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Where there is no endocrinologist— Outpatient workup and management of common thyroid disorders— selected case studies 9/19/13 Introductions Who are you? Who am I? Amy Robinson, M.D. Lobo Care Clinic 1101-A 4 Medical Arts Ave, NE [email protected] Asst. Professor, Division of General Internal Medicine Disclosures I have no known conflicts of interest OBJECTIVES 1) to help you perform better on standardized exams 2) to help you feel more comfortable managing some common thyroid problems in an outpatient setting. Some of the information presented here will be very basic—no offense intended Case #1: A healthy 28 year old female c/o one year history of painless swelling in her neck. She denies weight loss, fatigue, and anxiety. Family history is positive for thyroid disease in her mom and maternal grandmother who both take levothyroxine. She is thinking about trying to get pregnant. Case #1 continued: PE: BP 130/80, HR 94, RR 16, BMI 27. Heart, Lungs, Abdomen, Ext: normal Neck: thyroid gland palpable, minimally enlarged bilaterally, and firm; no nodules palpated; no cervical lymphadenopathy Labs: TSH = (normal = 0.358-3.740) Free T4 = 1.2 (normal = 0.7-1.6) Free T3 = 4.0 (normal = 0.5-30.0) Thyroid peroxidase antibodies = (normal <20) Q: What is the next most appropriate action? A. B. C. D. Fine-needle aspiration of the thyroid gland Start levothyroxine Observe; repeat TSH in 6 weeks Thyroid scan B: Start levothyroxine Important points: 1) What is her diagnosis? 2) Why is this her diagnosis? What: Subclinical hypothyroidism. Why: She has an elevated TSH with normal T4 and T3 These people often have minimal to no symptoms—you have probably already seen this in clinic. Treatment issue: At what TSH should treatment be initiated for subclinical hypothyroidism? TSH> 10—consensus for non-pregnant adult She is at risk of progression to overt hypothyroidism due to +anti-TPO antibodies, +family history and likely pregnancy What other problems might she encounter with untreated subclinical hypothyroidism? Mild elevation of Total Cholesterol, LDL, and CRP Increased risk for atherosclerosis and cardiac events (BTW—data does not yet show that RX with levothyroxine reverses these or improves outcomes ) What would most practitioners actually do in this situation? Given her possibility of pregnancy, +antiTPO antibodies, goiter and strong FHX, most practitioners would start levothyroxine despite her mildly elevated TSH (above normal but less than 10). Why not biopsy her thyroid? She did not have a palpable nodule. What are the risks of untreated or inadequately treated hypothyroidism in pregnancy? Low birth weight Increased risk of miscarriage Premature birth Fetal loss Why? The fetus requires transplacental transfer of maternal thyroid hormones during the first 12 weeks of gestation. What is the optimal TSH in a woman considering pregnancy? 0.5-2.5 Wow! Reference Lazarus, JH. The continuing saga of postpartum thyroiditis. J Clin Endocrinol Metab. 2011; 96(3):614-616. PMID: 21378224. Case #2: A 27 year old female has a positive HCG and is estimated to be at 4 weeks gestation. She has been well aside from a history of hypothyroidism. PMHX: Hashimoto’s thyroiditis Meds: levothyroxine 125 mcg daily, PNV, FeSo4 Case #2 continued: PE: T 37.1 C, BP 128/80, HR 95, RR 18, BMI 25. Neuro: fine hand tremor Normal heart, lungs, skin Neck: thyroid slightly enlarged but smooth texture; no nodules or bruits Labs: TSH = 4.2 (normal= 0.358-3.740) free T4 = 1.6 (normal= 0.7-1.6) Q: What do you recommend? A. increase the levothyroxine by 10% today B. increase the levothyroxine by 30% C. continue the same dose, repeat thyroid tests in 5 weeks D. repeat thyroid tests in the second trimester Answer: B. Increase the thyroid dose by 30% now! (and repeat the thyroid tests in 4 weeks) Why? Pregnancy will likely increase the levothyroxine requirements for most women already on thyroid replacement therapy, especially during the first and possibly the second trimester. Why? During the first half of pregnancy, there is increased serum thyroxine-binding globulin (TBG) and TSH Increased thyroid hormone requirement is due to both increased TBG production and decreased clearance The thyroid gland responds by increasing production of T3 and T4 This change will plateau at 20 weeks such that the overall production rate of thyroid hormones returns to prepregnancy rates Ross, Douglas S. “Overview of Thyroid disease in pregnancy,” UpToDateOnline, 10/3/2012. What are the goal TSH levels by trimester? --0.1-2.5 -- first trimester --0.2-3.2 – second trimester --0.3-3.0 – third trimester Why worry? Maternal subclinical or overt hypothyroidism may be associated with Fetal neurocognitive impairment Increased risk of premature birth Low birth weight Increased miscarriage Increased risk of fetal death Case Reference Yassa L, Marqusee E, Fawcett R, Alexander EK. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol Metab. 2010; 95 (7): 3234-3241. PMID: 20463094 A few other fun questions: 1) what is the prevalence of subclinical hypothyroidism? 2) what is the prevalence of overt hypothyroidism? 3) what should the normal range of TSH actually be? Fun question --answers 1) 4-15% = prevalence of subclinical hypothyroidism in community surveys. 2) 0.1-2% = prevalence of overt hypothyroidism (note that the prevalence of subclinical hypothyroidism is greater); hypothyroidism is 8x more common in women than in men. 3) the normal reference range of TSH is much debated. Some labs use 4-5 and others use values more in the 2-3 range. Many believe that the normal TSH distribution will drift up w/ age, so 6-8 might represent a normal value in an octagenarian. Fun questions (!) continued: 4) what is the most appropriate starting dose for the treatment of hypothyroidism? 5) After starting or changing levothyroxine, when do you recheck the TSH? 6) If the patient has a normal TSH, when do you next reassess the level? 7) What medications interfere with absorption of thyroid medication? More fun answers! 4) Supplementation is recommended at about 1.6 mcg/kg body weight which amounts to 112 mcg/ day for a 70 kg person. The actual requirement varies considerably ranging from 50 to over 200 mcg per day. It correlates better with lean body mass. 5) the plasma half life of levothyroxine is one week (7 days). It takes six half-lives for a steady-state level to be achieved, so it is advised to recheck the level in 6 weeks. 6) when stable, recheck the TSH annually or sooner if other important changes occur (e.g. pregnancy, significant weight change, initiation of medications which may affect absorption). 7) numerous drugs affect thyroid hormone levels by affecting binding in serum (e.g. oral contraceptives, tamoxifen, raloxifene, methadone, androgens, glucocorticoids, salicylates, furosemide and heparin). GI absorption is affected by cholestyramine, colestipol, omeprazole, lansoprazole (note—normal gastric acid levels are required for absorption), ferrous sulfate, calcium carbonate, and ciprofloxacin). 7) continued- T3 production is reduced by amiodarone. Thyroid hormone metabolism is affected by phenobarbitol, carbamazepine, and rifampin, among others. Reference: Surks, Martin I. “Drug Interactions with Thyroid Hormones,” UpToDateOnline. And more… 8) Should pregnant women be routinely screened for hypothyroidism? 9) How is hypothyroidism diagnosed? 10) How is hypothyroidism categorized? 8) there is some debate about this, but routine screening of all pregnant women is not currently recommended. It is advisable to check the TSH in at risk women which would include --symptoms of or family history of thyroid disease --risk factors including goiter, type 1 diabetes, history of head/neck radiation, iodine deficiency, or recent use of lithium or amiodarone. 9) diagnosis relies upon lab tests because there is a lack of specificity of clinical symptoms. 10) Primary hypothyroidism accounts for about 95% of cases and is characterized by elevated TSH with low free T4; subclinical hypothyroidism is characterized by elevated TSH with normal free T4; secondary (central) hypothyroidism is characterized by normal TSH and low T4. Case #3: A 40-year old male presents to you for evaluation of a small nodule in the right lobe of the thyroid gland on a CT scan obtained because of chest pain. He feels well now and denies palpitations, feeling nervous, neck discomfort, or dysphagia. His mom had papillary thyroid cancer that was diagnosed in her 30s. Case #3 continued: On exam, he appears healthy and alert. Vitals are normal; BMI is 28. Lungs, Heart, Abd—normal Neck—barely palpable thyroid; no nodules; no cervical lymphadenopathy Labs notable for normal TSH at 1.5 mU/L. Neck US demonstrates right lobe 6 mm hypoechoic nodule w/ microcalcifications, blurred margins and increased vascularity. No enlarged cervical lymph nodes seen. Which of the following is the most appropriate step? A. Fine-needle aspiration biopsy B. Repeat thyroid ultrasound in 3 months C. Right thyroid lobectomy D. Thyroid MRI FNA of the nodule—right! Key points: -Most thyroid nodules are benign -only about 5-15% are malignant -Biopsy results are usually categorized as one of the following: benign, suspicious for malignancy, follicular neoplasm or papillary thyroid cancer -FNA is the most sensitive and specific method to characterize the nodule How common are thyroid nodules? 30-50% of healthy people are likely to have a thyroid nodule on ultrasound How do you decide which nodules to biopsy? The American Thyroid Association recommends biopsy of a nodule of at least 5 mm diameter in a patient at high risk who also has worrisome sonographic findings. Our patient here has a first-degree relative with papillary thyroid cancer. Ultrasound showed concerning qualities of hypoechoic shadowing with blurred margins, microcalcifications and increased central vascularity. Why would it be inappropriate to observe and follow with repeat thyroid ultrasound in 3-6 months? His nodule demonstrated suspicious features and he had significant risk factors Why not perform thyroid lobectomy? Thyroid lobectomy would be appropriate for a cancerous thyroid nodule less than 1 cm diameter but is premature, because he does not yet have a diagnosis of malignancy. Why didn’t you order an MRI? It might be helpful in detecting local extension of thyroid malignancies or spread into the mediastinum or retrothyroid regions but is generally less clear than Doppler ultrasonography for imaging nodules within the thyroid gland. (Not to mention the copay….) Case reference American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer (errata in Thyroid. 2010; 20(6):674-675; and Thyroid. 2010:20(8):942). Thyroid. 2009; 19(11): 1167-1214. PMID: 19860588 Objectives covered so far: Case 1: management of subclinical hypothyroidism in a woman of childbearing age with multiple risk factors Case 2: management of hypothyroidism in a woman during early pregnancy Case 3: management of thyroid nodule with fineneedle aspiration Case #4: An 88 year old man comes in for a routine physical. He c/o moderate fatigue. He denies weight change, nervousness, constipation, dyspnea, and palpitations. PMHX: hypertension Meds: lisinopril, low dose aspirin P.E.: alert/oriented older gentleman Vitals: BP 140/85, others normal Heart: RRR with gr. 1/6 crescendo-decrescendo sys. murmur Lungs: normal exam Neck: thyroid gland not palpable; no cervical lymphadenopathy Ext/pulses--normal Case #4 continued: Labs: CBC normal CMP normal Thyroid function tests (repeated and confirmed): --TSH = 6.8 (normal = 0.358-3.740) --Free T4 = 1.1 (normal = 0.7-1.6) Thyroid peroxidase antibody titer = normal Which of the following is the most appropriate management? A. Prescribe levothyroxine B. Prescribe liothyronine C. Radioactive iodine test D. Observe D. Observe Why? “Several studies have shown that an elevated serum TSH level in older patients is not associated with detrimental medical outcomes (such as depressive symptoms and impaired cognitive function) but, in fact, is associated with a lower mortality rate. Although the precise numbers are somewhat controversial, the normal reference range most likely is approximately 1 to 7 microunits/mL (1-7 milliunits/L). It is now recognized that older patients generally should not be given levothyroxine solely for an elevated TSH level. A full consideration of the patient and clinical context is necessary.” Why not give levothyroxine? He is asymptomatic aside from some fatigue and is generally in good health. Given his unremarkable physical exam and normal TPO level, he does not need exogenous levothyroxine. Why not give liothyronine? There is no evidence to show clinical benefit of using liothyronine over levothyroxine in patients who require thyroid hormone supplementation. Liothyronine and other T3 preparations have a short half-life and have been associated with acute spikes in serum T3 levels. This is especially worrisome in older patients and those with cardiac abnormalities. Why not do a radioactive iodine test? This test is not used for the diagnosis of hypothyroidism and would therefore be inappropriate. Aside—when would you perform a radioactive iodine test? Choices: A. Never—I let the endocrinologist do this if needed. B. I order this if my patient has a thyroid nodule. C. I order this if my patient has a low TSH. D. I order this in a patient with a low TSH and a thyroid nodule. It depends… If you still work at UNM, consider calling the endocrinologist through the PALS line. If you work somewhere else, call the endocrinologist who you will send your patient to when you reach the limit of your expertise. Case 4 reference: Gussekloo, J, van Exel, de Craen AJ, Meinders AE, Frolich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004; 292 (21): 2591-2599. PMID: 1557217. Acknowlegements The cases presented here were forwarded to me by Dr. Colombo and come from the MKSAP review. Additional information was from assorted articles in UpToDateOnline. Cases on secondary amenorrhea, Graves’ disease, medullary thyroid cancer, myxedema coma and TSHsecreting pituitary tumor were not included due to their less common presentation in outpatient primary care settings and time constraints. Good luck And thank you for your attention!