XXVIII Congreso Nacional de Oncología

Cancun, Mexico
October 29, 2014
Actualizado 2017

Manejo de el Nódulo Tiroideo

Kepal N. Patel, MD, FACS

Attending Surgeon
Endocrine / Head and Neck Surgery
NYU Langone Medical Center
Assistant Professor of Surgery, Otolaryngology and Biochemistry
Definición

Lesión discreta dentro de la

glándula tiroides que es palpable
y/o radiológicamente distinta del
parénquima tiroideo que la rodea

The American Thyroid Association Guidelines Taskforce, 2009

Causas de Nódulos Tiroideos
Benignos

Bocio Multinodular
Tiroiditis Hashimoto’s
Quiste simple o
hemorrágico
Adenoma Folicular
Tiroiditis Sub-aguda
Causas de Nódulos Tiroideos
Benignos Malignos

Bocio Multinodular Carcinoma Papilar

Tiroiditis Hashimoto’s Carcinoma Folicular
Quiste simple o Carcinoma de células
de Hürthle
hemorrágico
Carcinoma Medular
Adenoma Folicular Carcinoma Anaplásico
Tiroiditis sub-aguda Linfoma
Lesión Metastàsica
Prevalencia de Nódulos Tiroideos
Palpación
70
60
Prevalence (%)

50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100
Edad
From Mazzaferri EL, NEJM 1993
Prevalencia de Nódulos Tiroideos
Ultrasonido/Autopsia Palpación
70
60
Prevalence (%)

50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100
Edad
From Mazzaferri EL, NEJM 1993
Prevalencia de Nódulos Tiroideos

• La prevalencia de nódulos tiroideos palpables es

~5% en mujeres y 1% en hombres

• El US de alta resolución puede detectar nódulos en

19–67% de individuos seleccionados y
randomizados con mayor frecuencia en mujeres de
edad avanzada
Concepto Actual “epidémico”
• La importancia clínica de los nódulos tiroideos radica
en la necesidad de excluir el cáncer tiroideo
• Solo el 5-10% de todos los nódulos son malignos

Como identificar los

nódulos que
requieren estudio?
Informe Actual

 Cada nódulo tiroideo necesita ser investigado ?

 Evaluar el riesgo basado en las características del
nódulo
 Evaluación y manejo de los nódulos de alto riesgo
Evaluar la estructura con imagen radiológica
Evaluar la función
 Aspiración con aguja fina
Manejo quirúrgico de la glándula tiroides
 Manejo de los nódulos de bajo riesgo y seguimiento
Debe cada nódulo tiroideo ser
investigado ?
Descubrimiento de nódulo/s
tiroideos
Inquietud del paciente

 Es esto un cáncer?
 Si no, es esto algo de
lo que deba
precuparme ?
Descubrimiento de nódulo/s
tiroideos
Inquietud del paciente Inquietud del Médico
Es esto un cáncer?
Si no, es esto algo de lo que deba  Esto es un cáncer?
precuparme ?
 Haré un subdx cáncer?
 Como debo investigarlo
y tratarlo?
Reglas generales para investigar un
nódulo

Investigar solo nódulos > 1 cm

porque los nódulos pequeños, aún
siendo malignos, éstos no tiene
significancia clínica
Reglas generales para investigar un
nódulo

Solo en raras ocasiones los tumores pequeños

<1 cm pueden tener cierta morbilidad, sin
embargo comparando el costo-beneficio , los
intentos para diagnosticar y tratar este tipo de
tumores pequeños causan mas daño que
beneficio

ATA Guidelines 2009

Cuándo investigar un nódulo <1 cm
 Caraterísticas sospechosas en el Us
 Riesgo alto basado en la historia clínica
 Alto riesgo basado en síntomas, signos y
hallazgos clínicos
 Ansiedad extrema en el paciente y el Médico
Cracterísticas de riesgo elevado en la
historia clìnica
 Edad <20 or >70 años
 Dieta baja en Iodo
 Historia de radioterapia en CyC
 Radiación total en trans-plantes de médula ósea
 Exposición a radiación nuclear (ej. Chernobyl) en
edad menor a 14 años
Incidencia de cáncer Chernobyl

Cancer cases per year

100 Belarus Ukraine Russia

80

60

40

20

0
1986 1987 1988 1989 1990 1991 1992 1993 1994
Year
Incidence of pediatric thyroid cancers in the countries receiving highest levels
of radiation contamination after the Chernobyl nuclear accident in 1986. Note
the major increase beginning in 1990. The southernmost region of Belarus,
immediately north of Chernobyl, was the most affected.
Alto riesgo características en la HC

 Age <20 or >70 years

 Low-iodine diet
 History of head and neck irradiation
 Total body irradiation for bone marrow transplantation
 Exposure to nuclear fallout (e.g. Chernobyl) under the age of
14 years
 Historia previa de cáncer – y/o metastasis al tiroides
 Historia familiar de cáncer tiroideo en fam de 1er
grado, o syndrome asociado a Ca tiroideo (Carney
complex, Cowden’s síndrome, FAP)
 Historia familiar de MTC or MEN2
Síntomas de alto riesgo

 Crecimiento rápido
 Ronquera persistente, disfonia, disfagia, o
disnea
 MEN 2A síntomas
Síntomas de alto riesgo

 Crecimiento rápido
 Ronquera persistente, disfonia, disfagia, o
disnea
 MEN 2A síntomas

La auscencia de síntomas no descarta

lesión maligna
Hallazgos físicos de alto riesgo

 Tamaño, el riesgo es igual en nódulos

palpables vs no-palpables
nódulos solitarios vs MNG
 Solitario, firme, o un nódulo duro
especialmente en masculinos ancianos
 Fijación a tejidos circundantes
 Parálisis de cuerda vocal
 Linfadenopatía cervical ipsilateral
PET Scan “Incidentaloma”
PET Scan “Incidentaloma”
 Focal vs Difuso
 Los Difusos son menos probables de ser
malignos
 30-50% pacientes con captación focal tienen
nódulos malignos
 La mayoría de los tumores malignos son
variantes de células insulares
 Los tumores “calientes” son de células
oncocíticas, Benignos y/o carcinomas de cel
de Hürthle
Riesgo basado en el abordaje de
nódulos tiroideos

Historia E. Físico

Estadificar riesgo

Bajo riesgo Alto riesgo

=/o >1cm
Observación
Investigar
Investigar los
nódulos de alto
riesgo
Riesgo basado en la evaluación

Historia E. Físico

Estadificar riesgo
Evaluación de la estructura

Evaluación de la función
Evaluación de la Estructura
Evaluación de la Estructura
 Ultrasonido de AD

 CT/MRI
Ultrasonografía

 No recomendada para screening o pacientes

con tiroides clínico normal y/o de bajo riesgo
para cáncer tiroideo

 No hay ningún signo US predictivo de

malignidad, excepto la invasion focal

 Ciertas características son útiles en la

evaluación del riesgo
Ultrasonografía
Alto riesgo para Cáncer Bajo riesgo para Cáncer
 Microcalcificaciones puntiformes
 Hipoecogénico
 Márgenes irregulares
 Ausencia de Halo
 Predominio sólido
 Forma más alta que ancha
 Vascularidad intranodular
 Invasión a tejidos cercanos
 Sospecha de mets en zlp
 Calc. amorfa en cáscara de huevo
 Hipercoico (coloide)
 Márgenes bien definidos
 Presencia de Halo
 Quístico puro
 Forma redonda
 Baja vascularidad
 Sin invasión
 Sin sospecha de mets en zlp
Mechanick et al 2006
Tac y Resonancia Magnética N

 No recomendadas para evaluación inicial de

nódulo común
 Menos sensible que el Us de alta resolución
 Indicadas si existen signos de invasion local
 Evitar medios de contraste con Iodo si el GGT
y/o el Tx con I 131 son una posibilidad
Evaluación de la Función
Tests available

TSH T4
Antithyroid Antibodies

Thyroglobulin
Calcitonin
Evaluación Inicial

TSH T4
If TSH: normalizarla con levotiroxina

Necesita evaluación
posterior con
FNA
Evaluación Inicial

TSH T4
TSH suprimida

Rastreo RAI
(GGT)
GGT

Nódulo Frío Nódulo caliente

+de los nódulos son fríos <5% N. calientes

Mayoría benignos
Algunos malignos - malignos
Los Nódulos calientes deben ser
investigados?
 Los nódulos Isofuncionantes o “calientes”
absorción del rastreo = circund al tej. T
 Diferente en N. hyperfuncionante o “caliente”
 Hot nodules rarely harbor malignancy- no
need for FNA.
 Warm nodules should be investigated
Initial evaluation

TSH T4
Antithyroid Antibodies

FNA is recommended even if Abs

because rate of malignancy in Hashimoto’s thyroiditis
is same or perhaps higher than normal thyroid glands
Tests available

TSH T4
Antithyroid Antibodies

Thyroglobulin
Calcitonin
Serum thyroglobulin

 Can be elevated in many thyroid diseases

 Insensitive & nonspecific test for thyroid
cancer
 Not helpful on its own
Serum calcitonin
 Prospective, nonrandomized studies suggest routine
serum calcitonin screening may detect C-cell
hyperplasia & MTC at an earlier stage and overall
survival may be improved
 Sensitivity, specificity, assay performance, and cost
effectiveness remain questionable
 Pentagastrin stimulation testing required to increase
specificity but no longer available in the US
 Unstimulated serum calcitonin > 100 pg/mL
indicative of MTC
Risk based approach to evaluation

H&P Imaging

Risk Stratification

Low risk High risk and/or

>1cm
Observe US FNA
Fine needle aspiration
Fine Needle Aspiration

 US guided FNA is the most cost effective

investigation
 USG FNA significantly more sensitive than
unguided FNA even for palpable nodule
 Ability to direct needle into region of highest
interest
 On site cytopathology to confirm sample
adequacy
Which nodule to biopsy?

 hypoechoic nodule
 irregular margins
 chaotic intranodular vascularity
 more-tall-than-wide shape
 Microcalcifications
 in complex thyroid nodules, sample solid
component BEFORE aspirating fluid
 if multiple nodules- sample largest and/or
most suspicious on ultrasound
Interpreting results of FNA

• Fine Needle Aspiration Reports

• Varies from pathologist to pathologist
• No uniform classification system
• Difficulty in reviewing the literature and
designing prospective studies
Interpreting results of FNA
 The Bethesda System for Reporting Thyroid Cytopathology was
developed to enhance the clarity of communication
 Recommends that each report begin with one of the six general
diagnostic categories
 Each of the categories has an implied cancer risk that links it to an
appropriate clinical management guideline
 Adoption of this framework will facilitate communication among
cytopathologists, endocrinologists, surgeons, and radiologists
 Facilitate cytologic–histologic correlation for thyroid diseases
 Facilitate research into the understanding of thyroid diseases
 Allow easy and reliable sharing of data from different laboratories for
national and international collaborative studies.
Interpreting results of FNA
FNA- Molecular Markers
 Indeterminate cytology, ‘‘follicular or Hurthle neoplasm’’ can be found in 15–30% of FNA
specimens (15–30% risk of malignancy)

 Atypical or follicular lesions of undetermined significance (FLUS) are variably reported (5–
15% risk of malignancy)

 Many molecular markers (galectin-3, cytokeratin, BRAF) have been evaluated to improve
diagnostic accuracy for indeterminate nodules

 Recent large prospective studies have confirmed the ability of genetic markers to improve
preoperative diagnostic accuracy for patients with indeterminate thyroid nodules

 It is likely that some combination of molecular markers will be used in the future to
optimize management of patients with indeterminate cytology on FNA specimens

 Recent ATA guidelines state: The use of molecular markers (e.g., BRAF, RAS, RET/PTC,
Pax8-PPARg, or galectin-3) may be considered for patients with indeterminate cytology on
FNA to help guide management
FNA- Molecular Markers

(14)

Nikiforov, Y. E. et al. J Clin Endocrinol Metab. 2009;94:2092-2098

FNA- Molecular Markers
 The detection of any mutation was highly predictive of
malignancy, and should provide a strong indication for
surgery
 Cytology + molecular status was more predictive of
malignancy than cytology alone
 This is of particular importance for the least worrisome
category of indeterminate cytology
 These patients would benefit most from molecular testing
 Accurate prediction of malignancy
 Eliminate delay in tx
 Avoid costs of repeat FNA
 Not cost effective to perform on all FNA’s- selective use
Surgical management
of suspicious or
malignant nodule
Surgical intervention

 For suspicious nodule/s appropriate thyroidectomy

followed by adjuvant treatment if indicated by path
report (example >4cm total thyroidectomy)

 For malignant nodule, appropriate treatment based

on cytology
Management of
low risk nodules
Risk based approach to evaluation

H&P Imaging

Risk Stratification

Low risk High risk

Observe US FNA
Nodules at Lower Risk for Cancer

Clinical Features Ultrasonography

 Female  Eggshell/amorphous calcification

 Stable size  Hyperechoic (colloid)
 Multinodular gland  Well defined margins
 No local symptoms  Presence of halo
 Prior benign FNA  Purely cystic
 Suppressed TSH  Round shape
 Low vascularity
 No invasion
 No abnormal LN’s
Rationale for continued follow up

 Up to 5% false-negative rate of benign FNA

 Most benign nodules exhibit slow growth

Recommendations for follow up

Easily palpable benign nodules

 US monitoring not required
 Follow clinically q 6-18m

All other benign nodules

 Monitor with serial ultrasound examinations
 First exam 6–18m after initial FNA
 Increase time (3-5y) to next follow-up
clinical examination / US if nodule is stable
Recommendations for re-biopsy
 No consensus on definition of nodule growth
or threshold for re-biopsy (US guided)

 > 20% increase in nodule diameter

with > 2 mm increase in > 2 dimensions

 > 50% change in volume

 False-negative rate for repeat FNA is low so

patients can continue to be followed carefully
Recommendations- long term
 Routine suppression therapy of benign
thyroid nodules in iodine sufficient
populations is not recommended
Recommendations- Children
 The diagnostic and therapeutic approach to
one or more thyroid nodules in a child should
be the same as it would be in an adult
(clinical evaluation, serum TSH, US, FNA)
Recommendations- Pregnancy
 Euthyroid and hypothyroid pregnant women
with thyroid nodules,
 FNA should be performed

 For women with low TSH levels that persist

after the first trimester, FNA may be deferred
until after pregnancy and cessation of
lactation, when a radionuclide scan can be
done
Recommendations- Pregnancy
 If PTC discovered early in pregnancy
 Monitored sonographically and if it grows by 24 weeks gestation,
surgery should be performed at that point

 If stable or diagnosed in the 2nd half of pregnancy

 Surgery may be performed after delivery

 More advanced disease

 Surgery in the 2nd trimester recommended

 Administration of LT4 therapy to keep TSH 0.1–1 mU/L.

Summary
 Assess risk of malignancy based on history &
physical findings in addition to imaging
characteristics
 Get further investigations based on risk
stratification
 Not all thyroid nodules need intervention or
surgery
 Understanding thyroid biology facilitates
successful outcome
Algorithm for thyroid nodule workup

ATA Guidelines 2009