Il nodulo tiroideo:
iter diagnostico
Mauro Maccario
Divisione di Endocrinologia e
Malattie del Metabolismo
Università di Torino
Diagnosi differenziale del nodulo tiroideo
• Lesioni tiroidee
–
–
–
–
–
–
gozzo nodulare
adenoma
tiroidite di Hashimoto
tiroidite subacuta
cisti del dotto tireoglosso
neoplasie maligne
• Lesioni non tiroidee
– linfoadenopatia
– adenoma delle
paratiroidi
– ascesso cervicale
– igroma cistico
– ectopia gh. salivari
– aneurisma
– laringocele
Tumori maligni della Tiroide
• Derivati dall’epitelio
follicolare
Forme differenziate o
scarsamente differenziate
- Papillare
- Follicolare (varianti: Ca a
cell. di Hurtle e Insulare)
- Carcinoma misto papillarefollicolare
Forme indifferenziate
- Carcinoma anaplastico
• Derivati dalle cellule
C parafollicolari
Carcinoma midollare
• Non-epiteliali
Linfomi
Sarcomi
Teratomi
• Secondari
Cancro della Tiroide - Epidemiologia
• meno dell’1% dei tumori maligni
(1,5% donne - 0,5% uomini)
• incidenza 5-10 / 100000 (in
Piemonte 150-300 nuovi casi /anno)
frequenza simile al mieloma ed al
carcinoma dell’esofago della laringe
e del collo dell’utero
doppia rispetto al m. di Hodgkin
• 0.4% dei decessi per neoplasia
Nodulo tiroideo - Epidemiologia
• 4-7 % popolazione U.S.A. ha un nodo
palpabile
• aumento di frequenza con l’età
• netta prevalenza femminile
• 40-50% della popolazione ha un
nodulo dimostrabile all’ETG
• raramente espressione di lesione
neoplastica evolutiva
Nodulo tiroideo - percorso diagnostico
Screening ?
Anamnesi
Incidentaloma
Esame obiettivo
Popolazioni a rischio
Esami di Laboratorio
Caratteri del nodulo
Imaging
TSH (fT3, fT4,)
Ecotomografia
AbTPO
Scintigrafia
Tireoglobulina
CT, RMN
Calcitonina
Esame citologico su agoaspirato
Carcinoma tiroideo
Screening in soggetti asintomatici?
• Beneficio della diagnosi precoce
– prognosi migliore?
– stadio alla diagnosi nella storia naturale
– storia naturale del tumore occulto
Importanza della diagnosi precoce
Cancer Res 1991 51(4):1234-41
Survival and causes of death in thyroid cancer: a population-based study of
2479 cases from Norway.
Akslen LA, Haldorsen T, Thoresen SO, Glattre E
Department of Pathology, Gade Institute, University of Bergen, Norway.
Survival and prognostic factors were studied in 2479 clinically presenting thyroid cancers
(TC) reported from the entire Norwegian population from 1970 to 1985. Complete follow-up
was obtained (median, 48 months), with information on causes of death. At the end of the
observation period, 498 patients were reported to have died of TC, representing 69.7% of all
deaths. Among 216 patients dying of other main causes, TC was considered to be a
contributing cause of death in 80 cases (11.2%). Multivariate regression analysis of TC deaths
showed no significant difference according to sex in any of the histological types. Age had a
strong impact on survival, and for papillary carcinomas this effect was apparent after the age
of 55 years. Marked differences were observed between various histological types, even
between papillary and follicular carcinomas when interactions were included. Furthermore,
tumor stage was a strong predictor of TC deaths, and a reduced survival was also found in
patients with lymph node metastases. In conclusion, the importance of age, histological type,
and tumor stage as major prognostic factors has been documented in this population-based
study from Norway.
Ca tiroide - Stadio alla diagnosi nella storia naturale
Cancro del polmone
Cancro della tiroide
da: DOH 1999, Cancer in the District of Columbia - 1996
Nodulo tiroideo
Screening in soggetti asintomatici?
• Beneficio della diagnosi precoce
– prognosi migliore?
– stadio alla diagnosi nella storia naturale
– storia naturale del tumore occulto
• Rapporto costo/beneficio
– autoscreening, screening periodico presso medico
generale o presso centro specialistico?
– efficacia dello screening
– rapporto nodi benigni / maligni
– modalità di screening (palpazione, ETG, …)
Palpazione del collo: sensibilità 44% vs ETG
J Clin Ultrasound 1992 Jan;20(1):37-42
Clinical versus ultrasound examination of the thyroid gland in common
clinical practice.
Brander A, Viikinkoski P, Tuuhea J, Voutilainen L, Kivisaari L
Hyvinkaa District Hospital, Finland.
In a prospective series of 72 patients, clinical and ultrasonographic examination of
the thyroid gland were compared in detail. Normal-sized lobes were differentiated
from enlarged ones both by inspection and by palpation. When lobar size was
assessed by palpation, the estimate was most clearly influenced by increase in width.
The correlation between two examiners in lobe size assessment was significant. In
the classification of thyroid disease as diffuse, solitary, or multinodular, clinical
Of
77 separate
nodules,correlated
43 escaped
detection
on one
clinical
examination
and ultrasonography
significantly.
However, only
third of
examination.
Ofnodules
theseproved
43,to 14
nodules
exceeded
2 cmOf in
the clinically solitary
be solitary
by ultrasound
examination.
77
separate
nodules,
43 escaped
detection
on clinical
examination.
Of these 43, 14
diameter.
It is
concluded
that
the use
of ultrasonography
nodules exceeded 2 cm in diameter. It is concluded that the use of ultrasonography
frequently
the evaluation
primary ofevaluation
of thyroid
nodularity
frequently altersalters
the primary
thyroid nodularity
based on palpation.
based on palpation.
Screening ecografico
Radiology 1991 Dec;181(3):683-7
Thyroid gland: US screening in a random adult population.
Brander A, Viikinkoski P, Nickels J, Kivisaari L
Hyvinkaa District Hospital, Finland.
High-frequency ultrasound examination of the thyroid was performed in 253 subjects (130
women and 123 men; age range, 19-50 years) that were randomly selected from the
population in an area of Finland where goiter is not endemic. Thyroid echo abnormalities
were detected in 69 subjects (27.3%). Prevalence of abnormalities increased with age, and
women showed more lesions than did men in each of the 3 decades. The abnormality was
solitary in 39 subjects (57%), multiple in 15 (22%), and diffuse in 15 (22%). Of the 68
individual nodules, 48 (70%) were smaller than 1 cm in diameter. Anechoic rounded
nodules 1-5 mm in diameter were found in 28 subjects. Fine-needle aspiration biopsy was
performed in 30 subjects. Cytologic examination revealed no unequivocal malignancies. In
eight subjects (3.2%) with a diffuse echo abnormality, cytologic evaluation indicated
lymphocytic thyroiditis. It is concluded that the prevalence of small thyroid echo
abnormalities in a randomly selected adult population is rather high, a fact that supports use
of a conservative approach to these types of findings.
The Canadian Guide to Clinical Preventive Health Care
Give Yourself The Thyroid "Neck Check"
It Could Save Your Life
TO TAKE THE THYROID NECK
CHECK...
All you will need is:
• A glass of water
• A hand-held mirror
1. Hold the mirror in your hand,
focusing on the area of your neck
just below the Adam's apple and
immediately above the
collarbone. Your thyroid gland is
located in this area of your neck.
2. While focusing on this area in
the mirror, tip your head back.
3. Take a drink of water and
swallow.
.
4. As you swallow, look at your
neck. Check for any bulges or a
protrusion in this area when you
swallow. Reminder: Don't confuse the
Adam's apple with the thyroid gland.
The thyroid gland is located further
down on your neck, closer to the
collarbone. You may want to repeat
this process several times.
5. If you do see any bulges or
protrusions in this area, see
your physician immediately.
You may have an enlarged
thyroid gland or a thyroid
nodule and should be checked
to determine whether cancer is
present or if treatment for
thyroid disease is needed.
The Cancer Related Check-up
Apart from participating in screening that has been recommended as part of a
population-based initiative, an individual's periodic encounters with
clinicians are viewed by the ACS as having potential for health counseling
and a cancer-related check-up. Health counseling may include guidance
about smoking cessation, diet, physical activity, and the benefits and risks of
undergoing various screening tests. These encounters may include casefinding examinations of the thyroid, testicles, ovaries, lymph nodes, oral
region, and skin. Also, self-examination of the skin and breasts can be
encouraged, as can the importance of awareness of symptoms of testicular
cancer in young men. The ACS recommends a cancer-related check-up every
three years for asymptomatic individuals between the ages of 20 and 39, and
annually for asymptomatic men and women ages 40 and older
U.S. Preventive Services Task Force - 1996
Effectiveness of Early Detection of Thyroid Cancer
The benefits of early detection of thyroid cancer in the
general population are not well defined. For all histologic
types, 5-year survival is significantly better with earlier
stage at diagnosis. A cohort study of mass screening found a
significantly higher 7-year cumulative survival rate in
patients whose cancer was detected by screening (98%)
when compared with those presenting with symptoms
(90%). no
Cancers
detected by
screening
were significantly
There have been
controlled
trials
demonstrating
that
more likely to have a favorable histology, however, and
asymptomatic both
persons
detected
bybiases
screening
a better
lead-time
and length
are likely have
in this study.
outcome
than
those
present
withdemonstrating
clinical symptoms
or signs.
There have
been
no who
controlled
trials
that asymptomatic
persons
detected
a betterthrough
outcome screening
than those who
In
addition,
notbyallscreening
cancershave
detected
are present
likely
withpresent
clinical symptoms
signs. In the
addition,
not all lifetime.
cancers detected
through
to
clinicallyorduring
patient's
In autopsy
screeningin are
clinically
patient's
lifetime. in
In
studies
thelikely
U.S., tothepresent
prevalence
of during
occult the
thyroid
carcinoma
autopsy studies in the U.S., the prevalence of occult thyroid carcinoma in
adults
rangesfrom
from2-13%;
2-13%;
contrast,
the annual
incidence
of
adults ranges
in in
contrast,
the annual
incidence
of thyroid
thyroid
carcinoma
is 4/100,000
only about
4/100,000 population.
carcinoma
is only about
population.
Incidentaloma tiroideo
Annals of Internal Medicine
REVIEW
Thyroid Incidentalomas: Management Approaches
to Nonpalpable Nodules Discovered Incidentally on
Thyroid Imaging
Annals of Internal Medicine, 1 February 1997. 126:226-231.
Gerry H. Tan, MD, and Hossein Gharib, MD
Mayo Clinic and Mayo Foundation, Rochester, Minnesota.
Incidentaloma tiroideo
G.H. Tan & H. Gharib, Annals of Internal Medicine, 1997. 126:226-231
Incidentaloma tiroideo
Conclusions: ...
Most of these lesions are
benign. For most patients
with non-palpable nodules
that are incidentally detected
by thyroid imaging, simple
follow-up neck palpation is
sufficient
G.H. Tan & H. Gharib, Annals of Internal Medicine, 1997. 126:226-231
Nodulo tiroideo - percorso diagnostico
Screening ?
Anamnesi
Incidentaloma
Esame obiettivo
Popolazioni a rischio
Esami di Laboratorio
Caratteri del nodulo
Imaging
Esame citologico su agoaspirato
Anamnesi - Esame obiettivo
CONDIZIONE
FAVOREVOLE
• Storia familiare di
tiroidite cronica
• Storia familiare di struma
• Sintomi di ipo- /
ipertiroidismo
• Dolore o tensione
associata al nodulo
• nodulo liscio e mobile
• gozzo multinodulare
CONDIZIONE
SFAVOREVOLE
•
•
•
•
Età < 20 o > 70 anni
Sesso maschile
Disfagia
Storia di radioterapia del
collo
• Nodulo duro, fisso,
irregolare
• Adenopatia cervicale
• Storia di cancro della
tiroide
Nodulo tiroideo - percorso diagnostico
Screening ?
Anamnesi
Incidentaloma
Esame obiettivo
Esami di Laboratorio
Imaging
TSH, fT3, fT4
AbTPO
Tireoglobulina
Calcitonina
Esame citologico su agoaspirato
Esami di laboratorio - funzionalità tiroidea
Bennedbaek FN, Perrild H, Hegedus L.
Diagnosis and treatment of the solitary thyroid nodule. Results of a European
survey. Clinical Endocrinol (Oxf) 1999; 50:357-363.
Tests
Case hystory
• 42 y old Caucasian women
• nodule 2x3 cm mobile
• present from 3 months
• no lymphadenopathy
• no family history of thyroid
disease
• no previous external
irradiation
TSH
Free T4 measurement
Calcitonin
Thyroid peroxidase (TPO) antibodies
Free T3 measurement
Thyroglobulin antibodies
Total T3
Total T4
Sedimentation rate
Thyroglobulin
Microsomal antibodies
Free T4 index
Tsh-receptor antibodies
TRH test
Urinary iodide excretion
Frequency
99
53
43
41
31
26
25
20
16
14
11
9
6
4
4
Esami di laboratorio - funzionalità tiroidea
TSH ultrasensibile
aumentato
AbTPO
positivo
Tiroidite cronica
autoimmune
(nodo poco sospetto)
diminuito
Scintigrafia Tc99
nodulo
captante
Nodo tossico
(non sospetto)
nodulo
non captante
Nodo
sospetto
Esami di laboratorio - Tireoglobulina
Bennedbaek FN, Perrild H, Hegedus L.
Diagnosis and treatment of the solitary thyroid nodule. Results of a European
survey. Clinical Endocrinol (Oxf) 1999; 50:357-363.
Tests
Case hystory
• 42 y old Caucasian women
• nodule 2x3 cm mobile
• present from 3 months
• no lymphadenopathy
• no family history of thyroid
disease
• no previous external
irradiation
TSH
Free T4 measurement
Calcitonin
Thyroid peroxidase (TPO) antibodies
Free T3 measurement
Thyroglobulin antibodies
Total T3
Total T4
Sedimentation rate
Thyroglobulin
Microsomal antibodies
Free T4 index
Tsh-receptor antibodies
TRH test
Urinary iodide excretion
Frequency
99
53
43
41
31
26
25
20
16
14
11
9
6
4
4
Esami di laboratorio - Tireoglobulina
AACE Clinical Practice Guidelines
for the Diagnosis
and Management of Thyroid Nodule
Developed by
The American Association of Clinical Endocrinologists
and The American College of Endocrinology
© 1996, AACE
..
A baseline serum thyroglobulin levels in the evaluation of solitary thyroid
nodule is not a useful or cost-effective test. The value of the thyroglobulin
levels lies in serial determinations after thyroid cancer has been diagnosed
and the patient has been treated by elimination of most or all of the thyroid
gland.
...
Esami di laboratorio - Calcitonina
Bennedbaek FN, Perrild H, Hegedus L.
Diagnosis and treatment of the solitary thyroid nodule. Results of a European
survey. Clinical Endocrinol (Oxf) 1999; 50:357-363.
Tests
Case hystory
• 42 y old Caucasian women
• nodule 2x3 cm mobile
• present from 3 months
• no lymphadenopathy
• no family history of thyroid
disease
• no previous external
irradiation
TSH
Free T4 measurement
Calcitonin
Thyroid peroxidase (TPO) antibodies
Free T3 measurement
Thyroglobulin antibodies
Total T3
Total T4
Sedimentation rate
Thyroglobulin
Microsomal antibodies
Free T4 index
TSH-receptor antibodies
TRH test
Urinary iodide excretion
Frequency
99
53
43
41
31
26
25
20
16
14
11
9
6
4
4
Esami di laboratorio - Calcitonina
J.R. Hahm et al.
Routine Measurement of Serum Calcitonin is Useful for Early Detection of Medullary
Thyroid Carcinoma in Patients with Nodular Thyroid Diseases.
Thyroid, 11:73-79, 2001
CT = calcitoninemia
MTC = carcinoma
midollare
PTC = carcinoma
papillare
FN = lesione follicolare
Esami di laboratorio - Calcitonina
Treatment Guidelines for Patients With Thyroid
Nodules and Well-Differentiated Thyroid Cancer
Arch Int Med 1996
..If the family history is non contributory, routine
serum calcitonin measurements are not costeffective...
1996
AACE Clinical Practice Guidelines for the
Diagnosis and Management of Thyroid Nodules
..In the absence of suspicion of medullary thyroid
cancer or multiple endocrine neoplasia II syndrome,
it is neither routinely necessary nor cost effective to
determine calcitonin levels in patients with solitary
thyroid nodule...
Nodulo tiroideo - percorso diagnostico
Screening ?
Anamnesi
Incidentaloma
Esame obiettivo
Esami di Laboratorio
Imaging
TSH, fT3, fT4
Ecotomografia
AbTPO
Scintigrafia
Tireoglobulina
CT, RMN
Calcitonina
Esame citologico su agoaspirato
Imaging - Scintigrafia
Bennedbaek FN, Perrild H, Hegedus L.
Diagnosis and treatment of the solitary thyroid nodule. Results of a European
survey. Clinical Endocrinol (Oxf) 1999; 50:357-363.
Diagnostic procedure
Case hystory
• 42 y old Caucasian women
• nodule 2x3 cm mobile
• present from 3 months
• no lymphadenopathy
• no family history of thyroid
disease
• no previous external
irradiation
Frequency
Scintigraphy
Scintigraphy
I 131
I123
Tc99m
66
66
4
10
86
Scintigraphy only
Ultrasonography
Size
Grey scale
Doppler
8
80
75
57
33
Ultrasonography only
Scintigraphy
ultrasonography
Scintigraphyand
and
ultrasonography
X-ray (chest-trachea)
22
58
7
Imaging - Scintigrafia Tc99m / I123
• In paziente ipertiroideo: verifica della
presenza di noduli iperfunzionanti
(raramente maligni)
• In paziente eutiroideo: verifica dello stato
funzionale dei noduli di un gozzo
multinodulare
Imaging - Scintigrafia
Treatment Guidelines for Patients With Thyroid
Nodules and Well-Differentiated Thyroid Cancer
Arch Int Med 1996
... with the exception of hyperfunctioning nodules, the thyroid scan will not
help to differentiate benign from malignant lesions. For this reason, many
endocrinologists no longer advocate obtaining thyroid scans as part of the
routine initial evaluation of a nodular goiter, and they prefer to perform an
FNAB first.
AACE Clinical Practice Guidelines for the Diagnosis and
Management of Thyroid Nodules
… Certainly, not all patients with thyroid nodules require nuclear
1996
imaging. In many centers, thyroid FNA biopsy has supplanted
nuclear thyroid imaging as the initial technical procedure in
evaluating nodules. AACE recommends that the physician use clinical
judgment in considering the appropriateness of a thyroid nuclear scan, as it
applies to each individual case.
Il nodulo tiroideo:
iter diagnostico
grazie per l’attenzione