4 % of the general population (F:M=9:1).

Familial character, may be associated with other autoimmune diseases (pernicious
anemia, vitiligo, miasthenia gravis, adrenal insufficiency, hypoparathyroidism)

peak of incidence:

during puberty and

menopause.

Histologic features: heavy infiltation of lymphocytes destruction of normal thyroidal

architecture; lymphoid follicles and germinal centers may be formed;

Destruction of the gland fall in the serum T4 and T3 and rise in TSH .

SYMPTOMS AND SIGNS

Goiter in an euthyroid patient / in a patient with mild
hypothyroidism
mild,
diffuse,
firm
tendency to lobulation;
polinodular (some cases)

Atrophic thyroid gland

No pain
Ocular changes may occur
Signs of other autoimmune disease (eg vitiligo)

Chronic autoimmune thyroiditis and vitiligo

LABORATORY FINDINGS

High titer of thyroid autoantibodies

Circulating T3, T4 may be normal or low;
normal/elevated TSH
Episodes of transient thyrotoxicosis may occur:
elevated T3, T4, inhibited TSH
RAIU: normal/ low
Scintigramm: inhomogenous uptake
Negative inflammatory tests (ESR, fibrinogen are
normal);
FNAB: large infiltration of lymphocytes and Hurtle cells
Ultrasound examination reveals hypoechogeneicity
with pseudomicronodular pattern.

DIFFERENTIAL DIAGNOSIS
From other causes of nontoxic goiter by
the presence of antithyroid antibodies
From Graves disease by scintigraphy
Increased uptake in Graves
Decreased uptake in Hashimoto

COMPLICATIONS
Hypothyroidism : becomes permanent in
15% of cases
Lymphoma of the thyroid gland (rapid
growth of the thyroid despite thyroxine
therapy)
Hashimotos thyroiditis may coexist with
differentiated carcinoma of the thyroid
(thyroid mass that fails to regress when
maximum tolerated dose of T4 is given)

TREATMENT
positive thyroid antibody test does not

require therapy
In patients with goiter and/or
hypothyroidism thyroxine therapy
Large goiter surgery
During transient thyrotoxicosis
Prednisone 30-40mg/day
If ophthalmopathy is present Treat as if
Graves disease is present

COURSE & PROGNOSIS

Without therapy goiter/hypothyroidism
myxedema

Transient thyrotoxicosis (with low RAIU and

white scintiscan)

Because Hashimotos thyroiditis may be a

part of multiple autoimmune diseases
monitor for other autoimmune diseases

OTHER FORMS OF
THYROIDITIS

Acute abscesses
very rare disease (between 1900-1985

only 253 cases)

local pain, tenderness, swelling
warmth and redness of the overlying skin
needle aspiration will confirm bacterial
infection, identifying the germ
treatment: antibiotics, incision, drainage

Lymphocytic subacute
thyroiditis (painless)

autoimmune disease

represents 5-20% of the hyperthyroidism cases

affecting predominately women

concerning all groups of age

frequently occurs postpartum

frequently relapses.
hyperthyroidism phenomena without:
infiltrative ophthalmopathy
pretibial myxedema
mild intensity and transient character;
the thyroid gland:
normal or slightly enlarged,
painless,
firm consistency.
Differential diagnosis

Gravesdisease;

Subacute granulocytic thyroiditis (De Quervains) ;

Chronic lymphocytic thyroiditis (Hashimotos) ;

Thyrotoxicosis factitia.

Chronic fibrous thyroiditis (Riedl)

rare disease - fibrous proliferative process :
goiter - hard consistency and
Extended fibrosis (mediastinum, retroperitoneum)

clinical features :

dyspnea,
dysphagia,
disphonia

treatment surgery followed by replacement therapy

(levo-thyroxine);
Tamoxiphene seems to be benefic in limiting fibrosis
prognosis - poor.

THYROID CANCER

 most frequent endocrine neoplasia in the

general population:
0.1-3.7/100 000 in men;
0.4-9.6/100 000 in women.

incidence of occult (unknown) cancer

1-30 % based on necroptic studies

Classification of thyroid tumors

histologic and
anatomo-clinical

Anatomo-clinical classification
benign tumors-adenomas:
- follicular;
- non-follicular;

malignant tumors:
- carcinomas:
papillary/
folliculary/
folliculo-papillary/
medulary/
undifferentiated/
epidermoid;
- others :
lymphoma /
sarcoma/
fibrosarcoma/

Clinical manifestations
Non-specific at the beginning
Diagnostic suspicion is represented by rapid
enlargement of a:
single thyroid nodule
Dominant nodule in a polynodular
goiter.

Thyroid nodule
intrathyroid process, combined with
influence of extrathyroid factors:
variations of iodine intake;
cervical irradiation;
heredity; association to autoimmune thyroid
diseases
(e.g. association of Hashimotos thyroiditis to thyroid
lymphoma).

Clinical suspicion of malignity

intense

MEN syndrome in

family
Rapid tumoral growth
Very hard nodule
Fixation on surrounding
structures
Vocal cords paralysis
Local lymphadenopathy
Presence of metastasis

moderate
age under 20 or age
over 60
history of cervical
irradiation
male gender
uncertain fixation on
surrounding tissues
diameter more than
3-4 cm.

Thyroid cancer differential diagnosis

thyroid adenoma
cysts
localised Hashimotos thyroiditis
peri-thyroid lymphadenopathy
peri-thyroid lipoma
carotidian aneurism
laryngocele.

Laboratory tests
Not of great value:
Normal thyroid hormone level is the rule.
There are not specific tumoral markers,
excepting calcitonin (marker for medullary
carcinoma).
serum thyroglobulin - useful only to
appreciate tumoral relapse after surgery.
Carcinoembryonic antigen - present in 20%
of cases of medular carcinoma.

Imaging studies

1. Ultrasonography
May detect:
cysts > 2 mm diameter

nodules > 3 mm diameter

cervical adenopathy

 cyst

 Multiple nodules and fibrous tissue

Benign nodule

Malignant nodule

Cyst (although cysts more irregular structure;

than 3 cm diameter could
be malignant in 8-12% of
cases);

bad defined limits;

Hyper- / isoechoic with

hypoechogenicity;

hypoechoic halo;

intratumoral punctiform

peripheral calcifications; calcifications.

Benign nodule

Malignant nodule

Microcalcifications

2. Gammagraphy
Using Iodine123 and Technetium 99
Thyroid nodules:
hypofunctional or cold
isofunctional or warm
hyperfunctional or hot.

Cannot efficiently evaluate nodules < 1 cm diameter.

Gammagraphy

2. Gammagraphy
Neoplasic lesions - cold (usually)
Cold benign lesions - represented by:
cysts
focal thyroiditis
intraparenchymatous hemorrhage.

Tumors:
cold for iodine,
could be hot for Tc99.

3. Conventional cervical X-ray

May reveal calcifications - frequent in :
papillary and
medullary carcinoma

4. Fine needle aspiration biopsy

Best method to differentiate
Benign from

Malignant nodules
Aspiration sample is
expressed onto a clean slide,
stained with Giemsas / Papanicolaus stain and
cytologically examined.

For small / deep nodules: ultrasound guidance

Useful method:
to evacuate the liquid content of a cyst
to introduce sclerogenic substances into the cyst.

Results interpretation limits:

follicular carcinoma - similitude with
follicular adenoma
autoimmune thyroiditis - similar to anaplasic
carcinoma
previous ATD therapy leads to histological
changes (follicular carcinoma-like aspect).

Anatomo-clinical forms
1.
2.
3.
4.
5.
6.
7.

Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
Occult carcinoma
Metastasis
Other: Lymphoma, sarcoma, teratoma

1. Papillary carcinoma

 the most frequent thyroid cancer (3050%).

50% of cases < 40 yrs of age

Radioiodine uptake - present in 50-75% of
cases.

 Metastasis:
ganglionar - even if the primary tumour is not
palpable ( high lymphophilia)
hematogenic dissemination - late, sometimes
after years of evolution.

rarely a cause of death (even if lung

metastasis are present).

cause of death - conversion to anaplastic

carcinoma.

Papillary carcinoma lymph nodes

metastasis

2. Follicular carcinoma
25% of thyroid cancer.

maximum incidence - 40-60 years.

may be indistinguishable from:
normal thyroid structure or
benign follicular adenoma.

 blood vessels invasion with distant

metastasis to:
bone or
lung.

Radioiodine - present in about 75 % of

cases.
These 2 forms of cancer may associate,
resulting different clinical profiles.

3. Anaplastic carcinoma
older patients.
the most aggressive form:
invading the cervical region and
producing metastasis (frequently).

Anaplastic carcinoma- cold area

4. Medullary carcinoma
develops on the C parafollicular cells,
after 40 years of age.

Medullary carcinoma
Sporadic (80 % of cases):
frequent at 50-60 years of age;

Familial:
within MEN (Multiple Endocrine
Neoplasia) type II
non MEN- the less aggressive

MEN type II:

IIa: - medullary carcinoma
- pheochromocytoma
- hyperparathyroidism

IIb:

the most aggressive form

- medullary carcinoma
- bilateral pheochromocytoma
- marfanoid phenotype.

Characteristics:
histologic large amounts of amyloid

carcinoembryonic antigen- presence

calcitonin level increase:
basal and
after stimulation test with:
- pentagastrin or
- alcohol.

Medullary cancer
has a slow evolution,
Produces adenopathy,
does not uptake iodine,
does not respond to external radiotherapy.

5. Occult thyroid carcinoma

represented by multiple
microscopic lesions

6. Secondary cancer
(thyroid metastasis)

represents 2-4 % of thyroid cancer.

cancers that may produce metastasis in the

thyroid gland are :
mammary,
pulmonary,
renal,
malignant melanoma

7. Other malignant thyroid tumors

primary lymphomas -may associate to
Hashimotos thyroiditis;

disseminated lymphomas;
sarcomas - very rare;
malignant teratomas.

Thyroid lymphoma

Management of thyroid
cancer

Papillary and follicular carcinoma

Lobectomy for small (<2cm) papillary and follicular carcinoma / total

thyroidectomy for larger lesions or extrathyroidal extension

Postoperative iodine scan and liothyronine 50-100mcg/d for 3 mo;
Medication is stopped for 2 weeks and low iodine diet is required
Whole body scintiscan
If residual tissue is evident, radioactive iodine therapy is effective treatment;
Levo-thyroxine therapy is then administered in a dose able to maintain TSH
at a low level;
Follow-up intervals of 6-12 mo: clinical examination, serum thyroglobulin,
chest x-ray, thyroid ultrasound, MRI;
If abnormalities are found, scintiscan should be repeated as described
above;
In case of positive result: therapeutic dose of radioactive iodine is
necessary;
In case of negative scintiscan, local excision or local x-ray therapy is
required

Medullary carcinoma
Total thyroidectomy followed by thyroxine

therapy
The marker for recurrent cancer is serum
calcitonin or serum carcinoembryonic antigen
(CEA)
If elevated serum calcitonin persists after
total thyroidectomy MRI of the neck/chest,
selective venous catheterization and
sampling for serum calcitonin are necessary
No radioactive iodine therapy; chemotherapy is
not effective

Anaplastic carcinoma
Does not fix radioactive iodine
external radiotherapy (cobaltotherapy)
chemotherapy (Doxorubicin 75mg/sqm,
every 3 weeks)

the results are transient.

Prognosis is very poor

Primary thyroid lymphoma:

treatment

radiotherapy
chemotherapy
corticotherapy.

Prognosis in differentiated
carcinomas
Good

Worse

Age

<40

>40

Gender

Tumor size

<4cm

>4cm

Local spread

No invasion

Local invasion

Initial surgery

lobectomy

I131 therapy

Total
thyroidectomy
Yes

T4 therapy

Yes

No

No

Prognosis in medullary carcinoma

Good survival in intrathyroidal small

lesions
Impaired survival in cases with
extrathyroidal invasion

Prognosis in anaplastic
carcinoma :
:
very poor prognosis
almost all are dead within 3
years.