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Thyroid Trivia MEGAN CHAN, PGY-1 UHCMC 2015 Diagnosis of Thyroid disease includes… 3 Aspects: Functional aspect Pathological aspect Anatomical aspect Example: Euthyroid Graves’ disease with Goiter http://what-when-how.com/wp-content/uploads/2012/08/tmp602f42_thumb22.png Hyperthyroidism Definitions What is the difference between “Thyrotoxicosis” & “Hyperthyroidism”? Thyrotoxicosis = Elevated T4/T3 that may be due to a variety of reasons (e.g. synthetic ingestion, thyroiditis) Hyperthyroidism = Elevated T4/T4 from the thyroid gland What are the common causes of hyperthyroidism? Graves’ disease (diffuse toxic goiter)—80% Plummer’s disease (multinodular toxic goiter)—15% Toxic thyroid adenoma (single nodule)—2% If transient: Hashimoto’s thyroiditis, subacute thyroiditis (early stage) Non-Thyroid Causes of Thyrotoxicosis Thyroid carcinoma TSH-R mutation Exogenous hormone Familial gestational Hydatiform mole Choriocarcinoma Excess TRH TSH-oma Pituitary T3 resistance hyperthyroidism Amiodarone INF-alpha induced HIV treatment Sunitinib therapy Struma ovarii Thyroid destruction Hyperemesis http://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/ Thyroid exam in Hyperthyroidism Guess the diagnosis based on the following thyroid exam: Thyroid Exam Diagnosis Diffusely enlarged, nontender Graves’ dz Diffusely enlarged, tender Subacute thyroiditis Bumpy, irregular, asymmetric Plummer’s dz Single nodule within atrophic gland Toxic adenoma Hypothyroidism Definitions What is Primary Hypothyroidism? What are some examples? Failure of the thyroid gland, accounts for 95% cases Hashimoto’s disease (chronic thyoriditis)—most common Iatrogenic: radioiodine tx, thyroidectomy, meds (e.g. lithium, amiodarone) What is Secondary Hypothyroidism? What is deficient? 2/2 pituitary disease Deficiency of TSH What is Tertiary Hypothyroidism? What is deficient? 2/2 hypothalamic disease Deficiency of TRH What are other causes of Hypothyroidism? Subacute hypothyroidism Increased TSH production maintains T4 wnl Subacute thyroiditis (late stage) Blood Work What is the best screening test for thyroid disease? TSH Always repeat TSH before starting Tx TSH ↓ in severe illness, steroids Why is obtaining free T4 helpful? T4 is helpful to see if TSH is inappropriately normal (e.g. pituitary cause) When should you obtain T3? Concerned for subclinical hyperthyroidism (can have T3 thyrotoxicosis) Iodine deficient diet (body makes T3 instead of T4) Conditions associated with transient ↑ Free T4 Condition Explanation Estrogen withdrawal Rapid decrease in TBG level Amphetamine abuse Possibly induced TSH secretion(2) Acute psychosis Hyperemesis gravidarum Unknown hCG, can cause thyrotoxicosis Iodide administration Thyroid autonomy Beginning of T4 administration Delayed T4 metabolism(3) Severe illness (rarely) Decreased T4 to T3 conversion (4) Amiodarone treatment Decreased T4 to T3 conversion, iodine load Gallbladder contrast agents Decreased T4 to T3 conversion, iodine load Propranolol (large doses) Inhibition of T4 to T3 conversion Prednisone (rarely) Inhibition of T4 to T3 conversion High altitude exposure Possibly hypothalamic activation Selenium deficiency Decreased T4 to T3 conversion http://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/ Blood Work What Ab tests are positive in Graves’ disease? Thyroid stimulating Ab (TSI) ~90% TSI binds TSH receptors on surface of thyroid cells & triggers synthesis of excess thyroid hormone TSI also binds tissues in the eye and skin exophthalmos & pretibial myxedema Thyrotrophin receptor Ab (TRAb) ~90%, High specificity Anti-peroxidase/microsomal Ab (TPO)—low titier >95% of pts Anti-thyroglobulin Ab ~50% of pts What Ab tests are positive in Hashimoto’s disease? Anti-peroxidase/microsomal Ab (TPO)—high titer ~90% of pts Non-specific 5-10% of healthy people test positive Anti-thyroglobulin Ab ~50% of pts Blood Work What does Thyroglobulin do? Makes T4/T3 When do you test for Thyroglobulin + Antithyroglobulin binding Ab? Testing for lack of thyroid tissue (e.g. s/p resection or ablation of thyroid cancer) Test in patient who might be taking exogenous hormone, as thyroglobulin in suppressed in this case What does Thyroid Binding Globulin (TBG) do? Binds T4 & T3 reversibly, making them inactive Free T4 is not influenced by TBG Increased in pregnancy, hepatitis, OPCs, ASA Decreased in glucocorticoids, nephritic syn, cirrhosis, androgens Imaging What is a Radionucleotide uptake scan most helpful for? Helps identify the cause of hyperthyroidism: diffuse uptake (Grave’s) vs patchy (Plummer’s disease) vs hot nodule. No real use in euthyroid or hypothyroid patients. Usually need to remove hot nodules (no remission) When should you order an ultrasound of the thyroid? If you see a goiter If you feel and enlargement or thyroid nodule What are signs of a malignant nodule? Benign if nodule <1mm Malignant: >2mm, irregular boarders, calcifications (papillary), blood supply via dopplers If multinodular, can perform radionucleotide uptake scan to determine which one to biopsy Imaging If a benign appearing nodule is found, what is your next step in management? Monitor with repeat US in 6 months to 1 year for 2-3 years. If remains stable can increase the interval. If a malignant appearing nodule is found, what is your next step in management? FNA or resection FNA is incorrect 10% of the time (false + or false -) Pocket Medicine, 4th ed. http://intranet.tdmu.edu.ua/data/kafedra/internal/vnutrmed2/classes_stud/en/med/lik/ptn/Internal%20medicine/4%20course/06.%20Hyperthyroidism.%20Patholo gy%20of%20parathyroid%20glands.htm Pocket Medicine, 4th ed. http://endocrine.surgery.ucsf.edu/media/ 5095649/thyroid_radionucleide_scan.jpg http://www.advancedonc.com/wpcontent/themes/royal/images/Ultrasound-Guided-FNA-2.jpg Hyperthyroid Treatment: Pharmacologic What is the preferred treatment for Hyperthyroidism? Methimazole Inhibits thyroid hormone synthesis Once a day med, Agranulocytosis in 0.5% What is the second line agent and when is it used? PTU (propylthiouracil) used if allergic to Methimazole or 1st trimester of pregnancy (↓ risk fetal anomalies) Inhibits thyroid hormone synthesis Inhibits conversion of T4 to T3 For both Methimazole & PTU, what labs should you check? LFTs, WBC, TSH What agents do you use for acute treatment of hyperthyroidism? Beta blockers for sxs control & partially inhibits T4 T3 conversion Sodium ipodate or iopanoic acid are iodineradiocontrast media that acutely lower serum T4 & T3 levels by preventing release and peripheral conversion Lugol’s solution (iodine salts) inhibits synthesis & release of thyroid hormone + ↓ size & vascularity of hyperplastic thyroid. Used for thyroid storm & in preparation for thyroid surgery due to rapid onset of action (2-7 days) & transient effects (several weeks) Thioamides= Methimazole & PTU Thiocynate (SCN- ) & Perchlorate (CLO4- ) block uptake of iodide into thyroid gland. However, rarely used clinically due to unpredictable effectiveness & risk for aplastic anemia with perchlorate. Lange Pharmacology, 10th ed. Hyperthyroid Treatment: Non-Pharmacologic When is Radioiodine 131 used? Elderly with Graves’ disease, solitary toxic nodule, Graves’ disease that fails medications, recurrent thyrotoxicosis Thyroid cells are the only cells in the body that absorbs iodine Contraindicated in pregnancy & breast feeding due to risk of cretinism >75% become hypothyroid When is surgical subtotal thyroidectomy performed? Mostly used in those with obstructive goiter Very effective but rarely used (only 1% of pts) due to high risk of side effects e.g. permanent hypothyroidism, recurrence of hyperthyroidism, recurrent laryngeal nerve palsy, permanent hypoparathyroidism Hyperthyroid Treatment Why is it important to treat Graves’ disease? If untreated, increased risk for systolic HTN due to increased CO and osteoporosis In Grave’s disease, only 20-25% go into remission spontaneously in the US Should you treat subclinical hyperthyroidism? No evidence to treat subclinical hyperthyroidism unless TSH <0.1 or symptomatic Progresses to overt hyperthyroidism ~15% in 2 years Hypothyroid Treatment How do you treat hypothyroidism? What is the starting dose? Start levothyroxine at 1.6 mcg/kg/day Can start at lower dose (0.3-0.5) if increased risk for arrhythmia (e.g. Afib) or ischemic heart disease May need increased doses with pregnancy (~30% ↑ by wk 8), estrogen replacement, poor GI absorption (concomitant Fe or Ca, PPI, sucralfate, celiac dz, IBD) How long does it take to see effects? When should you recheck TSH? Start to see effects in 2-4 weeks Recheck TSH & Free T4 in 6 weeks Why is it important to treat Hypothyroidism? If untreated, increased risk for diastolic HTN due to stiffened arteries & hyperlipidemia (↑LDL, ↓HDL) Should you treat subclinical hypothyroidism? Treat subclinical hypothyroidism if TSH > 8.0-12.0 or of symptomatic Progresses to overt hypothyroidism ~4% per year References Agabegi SS, Agabegi ED. Step-Up to Medicine, 3rd ed. 2013. Lippincott Williams & Wilkins. Philadelphia, PA. DeGroot, LJ. Diagnosis and Treatment of Grave’s Disease. Feb 2012. http://www.thyroidmanager.org/chapter/diagnosis-andtreatment-of-graves-disease/ Sabatine MS. Pocket medicine, 4th ed. 2011. Lippincott Williams & Wilkins. Philadelphia, PA. Trevor AJ, Katzung BG, Kruidering-Hall M, et al. Katzung & Trever’s Pharmacology: Examination & Board Review, 10th ed. 2013. McGraw-Hill. New York, NY. Weiner C, Fauci AS, Braunwald E, et al. Harrison’s Principles of Internal Medicine: Self-Assessment & Board Review, 17th ed & 18th ed. 2008, 2012. Lippincott Williams & Wilkins. Philadelphia, PA. Special thanks to Dr. Sood for the inspiration!