Neoplastic Thyroid Disease.thyroid Nodules Goiter and Thyroid Cancer

7/30/2019 Neoplastic Thyroid Disease.thyroid Nodules Goiter and Thyroid Cancer

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Thomas Repas D.O.

Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, Wisconsin

Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control ProgramMember, Inpatient Diabetes Management Committee, St. Elizabeths Hospital, Appleton, WI

Chairman, Diabetes Steering Committee, AMG/NHP, Appleton, WI

Tuesday March 15, 2005

Website: www.endocrinology-online.com

Neoplastic Thyroid Disease:Thyroid Nodules, Goiter, and Thyroid

Cancer


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Neoplastic Thyroid Disease

Thyroid Nodules

Goiter

Multinodular

Diffuse

Endemic

Thyroid Cancer

Well differentiated and poorly differentiated


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Thyroid Nodular Disease

Thyroid gland nodules are common in the

general population

Palpable nodules occur in approximately 5%of the US population, mainly in women

Most thyroid nodules are benign

Less than 5% are malignant Only 8% to 10% of patients with thyroid nodules

have thyroid cancer


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Multinodular Goiter (MNG)

MNG is an enlarged thyroid gland containing

multiple nodules

The thyroid gland becomes more nodular with

increasing age In MNG, nodules typically vary in size

Most MNGs are asymptomatic

MNG may be toxic or nontoxic

Toxic MNG occurs when multiple sites of autonomousnodule hyperfunction develop, resulting in

thyrotoxicosis

Toxic MNG is more common in the elderly


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Endemic Goiter

No longer a problemin the US and thedeveloped world

Still a serious healthconcern in parts ofthe world with iodinedeficiency includingmountainous areasor areas with highrainfall/flooding

Kaplan, E. et al. Thyro id Disease ManagerSurgery of the Thyroid Gland Chapter 21, May 99


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Thyroid Carcinoma

Incidence Thyroid carcinoma occurs relatively infrequently compared to the

common occurrence of benign thyroid disease

Thyroid cancers account for only 0.74% of cancers among men, and2.3% of cancers in women in the US

The annual rate has increased nearly 50% since 1973 toapproximately 18 000 cases

Thyroid carcinomas (percentage of all US cases) Papillary (80%)

Follicular (about 10%)

Medullary thyroid (5%-10%)

Anaplastic carcinoma (1%-2%)

Primary thyroid lymphomas (rare)

Metastatic from other primary sites (rare)


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Initial Evaluation of a Thyroid

Nodule/Mass


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Risk factors for Malignancy

Solitary thyroid nodules in patients >60

or 3 or 4 cm)

Growth of nodule


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Evaluating Thyroid Nodules

TSH measurement

Ultrasound of the thyroid

Fine needle aspiration

Radioactive iodine imaging

Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.

Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and

Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Castro MR, et al. Endocr Pract. 2003;9:128-136.


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Thyroid Ultrasonography


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Excellent for

characterizing size and

other features of nodule Useful in localizing

nodule for FNA

Cannot distinguish

between benign vs.

malignant


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Certain features may suggest greater risk of cancer:

Irregular or poorly defined borders of nodule

Lack of a "halo

Hypo-echogenicity

Evidence of microcalcifications Increased blood flow

Growth and interval change on serial

ultrasounds


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RAI imaging

Formerly had been used extensively in the initial

work up of nodular thyroid disease

FNA is now considered the gold standard


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RAI imaging

The problem:

Although hot nodules are usually

never cancer, only 5% of all nodulesare hyperfunctioning

The remaining 90-95% that are warm

or cold could be cancer and thusrequire FNA


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RAI imaging

Circumstances where RAI imaging may be

useful and indicated:

Suppressed TSH (more likely to have a

autonomously functioning nodule)

Multiple nodules, none dominant Other


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Thyroid FNA

Now considered the

most cost effective and

sensitive/specific

diagnostic test of thyroidnodules

The use of US has

expanded the role of

FNA in evaluatingnodules and improved

the validity of the results


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Thyroid FNA

Possible FNA Results

Benign: 70 -75 %

Malignant: Up to 5%

Suspicious: About 10%

Nondiagnostic: About 10 - 20%


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Thyroid FNA

Limitations

False negatives: (< 5% of FNA) more likely in large (>4cm)

or small (


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Management and Follow up


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Management of Thyroid Nodules

Depends on FNA results (see algorithm)

Benign:

False negatives rare, but be cautious in large(>4cm) or small nodules (


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Suspicious FNA

About 10% of all FNA results

CANNOT distinguish benign vs malignant

of hypercellular nodules (follicular/Hurthle

cell) by FNA alone

ALWAYS require surgical resection for dx

Up to 10 30% of these will be malignant


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Non-diagnostic FNA

About 15% of all FNA results

NEVER consider equivalent to benignFNA

Up to 10% of ND FNA will contain CA onresection

Be very cautious of a pathology report:

consistent with benign colloid nodule; iflimited/no follicular epithelial cells noted,then this is a ND FNA rather than benign


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Non-diagnostic FNA contd

Three options:

Repeat FNA now- may get valid FNA onrepeat up to 30 50% of the time

Follow-up US in 6 months, repeat FNA orresect then if any interval change

Surgical resection now- usually reserved

only for patients with history suggestive ofincreased risk or patients who are veryanxious and do not want to wait


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LT4 Suppression of Thyroid

Nodules


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LT4 Suppression of Nodules

Although once more commonly used, it hasbegun to fall out of favor

Some endocrinologists still recommend LT4suppression for a TSH between 0.1 0.5

However, studies demonstrate lack of efficacy orimproved outcome

There is significant risks associated with longterm iatrogenic hyperthyroidism (loss of bonedensity, arrhythmias in the elderly, etc.)


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LT4 Suppression of Goiter

Patients with a MNG especially could laterdevelop an autonomously functioning nodulewith subsequent thyrotoxicosis if not followed

closely

Is useful for goiter suppression in patientswith subclinical or overt hypothyroidism

May also have a role in goiter patients withTSHs in the upper limits of normal (>3.0) whoalso have + thyroid autoantibodies(controversial)


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Thyroid Carcinoma


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Typical Presentation of

Thyroid Cancer

Painless lump

Normal thyroid function tests

Found on routine examination or by the patient

Slow growth or no growth over several months

Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.

Thyroid Disease Manager Web site. Available at:

http://www.thyroidmanager.org. Accessed December 10, 2003.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.


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Newly Diagnosed Cancer in the

United States

Breast

Prostate

Lung

Colon

Lymphoma

Leukemia

Kidney

Thyroid

Multiple Myeloma

Hodgkin

0 50 100 150 200 250

Thyroid Cancer

22 000 new cases

1400 deaths

Cancer facts and figures.

American Cancer Society Web

site. Available at:

http://www.cancer.org/downloads/

STT/CAFF2003PWSecured.pdf.Accessed December 10, 2003.New Cases, Thousands


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Types of Thyroid Cancer

Papillary (80%-85%): develops from thyroid follicle cells in

1 or both lobes; grows slowly but can spread

Follicular (5%-10%): common in countries with insufficient

iodine consumption; lymph node metastases areuncommon

Medullary: develops from C-cells, can spread quickly;

sporadic and familial types

Anaplastic: develops from existing papillary or follicular

cancers; aggressive, usually fatal

Lymphoma: develops from lymphocytes; uncommon

Detailed guide: thyroid cancer. American Cancer Society Web site. Available at:http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.


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Papillary Thyroid Cancer

Most common type

Makes up about 80% of all

thyroid carcinomas in the UnitedStates

Females outnumber males 3:1

Highest incidence in women inmidlife

Detailed guide: thyroid cancer. American Cancer Society Web site. Available at:

http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.

Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org.Accessed December 10, 2003.

P ill Th id C


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Papillary Thyroid Cancer

Characteristics

Unencapsulated tumor nodule with ill-defined

margins

Tumor typically firm and solid

May present as nodal enlargement

Commonly metastasizes to neck and mediastinal

lymph nodes

40% to 60% in adults and 90% in children


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Follicular Thyroid Cancer

Second most common type

of thyroid cancer

Solid invasive tumors,

usually solitary and

encapsulated

Usually stays in the thyroid

gland, but can spread to the

bones, lungs, and central

nervous system Usually does not spread to

the lymph nodesThyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information

Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.

Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.

Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.

Follicular Thyroid

Cancer

F lli l Th id C


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Follicular Thyroid Cancer

Diagnosis and Prognosis

Most FTCs present as an asymptomatic

neck mass

If caught early, this type of thyroid cancer

is often curable

Tumors >3 cm have a much higher

mortality rateHebra A, et al. Solitary thyroid nodule. eMedicine Web site. Available at:http://www.emedicine.com/ped/topic2120.htm. Accessed December 10, 2003.

Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical

Information Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.

DeGroot LJ, et al. J Clin Endocrinol Metab. 1990;71:414-424.

Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of ThyroidDisease. Monticello, NY:Marcel Dekker, Inc.: 2001;239-241.


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Hrthle Cell Cancer

A variant of follicular

cancer that tends to be

aggressive

Represents about 3% to

5% of all types of thyroid

cancer High power magnification

Hrthle Cell Tumor

Aytug S, et al. Hrthle cell carcinoma. eMedicine Web site. Available at:

http://www.emedicine.com/med/topic1045.htm. Accessed December 10, 2003.

Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of ThyroidDisease. Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.

H thl C ll C


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Hrthle Cell Cancer

Prognosis

May be benign or malignant, based on

demonstration of vascular or capsular

invasion

Malignancies tend to have a worse

prognosis than other follicular tumors

and rarely respond to 131I therapy

Tend to be locally invasiveBraverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.

Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.

Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. EndocrineTumors. Cambridge, MA: Blackwell; 1993:278-333.


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Anaplastic Thyroid Cancer

Extremely aggressive

and exceptionally

virulent Composed wholly or in

part of undifferentiated

cells



Sherman SI. Lancet. 2003;361:501-511.

Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of MedicalInformation Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.

Anaplastic Th roid Cancer


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Anaplastic Thyroid Cancer

(Continued)

Tumor is typically hard, poorly circumscribed,

and fixed to surrounding structures

Often occurs in the elderly population (meanage: 65 years)

3-fold greater risk in iodine-deficient areas

Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.


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Medullary Thyroid Cancer

Tumor arising from the

calcitonin-secreting C-cells

of the thyroid gland

Mortality rate of 10% to

20% at 10 years Medullary (C-cell)Carcinoma




Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at:http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.



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Types

70% to 80% of cases are

sporadic disease

(median age=51 years)

20% to 30% are part of 3

familial autosomal

dominant syndromes

(MEN-2A, MEN-2B, orfamilial non-MEN medullary

thyroid cancer [median

age=21 years])Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text. 8th ed.Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.

Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at:http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.



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Metastases

Cervical lymph node metastases occur early

Tumors >1.5 cm are likely to metastasize,

often to bone, lungs, liver, and the centralnervous system

Metastases usually contain calcitonin and

stain for amyloid

Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at:

http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.

Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information

Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.

Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at:http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.


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Primary Thyroid Lymphoma

A rare type of thyroid

cancer

Affects fewer than 1in 2 million people

Constitutes 5% of thyroid

malignancies

Large Cell Lymphoma of the Thyroid

Braverman LE, Utiger RD, eds. Werner & IngbarsThe Thyroid: A Fundamental and Clinical Text.

8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.

Cabanillas F. Thyroid lymphoma. eMedicine Web site. Available at:http://www.emedicine.com/med/topic2271.htm. Accessed December 10, 2003.



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Characteristics and Diagnosis

Develops in the setting of pre-existing

lymphocytic thyroiditis

Often diagnosed because of airwayobstruction symptoms

Tumors are firm, fleshy, and usually pale

Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org.

Accessed December 10, 2003.

Braverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and

Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.Ansell SM, et al. Semin Oncol. 1999;26:316-323.

Newly Detected and Fatal Cases of


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Thyroid Cancer Cases

Diagnosed in 2000

(N=18 000 )

Deaths by 2010

(N=1426)

Papillary

80%

Follicular

14%

Anaplastic 1%Hrthle4% Papillary

50%

Follicular

27%

Anaplastic 11%

Hrthle

12%

Newly Detected and Fatal Cases of

Thyroid Cancer

Robbins R, et al.Adv Intern Med. 2001;46:277-294.

R d D th Aft


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Recurrence and Death After

Diagnosis of Thyroid Cancer

0

10

20

30

40

0 10 20 30 40 50

Years After Diagnosis

Cumulative,

%

Recurrence

Death

Mazzaferri EL, et al.Am J Med. 1994;97:418-428.

N=1355


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Etiology of Thyroid Cancers

Usually unknown

Radiation exposure

Medical uses during childhood in the1950s

Current medical uses in cancer

therapy

Nuclear accidents

Ron E, et al. Radiat Res. 1995;141:259-277.Tuttle RM, et al.Semin Nucl Med. 2000;30:133-140.


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Genetic Basis of Thyroid Cancer

Papillary and follicular thyroid cancer

Usually sporadic

Approximately 5% of patients have

other family members with thyroid

cancer

Rare genetic syndromes in which

thyroid cancer is associated with

other benign and malignantAlsanea O, et al. Curr Opin Oncol. 2001;13:44-51.


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Management and Follow up of Thyroid

Carcinoma


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Thyroid Cancer Risk Stratification

4 cm

Extraglandular

High

Present

Low Risk High RiskIntermediate Risk

Mixture of

Features

Shaha AR, et al.Acta Otolaryngol. 2002;122:343-347.Shaha AR. Cancer Control. 2000;7:240-245.

Age

Gender

Size

Extent

Grade

Distant

Metastases

Treated, %

Death Rate, %

39


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Surgery

Total

Thyroidectomy

Lobectomy

Isthmusectomy

Intermediate

and High RiskLow Risk


Shaha AR. Cancer Control. 2000;7:240-245.Kinder BK. Curr Opin Oncol. 2003;15:71-77.

Thyroid Cancer

Initial Treatment Strategy

Th roid Cancer


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RAI AblationPhysical Exam

Ultrasound

Thyroid Cancer

Initial Treatment Strategy

Surgery

Total

Thyroidectomy

Lobectomy

Isthmusectomy

Intermediateand High RiskLow Risk


Kinder BK. Curr Opin Oncol. 2003;15):71-77.

Sherman SI. Lancet. 2003;361:501-511.Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

Treatment of Thyroid Cancer With


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Treatment of Thyroid Cancer With

Radioactive Iodine

Destroys remnants of normal thyroid tissue

Destroys thyroid cancer cells Identifies distant metastases

Maximizes sensitivity and specificity of

serum thyroglobulin

Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.

Standard Treatment of


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Standard Treatment of

Thyroid Cancer

Whole Body Scan

Tg Assay

Suppression

Therapy

Total

Thyroidectomy

1 Year

RAI

Ablation

Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.

Mazzaferri EL, et al. J Clin Endocrinol Metab. 2003;88:1433-1441.


Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Mazzaferri EL, et al. Endocr Relat Cancer. 2002;9(4):227-247.

Standard Treatment of Thyroid Cancer


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Standard Treatment of Thyroid Cancer

Phases of Follow-Up

Initial surgery

RAI ablation

Whole body scan

Stimulated Tg

Suppressed Tg assayTSH assay

T4 assay

Neck examination

Phase 1Determine extent of disease

Treat detectable disease

Phase 2No detectable diseaseAt risk for recurrence

Phase 3Long-term disease-free survivor

Low risk for recurrence

Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.

Thyroid Stimulating Hormone Suppression


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Thyroid Stimulating Hormone Suppression

in Patients With Thyroid Cancer

Pituitary

TSH

ThyroidT4

-

+

Pituitary

TSH

ThyroidT4

-

+

Normal Thyroid Cancer Patients

Minimum LT4 to

suppress TSH

without thyrotoxicosisBraverman LE, Utiger RD, eds. Werner & Ingbars The Thyroid: A Fundamental and

Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.

Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.Sherman SI. Lancet. 2003;361:501-511.

Target TSH Suppression in Patients With


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Target TSH Suppression in Patients With

Thyroid Cancer


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Treatment of Thyroid Cancer

Summary

Papillary and follicular thyroid cancer Generally excellent prognosis

Risk for recurrence for as long as 30 years

Initial management Surgery and radioactive iodine

LT4 suppressive therapy Follow-up

Physical examination

Radioactive iodine scans

Serum Tg

Documents

Neoplastic Thyroid Disease.thyroid Nodules Goiter and Thyroid Cancer