Thyroid Disease PDF

THYROMEGALY AND GOITER, THYROID NODULE, NEOPLASTIC DISEASE, AND THYROIDITIS Clinical Medicine I Misty T. Justus, DMSc, PA-C  ◦ Thyroid Disorders Outline ◦ Hypothyroidism ◦ Hyperthyroidism ◦ Thyromegaly and Goiter ◦ Thyroid Nod...

THYROMEGALY AND GOITER, THYROID NODULE, NEOPLASTIC DISEASE, AND THYROIDITIS Clinical Medicine I Misty T. Justus, DMSc, PA-C  ◦ Thyroid Disorders Outline ◦ Hypothyroidism ◦ Hyperthyroidism ◦ Thyromegaly and Goiter ◦ Thyroid Nodule ◦ Thyroid Cancer ◦ Thyroiditis Thyroid Gland Hormonal Pathway ↑ TRH (thyrotropin-releasing hormone) from Hypothalamus ↑ TSH (thyroid stimulating hormone) from Anterior Pituitary ↑T3 (triiodothyronine) from Thyroid & ↑T4 (tetraiodothyronine, thyroxine) from Thyroid Gland Metabolize fats, proteins, & carbs, & helps maintain blood pressure, body temperature & heart rate  Metabolic Effects of Thyroid Hormones T3 & T4 ◦ Calorigenesis ◦ The ultimate catabolic hormone in nearly every tissue in the body ◦ Protein Metabolism ◦ Low levels stimulate protein synthesis & (+) protein balance ◦ Excess levels stimulate protein degradation & (-) nitrogen balance (not enough protein building) ◦ Carbohydrate Metabolism ◦ Low levels stimulate glycogen synthesis & glucose utilization ◦ Excess levels stimulate glycogenolysis & gluconeogenesis ◦ Lipid Metabolism ◦ Increase lipolysis & fatty acid oxidation ◦ Increase cholesterol synthesis a little, but increase cholesterol clearance even more ---> net effect is to decrease cholesterol  Thyroid Functions ◦ Increase the basal metabolic rate ◦ Control body temperature ◦ Affect protein synthesis ◦ Help regulate long bone growth (in conjunction with GH) ◦ Regulate protein, fat, & carbohydrate metabolism ◦ Produce calcitonin, regulating amount of calcium in the body through the parathyroid  Thyroid Functions ◦ T3 (Triiodothyronine) – Only about 20% of gland output – Shorter serum half-life – Most T3 produced by enzymatic peripheral conversion of T4 by de-iodination – Cells have 8x more affinity for T3  Thyroid Function ◦T4 (Thyroxine) – Primary gland output, about 80% – Longer serum half-life – Less physiologically active at cellular level  Thyroid Function Tests (TFTs) - complete ◦ TSH = hormone produced by anterior pituitary gland ◦ T3 (total) = bound & free T3 ◦ T3 uptake = measurement of unoccupied TBG, inver. propor. to TBG ◦ T4 (total) = bound & free T4 ◦ Free T4 = unbound T4, biologically active ◦ TBG = globulin that binds T3 & T4 ◦ FTI (free thyroxine index) = calculation of total T4 in face of abnormal TBG = total T4xT3 uptake/100 ◦ Ultra sensitive TSH & Free T4 ◦ Most accurate measurements of thyroid status  TSH Thyroid Stimulating Hormone – Acts directly upon the thyroid tissue to increase output of thyroxine – “Normal” range = 0.5 – 4.0 mU/L – Third-generation assays sensitive to 0.01  T3 Resin T3 (or T4) Uptake – Indirect inverse test of serum thyroid-binding proteins (TBP) – It is high when TBP is low – A high resin uptake means that a patient’s serum TBP is low or T4 is high – Used to correct total T4 for the effect of high or low binding – Normal range Total T3 = 75-220 ng/dL  Thyroxine or T4 Free vs. total T4 Protein binding & transport – Peripheral T4 is primarily bound to thyroxine-binding globulin (TBG) in the circulation Normal range fT4 = 0.8 – 1.8 ng/dL Normal range T4 = 4-11 mcg/dL  When to Test Thyroid Function Abnormal Thyroid Gland on Physical Exam Single or multiple nodules Diffuse Enlargement Pain Symptoms of Hyperthyroidism Symptoms of Hypothyroidism  When to Test Thyroid Function Screening Test All women (every 2-3 years) All men (every 4-5 years) Pregnancy Post-partum Neonatal screening  When to Test Thyroid Function Screening on Medication Thyroxine Replacement (every 6 months if stable) Anti-thyroid drugs (thionamides) Post-ablation Lithium Amiodarone (high iodine content) HYPOTHYROIDISM  Hypothyroidism ◦ Hypothyroidism = Clinical state of underproduction of T3 & T4 ◦ 95% = Primary hypothyroidism ◦ Failure of thyroid gland to produce T3 & T4 ◦ 5% = Secondary hypothyroidism ◦ Failure of anterior pituitary gland to produce TSH ◦ Subclinical Hypothyroidism = Asymptomatic, mild thyroid failure with normal T3 & T4, minimal elevation of TSH  Hypothyroidism: Epidemiology ◦ Affects 1% of general population & 5% of individuals > age 60 ◦ 0.3% of US population has primary hypothyroidism ◦ 4.3% subclinical hypothyroidism ◦ Highest in Caucasians & women, ↑ with age ◦ Women > Men ◦ Congenital Hypothyroidism is among the MC congenital diseases, incidence of 1/4000 newborns ◦ Increased risk seen in patients with: Family or personal hx of autoimmune diseases, women in postpartum period, primary pulmonary HTN, Genetic disorders, meds (lithium, amiodarone), age > 65 ◦ Iodine deficiency = Leading cause of hypothyroidism in developing countries ◦ Iodized salt has diminished the incidence of hypothyroidism Iodine Nutrition  Primary Hypothyroidism - Etiology ◦ Autoimmune Thyroiditis (Hashimoto disease) – Most common ◦ Annual mean incidence - 4:1000 women & 1:1000 men ◦ Peaks at ages 30-50 years ◦ 6% postpartum women = Transient form ◦ Iatrogenic/Damage to thyroid gland ◦ Surgery, radioactive iodine ablation, external irradiation therapy, chemotherapy ◦ Drugs/toxins: Iodine excess, lithium, antithyroid drugs, etc. ◦ Infiltrative diseases (amyloidosis, sarcoidosis, hemochromatosis, scleroderma) Primary Hypothyroidism – Clinical Presentation ◦ Onset is usually insidious ◦ Patient may become aware of symptoms only when euthyroidism is restored ◦ Patients with Hashimoto’s thyroiditis my presents with goiter (irregular & firm consistency) rather than sx’s Hypothyroidism - Differential Diagnosis Hashimoto’s thyroiditis Subacute thyroiditis Iodine deficiency Post-ablative Post-surgical Drugs Amiodarone Lithium  Thyroiditis: Hashimoto’s disease The basic defect is thought to be a genetic deficiency in antigen- specific suppressor T-cells Cytotoxic T cells attack follicular cells, along with unregulated T-helper cell proliferation & B cell autoantibody production Anti-TSH-receptor antibodies, anti-microsomal antibodies, anti- thyroglobulin antibodies, & other less frequently detected autoantibodies are directed against follicular cell membranes, colloid components, & the thyroid hormones  Hashimoto’s Thyroiditis ◦ Most common cause of hypothyroidism in North America ◦ 4/1000 women, 1/1000 men ◦ Found to be more prevalent in areas with high dietary iodine intake ◦ Smoking increases the risk ◦ Goiter, depression, & chronic fatigue are common ◦ Commonly seen in connection to other diseases: IBS, celiac disease, Turner’s syndrome, hepatitis C, adrenal insufficiency ◦ Diagnosis is made with elevated TSH, low thyroid hormone, & presence of anti-thyroid peroxidase antibodies ◦ May cause early transient hyperthyroidism by release of stored hormone during early destructive phase  Hashimoto’s Thyroiditis Marked facial swelling, peri-orbital edema Due to associated dilutional hyponatremia/SIADH syndrome Hashimoto’s Thyroiditis Same patient as in prior image Right - 6 months after restoration of normal thyroid function Severe Hypothyroidism - Myxedema  Myxedema Severe form of hypothyroidism in adults, characterized by dry skin, swelling around the lips & nose, mental deterioration, & a subnormal basal metabolic rate Characterized by firm inelastic edema, dry skin & hair, & loss of mental & physical vigor Myxedema coma: HIGH MORTALITY RATE Emergency Altered level of consciousness, seizures, other features of hypothyroidism Hypothermia, hypercapnea, hypoxia Primary Hypothyroidism – Diagnostic Evaluation ◦ ↑TSH ◦ ↓Free T4 ◦ Optional: ◦ Thyroid Auto Antibodies = ↑ in autoimmune thyroiditis ◦ Many hypothyroid patients have high serum cholesterol &/or triglyceride levels ◦ Make sure to screen for this as well Primary Hypothyroidism – Treatment & Monitoring ◦ Treatment: ◦ Levothyroxine (Synthroid) ◦ 50-200 mcg PO qd ◦ Start 1.6 mcg/kg PO qd then increase 12.5-25 mcg/day every 4-6 weeks ◦ Start low & increase slowly with elderly & cardiac pts ◦ Generally, once daily, 1 hour before a meal to maximize absorption ◦ Target dose = Normal TSH ◦ Usually lifelong treatment  Primary Hypothyroidism - Treatment & Monitoring ◦ Treatment: ◦ Current research indicates that in many instances, supplementation with both T3 & T4 may be superior to just T4 – considering the fact that many people do not process the T4 to T3 at a consistent rate ◦ To accomplish combination therapy: ◦ Armour thyroid ◦ Cytomel® (triiodothyronine) ◦ “Natural” compounds of T3 or T3/T4 Compounded T3/T4 is given either once or twice a day depending upon patient need/response Primary Hypothyroidism - Treatment & Monitoring ◦ Monitoring: ◦ Check TSH 4-6 weeks after start of treatment or dose change ◦ Stable pts. with normalized TSH – check TSH every 6-12 months ◦ Pregnant pts with Dx of hypothyroidism – TSH every 6 wks ◦ If patient continues to complain of hypothyroid symptoms after treatment is initiated & thyroid levels WNL, you must check for concurrent problems such as: – Adrenal insufficiency – Hypogonadism – Anemia – Depression  Secondary Hypothyroidism Hypothalamic or Anterior Pituitary gland dysfunction ◦↓TSH/dysfunctional TSH = ↓T3 & T4 ◦↓TRH if hypothalamic dysfunction/abnormality Secondary Hypothyroidism - Etiology ◦#1 = Pituitary adenoma ◦Any process that disrupts hypothalamic-pituitary function ◦Mass, infection, trauma, surgery, CVA, radiation, ischemia, cancer Secondary Hypothyroidism: Clinical Presentation ◦ Symptoms: ◦ Same as Primary hypothyroidism ◦ Possible symptoms of other pituitary hormone abnormalities ◦ Signs: ◦ Same as Primary hypothyroidism ◦ Possible: Vision changes, headaches, galactorrhea, skin pigmentation changes, acromegaly  Secondary Hypothyroidism: Diagnostic Evaluation ◦ TSH = Low, high, normal Coronal T1-weighted postcontrast MRI shows a homogeneously enhancing mass (arrowheads) in the sella turcica & suprasellar region compatible with a pituitary ◦ Free T4 = Low adenoma; the small arrows outline the carotid arteries. ◦ Serum Cortisol, PRL, LH & FSH, total Testosterone (men) ◦ MRI of Pituitary (CT as an alternative) Secondary Hypothyroidism: Treatment & Monitoring ◦ Treatment: ◦ Thyroxine replacement (same as Primary Hypothyroidism) ◦ Endocrine Consult ◦ Assessment & Management of underlying pituitary pathology ◦ Treat pituitary tumor – Radiation, Transphenoidal resection ◦ Treat adrenal insufficiency Secondary Hypothyroidism: Treatment and Monitoring ◦ Monitoring: ◦ Endocrinologist ◦ Initial Thyroxine dose titration based on Free T4 levels 24 hrs. after last dose then q4-8 weeks. ◦ Target = mid-upper range normal Free T4 levels ◦ TSH monitoring = NO VALUE HYPERTHYROIDISM  Hyperthyroidism ◦ Hyperthyroidism = ↑T3 & T4 (overproduction of thyroid hormones) ◦ Etiology: ◦ Graves Disease – TSH receptor antibodies ◦ Painless Lymphocytic Thyroiditis – Autoimmune-mediated inflammation ◦ Subacute Thyroiditis – Transient inflammation of thyroid ◦ Toxic Thyroid Adenoma – Typically single, large, hormonally active thyroid nodule ◦ Toxic Multinodular Goiter (MNG) – Most common in older pts Hyperthyroidism: Clinical Presentation  Graves Disease ◦Most common cause of hyperthyroidism ◦Pathophysiology: TSH receptor antibodies bind & activate the TSH receptor on the thyroid gland causing ↑ production of T3 & T4 ◦Signs & Symptoms unique to Graves disease = ◦Orbitopathy ◦Acropachy ◦Dermopathy (pretibial myxedema)  Graves Disease ◦ Features of Graves’ disease ◦ A. Ophthalmopathy in Graves’ disease; lid retraction, periorbital edema, conjunctival injection, & proptosis are marked ◦ B. Thyroid dermopathy over the lateral aspects of the shins ◦ C. Thyroid acropachy  Ophthalmopathy Upper eyelid retraction, lid lag, swelling, erythema, conjunctivitis, & bulging eyes (exophthalmos)  Acropachy Soft-tissue swelling of the hands & clubbing of the fingers Pretibial myxedema Skin lesions or areas of non- pitting edema on the anterior or lateral aspects of the legs or in sites of old or recent trauma Graves Disease: Diagnostic Evaluation ◦ ↓TSH ◦ ↑Free T3 & T4 ◦ ↑TSH receptor Abs ◦ ↑Thyroid radioactive iodine uptake (technetium 99) Graves Disease – Thyroid Radionucleotide Scan  Graves Disease: Treatment & Monitoring ◦ Treatment: ◦ Beta-Blockers ◦ Propranolol is generally used for symptomatic relief of tachycardia, tremor, diaphoresis, & anxiety until the hyperthyroidism is resolved ◦ Antithyroid Drugs ◦ Methimazole 10-30 mg/day PO given 1-3 divided doses ◦ Propylthiouracil 150-400 mg/day in 3 divided doses ◦ Thyroid replacement PRN ◦ Radioactive Iodine (I-131) – Ablates thyroid tissue ◦ Thyroidectomy – Total or subtotal Graves Disease: Treatment and Monitoring ◦ Thionamides (anti-thyroid) – Inhibit thyroid hormone synthesis ◦ Advantages: ◦ Chance of permanent remission (about 30-50%) ◦ May avoid permanent hypothyroidism ◦ Disadvantages: ◦ Minor side effects - rash, hives, GI, arthralgias ◦ Major SE: Risk of agranulocytosis 5% of the population ◦ Other causes include: ◦ Biosynthetic defects - Reduced efficiency of thyroid hormone synthesis, leads to increased TSH which stimulates compensatory thyroid growth to overcome the block in hormone synthesis ◦ Autoimmune disease ◦ Graves’ disease - TSH-R–mediated effects of thyroid-stimulating immunoglobulins ◦ Hashimoto’s thyroiditis - Lymphocytic infiltration & immune system–induced growth factors & acquired defects in hormone synthesis, consequent growth effects ◦ Nodular thyroid diseases - Disordered growth of thyroid cells which can be either hyperplastic or neoplastic Thyromegaly & Goiter: Management ◦Management is dependent on underlying etiology ◦The detection of thyroid enlargement on inspection or palpation during physical examination should prompt further evaluation to identify its cause  Diffuse Nontoxic (Simple) Goiter ◦ Epidemiology: Women > men ◦ Greater prevalence of underlying autoimmune disease ◦ Increased iodine demands associated with pregnancy ◦ Clinical Presentation: ◦ Most pts are asymptomatic if thyroid function preserved ◦ PE reveals symmetrically enlarged, nontender, & generally soft gland without palpable nodules ◦ If marked enlargement may have symptoms from compression of adjacent tissues  Diffuse Nontoxic (Simple) Goiter ◦ Diagnostic Evaluation: ◦ TFTs: TSH normal or slightly elevated, low total T4, with normal T3 (reflecting enhanced T4 → T3 conversion) ◦ TPO antibodies - Useful to identify patients at increased risk of autoimmune thyroid disease ◦ Low urinary iodine levels ( men ◦ Increases in prevalence with age ◦ MC in iodine-deficient regions but also occurs in regions of iodine sufficiency: multiple genetic, autoimmune, & environmental influences on the pathogenesis ◦ Typically wide variation in nodule size ◦ Wide spectrum of morphologies ranging from hypercellular, hyperplastic regions to cystic areas filled with colloid  Nontoxic Multinodular Goiter ◦ Physical Examination ◦ Thyroid gland is distorted ◦ Multiple nodules of varying size can be appreciated ◦ Often not possible to palpate all nodules as many nodules are deeply embedded in thyroid tissue or reside in posterior or substernal location ◦ Pemberton’s sign - Facial suffusion when the patient’s arms are elevated above the head ◦ Suggests that the goiter has increased pressure in the thoracic inlet ◦ Tracheal deviation is common – Inspiratory Stridor  Nontoxic Multinodular Goiter ◦ Diagnostic Evaluation ◦ TSH level - Usually normal, but should be measured to exclude subclinical hyper- or hypothyroidism ◦ PFT’s - Assess the functional effects of tracheal compression ◦ CT or MRI - Evaluate the anatomy of the goiter & the extent of substernal extension or tracheal narrowing ◦ Barium swallow - Reveal the extent of esophageal compression ◦ Ultrasonography - Identify which nodules should be biopsied based on a combination of size & sonographic features  Nontoxic Multinodular Goiter ◦ Treatment ◦ Most can be managed conservatively ◦ Contrast agents & other iodine-containing substances should be avoided ◦ Risk of inducing the Jod-Basedow effect - enhanced thyroid hormone production by autonomous nodules ◦ When acute compression occurs, glucocorticoid treatment or surgery may be needed ◦ Radioiodine has been used when surgery is contraindicated in areas where large nodular goiters are more prevalent  Toxic Multinodular Goiter ◦ Pathogenesis of toxic MNG appears to be similar to that of nontoxic MNG ◦ Major difference = Presence of functional autonomy in toxic MNG ◦ Clinical Presentation: ◦ In addition to features of goiter, the clinical presentation of toxic MNG includes subclinical or mild overt hyperthyroidism ◦ Patient is usually elderly & may present with: ◦ Atrial fibrillation or palpitations ◦ Tachycardia ◦ Nervousness ◦ Tremor ◦ Weight loss ◦ May have history of recent exposure to iodine (contrast dyes or other sources) that precipitated or exacerbate thyrotoxicosis  Toxic Multinodular Goiter ◦ Diagnostic Evaluation ◦ TSH is low ◦ T4 normal or minimally increased ◦ T3 often elevated to a greater degree than T4 ◦ Thyroid scan shows heterogeneous uptake (multiple regions of increased & decreased uptake) ◦ 24-h uptake of radioiodine may not be increased but is usually in the upper normal range ◦ US - Should be performed to assess the presence of discrete nodules corresponding to areas of decreased uptake (“cold” nodules) ◦ If present, fine-needle aspiration (FNA) may be indicated based on sonographic patterns and size cutoffs ◦ The cytology results, if indeterminate or suspicious, may direct the therapy to surgery TMG Radionucleotide Scan TMG Ultrasound  Toxic Multinodular Goiter ◦ Treatment ◦ Antithyroid drugs normalize thyroid function ◦ Particularly useful in the elderly or ill patients with limited lifespan ◦ Radioiodine is generally the treatment of choice – May need subsequent dose ◦ Treats areas of autonomy as well as decreasing the mass of the goiter by ablating the functioning nodules ◦ Surgery provides definitive treatment of underlying thyrotoxicosis as well as goiter ◦ Patients should be rendered euthyroid using an antithyroid drug before operation THYROID NODULE  Thyroid Neoplasia ◦ Neoplasm: A new & abnormal growth of tissue ◦ Tumor = Neoplastic mass ◦ Benign = Not malignant, not cancer ◦ Malignant = Cancer → Invasive, uncontrolled, metastatic ◦ Thyroid adenoma: Benign tumor of thyroid gland ◦ Adenoma = Benign tumor of glandular tissue ◦ Thyroid nodule: A thyroid mass – cystic or solid ◦ Could be benign or malignant  Thyroid Nodules ◦ Incidence: ◦ Female: Male = 3:1 ◦ 30% females at age 30 yrs. have nodule(s) - (detectable by US or autopsy) ◦ 50% females at age 50 yrs. have nodule(s) ◦ Detection: ◦ 40% self ◦ 30% physician (provider) ◦ 30% incidentally found on imaging ◦ Malignancy: ~10% ultrasound-detected nodules are malignant  Thyroid Nodules  Enlargement (goiter) may be diffuse or irregular (nodular)  Nodular goiter common in regions where iodine deficiency is prevalent  Past history of head/neck irradiation increases risk of thyroid nodules, including higher rate of thyroid cancer  Palpable solitary nodules are often benign adenomas or colloid nodules  Sometimes thyroid adenomas can function autonomously, enough to lead to thyrotoxicosis – toxic adenoma  Other pathology includes primary or metastatic neoplasms, thyroiditis, infections, & cysts  Evaluation of Thyroid Mass or Enlargement Evaluation of Thyroid Mass or Enlargement ◦ Imaging: ◦ Ultrasound of Thyroid – 1st choice ◦ Determine if one or multiple nodules ◦ Follow nodules clinically ◦ Guide difficult FNA ◦ Thyroid Scan (radionucleotide study) if ↓TSH ◦ To identify “Hot nodules”, distinguish between Graves disease vs. thyroiditis ◦ FNA is now used more that RAI scan ◦ CT, MRI: Seldom used due to expense & because US is more accurate ◦ Obtain Tissue: ◦ FNA = fine needle aspiration (preferred) ◦ Open Biopsy PRN  Thyroid Nodule US Sonographic patterns of thyroid nodules A. High suspicion ultrasound pattern for thyroid malignancy (hypoechoic solid nodule with irregular borders and microcalcifications) B. Very low suspicion ultrasound pattern for thyroid malignancy (spongiform nodule with microcystic areas comprising over >50% of nodule volume).  Thyroid Nodules: Radionucleotide Scan Cold (85%) Nodule Cells do not synthesize thyroid hormones (tissue is more abnormal) Do not take up Radioactive Iodine Appear white on thyroid scan 85% are benign → 15% malignant Warm (10%) Nodule Intermediate characteristics 90% benign → 10% malignant Hot (5%) Nodule Cells synthesize excess thyroid hormones Take up Radioactive Iodine Appear dark on thyroid scan 95% benign → 5% malignant The Nodular Thyroid: Diagnostic Evaluation  Fine needle aspiration (FNA) biopsy:  25-gauge needle  Care to avoid bloody dilution  Prepared on a slide, dried, & read by an experienced cytopathologist  70% benign, 10% suspicious, 5% malignant, 15% nondiagnostic US guided FNA  FNA Indications ◦ For solitary thyroid nodules, FNA is indicated for: ◦ Nodules >5mm diameter with suspicious appearance on US ◦ Nodules associated with abnormal cervical LN ◦ Nodules ≥ 1 cm diameter that are solid or have microcalcifications ◦ Mixed cystic-solid nodules >1.5 cm diameter with suspicious features or >2 cm with benign U/S appearance ◦ Spongiform nodules ≥ 2 cm Fine Needle Aspiration (FNA) - Thyroid FNA Thyroid – US guided  The Nodular Thyroid: Treatment Considerations  Regular follow-up & re-biopsy as indicated  Treat those nodules associated with elevated TSH with levothyroxine  Long-term suppression of TSH tends to keep nodules from enlarging, but few actually shrink; more useful in younger patients  Take care in treating patients with underlying cardiovascular disease, may increase risk for angina and/or arrhythmia  Levothyroxine suppression in postmenopausal women may cause loss of bone density Solitary Thyroid Nodule: Considerations  Solitary Thyroid Nodules:  FNA indicated  Cystic nodules – Remove the fluid & follow  Associated with hyperthyroidism -  Scan to distinguish toxic adenoma from Graves’ disease and include antithyroid antibody tests  “Hot” nodules usually benign, but removed to cure the hyperthyroidism  Hyperfunctioning Solitary Nodule: Toxic Thyroid Adenoma ◦ Toxic Thyroid Adenoma: ◦ Often single large thyroid nodule causing hyperthyroidism (↑T3 & T4) ◦ Requires Tx - does not spontaneously regress ◦ H&P: ◦ Possible C/O choking sensation, dysphagia, hoarseness ◦ Typical hyperthyroid sx ◦ Often palpable thyroid nodule ◦ Diagnosis: ◦ Thyroid scan showing single “hot” area & suppression of extranodular tissue  Hyperfunctioning Solitary Nodule: Toxic Thyroid Adenoma Treatment: ◦ Symptomatic Tx PRN (beta-blockers for tachycardia, etc.) ◦ Radioactive Iodine is treatment of choice (non-pregnant pt.) ◦ Subtotal thyroidectomy (PRN) ◦ Antithyroid drugs in pregnancy: ◦ Propylthiouracil – 1st trimester ◦ Methimazole – 2nd & 3rd trimester Nonpalpable (Incidental) Thyroid Nodule: Considerations  Nonpalpable Thyroid Nodules:  Detected in about 50% of neck scans like MRI, CT, or US done for other reasons  FNA only if the nodule is found to be larger than 1.5cm or in prior history of head/neck irradiation The Nodular Thyroid: Prognosis  Vast majority are benign, conversion rare  Only 1% increase in size with follow-up  Multinodular goiters persist or grow slowly  Incidental nodules rarely malignant THYROID CANCER  Thyroid Cancer  Epidemiology:  Incidence increases with age  Female:Male ratio is 3:1  Associated with past history of regional irradiation  Accounts for 1500 deaths in the U.S. annually  Clinical Presentation:  Most commonly - asymptomatic thyroid nodule found on palpation or ultrasound in a female 30-40 years of age  May have painless swelling  Thyroid Cancer  Diagnostic Evaluation  TFTs usually normal  US to determine size, location of masses  *Positive FNA biopsy  Radioisotope scans for bone metastases, as well as CXR, CT  Most differentiated thyroid cancers secrete thyroglobulin, so can be used as a marker after thyroidectomy (treatment)  Treatment:  Total thyroidectomy + radioactive iodine ablation + TSH suppression (high dose levothyroxine (papillary or follicular))  Tailored Tx for uncommon types (medullary, lymphoma, anaplastic)  Thyroid Cancer Histological Types 80-85%% - MC Papillary: Usually well differentiated & multifocal Lymphatic invasion & spread >90% 10-year survival, recurrence, & metastasis risk = low 10% Follicular: Direct hematogenous invasion & spread often with systemic metastasis Slightly worse prognosis than papillary 4% Medullary: Early lymph node spread 80% 5-year survival Anaplastic: Rare (survival = a few months) Lymphoma: Rare (80% stages I or II) & have an excellent prognosis  Mortality is markedly increased in stage IV disease, especially in the presence of distant metastases (1% of pts)  Follicular Carcinoma (FTC)  Accounts for ~5-10% of thyroid cancers dx in the US  Usually more aggressive than papillary thyroid CA  Can secrete enough thyroxine to cause overt thyrotoxicosis  Metastasis common to neck nodes, bone, lung, & CNS  Mortality rates less favorable than for PTC, in part because a larger proportion of patients present with stage IV disease  Poor prognostic features include:  Distant metastases  Age >50 years  Primary tumor size >4 cm  Hürthle cell histology  Presence of marked vascular invasion  Medullary Thyroid Carcinoma  3-5% of thyroid cancers  1/3 are sporadic - (onset ~ 50y/o)  Remainder familial - associated with MEN IIA & IIB or familial MTC without other features of MEN  All patients with MTC should be tested for RET mutations, because genetic counseling & testing of family members can be offered to those individuals who test positive for mutations  The management of MTC is primarily surgical - Prior to surgery pheochromocytoma should be excluded in all patients with a RET mutation  Elevated serum calcitonin provides a marker of residual or recurrent disease THYROIDITIS “Inflammation of the thyroid gland”  Subtypes of Thyroiditis Subtypes Causes Chronic lymphocytic thyroiditis, hashimoto’s thyroiditis, chronic Autoimmune autoimmune thyroiditis, lymphadenoid goiter Subacute lymphocytic thyroiditis, postpartum thyroiditis, sporadic painless Autoimmune thyroiditis, silent sporadic thyroiditis Acute infectious thyroiditis, Microbial inflammatory thyroiditis, suppurative Bacterial, Parasitic, Fungal thyroiditis, pyrogenic thyroiditis, bacterial thyroiditis De Quervain’s thyroiditis, subacute granulomatous thyroiditis, Giant-cell Viral thyroiditis, painful subacute thyroiditis Riedel’s thyroiditis, Riedel’s struma, Invasive fibrous thyroiditis Unknown  Painless Lymphocytic Thyroiditis ◦ Autoimmune-mediated inflammation of thyroid gland ◦ Clinical Course = Transient Hyperthyroidism → Hypothyroidism → Euthyroid state ◦ Various rates of progression ◦ ↑Risks = Postpartum, lithium Tx, biologic Tx, cytokine Tx ◦ Diagnosis: Radioiodine uptake dysphagia, dyspnea, hoarseness, pain ◦ Signs & symptoms related to other affected body areas ◦ Diagnostic Evaluation: ◦ Biopsy ◦ Clinical Course = Most patients remain euthyroid. ~30% become hypothyroid & very few patients hyperthyroid ◦ Treatment: ◦ Tamoxifen, 20 mg PO BID - usually induces partial to complete remissions within 3–6 months & must be continued for years ◦ Short-term glucocorticoid treatment for relief of pain & compression symptoms ◦ Rituximab may be useful for cases refractory to tamoxifen & glucocorticoids ◦ Surgery: Usually fails to permanently alleviate compression & is difficult due to dense fibrous adhesions