F.

Scott Ross, MD Internal Medicine Hospitalist Associate Internal Medicine Clerkship Director Cleveland Clinic Florida

Thyroid disorders are the most common endocrine conditions encountered in clinical practice Almost all forms of thyroid disease are more common in women Increase in frequency with age

The thyroid gland primarily secretes thyroxine (T4) with peripheral conversion to bioactive triiodothyronine (T3) as required. Adequate iodine intake is imperative for thyroid hormone production

Pregnant and lactating women require 50% and 100%, respectively, more iodine intake than the general population.

80% of thyroid diseases are autoimmune:

Hashimotos, Graves disease

Others: subacute thyroiditis, goiter, thyroid nodules, thyroid cancer Primary thyroid problems 99%

Only < 1% are due to hypothalamic/pituitary disturbances

TSH is the best screening tool

Can be misleading
Central hypothyroidism

Non thyroid illness Sick Euthyroid Syndrome Gestational thyrotoxicosis

Screening TSH only

If symptoms TSH and Free T4

Elevated TSH

Low TSH

Hypothyroidism
Subclinical hypothyrodism TSH secreting tumor

Hyperthyroidism
Subclinical hyperthyroidism Central hypothyroidism

99% of T4 is bound T4

Hypothyroidism or euthyroid with Thyroid Binding Globulin (TBG) Anabolic steroids, liver disease, steroid excess, nephrotic syndrome

T4

Hyperthyroidism or euthyroid with TBG Estrogen, tamoxifen, hepatitis, biliary cirrhosis

Free T4

Hyperthyroidism Hypothyroidism 80% from peripheral conversion of T4

T3

A 42 yo woman is seen for palpitations. She has lost 20# in the past 2 months. PE: HR=120 bpm, (+) tremor, (-) proptosis or obvious goiter (difficult exam though non-tender). T4=18.3 (512), TT3=230 (60-160), TSH<0.04. The appropriate next step includes: A. Thyroid scan B. Thyroid antibodies C. Obtain a TSI D. Begin therapy with PTU E. RAI ablation

A 42 yo woman is seen for palpitations. She has lost 20# in the past 2 months. PE: HR=120 bpm, (+) tremor, (-) proptosis or obvious goiter (difficult exam though non-tender). T4=18.3 (512), TT3=230 (60-160), TSH<0.04. The appropriate next step includes: A. Thyroid scan B. Thyroid antibodies C. Obtain a TSI D. Begin therapy with PTU E. RAI ablation

Hyperthyroidism:

Increased thyroid hormone synthesis

Thyrotoxicosis:

Includes all causes of excess thyroid hormone including hyperthyroidism, thyroiditis and exogenous thyroid hormone excess

Decreases in TSH suggest hyperthyroidism

decreased TSH with normal T4 subclinical hyperthyroidism decreased TSH with low T4 seen in non-thyroidal illness and pituitary defect
Graves INCREASED UPTAKE Toxic adenoma Toxic MNG Thyroiditis [painful (deQuervains), painless (lymphocytic)] Exogenous T4 Ectopic

DDX

DECREASED UPTAKE

A state of increased tissue exposure to increased circulating thyroid hormone. It is a syndrome, not a diagnosis

Etiology:
90% Graves/toxic multinodular goiters 10% Thyroiditis < 1% TSH tumors, struma ovarii Choriocarcinoma Iodine induced

Exogenous:

No goiter, elevated T4/T3, decreased uptake

Usually in patients taking synthroid by accident or

intentionally

Toxic multinodular:

lumby/bumpy, patchy scan, uptake may be high, low or normal High Uptake scan

Autoimmune: Hot nodules

Graves (Diffuse Toxic Goiters) goiter with hyperthyroidism

Autoimmune process characterized by the production

of Thyroid Stimulating Immunoglobulins

Leads to stimulation of autonomous thyroid gland function

Factors associated include family history, other

autoimmune disease, stressors, some viral illnesses

 Tachycardia, elevated systolic blood pressure with a widened pulse pressure Palpable goiter classically smooth Thyrotoxic stare due to lid retraction, proptosis and infrequently an infiltrative dermopathy Depression, CHF, myopathy, chronic diarrhea, anovulation, gynecomastia Heat intolerance , tremors, weight loss, etc.

TSH with Normal Free T4 When to Treat:

Older Patients TSH < 0.1 Osteoporosis Heart Disease Symptoms Goiter Thyroid tests in upper of normal range Increased Radioiodine uptake Hyperlipidemia

A non-autoimmune inflammation of the thyroid gland usually self-limiting Typically follows an URI or acute viral syndrome Gland is firm and painful. Malaise, fever, elevated ESR and high thyroglobulin levels Radioactive iodine uptake in decreased Treatment is supportive with NSAIDs

Beta Blockers for symptomatic relief

A 42 yo woman is seen for palpitations. She has lost 20# in the past 3 months. PE: HR=120 bpm, (-) proptosis or obvious goiter (difficult exam though nontender). T4=18.3, T3=230, TSH<0.04. Thyroid scan shows very low uptake. Serum thyroglobulin was undetectable. The likely dx: A. Hashimotos thyroiditis B. DeQuervains thyroiditis C. Graves disease D. Thyrotoxicosis factitia

A 42 yo woman is seen for palpitations. She has lost 20# in the past 3 months. PE: HR=120 bpm, (-) proptosis or obvious goiter (difficult exam though nontender). T4=18.3, T3=230, TSH<0.04. Thyroid scan shows very low uptake. Serum thyroglobulin was undetectable. The likely dx: A. Hashimotos thyroiditis B. DeQuervains thyroiditis C. Graves disease D. Thyrotoxicosis factitia

The lack of uptake on scan rules out Graves disease and the low level of thyroglobulin rules out thyroiditis (painless or painful). Tg helps differentiate between exogenous T4 (Tg low) and thyroiditis (Tg) normal or high (at least on board exams)

A 56 yo man is admitted to the hospital ICU with sepsis and a GI bleed. On the 7th hospital day TFTs reveal: FT4=0.8 (0.8-1.4), TT3=30 (60160), TSH=0.02. You should: A. Start therapy with T4 B. Start therapy with T3 C. Institute no thyroid hormone treatment D. Start Rx. with hydrocortisone then T4

A 56 yo man is admitted to the hospital ICU with sepsis and a GI bleed. On the 7th hospital day TFTs reveal: FT4=0.8 (0.8-1.4), TT3=30 (60160), TSH=0.02. You should: A. Start therapy with T4 B. Start therapy with T3 C. Institute no thyroid hormone treatment D. Start Rx. with hydrocortisone then T4

There is no data to suggest that thyroid hormone replacement in euthyroid sick syndrome is helpful. There is a correlation between reduced survival and low levels of T4.

Post-partum Graves Disease:

Proptosis, thyroid bruit, and dermography are in favor

of Graves as etiology TSH receptor antibodies will be positive in Graves Can treat with PTU safe during pregnancy

Post-partum thyroiditis: Subacute Lymphocytic Thyroiditis

Treated with observation and beta blockers in the

thyrotoxic phase Can be followed with a hypothyroid recovery phase and then euthyroid Usually self-limiting approx. 12 months.

How do you tell the difference between Post-partum Thyroiditis and Sheehans Syndrome

Never order thyroid scan or give radioactive iodine for any reason to a women who might be pregnant or nursing.

Graves, toxic multi-nodular goiter and autoimmune thyroid nodule

Anti-thyroid drugs
PTU or methimazole

Surgical resection Radioactive Iodine The patient must be euthyroid prior to radioactive iodine administration or surgery Not used in patients with severe Graves ophthalmopathy Complication is always Hypothyroidism

Beta Blockers for Symptom relief

Atrial Fibrillation

Atrial flutter, PAT

Thyrotoxic Heart Disease Thyroid Crisis/Storm Graves Orbitopathy

An elderly man comes to see you in the clinic. His wife died last year and he has been depressed and lost some weight. History of HTN on toprol XL. He smokes 1 pack per day for 30 years. BP: 128/80, pulse: 89 PE is unremarkable Labs all normal CBC, CMP, CXR What should you order next?

Typically seen in elderly population

Lacks usually presentation Presents with only atrial fibrillation, new-onset atrial fibrillation, depression, withdrawn behavior, poor attention, weight loss

Risk factors:

Family history of autoimmune hypothyroidism, post-partum women, head and neck irradiation/surgery, other autoimmune endocrine conditions (type I DM, adrenal insufficiency, ovarian failure. Increased risk celiac disease, vitiligo, pernicious anemia, Sjogrens syndrome Develops more frequently in individual with Downs and Turners syndromes

Hashimotos thyroiditis is the most common cause of hypothyroidism in US

Chronic autoimmune thyroiditis with lymphocytic infiltration Women > Men (10 x) Antibodies are created to thyroglubulin and thyroid peroxidase Can imitate Graves
Uptake will be low

Slowing of metabolism:

Fatigue, slow movement and speech, cold intolerance, constipation, weight gain, delayed relaxation of DTRs, bradycardia Coarse hair and skin, puffy face, macroglossia, hoarseness

Accumulation of glycosamonioglycans:

Others:

Pericardial effusion, HTN, hyperlipidemia, obstructive sleep apnea, elevated prolactin, carpal tunnel syndrome, hyponatremia

Primary hypothyroidism:

Low T4, High TSH

Low T4, inappropriately low TSH Normal T4, elevated TSH

Central hypothyroidism:

Subclinical hypothyroidism:

Primary thyroid disease is responsible for 95% of cases of hypothyroidism

Clinically euthyroid TSH > 4.0, T4 normal Associated with high LDL cholesterol Increase risk for CAD Should treat with thyroxine if antithyroid antibodies are present or TSH > 10 or hyperlipidemia noted

Amiodarone:

Iodine comprised 40% of the drug by weight May cause a drug induced thyroiditis Iodine excess can lead to hypo- or hyperthyroidism
Causes decreased radioactive iodine uptake

Lithium:

Decreases the synthesis and secretion of thyroid hormone

Associated with goiter and hypothyroidism

Physical exam:

Fever, tachycardia, changes in mental status and history of marked hyperthyroidism. Almost anything can precipitate this condition:
Patient usually suffers from a relative adrenal insufficiency secondary to thyroid overload and stress on body Treatment:

Surgery, trauma, infection, iodine load

Steroids (glucocorticoids) Most important aspect of treatment Beta blockers Iodine PTU/methimazole

Severe hypothyroidism

Leads to decreased mental status, hypothermia, hyponatremia, hypoventilation and hypoglycemia Precipitating events:
Infection, acute MI, cold exposure, sedatives

Always consider associated adrenal insufficiency

ALWAYS give steroids

Give IV thyroxine - PO poorly absorbed due to edema

TSH, Free T4 Ultrasound Fine Needle Aspiration First step is to obtain a complete history and physical to determine if thyroid function is normal. More common in females, increases with age. Almost always benign

Is it Cancer? - FNA Is it associated with thyroid dysfunction? TSH Is it causing a compression effect? MRI/CT
Nodules smaller than one cm appears to have low risk for malignancy and can be monitored without FNA Ultrasound showing calcifications, irregular borders and increased blood flow have increased risk for malignancy

Family history of thyroid cancer History of neck irradiation Firm, fixed, fast growing nodule (3 Fs) Dysphagia Respiratory Obstruction Cervical lymphadenopathy New nodule, age < 20 or > 60

If patient is euthyroid with a single palpable nodule, FNA may be done bypassing the nuclear thyroid scan. If there are several cold nodules concentrate of the largest one for FNA If FNA is indeterminate, repeat study

If result is still indeterminate, send the patient for surgical evaluation for removal

Results:

If benign findings, no further work-up is indicated Malignant Findings, surgery Insufficient Number of cells, repeat FNA Indeterminate, repeat FNA, if same result, resection is indicated.

Should be performed in patients who are hyperthyroid to determine if the nodule is autonomous (HOT) or hypofunctioning (COLD) Malignancy in HOT nodules is rare and surgery is seldom required Overt hyperthyroidism is seen when nodule is > 3 cm in diameter

Papillary carcinoma is the most common subtype

Dissemination is via lymphatic drainage into lymph nodes.

Spreads by hematogenous route. Rarely causes thyrotoxicosis

Follicular carcinoma

Medullary carcinoma

Production of calcitonin Highly related to other neuroendocrine tumors Associated with MEN-type 2A and MEN 2B

Anaplastic carcinoma presents as a thyroid mass with compressive neck surgery

Extremely poor prognosis and overall outcomes

Surgery is the treatment of choice for differentiated cancer. After initial surgery, all patients should receive levothyroxine both to prevent hypothyroidism and to minimize potential TSH stimulation of further tumor growth.

Radioactive iodine is then administered postoperatively to patients who have multiple tumors of the thyroid gland, large tumors, locally invasive tumors or remote metastases. May improve survival in patients with papillary and follicular tumors

*** TSH should be kept < 0.1 ***

Thyroid Cancer Follow-up

Periodic total body scans Periodic thyroglobulin levels

Risk of Recurrent Cancer

Tumor size > 4 cm Age > 40 at diagnosis Direct invasion of local structures Distant metastasis Poor tumor differentiation Mediastinal or cervical lymph node metastasis Extensive capsular and vascular invasion