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Thyroid Disorders in Primary Care Dawn O’Reilly, Ph.D., MMS, PA-C August 25th, 2016 NCAPA Summer Conference Disclosure I have nothing to disclose during this presentation. Objectives 1.Explain the normal anatomy and regulation of thyroid function 2. Discuss the evaluation of patients with thyroid disorders 3. Describe the expected changes in TSH and thyroid hormone levels in patients with thyroid disorders 4. Define the treatment options for thyroid disorders Patient Case 31yo female patient presents to your office with chief complaints of feeling tired and she is always cold. She said that she has been stressed lately with just starting as a new PA in family medicine, being a police wife, and her one year old son. She just assumed this is why she is always tired. She said her husband is also very annoyed that she always has cold hands and feet and needs the heat on when its 80 degrees. She would like to plan to have another child soon. She lives a very active lifestyle, exercises daily, and eats healthy most of the time. Allergies: None Current Medications: Prenatal Vitamins PMH: None Surgical History: L4 fixation 2002, L4/L5 fusion 2006 FH: Hypertension, Hyperlipidemia Vitals: BP: 118/68, HR: 65, Temp: 98.8, R: 16 Where does the Thyroid Function all Begin? • The thyroid gland is part of the neuroendocrine system. • The Hypothalamus is the major integrating link between these systems and receives input and controls the pituitary gland with 9 different releasing and inhibiting hormones. • It regulates virtually all aspects of growth, development, metabolism, and homeostasis. Endocrine glands: secrete products(hormones) into the bloodstream(pituitary, thyroid, parathyroid, adrenal) Exocrine glands: secrete products into ducts which empty into body cavities or body surface(sweat, oil, mucous and digestive) Where does the Thyroid Function all Begin? • The hypothalamus regulates thyrotroph cells which produce TRH(thyrotropin-releasing hormone) which then stimulates the ANTERIOR pituitary gland to produce TSH(thyroid stimulating hormone) • TSH stimulates virtually all aspects of thyroid follicular cell activity! The Thyroid Gland • The thyroid consists of the thyroid follicles composed of follicular cells, which secrete the thyroid hormones thyroxine(T4) and triiodothyronine(T3), and parafollicular cells, which secrete calcitonin(CT). Did You Know? The Thyroid Gland is the ONLY endocrine gland that stores its secretory product in large quantities-normally about a 100-day supply?! So How Does it Do All That?! Thyroid Hormone Synthesis: The formation, storage, and release steps include: 1. iodide trapping 2. synthesis of thyroglobulin 3. oxidation of iodide 4. iodination of tyrosine 5. coupling of T1 and T2 6. pinocytosis and digestion of colloid 7. secretion of thyroid hormones(T3 and T4), and transport to the blood What is the role of Thyroid Hormones? T3&T4: responsible for metabolic rate, synthesis of protein, breakdown of fats, use of glucose for ATP production Calcitonin: responsible for building of bone and stops reabsorption of bone (lowers blood levels of Calcium) Negative Feedback System Where is TSH produced? A. Hypothalamus B. Anterior Pituitary Gland C. Posterior Pituitary Gland D. Thyroid Gland Where is TSH produced? A. Hypothalamus B. Anterior Pituitary Gland C. Posterior Pituitary Gland D. Thyroid Gland What is the role of the Thyroid Gland? A. Regulate Oxygen and Basal Metabolic Rate B. Cellular Metabolism C. Growth and Development D. All of the Above What is the role of the Thyroid Gland? A. Regulate Oxygen and Basal Metabolic Rate B. Cellular Metabolism C. Growth and Development D. All of the Above What happens when the thyroid gland doesn’t work? • 0.1-2.0% of American adults have overt hypothyroidism and 4-10% have subclinical hypothyroidism • 1.3% have hyperthyroidism • Thyroid dysfunction is 5x higher in woman • Framingham Study: Clinically apparent thyroid nodules were present in 6.4% of women and 1.5% of men • 37-57% of patients had thyroid nodules in autopsy surveys Who should be checked for hypothyroidism? • Anyone with symptoms that could be consistent with hypothyroidism • Anyone with laboratory or radiologic abnormalities • Patients with risk factors for hypothyroidism (ex: h/o autoimmune diseases or family history of autoimmune thyroiditis) • Patients who take drugs that can impair thyroid function • Women who are trying to become pregnant or already pregnant Patient Case 31yo female patient presents to your office with chief complaints of feeling tired and she is always cold. She said that she has been stressed lately with just starting as a new PA, being a police wife, and her one year old son. She just assumed this is why she is always tired but wanted to make sure. She said her husband is also very annoyed that she always has cold hands and feet and needs the heat on when its 80 degrees. She would like to plan to have another child soon. She lives a very active lifestyle, exercises daily, and eats healthy most of the time. Allergies: None Current Medications: Prenatal Vitamins PMH: None Surgical History: L4 fixation 2002, L4/L5 fusion 2006 FH: Hypertension, Hyperlipidemia Vitals: BP: 118/68, HR: 65, Temp: 98.8, R: 16 What kind of physical exam would you pay attention to? A comprehensive physical exam should be performed • Weight and blood pressure • Pulse rate and cardiac rhythm • Thyroid palpation and auscultation(to determine thyroid size, nodularity, and vascularity) • Neuromuscular examination • Eye examination (to detect evidence of exophthalmos or opthalmopathy) • Dermatologic examination • Cardiovascular examination • Lymphatic examination (nodes and spleen) Patient Case General: Well Developed, Well Nourished, No distress, Head, Eyes, Ears, Nose, Throat: Normocephalic, atraumatic, PERRLA, Conjunctiva normal, Nares normal, Oropharynx moist and clear Neck: Supple with normal range of motion, No lymphadenopathy, no thyromegaly or palpable nodules Cardiovascular: S1S2, regular, rate, and rhythm without murmurs, gallops, or rubs Lungs: Clear to auscultation with normal effort Neurologic: No deficits Skin: warm and dry What would you order now? What tests should I order initially to screen for hypothyroidism? What tests should I order initially to screen for hypothyroidism? Answer: TSH ONLY What should I do next if TSH is elevated? What should I do next if TSH is elevated? Repeat the TSH along with a free T4 Total T4 vs. Free T4 • Should I order a Total T4 Level instead of a free T4?— NO • 99.97% of T4 is bound to either thyroxine-binding globulin(TBG), transthyretin(pre-albumin) or albumin • Total and free T4 levels can be discordant due to binding protein abnormalities from drugs, illness, and genetics • “Direct” free T4 assays don’t actually measure free T4 levels. Instead they provide values that take binding protein abnormalities into account. Settings where TSH alone is not useful: • Known or suspected pituitary or hypothalamic disease • Hospitalized patients (sick euthyroid syndrome) • Patients on medications or with underlying diseases that can affect TSH secretion Patient Case Lab Results: TSH: 9.80 (0.450-4.500) T4, total: 6.3 (4.5-12.0ug/dL) Other Labs to consider adding on Thyroid Peroxidase: 180 (023IU/ml) Thyroglobulin Ab: 1.3 (0.0-0.9IU/ml) Hypothyroidism • High TSH and low free T4—>Clinical Hypothyroidism • Treatment can be started immediately if the patient is symptomatic • High TSH and normal free T4—>SubClinical Hypothyroidism • Further evaluation should be considered before starting treatment • When should I start treatment with this? • TSH above 10 • Symptoms? • When the patient is at high risk for progression to overt hypothyroidism • Hashimoto’s disease-positive thyroid autoantibodies • Palpable diffuse goiter • FH of hypothyroidism • Women who are pregnant, wish to become pregnant or ovulatory dysfunction Primary Hypothyroidism-Causes • Hashimoto’s thyroiditis (chronic autoimmune thyroiditis)-Most common cause in the U.S. • Iodine deficiency: Most common cause in the world • Other Causes: • Iatrogenic (thyroidectomy, radiation) • Drugs-thionamides, lithium, amiodarone, interferonalfa, interleukin-2, perchlorate • Transient hypothyroidism • Congenital thyroid agenesis, dysgenesis, or defects in hormone synthesis • Infiltrative diseases-fibrous thyroiditis, hemochromatosis, sarcoidosis Hashimoto’s Thyroiditis • Autoimmune disorder where the immune system attacks the thyroid leading to hypothyroidism. • Characterized by gradual thyroid failure, with or without goiter formation • Affects 14 million people in the United States alone. • 7 times more common in women than men. • Causes: Infection, stress, gender, pregnancy, iodine intake, radiation exposure. • Thyroid autoantibodies(anti-thyroid peroxidase and anti-thyroglobulin autoantibodies) are 95% positive in patients with this. These antibodies are directed against TPO and TG, resulting in a lymphocyte infiltration of the thyroid gland, which causes it to cease functioning partially or entirely. Iodine Deficiency Table 1: Recommendations for iodine intake (µg/day) by age or population group a Recommended Daily Allowance. b Adequate Intake. c Recommended Nutrient Intake. Age or population groupa U.S. Age or Institute population of groupc Medicine (ref.5) Infants 0–12 months b 110-130 Children 0-5 years Children 1-8 years 90> Children 9-13 years 120> Adults ≥14 years World Health Organization (ref.1) FIG. 1. Large nodular goiter in a 14-yr-old boy photographed in 2004 in an area of severe IDD in northern Morocco, with tracheal and esophageal compression and hoarseness, likely due to damage to the recurrent laryngeal nerves 90 Children 612 years 120 150 Adults >12 years 150 <Pregnancy 220 Pregnancy 250 Lactation 290 Lactation 250 Zimmermann, M. B. Endocr Rev 2009;30:376-408 Imaging for Thyroid • Should I get a Thyroid Ultrasound for Hypothyroidism?--No • “Heterogeneic echotexture with 12 left-sided and 16 right-sided nodules measuring 2-8mm in size” Hashimoto’s Thyroiditis • Should I order a Thyroid Uptake Scan for Hypothyroidism?—No, your patient will not be happy with you. Treatment of Hypothyroidism • Levothyroxine(Synthroid) or LT4 • 100% thyroid replacement is roughly 1.6mcg/kg/day(112mcg in a 70kg adult) • Euthyroidism is achieved more rapidly when total replacement dose started, however hyperthyroidism may occur if patient has mild hypothyroidism prior to initiation of medication. • Clinical judgement necessary based on TSH level and clinical symptoms. • Generic vs. Brand? • Cytomel: synthetic pure T3, uniform, fast absorption, fast onset. Greater risk of toxicity, twice daily dosing. How to take Levothyroxine/Synthroid? • Only about 50% of LT4 is absorbed under optimal conditions • It can be reduced with food and medications • Medications • calcium carbonate • ferrous sulfate • PPIs • bile acid resins Synthroid Dosing Guidelines Some Common Over The Counter Thyroid Supplements Armour Thyroid Is Armour Thyroid better than Levothyroxine because it’s natural? Not necessarily… What is it? • Desiccated porcine thyroid • 1 grain(60mg) contains 38mcg T4 and 9mcg T3(equivalent to 36mcg T4). • T3:T4 ratio is much higher in pigs than in humans(1:20 to 1:100) • T4 and T3 levels should never be used for monitoring. • FDA regulated: Can use if patient insists and TSH is monitored. • AACE do not recommend using this as first line treatment How Often should I monitor TSH Levels? How Often should I monitor TSH Levels? Answer: 6-8 weeks Once stable, every 6 months