Common Thyroid Disorders

8/29/16 Anatomy of the Thyroid Gland Common Thyroid Disorders Heather Cuevas PhD, RN, ACNS- BC Texas Diabetes and Endocrinology The University of Texas at Austin School of Nursing Hypothalamic- Pituitary- Thyroid Axis Physiology Hypothalamus Production of T4 and T3 TRH Pituitary TSH reflects tissue thyroid hormone actions T4 is the primary secretory product of the thyroid TSH as an index of therapeutic success and potential toxicity The thyroid secretes approximately 70-90 µg of T4 TSH T4 Target Tissues T3 Heart Thyroid Gland Liver T3 T4 è T3 Liver per day T3 is derived from 2 processes The total daily production rate of T3 is about 15-30 µg About 80% of circulating T3 comes from deiodination of T4 in peripheral tissues Largely liver and kidneys TR T4 gland, which is the only source of T4 Bone About 20% comes from direct thyroid secretion CNS Free Hormone Concept Only unbound (free) hormone has metabolic activity and physiologic effects Total hormone concentration Normally is kept proportional to the concentration of carrier proteins Is kept appropriate to maintain a constant free hormone level 1

8/29/16 Drugs and Conditions That Increase Serum T4 and T3 Levels by Increasing TBG Drugs that increase TBG Oral contraceptives and other sources of estrogen Methadone Conditions that increase TBG Pregnancy Infectious/chronic active hepatitis Clofibrate HIV infection 5- Fluorouracil Biliary cirrhosis Heroin Acute intermittent porphyria Tamoxifen Genetic factors Evaluate for thyroid disease All >35 years of age, every 5 years Patients >60 Women >50 with incidental finding suggestive of thyroid disease USPSTF: insufficient evidence for screening Symptoms Hypothyroidism Exam Hyperthyroidism Fatigue Fatigue Depression Insomnia Weight gain Weight loss or gain Loss of body hair Heat intolerance Dry skin Light periods Elevated lipids Visual changes Slower heartbeat Diarrhea Constipation Tremor Muscle weakness Tachycardia Heavy periods Irritability TSH Look Palpate Imaging? Thyroid- Stimulating Hormone (TSH) Assays Key test for diagnosis of hypothyroidism and hyperthyroidism TSH assay sensitivity has improved with subsequent test generations First generation: RIA Sensitivity: 1.0 µiu/ml Second generation: IRMA Sensitivity: 0.1 µiu/ml Third generation: ELISA Sensitivity: 0.03 µiu/ml Ladenson PW, et al. Arch Intern Med. 2000;160:1573-1575. Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Zophel K, et al. Nuklearmedizin. 1999;38:150-155. 2

8/29/16 Interpretation Influencing Medications FT4 FT3 TSH Hypothyroid Low Low High Subclinical Hypothyroid Normal Normal High Hyperthyroid High or high- normal High Low Non- compliance with LT4 High Low Comments TSHRAb- sensitive and specific for Graves High Hyperthyroid Mr. Smith is a 49 year- old, smoker, hx of HTN. C/O insomnia. Wife says she thinks he s lost weight. Labs show: TSH <0.1, FT4 2.3; CMP and CBC wnl. Exam: Lid lag, HR 110, tremor, warm/sweaty, thyroid = diffusely enlarged FT4 FT3 TSH Glucocorticoids Dopamine Normal Normal Low Lithium, iodine Low Low High Amiodarone Normal to high Low High or low Phenobarbitol Carbamezapine Phenytoin Rifampicin Low Low Normal Graves Disease (Toxic Diffuse Goiter) The most common cause of hyperthyroidism Accounts for 60% to 90% of cases Incidence in the United States estimated at 0.02% to 0.4% of the population Affects more females than males, especially in the reproductive age range Imaging Graves disease is an autoimmune disorder possibly related to a defect in immune tolerance Treatment of Hyperthyroidism Antithyroid drugs Inhibit the synthesis of T4 and T3 Surgical resection Remove hyperplastic and adenomatous tissues Restore normal thyroid function and, consequently, pituitary function Radioactive iodine therapy Iodine 131 taken up by functioning thyroid tissue can decrease thyroid hormone production Anti- thyroid Drugs Methimazole Inhibits organification of iodide Decreases production of T4 and T3 Dose is 10-20mg/day Side effects Rash Agranulocytosis Aplasia Cutis Hepatotoxicity Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. 3

8/29/16 Anti- thyroid Drugs Thyroid Storm Propylthiouracil Inhibits organification of iodide Decreases production of T4 and T3 and conversion of T4 to T3 Dose is 100-600 mg/day Side ffects Rash Agranulocytosis Hepatotoxicity Boxed Warning Which ATD? Monitoring in ATD Methimazole CBC All except first trimester Start 10-20mg qd; maintenance 5-10mg PTU TFTs: FT4 & TSH 4 weeks after starting med Liver Start 50-150 tid; maintenance 50mg tid Allergy Relapse Pregnancy Hypothyroid Hypothyroidism: Types Ms. Smith is a 49 year- old, smoker, hx of HTN. Seeing Primary hypothyroidism Labs show: TSH 26, FT4 0.2; CMP and CBC wnl. Central or secondary hypothyroidism you for weight gain, fatigue, and cold intolerance. Exam: thyroid diffusely enlarged, HR 62, +1 pedal edema. From thyroid destruction From deficient TSH secretion, generally due to sellar lesions such as pituitary tumor or craniopharyngioma Infrequently is congenital Central or tertiary hypothyroidism From deficient TSH stimulation above level of pituitary ie, lesions of pituitary stalk or hypothalamus Is much less common than secondary hypothyroidism Bravernan LE, Utiger RE, eds. Werner & Ingbar's The Thyroid. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins 2000. Persani L, et al. J Clin Endocrinol Metab. 2000; 85:3631-3635. 4

8/29/16 Chronic Autoimmune Thyroiditis (Hashimoto s Thyroiditis) Occurs when there is a severe defect in thyroid hormone synthesis Patients present with hypothyroidism, painless goiter, and other overt signs Persons with autoimmune thyroid disease may have other concomitant autoimmune disorders Treatment of Hypothyroidism Thyroid Hormone Replacement Treatment of choice: levothyroxine (synthetic levothyroxine, LT4) ½ life of 1 week Chemically stable T4 converted to T3 in periphery Other therapies (T3 or T3 and T4 mixtures) Thyroid USP, liothyronine, liotrix, thyroglobulin Some disadvantages Singer PA, et al. JAMA. 1995;273:808-812. Endocr Pract. 2002;8:457-469. Braverman LE, et al. Werner & Ingbar s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Hypothyroidism Treatment Primary Hypothyroidism Treatment Algorithm Initial Levothyroxine Dose Levothyroxine sodium is the treatment of choice for the routine management of hypothyroidism Adults: about 1.7 µg/kg of body weight/day Children up to 4.0 µg/kg of body weight/day 6-8 Weeks TSH >4 µiu/ml Elderly <1.0 µg/kg of body weight/day until the serum TSH concentration is normalized levothyroxine therapy, it is preferable to maintain the patient on the same brand throughout treatment Increase Levothyroxine Dose by 12.5 to 25 µg/d Singer PA, et al. JAMA. 1995;273:808-812. Endocr Pract. 2002;8:457-469. Percentage of Euthyroid, Subclinical and Hypothyroid Patients Reporting Symptoms 60% euthyroid have 1 symptom 15% 4 symptoms TSH <0.3 µiu/ml TSH 0.5-2.0 µiu/ml Symptoms Resolved Clinical and biochemical evaluations at 6- to 8- week intervals Given the narrow and precise treatment range for Repeat TSH Test Continue Dose Measure TSH at 6 Months, Then Annually or When Symptomatic Decrease Levothyroxine Dose by 12.5 to 25 µg/d Singer PA, et al. JAMA. 1995;273:808-812. Demers LM, Spencer CA, eds. The National Academy of Clinical Biochemistry Web site. Available at: http://www.nacb.org/lmpg/thyroid_lmpg.stm. Accessed Aug. 2007 Thyroid hormone impact on weight in euthyroid patients Not effective weight loss drug May increase metabolism but increases appetite Canaris et al. Kaptein JCEM 2009 Fig 2b 5

8/29/16 Hazards of Overtreatment Heart, Bone, Psychiatric High risk subclinical hyperthyroid in patients on Factors That May Reduce Levothyroxine Effectiveness Malabsorption Syndromes Postjejunoileal bypass thyroid medication surgery Short bowel syndrome Celiac disease Colorado Prevalence Study, 2000 20.7% (316) of patients on thyroid medication had subclinical hyperthyroidism 0.9% (13) Overt hyperthyroidism Reduced Absorption More adverse effects with poor monitoring Only 56% received standard monitoring Atrial fibrillation, unstable angina with poor monitoring Colestipol hydrochloride Sucralfate Ferrous sulfate Food (e.g. soybean formula) Aluminum hydroxide Cholestyramine Calcium carbonate Drugs That Increase Clearance Rifampin Carbamazepine Phenytoin Factors That Reduced T4 to T3 Clearance Amiodarone Selenium deficiency Other Mechanisms Lovastatin Sertraline Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8th ed. 2000. Synthroid [package insert]. Abbott Laboratories; 2003. When is T3 given? Not recommended by American Thyroid Association Experimental use ok by European Thyroid Association Genetic condition Has a Role in the Treatment of Hypothyroidism Been Demonstrated with T3? 10 15% of patients feel unwell on LT4 monotherapy, as they still have complaints in spite of TSH normalization. The thyroid gland secretes both T4 and T3, suggesting a physiological role for the amount of T3 directly secreted by the thyroid, and not originated by peripheral conversion of T4. Endpoints have been mostly affective ones Trials have been relatively short Studies to date mixed and meta- analyses negative, but not completely Combination therapy still not yet completely understood in the setting of patient preferences Counsel Patients Taking Alternative Therapies About Potential Side Effects and Hazards Liothyroinine Supraphysiologic amounts LT3 or Cytomel of iodine may alter thyroid status, particularly in those with disease Many thyroid- enhancing products have sympathomimetic amines and iodine Many thyroid support products have significant amount of thyroid hormone Short- acting About 4 times as potent Watch for hyperthyroid symptoms Take bid, avoid evening dosing May need to reduce LT4 6

8/29/16 Desiccated thyroid Thyroid hormone conversions Combination of T4/T3 1 grain = about 100mcg Synthroid No RTCs of desiccated thyroid until 2013. Case #1 Case #1 Ms. A has been hypothyroid since age 35. Soy milk She takes Synthroid 0.088mg qd and an MVI Calcium supplements TSH 7.5 Iron She is now 52 and in menopause Coffee Complains of hot flashes and trying to treat with soy products What could be happening? Separate food, supplements, other medications by at least 2 hours Coffee by 1 hour Case #2 Again Mr. B has had hypothyroidism for 5 years. Take LT4 at the same time of day He takes Armour 1gr qd. TSH was 0.3 at lov. No food, no coffee, no milk Recently started on Lithium to treat bipolar ½ hour prior to eating or 2 hours after eating He complains of weight gain, increased fatigue and is worried Make sure to ask about any new medications the psych regimen is not working. TSH is now 28 May not be able to change the other meds MONITOR 7

8/29/16 Case #3 Ê Mr. B takes Synthroid 0.1mg qd. Ê TSH <0.1, FT4 4.7 Ê Complains of fatigue and says he takes an extra Synthroid when tired. Ê Remind patients of the problems with over- replacement. Ê AF, bone loss Ê Can t asses dose properly Incidence of Atrial Fibrillation (%) Consequences of Mild Thyrotoxicosis Atrial Fibrillation 30 25 20 15 10 5 TSH 0.1 mu/l TSH >0.1 0.4 mu/l 0 0 1 2 3 4 5 6 7 8 9 10 Years N=2007 pts > 60 Normal TSH (>0.4 5.0 mu/l) Adapted from: Sawin CT, et al. N Engl J Med. 1994;331:1249-1252. Case #4 Case #4 Ê TSH is 12, FT4 is 5 Ê Pt presents with these labs. Exam is normal. Pt states she was on a cruise and gained about 5 pounds. Otherwise feels well, energetic, and attributes the weight gain to overeating. Ê She forgot her meds on vacation Ê Tried to catch up by taking 2 0.05mg Levothyroxine qd for the past week when she returned home. Ê What can explain the labs? Questions? 8