THYROID DISEASE – QUESTIONS AND ANSWERS 100% - VERIFIED

THYROID DISEASE – QUESTIONS AND ANSWERS 100% - VERIFIED The most common thyroid function disorder is? Correct ans - 1) Graves' disease 2) Hypothyroidism 3) Sub-acute thyroiditis 4) Thyroid cancer The most sensitive test for thyroid function is? Correct ans - 1) Free T4 2) Free T3 3) TSH 4) Thyroid ultra so The best assay to confirm that a patient's hypothyroidism is autoimmune in nature? Correct ans - 1) Thyroid stimulating immunoglobulins 2) Anti-nuclear antibody 3) TSH 4) Thyroid peroxidase antibodies The best assay to confirm that a patient's hyperthyroidism is autoimmune in nature? Correct ans - 1) Thyroid stimulating immunoglobulins 2) Anti-nuclear antibody 3) TSH 4) Thyroid peroxidase antibodies Which is the best study to confirm the etiology of a patient's thyrotoxicosis? Correct ans - 1) I123 thyroid scan/uptake 2) Neck CT or MRI 3) Thyroid ultrasound 4) Fine needle aspiration of the thyroid Which is the best study to make the initial evaluation Which is the best study to make the initial evaluation for thyroid nodules discovered on routine physical exam? Correct ans - 1) I123 thyroid scan/uptake 2) Neck CT or MRI 3) Thyroid ultrasound 4) Fine needle aspiration of the thyroid : Patient has a thyroid U/S showing a solid dominant (>10mm) nodule and normal thyroid function, what is your next step? Correct ans - 1) Recheck thyroid U/S in 1 year 2) Fine needle aspiration of the thyroid 2) Neck CT or MRI 4) I123 thyroid scan/uptake Thyroid U/S shows homogeneous increased radiotracer uptake, the diagnosis is? Correct ans - 1) Metastatic thyroid cancer 2) Graves' disease 3) Toxic multi-nodular goiter 4) Toxic thyroid nodule Methimazole or propylthiouracil and used to treat hypothyroidism? Correct ans - 1) True 2) False : Which in not an appropriate treatment for Graves' disease? Correct ans - 1) Thyroidectomy 2) Anti-thyroid medications such as propylthiouracil or methimazole 3) Levothyroxine sodium 4) I131 radioactive iodine OBJECTIVES Correct ans - Order and interpret appropriate labs and studies necessary for the diagnosis of the thyroid disorders discussed in this lecture. Describe the common signs and symptoms of hyper/hypothyroidism, workup, treatment, and follow-up. Provide a practical approach to the work-up and diagnosis of thyroid nodules. Know when to refer. Major Thyroid Abnormalities Correct ans - Major Thyroid Abnormalities Hypothyroidism Hyperthyroidism Structural / Anatomy Thyroid Goiter Nodules Cold Warm or Hot Cysts Malignancies At Risk Population for Thyroid Dysfunction Correct ans - Women, elderly, postpartum 4-8 months. FamHx of Hashimoto's or Graves' dz. PMHx or FamHX autoimmune diseases - SLE, RA, DM1, Addison's, vitiligo, pernicious anemia. Type 1 DM: ~20% increase risk for thyroid dysfunction, mainly hypothyroid. Patients treated with amiodarone, lithium, others. HYPOTHALAMIC / PITUITARY THYROID AXIS Correct ans - TRH: stimulate anterior pituitary to release TSH. TSH: stimulate thyroid for synthesis and release of T4 and T3. Low T4, Low T3: stimulate TSH and TRH. High T4, High T3: inhibit TSH and TRH. THYROID HORMONES Correct ans - T4 to T3 secretion ratio of 10:1. T3 is 4X more biologically active than T4. T1/2: T4 = 7days, T3 = 1 day. T4,T3: 99% bound to protein, i.e. metabolically inactive. From thyroid: 100% - T4, 20% - T3 remainder of T3 is from T4 to T3 conversion in peripheral tissues. THYROID TESTING Biochemical Correct ans - 1) TSH - highly sensitive, best test for thyroid function. Free T4 (FT4)- biologically active. Free T3 (FT3) - biologically active. - rarely need to check unless, TSH is low or undetectable with a normal FT4. THYROID TESTING (more specific) Correct ans - Thyroid Peroxidase Antibodies (TPO-Ab's) - Hashimotos Thyroiditis Thyroid Stimulating Immunoglobulins (TSI's) or TSH receptor antibodies (TRAb). - Unique to Graves' disease I-123 RAIU (Radio Active Iodine Uptake) evaluation for thyrotoxicosis, shape, size. Don't use to confirm hypothyroidism DON'T FORGET THE BASICS Correct ans - History of present illness and ROS. PMHx - postpartum Past Hx of thyroid pain/tenderness/nodule/ enlargement or goiter H/O autoimmune diseases FamHX - thyroid dysfunction, thyroid cancer, Autoimmune diseases. Medications Systematic physical exam Hypothyroidism Correct ans - Prevalence: 4 - 8% general population. Mean age of Dx: 5th decade of life Female to male ratio: 10:1 PRIMARY HYPOTHYROIDISM Correct ans - Identification on clinical basis can be challenging. Symptoms generally vague. Frequently goes unnoticed, confused as other health problems. Insidious onset + poor index of suspicion = misdiagnosis Etiology Correct ans - Autoimmune: - Chronic lymphocytic thyroiditis = Hashimoto's - positive TPO-Ab's - remember postpartum thyroiditis Iatrogenic: I-131 RAI, total/subtotal thyroidectomy, neck irradiation. Congenital: agenesis, dysgenesis. Drug induced: lithium, amiodarone, chemotherapy, others. Clinical Symptoms of Hypothyroidism Correct ans - Fatigue Lethargy Cold intolerance Constipation Decreased memory Depression Mental Impairment Arthralgias Hoarseness Heavy menstrual flow Paresthesias Sleepiness Weight gain ,edema Muscle cramps Clinical Signs of Hypothyroidism Correct ans - Bradycardia Coarse hair, hair loss Delayed relaxation phase of deep tendon reflexes Dry, cool, pale skin Goiter Hoarseness Non-pitting edema (myxedema) Puffy eyes and face Slow movements Slow speech Thinning lateral third of eyebrows Example of Clinical Manifestations of Hypothyroidism Correct ans - Patient example Fatigue ("no energy"), cold intolerance, constipation, weight gain, fatigue, problems with concentration ("mental clouding"), dry skin CLINICAL MANIFESTATONS EXAM Correct ans - NECK: thyroid may be normal, enlarged, symmetric/asymm., smooth or lumpy. HEART: bradycardia. EXTREMS: pretibial/ankle edema, dry cool skin, brittle nails. NEURO: DTR's with delayed relaxation phases HEENT: periorbital puffiness, loss of lateral eyebrows, coarse/thinning hair. LABORATORY EVALUATION Correct ans - TSH - high Free T4 - low Check both if new diagnosis to make sure PITUITARY-THYROID AXIS intact. Consider TPO-Ab Levothyroxine Sodium (LT4 ) Correct ans - Exogenously administered LT4 hormone Indistinguishable from endogenous T4, both in its physiologic effects and its quantification as measured in blood LT4 is the treatment of choice as replacement or supplemental hormone therapy Branded preparations are preferred TREATMENT Correct ans - Levothyroxine (LT4), narrow therapeutic range 0.3 - 3.0 IU/mL, caution in lower range TSH. Brand vs. generic vs. T4 + T3 combination. Lifelong treatment, most cases Dosing: 1.6 mcg/kg/day = ~100 - 125 mcg/day. Compliance, empty stomach, competing agents for absorption (Iron, Calcium ) Check TSH no sooner than 6 weeks after initial start of LT4 or any adjustment. Therapy Monitoring Correct ans - Clinical and laboratory monitoring enable Evaluation of the clinical response Assessment of patient compliance Assessment of drug interactions, if applicable Adjustment of dosage, as needed Clinical and laboratory evaluations should be performed At 6- to 8-week intervals while titrating Annually once a euthyroid state is established Therapy Monitoring. Periodic monitoring of patients receiving levothyroxine therapy is essential for effective management.1 Clinical evaluations and laboratory monitoring of serum TSH levels permit evaluation of the clinical response to the medication, assessment of patient compliance, assessment of drug interactions (if applicable), and adjustment of dosage as required in response to changes in patient lifestyle or circumstances.1 It is recommended that clinical and laboratory evaluations be performed at 6- to 8-week intervals (2 to 3 weeks in severely hypothyroid patients).2 The levothyroxine dosage should be adjusted by 12.5 to 25 µg increments until serum TSH concentration is normalized and signs and symptoms resolve.2 Annual testing is recommended after a euthyroid state is established.2 References 1. Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds. 2. Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: Factors That May Reduce Levothyroxine Effectiveness Correct ans - Malabsorption Syndromes Post jejunoileal bypass surgery Short bowel syndrome Celiac disease Reduced Absorption Colestipol hydrochloride Sucralfate Ferrous sulfate Food (eg, soybean formula) Aluminum hydroxide Cholestyramine Sodium polystyrene sulfonate Drugs That Increase Clearance Rifampin Carbamazepine Phenytoin Factors That Reduced T4 to T3 Clearance Amiodarone Selenium deficiency Other Mechanisms Lovastatin Sertraline Factors That May Reduce Levothyroxine Effectiveness. There are several drugs and clinical conditions that may reduce levothyroxine effectiveness and alter optimal dosing ranges.1 Syndromes associated with malabsorption of T4, such as postjejunoileal bypass or short bowel syndrome can lead to an increased dosing requirement.1 Drugs that reduce T4 absorption leading to a decrease in levothyroxine effectiveness include sucralfate, aluminum hydroxide, ferrous sulfate, cholestyramine, colestipol hydrochloride, sodium polystyrene sulfonate, and foods, such as soybean formula.1,2 Drugs that affect metabolism include rifampin, carbamazepinephenytoin, phenobarbitaland amiodarone. A selenium deficiency can also reduce the conversion of T4 to T3.1 Food may also be an additional factor affecting the effectiveness of levothyroxine.2 Before increasing the dose of levothyroxine, its ingestion should be separated from iron and the medications listed.1 References 1. Braverman LE, et al. Werner & Ingbar's The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. 2. Synthroid® [package insert]. Abbott Laboratories; 2003. Thyroid Hormone Therapy Special Treatment Populations Correct ans - Patients 50 years of age or with underlying cardiac disease Initial dose of LT4 - 25 to 50 mcg/d Elderly patients with cardiac disease Initial dose of LT4 - 12.5 to 25 mcg/d Patients with heart failure Both hypo- and hyperthyroidism can worsen heart failure Thyroid Hormone Therapy. Special Treatment Populations. An initial starting dose of 25 to 50 g/d of LT4 is recommended for patients older than 50 years of age or for patients under 50 years of age with underlying cardiac disease.1 Gradual dosage increments are recommended at 6- to 8-week intervals as needed. For elderly patients with cardiac disease, the recommended starting dose is 12.5 to 25 g/d, gradually increasing the dosage by 12.5- to 25-g at 4- to 6- week intervals. Maternal thyroid hormone status, particularly during early pregnancy, is important to the well being of the fetus. Early in pregnancy, the fetus is totally dependent on receiving thyroid hormone from the mother.1 Hypothyroidism during pregnancy has been associated with lower IQ scores in these children. Clinical practice guidelines and product labels for LT4 products advise careful monitoring and treatment of thyroid disease patients who also suffer from heart failure because both hypo- and hyperthyroidism can worsen heart failure. Reference 1. Levothyroxine Bioequivalence Briefing Document. Available at: Accessed September 1, 2003. Treating Hypothyroidism Before and During Pregnancy Correct ans - Encourage adherence with LT4 replacement therapy before conception Monitor TSH levels before conception and during first trimester Consider increase of LT4 dosage in athyreotic patients by 25% - 50% when pregnancy is confirmed Monitor TSH levels every 6 to 8 weeks throughout pregnancy Reinstate pre-pregnancy LT4 dosage immediately following delivery Treating Hypothyroidism Before and During Pregnancy. Women with hypothyroidism who wish to conceive are encouraged to have their TSH level measured and to establish a stable dose of thyroxine replacement before becoming pregnant.1 In addition, preliminary studies suggest that the first trimester may be a critical period during which to maintain euthyroidism because of developmental processes in the fetus.1 These findings reinforce the importance of testing TSH levels before pregnancy, again during the first trimester of their pregnancy, and making appropriate adjustments in the levothyroxine dose.1 A 25%-50% increase in levothyroxine dose is recommended in women known to be athyreotic when pregnancy is first recognized.2 References 1. Gharib H, et al. Endocr Pract. 1999;5:367-368. 2. Mandel SJ, et al. N Engl J Med. 1990;323:91-96 Over-Replacement Risks Correct ans - Switching a narrow therapeutic index drug, such as LT4, without retesting and re-titrating can cause inconsistent TSH control, resulting in over-replacement Over-replacement risks (TSH <0.5 IU/mL) Iatrogenic thyrotoxic state Increased heart rate and myocardial contractility For cardiac patients, increased risk of angina and MI Reduced bone density/osteoporosis Psychiatric symptoms, such as anxiety, sleep disturbance, irritability, and fatigue Over-Replacement Risks. Levothyroxine is a narrow therapeutic index drug.1 Switching a narrow therapeutic drug, such as levothyroxine, without retesting and retitrating can cause inconsistent TSH control that results in over- or under-treatment.1 Over-replacement of levothyroxine may increase the patient's risk of reduced bone density and associated osteoporosis.2 In addition, it may increase heart rate and myocardial contractility, leading to increased myocardial oxygen demand.2 Over-replacement in patients with cardiovascular disease may lead to angina or possibly MI.3 Therefore, particular caution should be used in patients receiving levothyroxine therapy who also have cardiovascular disease.2 References 1. Synthroid® [package insert]. Abbott Laboratories; 2003. 2. Braverman LE, et al. Werner & Ingbar's The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. 3. Felicetta JV. Consultant. 2002;. Available at: . Accessed July 1, 2003. Case 1 SUBCLINICAL HYPOTHYROIDISM Correct ans - 46 y.o. female presents with a 3 - 4 month history of heavier than usual menstrual cycles, fatigue, "feeling sleepy all of the time", depressed, constipation, problems concentrating, cold intolerance. PMHx: unremarkeable FAMHx: Adopted. P.E. : DTR's show delayed relaxation phases of biceps and brachioradialis, non tender symmetric goiter @ 2 times normal size without nodules. LABS : TSH 77.02 (0.45-4.50) Free T4 0.38 (0.8 - 1.50) TPO-Ab 267 reactive greater 40. Dx: Hashimoto's Thyroiditis Tx: 100 mcg qd, non-generic LT-4 Follow-up in 6 weeks and recheck TSH F/U: Feeling "90% better" TSH 7.62 Increase to 112mcg qd. Follow-up in 2 months. 2 months later TSH - 2.11 (0.50 - 3.00). Plan: follow and adjust LT-4 based on TSH Very difficult to diagnose clinically High index of suspicion, may be asymptomatic 4 -15% of general population* 20% of pts. over 60 y.o. (esp. women)** LABS: TSH - minimally high (6 - 10 IU/mL) Free T4 - low normal TREATMENT: controversial, consider if symptoms, lipid abnormality, if TPO-Ab positive Low dose LT-4 vs. surveillance, education Mild Thyroid Failure and Neurobehavioral Abnormalities Correct ans - Conditions reported to occur more frequently in patients with mild thyroid failure Depression Anxiety Somatic complaints Cognitive abnormalities Rationale for Treating Mild Thyroid Failure Correct ans - Potential benefits from treatment Prevent progression to overt hypothyroidism Improve serum lipid profile, which may reduce the risk of death from cardiovascular causes Reduce symptoms, including psychiatric and cognitive abnormalities Rationale for Treating Mild Thyroid Failure. Treatment of mild thyroid failure may provide benefits in 3 areas: Preventing the progression of the patient's condition to overt hypothyroidism, with its attendant morbidity, with the use of levothyroxine therapy.1 Levothyroxine therapy may improve the patient's serum lipid profile, potentially reducing the risk of death from cardiovascular disease. Treatment may reverse the symptoms of mild hypothyroidism, including psychiatric and cognitive abnormalities. Reference 1. Cooper DS. N Engl J Med. 2001;345:260-264. Case 2 Correct ans - Hx: 32 y.o. women referred for mildly increased TSH 8.69 (0.46-4.68) Symtoms: mild fatigue, dry skin, "not feeling my usual self" PMHx: no H/O thyroid disorders, or recent of remote thyroid pain/tender. FAMHx: Mother, two maternal aunts with hyperthyroidism. P.E. : Thyroid minimally enlarged and non-tender, no nodules. remainder of exam unremarkable. Labs: TSH 7.5 (.46 - 4.68) FREE T4 0.82 (0.80-1.50). TPO-Ab 317 reactive greater than 40 DX: Subclinical Hypothyroidism Hashimotos thyroiditis Tx: "Brand LT4" 25 mcg q.d. Follow-up and TSH in 2 months. Follow-up: patient feeling better without complaints TSH 1.89 (0.5 - 3.0) Education, need to follow Hyperthyroidism Correct ans - ... HYPERTHYROIDISM ETIOLOGY Correct ans - Graves' disease ( autoimmune ). Toxic multi-nodular goiter ( toxic MNG ). Toxic nodule (hot or warm nodule) Common Symptoms and Signs of Thyrotoxicosis Correct ans - Symptoms Nervous / shaky Fatigue Muscle weakness Increased perspiration Heat intolerance Tremor Palpitations Appetite/weight changes Menstrual disturbances Signs Goiter Hyperactivity Tachycardia / arrhythmiaSystolic hypertension Warm, moist, or smooth skin Stare and eyelid retraction Tremor Hyper-reflexia GRAVES' Dz Correct ans - ~75% of cases of hyperthyroidism. Thyroid Stimulating Immunoglobulins (TSI's) and / or TSH receptor antibodies (TRAb) levels usually increased Incidence 2nd - 4th decade of life. ~5 times more likely in women. Thyrotoxicosis - work-up Correct ans - Labs- demonstrate thyrotoxicosis. TSH - Low or undetectable Free T4 and/or Free T3 - Increased I123 thyroid scan / uptake Uptake is increased. 4 hour: normal ref. (5 - 15%) 24 hour: normal ref. (6 - 30%) Scan (anatomical findings via radiotracer uptake) Homogeneous ( Graves' Dz) multiple areas (Toxic MNG) single area (Hot or warm nodule) PATIENT EXAMPLE GRAVES' Correct ans - 30 y.o. female with nervousness, shakiness, heat intolerance, "fast / pounding heart beat", wt loss, light menses, and muscle weakness for 3 months. P.E. HR=118 Eyes— lid lag, stare,Skin: warm/moist Thyroid: large symmetric non-tender gland Neuro—tremors, DTR's - brisk, hyper-reflexic LABS: TSH: < 0.03 (0.45 - 4.50) FT4: 2.8 (0.8-1.8) Graves' Work up Cont. Correct ans - I123 thyroid S/U 4hr = 28% (5 - 15%) 24hr = 76% (6 - 30%) diffuse homogeneous uptake. TREATMENT options Treatment Options for Thyrotoxicosis Correct ans - I131 RAI thyroid ablation Anti-Thyroid Drugs (ATD's) Methimazole Propylthiouracil (PTU) Surgery: very rarely indicated Treatment with 1131 RAI Correct ans - Treatment of choice Goal is complete ablation i.e. hypothyroid Hypothyroid about 3-5 months post I131 Tx Follow Free T4 q 4-6 weeks until low Treatment: "brand" LT4 Follow and treat as you would for hypothyroid Exception: the low TSH usually lags behind, often for months, the normalization of the Free T4. Check Free T4 and TSH until the TSH becomes normal or high, then only follow the TSH. Treatment with ATD's Correct ans - Anti-Thyroid Drugs (ATD's) Methimazole: 10 - 60 mg/day, first choice PTU: 100 - 600 mg/day in 2-3 divided doses Only recommended for first trimester pregnancy then change to methimazole Risk for liver failure with PTU Follow CBC - risk for agranulocytosis with either. Hepatic function panel - esp. with PTU Check TSH, Free T4 four weeks after start of Tx. Once patient stable and TSH normalized, check TSH q 3-4months. Thyroid Nodules Correct ans - ... How thyroid nodules or masses are found? Correct ans - By HCP: palpation on routine exam By patient: rarely Incidentally CT scan or MRI of chest / neck Carotid Dopplers Thyroid Ultrasound I123 thyroid scan / uptake Thyroid Nodules Correct ans - 5 categories: Benign Non-diagnostic Follicular neoplasm/lesion Suspicious Malignant. Size - >1cm "dominant nodule" I123 thyroid scan / uptake Hot or warm - hormone secreting nodules Cold nodules can be: Cysts Benign adenomas Malignant tumors others Ultrasound findings that increase the risk of malignancy Correct ans - Hypoechoic Microcalcifications Irregular margins Intranodular vascularity Rounded appearance; more tall than wide, shape of the nodule Suspicious for malignancy Correct ans - Growing nodule Fixed nodule Firm or hard consistency Cervical adenopathy History of head and neck irradiation Family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC) Persistent dysphonia, dysphagia or dyspnea Age <30 or >60 years Male sex Thyroid Nodule Work-up Correct ans - Assess for biochemical abnormality. (TSH, FT4, ?FT3) If normal Labs U/S to evaluate: number and echotexture. Cytopathological Eval. Fine needle aspiration (FNA) with or without U/S guidance. If abnormal Labs: low TSH and or increased FT4/FT3 I123 thyroid scan and uptake Nodule(s) hot or warm Treat options: I131 RAI, ATD's, Surgery, refer to endocrinologist for treatment Cold Nodules on I123 Thyroid scan/uptake Correct ans - TSH and Free T4 normal Consider thyroid cancer, benign adenoma, or thyroid cyst Ultrasound to delineate solid vs. cystic lesion Referral for ultrasound guided FNA biopsy If biopsy is suspicious for cancer or demonstrates cancer, referral to surgeon with ample experience in thyroid surgery. Thyroid Malignancies Correct ans - Papillary: ~80% Follicular: ~15% Medullary: ~3-5% Anaplastic: < 2%