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Common Thyroid Disorders

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Common Thyroid Disorders 9/7/17 Common Louie Riesch MSN, MPH, RN, ACNS-BC, CDE Thyroid Texas Diabetes and Endocrinology Disorders Anatomy of the Thyroid Gland Hypothalamic-Pituitary-Thyroid Axis Physiology Hypothalamus TRH • TSH reflects tissue thyroid – hormone actions • TSH as an index of Pituitary therapeutic success and – potential toxicity TSH T4 Target Tissues T3 Heart Thyroid Gland Liver T4 T3 TR Bone T4 è T3 Liver CNS 1 9/7/17 Production of T4 and T3 Ê T4 is the primary secretory product of the thyroid gland, which is the only source of T4 Ê The thyroid secretes approximately 100 nmol of T4 per day Ê T3 is derived from 2 processes Ê The total daily production rate of T3 is about 15-30 µg Ê About 80% of circulating T3 comes from deiodination of T4 in peripheral tissues Ê Largely liver and kidneys Ê About 20% comes from direct thyroid secretion Free Hormone Concept Ê Only unbound (free) hormone has metabolic activity and physiologic effects Ê Total hormone concentration Ê Normally is kept proportional to the concentration of carrier proteins Ê Is kept appropriate to maintain a constant free hormone level 2 9/7/17 Drugs and Conditions That Increase Serum T4 and T3 Levels by Increasing TBG Drugs that increase TBG Conditions that increase TBG Ê Oral contraceptives and other Ê Pregnancy sources of estrogen Ê Infectious/chronic active Ê Methadone hepatitis Ê Clofibrate Ê HIV infection Ê 5-Fluorouracil Ê Biliary cirrhosis Ê Heroin Ê Acute intermittent porphyria Ê Tamoxifen Ê Genetic factors Evaluate for thyroid disease Ê All >35 years of age, every 5 years Ê Patients >60 Ê Women >50 with incidental finding suggestive of thyroid disease Ê USPSTF: insufficient evidence for across-the- board screening Symptoms Ê Hypothyroidism Ê Hyperthyroidism Ê Fatigue Ê Fatigue Ê Depression Ê Insomnia Ê Weight gain Ê Weight loss or gain Ê Loss of body hair Ê Heat intolerance Ê Dry skin Ê Light periods Ê Elevated lipids Ê Visual changes Ê Slower heartbeat Ê Diarrhea Ê Constipation Ê Tremor Ê Muscle weakness Ê Tachycardia Ê Heavy periods Ê Irritability 3 9/7/17 Exam Ê TSH Ê Look Ê Palpate Ê Imaging? Thyroid-Stimulating Hormone (TSH) Assays Ê Key test for diagnosis of hypothyroidism and hyperthyroidism Ê TSH assay sensitivity has improved with subsequent test generations Ê First generation: RIA Sensitivity: 1.0 µIU/mL Ê Second generation: IRMA Sensitivity: 0.1 µIU/mL Ê 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. 4 9/7/17 Interpretation FT4 FT3 TSH Comments Hypothyroid Low Low High Subclinical Normal Normal High Hypothyroid Hyperthyroid High or high- High Low TSHRAb- normal sensitive and specific for Graves’ Non- High Low High compliance with LT4 Influencing Medications FT4 FT3 TSH Glucocorticoids Normal Normal Low Dopamine Lithium, iodine Low Low High Amiodarone Normal to high Low High or low Phenobarbitol Low Low Normal Carbamezapine Phenytoin Rifampicin Hyperthyroid Ê Mr. Smith is a 49 year-old, smoker, hx of HTN. C/O insomnia. Wife says she thinks he’s lost weight. Ê Labs show: TSH <0.1, FT4 2.3; CMP and CBC wnl. Ê Exam: Lid lag, HR 110, tremor, warm/sweaty, thyroid = diffusely enlarged Ê Imaging 5 9/7/17 Graves Disease (Toxic Diffuse Goiter) Ê The most common cause of hyperthyroidism Ê Accounts for 60% to 90% of cases Ê Incidence in the United States estimated at 0.02% to 0.4% of the population Ê Affects more females than males, especially in the reproductive age range Ê Graves disease is an autoimmune disorder possibly related to a defect in immune tolerance Treatment of Hyperthyroidism Ê Antithyroid drugs Ê Inhibit the synthesis of T4 and T3 Ê Surgical resection Ê Remove hyperplastic and adenomatous tissues Ê Restore normal thyroid function and, consequently, pituitary function Ê Radioactive iodine therapy Ê Iodine 131 taken up by functioning thyroid tissue can decrease thyroid hormone production Braverman LE, et al. Werner & Ingbar’s The Thyroid. A Fundamental and Clinical Text. 8th ed. 2000. Anti-thyroid Drugs Ê Methimazole Ê Inhibits organification of iodide Ê Decreases production of T4 and T3 Ê Dose is 2.5 – 40 mg/day Ê Side effects Ê Rash Ê Agranulocytosis Ê Aplasia Cutis Ê Hepatotoxicity Ê Used preferentially over PTU – less incidence of side effects 6 9/7/17 Anti-thyroid Drugs Ê Propylthiouracil Ê Inhibits organification of iodide Ê Decreases production of T4 and T3 and conversion of T4 to T3 Ê Dose is 100-600 mg/day Ê Side ffects Ê Rash Ê Agranulocytosis Ê Hepatotoxicity Ê Boxed Warning Ê Used preferentially in 1st trimester of pregnancy Thyroid Storm Which ATD? Ê Methimazole Ê All except first trimester Ê Start 10-30 mg qd; maintenance 2.5 mg - 10mg Ê PTU Ê Start 50-150 tid; maintenance 50mg tid 7 9/7/17 Monitoring in ATD Ê CBC Ê TFTs: FT4 & TSH 4 weeks after starting med Ê Liver Ê Allergy Ê Relapse Ê Pregnancy Hypothyroid Ê Ms. Smith is a 49 year-old, smoker, hx of HTN. Seeing you for weight gain, fatigue, and cold intolerance. Ê Labs show: TSH 26, FT4 0.2; CMP and CBC wnl. Ê Exam: thyroid diffusely enlarged, HR 62, +1 pedal edema. Hypothyroidism: Types Ê Primary hypothyroidism Ê From thyroid destruction Ê Central or secondary hypothyroidism Ê From deficient TSH secretion, generally due to sellar lesions such as pituitary tumor or craniopharyngioma Ê Infrequently is congenital Ê Central or tertiary hypothyroidism Ê From deficient TSH stimulation above level of pituitary—ie, lesions of pituitary stalk or hypothalamus Ê 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. 8 9/7/17 Chronic Autoimmune Thyroiditis (Hashimoto’s Thyroiditis) Ê Occurs when there is a severe defect in thyroid hormone synthesis Ê Patients present with hypothyroidism, painless goiter, and other overt signs Ê Persons with autoimmune thyroid disease may have other concomitant autoimmune disorders Treatment of Hypothyroidism Thyroid Hormone Replacement Ê Treatment of choice: levothyroxine (synthetic levothyroxine, LT4) Ê ½ life of 1 week Ê Chemically stable Ê T4 converted to T3 in periphery Ê Other therapies (T3 or T3 and T4 mixtures) Ê Thyroid USP, liothyronine, liotrix, thyroglobulin Ê 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 Ê Levothyroxine sodium is the treatment of choice for the routine management of hypothyroidism Ê Adults: about 1.7 µg/kg of body weight/day Ê Children up to 4.0 µg/kg of body weight/day Ê Elderly <1.0 µg/kg of body weight/day Ê Clinical and biochemical evaluations at 6- to 8-week intervals until the serum TSH concentration is normalized Ê Given the narrow and precise treatment range for levothyroxine therapy, it is preferable to maintain the patient on the same brand throughout treatment Singer PA, et al. JAMA. 1995;273:808-812. Endocr Pract. 2002;8:457-469. 9 9/7/17 Primary Hypothyroidism Treatment Algorithm Initial Levothyroxine Dose 6-8 Weeks TSH >4 µIU/mL Repeat TSH Test TSH <0.3 µIU/mL TSH 0.5- 2.0 µIU/mL Symptoms Resolved Increase Continue Dose Decrease Levothyroxine Levothyroxine Dose by Dose by 12.5 to 25 µg/d Measure TSH at 6 Months, 12.5 to 25 µg/d Then Annually or When Symptomatic 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 Percentage of Euthyroid, Subclinical and Hypothyroid Patients Reporting Symptoms 60% euthyroid have ≥ 1 symptom 15% ≥ 4 symptoms Canaris et al. Thyroid hormone impact on weight in euthyroid patients Not effective weight loss drug May increase metabolism but increases appetite Kaptein JCEM 2009 Fig 2b 10 9/7/17 Hazards of Overtreatment – Heart, Bone, Psychiatric Ê High risk subclinical hyperthyroid in patients on thyroid medication Ê Colorado Prevalence Study, 2000 Ê 20.7% (316) of patients on thyroid medication had subclinical hyperthyroidism Ê 0.9% (13) Overt hyperthyroidism Ê More adverse effects with poor monitoring Ê Only 56% received standard monitoring Ê Atrial fibrillation, unstable angina with poor monitoring Factors That May Reduce Levothyroxine Effectiveness Ê Malabsorption Syndromes Ê Drugs That Increase Clearance Ê Postjejunoileal bypass Ê Rifampin surgery Ê Carbamazepine Ê Short bowel syndrome Ê Phenytoin Ê Celiac disease Ê Factors That Reduced T4 to T3 Ê Reduced Absorption Clearance Ê Colestipol hydrochloride Ê Amiodarone Ê Sucralfate Ê Selenium deficiency Ê Ferrous sulfate Ê Food (e.g. soybean formula) Ê Aluminum hydroxide Ê Other Mechanisms Ê Cholestyramine Ê Lovastatin Ê Calcium carbonate Ê 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? Ê Not recommended by Ê 10–15% of patients feel American Thyroid unwell on LT4 monotherapy, Association as they still have complaints in spite of TSH normalization. Ê “Experimental” use ok by Ê The thyroid gland secretes European Thyroid both T4 and T3, suggesting a Association physiological role for the amount of T3 directly Ê Genetic condition secreted by the thyroid, and not originated by peripheral conversion of T4.
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