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Thyroid Cancer
Steven W. Harris MHS, PA-C
Epidemiology

Annual Incidence of 23,600


3:1 female to male ratio
Increases with age

2% of clinically detected malignancies

14th Most common malignancy in the US

Falls behind:
 Lung
 Breast
 Prostate
 Colon
 Pancreas
 Bladder
2003 Estimated US Cancer Cases*
Men
675,300
Women
658,800
32% Breast
Prostate
33%
Lung & bronchus
14%
Colon & rectum
11%
Urinary bladder
6%
6%
Melanoma of skin
4%

Non-Hodgkin
lymphoma
Kidney
3%
Oral Cavity
3%
Leukemia
3%
Pancreas
2%
All Other Sites
17%
12% Lung
& bronchus
11% Colon
4%

& rectum
Uterine corpus
4% Ovary
4%Non-Hodgkin
lymphoma
3%
Melanoma
of skin
3%
Thyroid
2%
Pancreas
2%
Urinary bladder
20% All
Other Sites
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2003.
So WHY are we discussing this today?

Additional epidemiology

Incidence of thyroid cancer is growing faster
than any other malignancy


Treatment is highly effective




3.8 % annual increases from 1992 to 2001
> 95 % of all patients survive
> 300,000 thyroid cancer survivors in the US
All require monitoring for recurrent disease
PLUS…
So WHY are we discussing this today?
Thyroid Gland Anatomy



Largest endocrine gland, very vascular
Anterior and lateral sides of trachea
2 large lobes connected by isthmus
Thyroid Physiology

thyroid hormone secretion


controlled by TSH
hormones:
 Thyroxine
(3,5,3’,5- Tetraiodothyronine) T4
 greatest amount of thyroid hormone
 Triiodothyronine ( 3,5,3’, L-triidothyronine) T3
 most biologically active
 liver also converts T4 into T3 (80% of T3 via
liver)
 Reverse-Triiodothyronine
active thyroid hormone
RT3 minor biologically
Thyroid Anatomy & Physiology
thyroid hormone production strictly
dependent on Iodine
 90% of body stores of Iodine found in
thyroid gland most of which is bound to
thyroglobulin
 from dietary sources ~700ug day
 thyroglobulin in thyroid gland traps iodide
and oxidizes into iodine

Thyroid Hormone Effects
General Characteristics

Papillary carcinoma
76%

Follicular carcinoma
16%

Medullary carcinoma
4%

Lymphoma/metastatic
3%

Anaplastic carcinoma
1%
Distinguishing Characteristics.

Papillary carcinoma




Follicular carcinoma


Hematogenous metastasis
Medullary carcinoma



Lymphatic Metastasis
Least aggressive
Associated with increased dietary iodine
flushing, pruritus, and diarrhea
Associated with MEN-II
Anaplastic carcinoma


Generally pts over 60
Most Aggressive
Etiology and Pathogenesis

Genetic Predisposition

Familial syndrome
 Familial adenomatous polyposis (APC gene
mutation)
 Cowden syndrome: hamartoma (PTEN gene
mutation)
 Familial isolated papillary thyroid cancer
 Familial Multiple Endocrine Neoplasia
 MEN-II
10 % of all thyroid cancers

Etiology and Pathogenesis
Thyroid irradiation
 Accidental radioiodine exposure
 Radiotherapy: tonsillitis, lymphoma



Radioactive iodine fallout (I-131)


Common prior to 1950s
http://www.cancer.gov/cancer_information/doc.aspx?vie
wid=4ea8b4a2-b6d8-44b3-8e2f-7ce624a130d2
Unknown
Controversial Evidence
Preexisting benign thyroid conditions
 Parity
 Estrogen therapy
 Therapeutic radioiodine exposure
 Dietary Factors



Iodine intake
more papillary cancers in populations with
generous dietary iodine content.
Presentation

Common


Painless neck swelling
Palpable solitary nodule





Fixed
Stony/hard
Euthyroid
Incidental finding
Ipsilateral cervical
lymphadenopathy

Less common


Pain
Hoarseness



anaplastic
Hemoptysis
Dysphagia
A nodule or a NODULE?
Nodules found in 6% of females and 2%
of males
 5% - 10% are malignant
 Increased suspicion



Enlargement over weeks to months
Decreased suspicion


Stable size
Sudden appearance: hemorrhage
Workup of a nodule

TFT


Ultrasound


solid or cystic
Thyroid scan


usually normal
hot or cold
FNAB

histology
Thyroid Ultrasonography

dimensions of thyroid lobes or nodules


down to 1 mm
<1 cm no clinical significance
solid, cystic, or mixed
 suggests if papillary adenocarcinoma
 used for monitoring nodules


growth (i.e. not “normal tissue”) during TSH
suppression, may prompt repeat biopsy or surgery
Thyroid Imaging: Radionuclide Scanning

technetium (99mTc) or isotope of iodine (131I)
 99mTc can be concentrated, but not bound to TBG
and thus not stored in colloid, so some cold nodules
can appear warm
 131I –both concentrated & organified to TBG; scan
24 hours after oral 131I
 qualitative-size
 quantitative-uptake
 used to determine if nodule “Hot” or “Cold”
 almost all cancers are cold however most benign
lesions cold also
 replaced by fine needle biopsy as TOC for nodule
work-up
FNAB
Cold Nodule
Treatment: Papillary/Follicular

Total or near-total thyroidectomy


selective lymph nodes vs. radical neck
dissection
Adjunctive Radioactive Iodine ablation


Residual disease
TSH stimulation



thyroid hormone withdrawal
Recombinant TSH
Increased TSH, increases residual thyroid
tissue uptake of Iodine
Treatment cont.

TSH suppressing thyroid hormone therapy



Euthyroid
Suppression of tumor recurrence
Long-term follow-up to detect recurrent
disease





Circulating serum thyroglobulin
Thyroid ultrasound
CT of chest
Whole body scan
Repeat surgery
Treatment: Medullary
Thyroidectomy
 Thyroid replacement therapy



Not TSH suppression
Monitor with serial serum markers




Calcitonin
CEA
Repeat surgery
External beam radiotherapy
Treatment Lymphoma


Lymphoma
combined
chemotherapy and
radiation therapy

Anaplastic



typically nonresectable
treated with combined
external-beam
radiotherapy and chemo
therapy.
Only in exceptional
cases, however, do
these interventions
significantly alter the
grim prognosis.
Complications

Natural Course










Hoarseness
Dysphagia
Dyspnea
Esophageal
strangulation
Malnutrition
Pulmonary failure
Paresis
Bony fractures
Neurological cons.
Thyrotoxicosis

Treatment



Hoarseness
Hypoparathyroidism
Radioiodine


Gastritis
Sialoadenitis
 Dental caries
 Dry mouth

leukemia
Prognosis: post therapy

High survival rates



98% Papillary
92% Follicular
80% Medullary
33% of papillary tumors recur
 Extracervical medullary CA is incurable



Slow progression
Anaplastic cancers unfortunately can be
among the most aggressive and
treatment-resistant malignancies known
Monitoring
Evaluate thyroglobulin serum levels every
6-12 months for at least 5 years
 Repeat the nuclear scan 6-12 months
after ablation and, thereafter, every 2
years.



Before the scan, levothyroxine must be
withdrawn for approximately 4-6 weeks to
maximize thyrotropin (TSH) stimulation of the
eventual remaining thyroid tissue
OR
rTSH two days before scan
Check those thyroids!