thomas repas d.o. diabetes, endocrinology and nutrition center, affinity medical group, neenah,...

Thomas Repas D.O.Thomas Repas D.O.

Diabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, WisconsinDiabetes, Endocrinology and Nutrition Center, Affinity Medical Group, Neenah, WisconsinMember, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program Member, Diabetes Advisory Group, Wisconsin Diabetes Prevention and Control Program

Member, Inpatient Diabetes Management Committee, St. Elizabeth’s Hospital, Appleton, WIMember, Inpatient Diabetes Management Committee, St. Elizabeth’s Hospital, Appleton, WIChairman, Diabetes Steering Committee, AMG/NHP, Appleton, WIChairman, Diabetes Steering Committee, AMG/NHP, Appleton, WI

Tuesday March 15, 2005Tuesday March 15, 2005Website: www.endocrinology-online.comWebsite: www.endocrinology-online.com

Neoplastic Thyroid Disease:Neoplastic Thyroid Disease: Thyroid Nodules, Goiter, and Thyroid Thyroid Nodules, Goiter, and Thyroid

CancerCancer

Neoplastic Thyroid DiseaseNeoplastic Thyroid Disease

• Thyroid NodulesThyroid Nodules

• GoiterGoiter– MultinodularMultinodular– DiffuseDiffuse– EndemicEndemic

• Thyroid CancerThyroid Cancer– Well differentiated and poorly differentiatedWell differentiated and poorly differentiated

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

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 autonomous

nodule hyperfunction develop, resulting in thyrotoxicosis– Toxic MNG is more common in the elderly

Endemic Goiter

• No longer a problem in the US and the developed world

• Still a serious health concern in parts of the world with iodine deficiency including mountainous areas or areas with high rainfall/flooding

Kaplan, E. et al. Thyroid Disease Manager “Surgery of the Thyroid Gland” Chapter 21, May 99

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,

and 2.3% of cancers in women in the US– The annual rate has increased nearly 50% since 1973 to

approximately 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)

Initial Evaluation of a Thyroid Nodule/Mass

Risk factors for Malignancy

• Solitary thyroid nodules in patients >60 or <30 years of age

• Irradiation of the neck or face during infancy or teenage years

• Symptoms of pain or pressure (especially a change in voice)

• Male sex

• Large Nodules (>3 or 4 cm)

• Growth of nodule

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 & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.

Castro MR, et al. Endocr Pract. 2003;9:128-136.

Thyroid Ultrasonography


• Excellent for characterizing size and other features of nodule

• Useful in localizing nodule for FNA

• Cannot distinguish between benign vs. malignant


• 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

RAI imaging

• Formerly had been used extensively in the initial

work up of nodular thyroid disease

FNA is now considered the gold standard

RAI imaging

• The problem:

– Although “hot” nodules are usually never cancer, only 5% of all nodules are hyperfunctioning

– The remaining 90-95% that are warm or cold could be cancer and thus require FNA

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

Thyroid FNA

• Now considered the

most cost effective and

sensitive/specific

diagnostic test of thyroid

nodules

• The use of US has

expanded the role of

FNA in evaluating

nodules and improved

the validity of the results

Thyroid FNA

Possible FNA Results– Benign: 70 -75 %

– Malignant: Up to 5%

– Suspicious: About 10%

– Nondiagnostic: About 10 - 20%

Thyroid FNA

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

or small (<1cm) nodules

• Suspicious FNA (Follicular and Hurhtle cell neoplasm):

cannot distinguish benign vs malignant of hypercellular

nodules by FNA alone, ALWAYS require surgical pathology

for dx (up to 10 – 30% of these will be CA)

• Non-diagnostic results: NEVER consider equivalent to

benign, up to 10% of ND FNA will contain CA on resection

Management and Follow up

Management of Thyroid Nodules

Depends on FNA results (see algorithm)• Benign:

– False negatives rare, but be cautious in large (>4cm) or small nodules (<1cm) , repeat US in 6 to 12 months to assess for interval change

– Consider surgical resection if change or suspicious

• Malignant: – Surgery and RAI ablation

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

Non-diagnostic FNA

• About 15% of all FNA results• NEVER consider equivalent to benign

FNA• Up to 10% of ND FNA will contain CA on

resection• Be very cautious of a pathology report:

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

Non-diagnostic FNA cont’d

Three options:• Repeat FNA now- may get valid FNA on

repeat up to 30 – 50% of the time• Follow-up US in 6 months, repeat FNA or

resect then if any interval change• Surgical resection now- usually reserved

only for patients with history suggestive of increased risk or patients who are very anxious and do not want to wait

LT4 Suppression of Thyroid Nodules

LT4 Suppression of Nodules

• Although once more commonly used, it has begun to fall out of favor

• Some endocrinologists still recommend LT4 suppression for a TSH between 0.1 – 0.5

• However, studies demonstrate lack of efficacy or improved outcome

• There is significant risks associated with long term iatrogenic hyperthyroidism (loss of bone density, arrhythmias in the elderly, etc.)

LT4 Suppression of Goiter

• Patients with a MNG especially could later develop an autonomously functioning nodule with subsequent thyrotoxicosis if not followed closely

• Is useful for goiter suppression in patients with subclinical or overt hypothyroidism

• May also have a role in goiter patients with TSHs in the upper limits of normal (>3.0) who also have + thyroid autoantibodies (controversial)

Thyroid Carcinoma

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.

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

Types of Thyroid Cancer

• Papillary (80%-85%):Papillary (80%-85%): develops from thyroid follicle cells in 1 or both lobes; grows slowly but can spread

• Follicular (5%-10%):Follicular (5%-10%): common in countries with insufficient iodine consumption; lymph node metastases are uncommon

• Medullary:Medullary: develops from C-cells, can spread quickly; sporadic and familial types

• Anaplastic:Anaplastic: develops from existing papillary or follicular cancers; aggressive, usually fatal

• Lymphoma: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.

Papillary Thyroid Cancer

• Most common type

• Makes up about 80% of all

thyroid carcinomas in the United

States

• Females outnumber males 3:1– Highest incidence in women in

midlife

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.


Papillary Thyroid CancerCharacteristics

• 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

• <5% of patients have distant metastases at time of

diagnosis

– Lung is most common siteBraverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed.

Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000


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 nodes

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.



Follicular Thyroid Cancer

Follicular Thyroid CancerDiagnosis 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.


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 Thyroid Disease. Monticello, NY:Marcel Dekker, Inc.: 2001;239-241.

Hürthle 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

Hürthle Cell Tumor

Aytug S, et al. Hürthle 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 Thyroid Disease. Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.

Hürthle 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 & Ingbar’s The 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. Endocrine Tumors. Cambridge, MA: Blackwell; 1993:278-333.

Anaplastic Thyroid Cancer

• Extremely aggressive

and exceptionally

virulent

• Composed wholly or in

part of undifferentiated

cells


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


Anaplastic Thyroid Cancer (Continued)

• Tumor is typically hard, poorly circumscribed,

and fixed to surrounding structures

• Often occurs in the elderly population (mean

age: 65 years)

• 3-fold greater risk in iodine-deficient areas


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.

Medullary Thyroid CancerTypes

• 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, or familial non-MEN

medullary thyroid cancer

[median age=21 years])Braverman LE, Utiger RD, eds. Werner & Ingbar’s The 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.

Medullary Thyroid CancerMetastases

• Cervical lymph node metastases occur early

• Tumors >1.5 cm are likely to metastasize,

often to bone, lungs, liver, and the central

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

Primary Thyroid Lymphoma

• A rare type of thyroid cancer

– Affects fewer than 1 in

2 million people

• Constitutes 5% of thyroid

malignancies Large Cell Lymphoma of the Thyroid


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

Primary Thyroid LymphomaCharacteristics and Diagnosis

• Develops in the setting of pre-existing

lymphocytic thyroiditis

• Often diagnosed because of airway

obstruction symptoms

• Tumors are firm, fleshy, and usually pale



Ansell SM, et al. Semin Oncol. 1999;26:316-323.

Thyroid Cancer Cases Diagnosed in 2000

(N=18 000 )

Deaths by 2010(N=1426)

Papillary80%

Follicular14%

Anaplastic 1%Hürthle4% Papillary

50%

Follicular27%

Anaplastic 11%

Hürthle12%

Newly Detected and Fatal Cases of Thyroid Cancer

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

Recurrence and Death After Diagnosis of Thyroid Cancer

0

10

20

30

40

0 10 20 30 40 50

Years After Diagnosis

Cum

ulat

ive,

%

Recurrence

Death

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

N=1355

Etiology of Thyroid Cancers

• Usually unknown

• Radiation exposure

– Medical uses during childhood in the 1950s

– 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.

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 malignant neoplasms

Alsanea O, et al. Curr Opin Oncol. 2001;13:44-51.

Management and Follow up of Thyroid Carcinoma

Thyroid Cancer Risk Stratification

<45 years

Female

<2 cm

Intraglandular

Low

Absent

>45 years

Male

>4 cm

Extraglandular

High

Present

Low Risk High RiskIntermediate Risk

Mixture ofFeatures

Shaha AR, et al. Acta Otolaryngol. 2002;122:343-347.

Shaha AR. Cancer Control. 2000;7:240-245.

Age

Gender

Size

Extent

Grade

DistantMetastases

Treated, %

Death Rate, %

39

<1

39

13

22

53

Surgery

TotalThyroidectomy

LobectomyIsthmusecto

my

Intermediate and High Risk

Low Risk

Diagnosis of Thyroid Cancer

Shaha AR. Cancer Control. 2000;7:240-245.

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

Thyroid Cancer Initial Treatment Strategy

RAI AblationPhysical ExamUltrasound

Thyroid Cancer Initial Treatment Strategy

Surgery

TotalThyroidectomy

LobectomyIsthmusecto

my

Intermediateand High RiskLow Risk

Diagnosis of Thyroid Cancer

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



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


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

Standard Treatment of Thyroid Cancer

Whole Body ScanTg Assay

SuppressionTherapy

TotalThyroidectomy

1 Year

RAIAblation





Mazzaferri EL, et al. Endocr Relat Cancer. 2002;9(4):227-247.

Standard Treatment of Thyroid Cancer Phases of Follow-Up

Initial surgeryRAI ablation

Whole body scanStimulated Tg

Suppressed Tg assayTSH assay

T4 assayNeck 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



Thyroid Stimulating Hormone Suppression in Patients With Thyroid Cancer

PituitaryTSH

ThyroidT4

-

+

PituitaryTSH

ThyroidT4

-

+

Normal Thyroid Cancer Patients

Minimum LT4 tosuppress TSH

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

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



Target TSH Suppression in Patients With Thyroid Cancer

<0.1 0.1 to 0.4 0.5 to 1

Low to Undetectable

Suppressed butDetectable Low Normal

• Most patients with no evidence of disease

• Persistent or recurrent disease

• High-risk patients

• Very low-risk patients

• Long-term survivors

TSH,mIU/L

Patients

Optimal TSH




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– TSH and T4

thomas repas d.o. diabetes, endocrinology and nutrition center, affinity medical group, neenah,...

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