Download thyroitis, thyroid cancer

THYROITIS
Definition: inflammatory diseases of the thyroid gland with different etiologic,
biologic, histologic and clinical aspects
CLASSIFICATION
• ACUTE: bacterial, viral
• SUBACUTE: de Quervain’s thryoiditis
• CHRONIC:
• chronic autoimmune thyroidits
• Tuberculous
• Mycotic
• Riedel’s thyroidits
ACUTE BACTERIAL THYROIDITIS
Signs and symptoms
• Fever
• Pain profound and severe
• Dysfagy - 90 % din cazuri
• Dyspnea – 50 %
• spasmodic cough
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Laboratory data
increased ESR
leukocytosis with neutrophilia
Ultrasound: small or large hypoechoic areas
FNB: isolation of germs
Treatment : antibiotics or surgery if an abscess is formed
SUBACUTE ”DE QUERVAIN’S” THYROIDITIS
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Sex ratio F/M: 3,6/1 – 10,6 /1
1 caz TS for 5 cases of Graves disease and for 20 cases of AIT
0,01 % of all hospitalized patients
1,89 % of all patiens hospitalized for thyroid diseases
9,9 % of subjects presenting with thyrotoxicosis
1,52 % of patients investigated by FNB
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ETIOLOGY
probably the disease is a response to a viral infection
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GENETICS
those with HLA-Bw35 have a risk to develop the disease of 8-56.6 %
HLA-Bw35 allows the development of clinical symptoms
it has no relationship with the evolution of the disease
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PATOGENICITY
interleukine 6 produced by monocytes si macrophages determine inflammation
interleukine 2 +TNF  + interferon  determine destructive thyroiditis in 10 % of
cases
VEGF, basic FGF, PDGF determine granulomatous reaction
EGF determines by mitogenic effect the regeneration of the follicles
PATHOLOGY
Follicular disruption with thyroglobulin liberation is responsible for the initial
phase of thyrotoxicosis
granuloma:
• a center of giant cells surrounded by macrophages
• epithelial cells surrounded by a crown of macrophages involved with
antigen presentation
Clinical signs and symptoms
History of viral infection
Painful thyroid
Fever
Dysfagy
Painful thyroid enlargement
Pain irradiates to the ears
Simptoms of thyrotoxicosis
Malaise
Laboratory data
Classical
form
1/3
90 %
90 %
Non classical form
18 %
90 %
50 %
76 %
42 %
Imagery
Important increase of ESR
Hipoechogenicity
generalized
Leukocytosis
disseminated points
FT4 si FT3 increased
Localized hipoechogenicity
Suppressed TSH
Absent Tc 99 m uptake
Increased
thyroglobulin
Transitory Reduced iodine uptake on scintigram
increased antithyroid antibodies
67 Gallium citrat: scintiscan
HLA-Bw 35+
or
Differential diagnosis
Evolution and complications
Cyst with intracystic hemorrhage
Transient hypothyroidism second phase
Tirotoxicosis induced by iodine loading of evolution Recurrent disease
is
(amiodarone)
unpredictable
Thyroid cancer: FNB
Definitive recovery with euthyroidism
Definitive hypothyroidism <1/10
Painless forms
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SUBACUTE THYROIDITIS – TREATMENT
FORME SEVERE:
GLUCOCORTICODS:
Prednisone: 30-40 mg / day at the beginning of the disease with further reduction
of the dosage
Dexametazone: 3-4 mg /zi
MILD FORMS:
Nonsteroid anti inflammatory drugs
TUBERCULOUS THYROIDITIS
Is a very rare disease. Its clinical manifestation may be as a form of milliary
tuberculosis or in most of cases as a form of thyroid nodule. Thyroid ultrasound shows
usually a thyroid nodule with internal necrosis. The only way to make a certain diagnosis
is the fine needle biopsy with identification of BK on smears and culture of BK on
specific medium.
AUTOIMMUNE THYROIDITIS
INCIDENCE
As most of autoimmune diseases autoimmune thyroiditis occurs most frequently
in women with a sex ratio between women and men of 1.5/1 or more.
• 3,5 – 4,5 % of population present autoimmune thyroid diseases
• 4,6 % of women and 1,23 %of men have antithyroid antibodies
• 15 % of women over 60 years
• lymphocytic infiltrations: 6,8 5 of women and 2,7 % of men
• 50 % of those with antithyroid antibodies have TSH > 6 U.I./ml
• 60 % of those with TSH > 6 U.I./ml have anti thyroid antibodies
• 80 % of those with TSH > 10 6 U.I./ml have anti thyroid antibodies
• 5 % of those with TSH > 6 U.I./ml develop overt hypothyroidism each year
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PATOGENY
genetic predisposition
Viral aggression that determine liberation of thyroglobulin and other components
of thyroid cells into circulation leading to antibody formation
excessive iodine supply leading to over iodinated thyroglobulin which becomes
antigenic
GENETIC PREDISPOSITION is confirmed by the following facts:
affected individuals have relatives with autoimmune thyroid diseases
the disease occurs in individual with type DR3 and DR5 HLA which play the
most important role in antigen presentation to immune system by macrophages
it occurs in patients with genetic abnormalities :Turner, Klinefelter, Down
syndrome
it occurs frequently in association with other autoimmune diseases:
multiple autoimune endocrine diseases type I and II (type 1 diabetes mellitus,
adrenal failure, ovarian failure with precocious menopause), autoimmune
hypophysitis Biermer disease , Sjogren’s syndrome, systemic lupus eritematosus,
rheumatoid arthritis , miastenia gravis, interstitial lung disease,
HLA-DR3 si HLA-DR4
ANTIBODIES
THIROIDITIS and other diseases
ANTI-TPO (PEROXIDASE)
ANTI – Tg Ab
Hashimoto’s thyroiditis, Post partum
thyroiditis
Hashimoto’s thyroiditis
TSH -receptor stimulating antibodies
Hashitoxicosis
TGI – thyroid growth immunoglobulins Hashimoto’s thyroiditis with goiter
Thyroid stimulating blocking Ab
TGBI – thyroid
immunoglobulins
growth
Anti T3 –Ab , anti T4 - Ab
Atrophic thyroiditis
“Spontaneous” mixoedema in the adult
blocking Atrophic thyroiditis
“Spontaneous” mixoedema in the adult
May interfere with hormone assessment
Anti pancreatic islet
Diabetes mellitus
Anti salivary ducts
Sjogren’s syndrome
Anti neuro-muscle plate
Miastenia gravis
Anti other endocrine glands: pancreas, Poli immune endocrine disease (PIE):
adrenals, gonads
Type 1: adrenal failure, diabetes mellitus,
mucocutaneous candidiasis
Type 2 : adrenal failure, autoimmune
thyroiditis, autoimmune precocious
ovarian failure (or testicular failure)
Relationship between auto anti thyroid antibodies and
diseases produced by these antibodies
The presence of antithyroid antibodies attracts locally lymphocytic infiltration
that progressively leads to limitation of functional thyroid tissue and thyroid
hypofunction
Formes of autimmune thyroiditis
HASHIMOTO’S thyroiditis: signs and symptoms
• goiter
• metabolic state
• eutiroidism – 80 %
• hipothyroidism – 15 %
• hiperthyroidism – 5 %
• some may have subclinical hypothyrodism with slightly increased TSH and
normal fT4
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LABORATORY DATA
T4, T3 are frequently normal
TSH normal or slightly elevated
in autoimmune thyroiditis with thyrotoxicosis TSH is decreased under normal
limits
increased response of TSH to TRH in subclinical or overtly hypothyroid patients
anti TPO – antibodies – 100 %
anti TG-antibodies – 90 %
TSH receptor blocking immunoglobulins – 15-20 %
ULTRASOUND EXAMINATION
THYROID VOLUME: Increased, normal or decreased
Intense hypoechogenicity
Scintiscan : patchy hypoechogenicity
Classical Hashimoto’s thyroiditis has an increased thyroid volume and intense
hypoechogenicity in ultrasound examination
FNB: lymphocytes and Hurthle cells
Evolution: in most cases antithyroid antibodies and lymphocytic infiltration
determine progressive loss in thyroid function with subclinical hypothyroidism and than
overt hypothyroidism. Subclinical hypothyroidism means slightly increased TSH, normal
T4 and absence of obvious clinical signs and symptoms of hypothyroidism. Subclinical
hypothyroidism is a risk factor for hypercholesterolemia, atherosclerosis and ischemic
hearth disease
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CLINICAL FORMS
HASHOTOXICOSIS: autoimmune thyroiditis and thyrotoxicosis
IN CHILDREN AND ADOLESCENTS: diffuse euthyroid goiter 10-15 % of
goiters at in children and adolescents are produced by autoimmune thyroiditis
ATROPHIC thyroiditis causes “spontaneous” mixedema in adults and elderly
patients
SILENT or PAINLESS thyroiditis occurs mainly between 30-60 years and may
produce hypothyroidism in time
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POSTPARTUM THYROIDITIS : TPO-Ab are detectable in predisposed cases in
the 6th month of pregnancy:
hyperthyroid state + depression it occurs
postpartum weeks 11-12 and is followed by transient or definitive
hypothyroidism.
AUTOIMMUNE THYROIDITIS and MALIGN LYMPHOMA: primary
lymphoma of the thyroid may develop in a thyroid previously affected by
autoimmune thyroiditis
AUTOIMMUNE THYROIDITIS and THYROID CANCER. Autoimmune
thyroidits is not a factor of predisposition for thyroid cancer. Papillary thyroid
cancer in the most frequently associated with autoimmune thyroiditis. A thyroid
nodule in a patients with known autoimmune thyroiditis must be assessed as all
thyroid nodules in order to confirm a thyroid neoplasia.
IATROGENIC: interpheron, increased iodine intake, external radiotherapy may
also produce autoimmune thyroiditis by interfering with immune system.
TREATMENT
THYROID HORMONES if clinical or subclinical hypothyroidism occurs.
Surgery may be done if it a suspicion for an association with thyroid lymphoma
or with a thyroid carcinoma as well in cases in which there are compressive symptoms
due to large goiter that does not respond to thyroid hormones treatment or even small
goiter that does not respond to hormone treatment
THYROID NODULES
The incidence of thyroid nodules depends of the way of assessment of the thyroid
gland:
• CLINICAL : 4-7 % (5-20%)
• NECROPSIES:40-50 % (30-60%)
• ULTRASOUND EXAMINATION 16-67 %
CLINICA OF ENDOCRINOLOGY IASI:
- MEN : 27,37 %
- WOMEN: 30,3 %
- CHILDREN: 1-2%
• THE PREVALENCE INCREASES WITH AGE BY : 0,08 % / year
THYROID CANCER: < 10 % OF PALPABLE NODULES, <5 % OF
NODULES DETECTED BY ULTRASOUD
NODULS 4 % OF POPULATION X 4% RISK= POSSIBLE INCIDENCE:
1,6/103
TRUE PREVALENCE : 0.025-0,050/100
1/30 THYROID MICROCANCERS BECOME CLINICALY DETECTABLE
Thyroid nodules are more frequent in iodine deficient areas
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Lesions that could appear as thyroid nodules
Cyst
Heterogenous endemic multinodular goiter
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Adenoma
Thyroiditis
Thyroid cancers
Lymphoma
Extrathyroidal lesions
AUTHOR (YEAR)
Reshetnikov 1990
INVESTIGATED AREA
CIS
INCIDENCE OF NODULS
18,8 %
Filatov 1991
CIS
3,45 %
Finland
27,3 %Solitar – 57 %
Multinodular 43 %
Brander 1991
Hintze 1992
Grun 1992
Germany > 60 YEARS
24,78 %
Endemic area
Germany
27,6 %
Goiter prevalence: 37,7 %, women 36 %, men: 18,8 %
Mettler1992
Ukrain, Cernobil area
Mogos 1994
Iasi, Romania
children: 0,5 %
Adults 14,9 %
women: 30,3 %
meni: 27,7 %
61,84 < 1 cm, 21 % 1-2 cm.9,2
%> 3 cm
Incidence of thyroid nodules detected by ultrasound examination
THYROID CANCERS
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INCIDENCE
Males /106
Females /106
USA:
2,4-2,8
5,6-6,2
Australia: 0,7
2,1
Japan: 1.1
2
Hawai:
3,1
4
Germany:
2,7
USA: ’85-’95: 13.856 cases = 1 % Cancer Data Base
Necropsies:
Honolulu: 15,16%
Hiroshima: 25,3
USA: 1,09-1,84
There is a trend to increase of papillary thyroid carcinoma in the last
decades but its prognosis is very good.
MORBIDITY:
NEW CASES /106/ year
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SOKAL 1954:
CUTTLER 1975:
12 / 106/ year
women: 52 /106/year
men: 21/ 106/year
INGBAR 1981:
36 / 106/year
IMPIERI 1984:
10-30 / 106/year
MAZAFFERRY 1988 : 37 / 106/year
In all reported date the incidence of thyroid cancer increases with age and is more
frequent in women than in men. The incidence increases with age as well as the severity
of the disease concerning tumor stage and histological form. Survival rate decreases with
age. The cut-off age being that of 45 years.
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Classification of thyroid tumors
Benign – derived from follicular epithelium
Follicular adenoma
Atipical follicular adenoma
Trabecular adenoma
Oxifilic adenoma
Other adenomas
Benign – non derived from follicular epithelium
Paraganglioma
Teratoma
Mezenchymal tumors
• vascular
• myogenic
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neural
Thyroid cancers
a. Derived from follicular epithelium
Differentiated
• Papillary carcinoma
• Follicular carcinoma
Undifferentiated
• Anaplastic (undifferentiated carcinoma)
b. Derived from calcitonin producing cells
 Medullary thyroid carcinoma - MTC
- Sporadic MTC
- Familial MTC
- MTC as part of Multiple Endocrine Neoplasia (MEN) type 2 A and 2B
Other malignan tumors
• Derived from lymphocytes
• Hodgkin lymphoma
• Nonhodgkin lymphoma
• Plasmocitoma
Sarcomas
Metastasis
Malignant thyroid tumors
Thyroid cancers derived from cell normally located into the thyroid gland, their
frequency and prognosis
Causes of thyroid tumors derived from follicular epithelium
Differentiated thyroid cancer: papillary and follicular carcinoma
- external irradiation is the only established cause for most of papillary thyroid
carcinoma. It was first recognized by Duffy and Fitzgerald 1936, after head and neck
irradiation for other diseases. Than it was recognized in individual after the nuclear
accident from Tcernobil (Ukrain) which was followed by an impressive increase of
papillary thyroid carcinoma, especially in children under 14 years (78.8 %).
- iodine intake favor the development and increased incidence of papillary thyroid
carcinoma with a very good prognosis, the decrease in incidence of follicular
carcinoma with a less good prognosis and decreased impressively the incidence of
undifferentiated (anaplastic) carcinoma.
- papillary carcinoma represents till 70 % of thyroid cancers in areas with high or
sufficient iodine intake and less in area with iodine deficiency.
- follicular thyroid cancer is more frequent in areas with iodine deficiency as well
as undifferentiated thyroid cancer. Taking into account this situation, iodine profilaxis
becomes also a profilaxis for the development of aggressive thyroid cancers.
Normal thyroid cell have a proto-oncogene called RET (10q 11.2)
that encodes a receptor thyrozine kinase receptor for Glyal-derived Nerve Growth
Factor(GDNGF) and Neurturin. Binding of its specific ligand leads to receptor
dymerization and a cascade of events involving tyrosine-kinase, Braf and RAS gene
activation that finally result in cell proliferation and cancer development. This gene is
not expressed in normal follicular cells but normally expressed in parafollicular cell
(calcitonin secreting cells of neural origin).
In papillary thyroid cancer it is supposed that external irradiation produces a
breakdown of DNA and during the process of DNA repair RET protoncogene is placed
by a translocation mechanism under the control of genes normally express in follicular
cells and become activated. This process is called RET/PTC rearrangement and was
described first in papillary cancers that occurred after Tcernobil accident and is now
discovered in most papillary thyroid carcinomas.
Most of undifferentiated thyroid cancer, with a very poor prognosis are derived
from previously diffentiated papillary of follicular cancer due to mutation or lost of
Tumors Suppressor Gene – p53.
In medullary thyroid carcinoma point mutations of different codons of RET
protooncogene result in different forms of medullary thyroid carcinomas (sporadic
or associated with other cancers of cells derived from neural crest (see below).
Clinical presentation of thyroid carcinomas:
All forms of thyroid cancers are more frequently in women. Sex ratio depends of the
histological form.
Important facts:
There are an important differences between differentiated thyroid cancers and other
cancers, because differentiated forms preserve the ability to uptake iodine and are
sensitive to TSH stimulation. On the bases of these characteristics differentiated
thyroid carcinomas may be treated in multimodal way by association between total
thyroidectomy and treatment with radioiodine and thyroxine treatment for
suppression of TSH and therefore further growth of tumors. For these reasons
differentiated thyroid cancer have a good prognosis and a long evolution.
Papillary thyroid cancer. It is the most frequent of thyroid cancers and occurs in 7080 % on patients residents in areas of sufficient iodine intake. Clinically papillary
thyroid carcinoma presents as a solitary thyroid nodule, but multinodular goiter may
be also present. Lymph node involvement occurs frequently and some o cases may be
announced by previous metastases. In ultrasound examination it presents as a
hypoechoic thyroid nodule with irregular margins and microcalcifications.ultrasound
guided fine needle biopsy establishes the diagnosis in most cases bringing
characteristic cells. The evolution of the disease is slow the tumor remains for a long
time confined to the thyroid gland. Most frequent metastases occurs in cervical lymph
nodes and than in lung and liver. Bone metastases are rare. Most cases especially
those occurring in women under 45 years old have an excellent prognosis.
Follicular thyroid cancer occurs also most frequently in women, later than papillary
thyroid cancer. Is more frequently seen in area of iodine insufficiency. Iodine supply
in iodine deficient areas decreased the ratio between follicular and papillary thyroid
cancer and taking into account that follicular cancer have a less good prognosis than
papillary cancers iodine supplementation lead to an overall better prognosis of thyroid
cancers. Clinically follicular carcinoma presents as a solitary thyroid nodule that may
invade the adiacent structures and give distant metastases by route of blood to liver,
bone and brain and spine. Sometimes the diagnosis is made due to distant metastases.
The prognosis is less good than in papillary thyroid cancers. Ultrasound examination
reveals a solitary thyroid nodule, with irregular margins, without microcalcifications.
Scintigraphy shows a cold nodule. Fine needle biopsy is less relevant because the
pathologist may say only that is a “follicular neoplasia” but not certainly a follicular
cancer. 40 % of nodules with a biopsy of follicular neoplasm may truly have a
follicular cancer. As most differentiated thyroid cancer follicular carcinoma may be
treated by total thyroidectomy and radioactive iodine if patient is at high risk: large
tumor with surrounding structures invasion, distant metastases, particular histologic
forms.
Anaplastic thyroid carcinoma
Ussualy occurs in old patients, it is more frequently seen in areas with low iodine
supply and the cause is lost of the Tumor Suppressor Gene p53, in some previously
differentiated thyroid cancers.
Clinical picture of anaplastic carcinoma is that of a rapidly progressive thyroid
tumor, with lymph node involvement, invasion of neck structures with compressive
symptoms, and frequently distant metastases at the time of diagnosis.
Medullary thyroid cancer (MTC).
It develops from calcitonin-secreting cells which are of neuroectodermal origin.
Calcitonin-secreting cells preserve their ability to produce as other neuroendocrine
cells other hormones and mediators: histamine, serotonine, somatostatine, carcinoembrionary antigen, bombesine, ACTH (adreno-corticotropic hormone), CRH
(corticotrophin-releasing hormone). The disease is occurs with equal frequency in
men and women. More than 70 % of cases occurs as sporadic forms and the others
familial forms: isolated familial MTC, MTC as a part of Multiple Endocrine
Neoplasia (MEN) type 2A and 2B (see below).
Thyroid tumor may have different dimensions from some millimeters to
centimeters, is firm and frequently associated with lymph node involvement. Signs
and symptoms of calcitonin and other hormone secretions may produce: flushes
(calcitonin ans serotonin), diarrhea (calcitonin), ACTH-dependent Cushing’s
syndrome. In familial forms of MEN other signs and symptoms occur: arterial
hypertension
(pheochromocytoma),
hypercalcemia
(hyperparathyroidism),
ganglioneuromatosis of lips and eyelids (also see below). Increased basal calcitonin
and carcinembriogenetic antigen are markers of the disease. In cases in which
calcitonin in not obviously elevated calcitonin may be stimulated by pentagastrin or
calcium infusion.
Mutations that occurs in codons that are part of RET gene lead to different forms of
medullary thyroid carcinoma, sporadic, familial MTC, or Multiple Endocrine Neoplasia
type 2A/B
Syndromes associated with MTC
FMTC
MEN-2A
MEN-2B
Sporadic
MTC
Germinline
Germlin e
Germlin e
somatic
Exon
10,11,13,14,15
10,11
16,(15)
10,11,13,16
CMT
100%
100%
100%
100%
<20,>50
<20
<20
<40
Multiplicit y
100%
100%
100%
rara
Bilateral
100%
100%
100%
rara
C cell h yperp lasia
100%
100%
100%
rar
Pheocromocytoma
0%
10-60%
50%
0%
Hyp erparatiro idism
0%
10-25 %
0%
0%
Notalgia –cutaneous lich en
am yloido sis
Hirschprung disease
0%
< 10 %
Codon: 618,620
0%
0%
Ganglioneurom atozis
0%
0%
100 %
0%
Marfan-like appearance
0%
0%
100 %
0%
RET mutation
Age at diagnosis
Modigliani 2000, Schlumberger M. 2000
MTC and syndromes associated with MTC
A genetic predisposition was also identified in cancers derived from follicular
epithelium in carrier for the gene MNG (multinodular goiter)
Evaluation of thyroid nodules and thyroid cancer
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- thyroid examination
- history of the disease in individual and relatives
- scintigraphy
- fine needle biopsy
- TSH, T4,
- Antithyroid antibodies
- Calcitonin measurement
Ultrasound examination of thyroid nodules
Identifies that lesion belongs to the thyroid , if it is solitary or multiple and has or
not has lymph node enlargement
It is the guide for fine needle biopsy
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It allows to detect the anatomic rapports with other structures
Low risk: pure cyst, hyper or isoechoic, transonic hallo, peripheral large
calcification
High risk: irregular margins, microcalcifications, cyst with solid content inside
Color Flow Doppler ultrasound: benign: vascular hallo , a few echos inside the
nodule, malign: intense vascularity inside, transcapsular vesels.
Scintigraphy of thyroid nodules
Differentiated thyroid cancer
CLASSICAL:
131
I most used ( no uptake in the nodule “cold nodule), also used for follow-up
99m Tc : false negative in some cases of thyroid cancers. Nodules positive for
99m Tc but without iodine uptake may be cancers
New scinigraphies
99 Tc MIBI:
o bone metastasis: sensitivity: 73 %, specificity; 90%
o lung metastasis: sensitivity: 21 %, specificity: 94 %
99 mTc tetrafosmin
201 Tl positive for differentiated thyroid cancers
In some cases computed tomography and MRI imaging allows the surgeon to
obtain details about the relationship between nodule and surrounding tissues. Computed
tomography is not indicated because it may lead to iodine saturation of thyroid tissue and
interfere with further radioactive iodine administration after surgery if the nodule was a
differentiated thyroid cancer.
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Fine needle biopsy in thyroid nodules
FNB is the most reliable assessment of thyroid nodules and allows:
a good detection for papillary, medullary and anaplstic carcinoma
planning for surgery
selection of tumors in which other therapy may be beneficial (lymphoma)
non-conventional therapy for thyroid nodules: cyst evacuation, necrotizating of
functioning adenomas
Assessment of thryoid nodules
Thryroid nodule
cyst
ultrasound
Solid or m ixed solid and cystic
FNB
BENIGN
FNB
scintigraph y
Ev acuation of
the cyst conyent
heeling
W ARM
T4
MALIGN
cold
Low risc
persistence
suspicious
High risk
THYOIDECTOMY
Follo w up
E.Zbranca si col.Simp .Nat.Endocrino l.1995,
Endocrinologie Clinica 1997
Algorithm for diagnosis in thyroid nodules
Elem ent
Benignit y
Malignancy
Histor y
Endemci goiter area, h ystoru of
benign th yroid patholog y, female
sex, advan ced age.
Histor y of ext ernal irradiation of the neck,
family h istor y of CMT, so litar y nodule with
rappid gro wth, compr ession, m ale sex,
young age, child
Clinical features of
the nodule
Multiodular goiter, soft nodule
without lymp node enlarg ement
Solitar y nodule, lymph node enlargem ent,
distant metastases
Laborator y
assessment
Antith yroid antibodies increased
Increase calcitonin
Ultrasound
Pure cyst, normo echoic or
hyp erechoic, periph eral gross
calcification
Irregular margin s, absen ce of h allo, nodule
development more in the depth of the lob e
than in its long est, lymp node enlargement,
microcalcifications.
Scinigr aph y
W arm or hot nodule
“cold nodule”
Fine needle b ipsy
“benign”
Suspicious or m align ant
Response to
suppresive tr eatment
with thyro id
hormones
Some r eduction. Nodules associated
with lo w TSH levels at diagnosis ar e
more probable to be b enign
No reduction or continuous gro wth.
Nodules which have high TSH at diagnosis
have more chances to b e malignant
Elements that plead for benignity or malignancy in thyroid nodules
A history of Graves disease of Graves disease in evolution increases the
probability of a nodule to be malign.
Staging of thyroid cancers
CLINICAL STAGING OF PAPILLARY AND FOLLICULAR CANCERS
Patients under 45 years
Patients older than 45 years
STAGE I - any T, any N, M0
STAGE I - T1, N0, M 0
ATAGE II - anyT, any N, M 1
STAGE II - T2 / T3, N0, M 0
STAGE III - T4, N0,M 0, orice T,N1,M 0
ASTEGE IV – orice T, orice N, M 1 AND
ANAPLAS TI C THY RID C ARCI N MA IN DEPENDEN TLY OF
EXTE NSION
STAGING OF MEDULALRY THRYOID CARCINMA
STAGE I - T1, N0, M 0
STAGE II - T2 / T3 / T4 , N0, M 0
STAGE III – ANY T, N1, M 0
STAGE IV – ANY T, ANY N, M 1
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TREATMENT OF DIFFERENTIATED THYROID CANCER
SURGERY
always total or near total thyroidectomy
loboistmectomy: small papillary carcinoma in low-risk patients, children, young
adults
Side effects :
laringeal palsy : 2-8 %
hypoparatiroidism: 1-4 %
After surgery patients are classified into:
- Low risk: small papillary or follicular carcinoma in women under 45 years old
- High risk: larger tumors with lymph node involvement, both sexes after 45
years, toll cell tumors, sclerosing papillary tumors
RADIOACTIVE IODINE IN THE TREATMENT OF DIFFRENTIATED
THYROID CARCINOMA
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Ablation of thyroid remnant after surgery
In high risk patients is always indicated
controversial in other patients
not indicated in low risk patients
Ablative dose between 30 – 100 mCi depending of the tissue left after surgery and
histology
Treatment and follow-up of patients with differentiated thyroid cancer
Suppressive treatment :
• L-Thyroxina >/= 200 g/day
• 2,1-2,8 g/b.w./day
• TSH may be maintained < 0.1 UI/ml
Follow-up:
Tiroglobulin (IRMA) is best indicator for cure or persistent or recurrent disease
• undetectable in 98 % of those in remission
• if detectable when THS values are very high after thyroid hormone withdrawal
there is persistent or recurrent disease and a new dose of radioactive iodine is
given
Whole
body
scanning
after
T4
withdrawal
for 4 week until TSH reaches values of at least 30 mIU/L
rhTSH 0.9 mg may replace thyroid hormone withdrawal
in patients who do not tolerate prolonged hypothyroidism
Tg < 10 ng/ml : treatment with radioactive iodine in dose less than 100 mCi
Tg > 10 ng/ml: treatment with 100 mCi
Immediately patients will receive suppressive doses of l-thyroxine
For those with Tg + si WBS negative: 18 F-FDG-PET
Lung metastases are responsive to large doses of radioiodine and suppressive therapy
for TSH with thyroxine. Bone metastases are less responsive and may be surgically
removed or irradiated.
TREATMENT AND FOLLOW-UP OF
DIFFERENTIATED THYROID CANCERS
Total thyroidectomy
131 I ablation and + Whole Body Scanning
3 m onth (sub fT4:
FT3-TSH-Tg
Thyroglobulin
> 5 ng/ml
6-12 month- stop T4
Determ ine TSH/Tg
131 I WBS (2-5 mCi
Thyroglobulin
undetectable
Annualy
control of
Tg on T4
Tg < 10 ng/m l
131I
Tg +
WBS ( 2-5 mCi)
Negativ: repete every 2-5
years
Tg > 10ng/ml
or WBS +
131I100
mCi
+WBS
Treatment and fo llow up of medullary thyroid
carcinoma
Total
thyroidectomy
6 week
N
CE A,CT,Test
Pentagastrine
Repeat
anulally
Repeat at 2
years
Negative
Stable disease
CT<50
Pg-CT<500
No
detectable
metastas es
CT>50
Repeat
anually
negative
PG-CT>500
Micrometast
ases
Distant
metastases
Increased
calcitonin
and CEA
US,CT,RMN
Positron em ission
scintigraph y)
PG – CT =N
repeat
No tumor detectable
Incompelte
surgery
Local
recuren ce or
metastases
Repeta anu al
Surger y
Modigliani 2000
SCREENING AND MANAGEMENT OF FAMILIAL
MEDULALRY THYROID CARCINMA AND MEN 2A
Patient with CMT (index case)
Germline mutation for RET
RET positive/hereditary
disease
RET negative
RET mutation anlysis in first
degree relatives
•RET
pozitive
Negative
No investigation
is necessar y
Pentagastrine test
Surgery as
soon as
possible
Pozitive- surgery
Surgery refused
Test
pentagastrin
stimulation test
for calcitonin
unsignificant
Minimal risk
Negativ repeat
annualy PG- CT
In the case of familial MTC or MEN2A/B there are the flowing recommendations
for screening of patients with inherited disease (vide supra).
Anaplastic thyroid cancer could be treated by surgery, followed by external
irradiation and chemotherapy, but survival is very poor independently of the treatment .