Evaluation of Thyroid Nodulesand Abnormal TFT’s

Michael L. Tuggy, MD

Swedish Family Medicine, Seattle, WA

Case 1

• 42 y.o. male with no active medical problems. During your routine physical, note a thyroid nodule. Told by ENT last year not to worry about it.

• PE: 1 x 2cm R lower pole nodule.

What information do you want from the patient?

Age as a Risk Factor

• Age – young patients (<20 years of age)– thyroid nodules are much more likely to be

malignant (40-50%).– elderly (>60 years of age) -higher risk,

especially of more aggressive thyroid tumors.

Gender and Thyroid Nodules

• Gender – male -higher risk if nodule present– females

• have many more nodules

• less likely to be malignant.

• still have majority of thyroid cancers

Other major risks

• Radiation to head and neck. – 40% risk of thyroid cancer usually 25 years

later.– Exposed populations- Polynesian studies

• Family History of MEN II, Gardner’s Syndrome, Cowden’s disease.

Historical Red Flags

• Recent growth

• Soft tissue swelling

• Vocal changes

• Dysphagia

• Signs of thyroid dysfunction

Case 2• 26 y.o. Eritrean female with a 2-3 year history

of goiter. No symptoms but noted enlargement on right for 1 year.

• P.E.: 3x4 cm Right sided thyroid mass, firm, adherent to soft tissue.

What physical findings are worrisome?

How can you best clarify the nature of the nodule?

Physical Exam of the Thyroid

• Use both hands simultaneously to evaluate for symmetry

• Patient upright - screening exam• Patient supine with neck in extension-

detailed exam. Swallowing assists in elevating gland.

• Evaluation of other neck structures.• Voice changes (recurrent laryngeal nerve).

Exam while sitting

Supine Exam

Thyroid Scans

• Purpose – Determine function of the gland and/or a nodule

within the gland

• Hot nodules - usually independently functioning nodules – Rarely, rarely malignant

• Cold nodules - either adenoma or maligancy– 15% chance of malignancy in adults.

Thyroid Ultrasound

• Can identify presence of nodules.

• May be able to characterize follicular vs. solid.

• Not able to rule our malignant nodule

• Aid in biopsy.

Thyroid

Case 3

• 30 y.o. WF with enlarging cold benign thyroid adenoma (diagnosis from previous FNA biopsy).

• PE: 4 x 5 cm mass on Right

What do you do now?

Fine-Needle Aspiration• Best tool for determining pathology other than

surgical excision.

• Can be as high as 80 % sensitive and 95% specific.

• Operator dependent in obtaining adequate amount of tissue. 25 gauge needle is optimal.

• Should not be relied on if negative in patient with previous neck irradiation.– Multifocal tumors common.

Interpreting the Biopsy Report• What you get:

– benign (low probability)– indeterminate– suspicious (high probability)– inadequate specimen

• What it means:– benign - 90-95% likelihood it is benign– indeterminate- who knows?– suspicious- it’s malignant.– inadequate specimen - do it again (and again)

Thyroid Malignancies- Papillary• Most common

• 30% have node metastasis at diagnosis

• Radiation related

• Histologically, psammoma bodies distinguish from benign adenoma.

Thyroid Malignancies-Follicular

• 20 % of malignancies

• Distinguished from normal follicular adenomas by invasion of capsule or blood vessels.

• May be difficult to determine on FNA

Thyroid Malignancies- Medullary

• 5-10% of cases

• arise from the C cells which produce calcitonin

• diagnosis based on elevated thyrocalcitonin levels and thyroid nodule (cold)

Thyroid Malignancies- Anaplastic

• < 10%

• Highly aggressive with local extension at time of diagnosis.

• No suitable therapy

• Prognosis < 1 yr from diagnosis

Treatment• For all malignancies, excision of the the lobe (or if

post-radiation the entire gland).

• XRT- very specific and well tolerated- I131 therapy.

• Anaplastic tumors - palliative radiation and XRT.

• F/U after Rx: TSH antibody scan, I131 scan or newer tagged antibody test to look for metastasis.

What about those benign nodules?

• No specific treatment is needed.

• Thyroid suppression may shrink size of adenomas

• Not proven to be effective or necessary

• May hide malignancies - ? Periodic biopsies or scans.

Outcomes• Case 1. - Papillary cancer - 3 (+) nodes

– no metastasis at 5 year.

• Case 2. - Follicular cancer - 5 (+) nodes– lost to follow-up, negative at 1 year.

• Case 3. - Large adenoma with incidental 1 cm papillary carcinoma superior to nodule.– Negative I131 scan one year out.

Summary:Solitary Nodule Evaluation

• Do I scan first or FNA first?-– high risk - scan and FNA

• Is the nodule cold or hot?

• Cold - FNA biopsy

– low risk - FNA• if indeterminate- scan and re-biopsy or just re-biopsy.

• Can I believe the results of the biopsy?– Review results with pathologist and patient.

• Don’t suppress undiagnosed nodules - you need a diagnosis first.

Never assume a solitary thyroid nodule is benign. Prove it.

Evaluation of Abnormal Thyroid Function Tests

Part duex...

Case A.

• 19 y.o. BF with 3 month history of fatigue, weight loss, jitteriness and difficulty sleeping.

• Exam: diffusely enlarged, non- tender thyroid. No nodules.

• TSH: 0.1

• T4- 28!

What ya get...

• TSH- new assays very sensitive to thyroid state. (Tells you what the brain sees)

• Free T4, T3 levels - highly accurate (tells you what the body sees)

• T3-RU, total T3, T4 - no longer needed with new assays for free T3 and T4.

Hyperthyroid States• Suppresses TSH

• Elevated T4, T3 (one or both)

• DDx: – Graves, – acute thyroiditis– early pregnancy, molar pregnancy– exogenous hormone ingestion.– Toxic goiter– ? Congenital TSH deficiency (hypothyroid)

Hypothyroid States

• Elevated TSH (usually > 20), decrease T3, T4.

• DDx– Primary– severe illness– TSH tumor (pituitary) – Panhypopituitarism (low TSH)

Case B.• 29 y.o. trekker with complaint of fatigue for the

past 2 weeks while hiking at 12-15,000 ft., sore throat for the past 7 days

• Exam: mild erythema of lower neck

• Tender thyroid.

• Dx: Acute thyroiditis - De Quervain’s. (Type 1)

• Prognosis: good, self-limited.

• RX: ASA ii p.o. TID x 14 days.

Thyroiditis

• Type 1 Autoimmune Thyroiditis (Hashimoto's Disease Type 1) – 1A Goitrous

– 1B Nongoitrous

– Status Euthyroid with normal TSH level. Autoantibodies to Tg and TPO usually present.

Thyroiditis• Type 2 Autoimmune Thyroiditis

(Hashimoto's Disease Type 2) – 2A Goitrous (classic Hashimoto's disease)

– 2B Nongoitrous (primary myxedema, atrophic thyroiditis)

• Status Persistent hypothyroidism with increased TSH levels. Autoantibodies to Tg and TPO usually present. Some type 2B is associated with blocking-type TSH receptor autoantibodies.

Thyroiditis

– 2C Transient aggravation of thyroiditis • Status May start as transient thyrotoxicosis

(increased serum thyroid hormones with low thyroidal radioactive iodine uptake). Often followed by transient hypothyroidism. However, patients may show transient hypothyroidism without the preceding thyrotoxicosis. Autoantibodies to Tg and TPO present. Example: postpartum thyroiditis.

Thyroiditis

• Type 3 Autoimmune Thyroiditis (Graves' Disease) – 3A Hyperthyroid Graves' disease

– 3B Euthyroid Graves' disease • Status Hyperthyroid or euthyroid with suppressed

TSH. Stimulatory autoantibodies to the TSH receptor are present. Autoantibodies to Tg and TPO are also usually present.

Thyroiditis

– 3C Hypothyroid Graves' disease • Status Orbitopathy with hypothyroidism. Diagnostic

levels of autoantibodies to the TSH receptor of the blocking or stimulating variety may be detected. Autoantibodies to Tg and TPO are usually present.

Grave’s Management

• PTU or methimazole– PTU in pregnancy at lowest possible doses

• Beta-blockade: Propranolol 20-80mg q 8 or atenolol 50-100mg q day.

• Iodine (I131 therapy

• Dexamethasone 2mg q 6

Goiters

• Diffuse or multi-nodular enlargement

• Clinical trials suppressing TSH down to 0.5 to 1.0 show 58% had significant reduction in size compared to placebo (5%).

• I131 treatment will reduce size also but 25-40% will become hypothyroid over 5 years.

Summary

• Newest tests for TSH and T4/T3 levels allow for better diagnosis

• Auto-antibody testing less useful due to extensive overlap in thyroiditis.

• Many forms of thyroiditis are self-limited but should be followed q 3 months until resolved.

• Options for therapy for Grave’s disease.