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MENNONITE COLLEGE OF NURSING NUR 475 - Family Nurse Practitioner III Thyroid Dysfunction Screening US Preventive Services Task Force http://www.uspreventiveservicestaskforce.org/3rduspstf/thyroid/thyrrs.htm The USPSTF concludes the evidence is insufficient to recommend for or against routine screening for thyroid disease in adults. (Rating: I Recommendation.) Rationale: The USPSTF found fair evidence that the thyroid stimulating hormone (TSH) test can detect subclinical thyroid disease in people without symptoms of thyroid dysfunction, but poor evidence that treatment improves clinically important outcomes in adults with screen-detected thyroid disease. Although the yield of screening is greater in certain high-risk groups (e.g., postpartum women, people with Down syndrome, and the elderly), the USPSTF found poor evidence that screening these groups leads to clinically important benefits. There is the potential for harm caused by false positive screening tests; however, the magnitude of harm is not known. There is good evidence that over-treatment with levothyroxine occurs in a substantial proportion of patients, but the long-term harmful effects of over-treatment are not known. As a result, the USPSTF could not determine the balance of benefits and harms of screening asymptomatic adults for thyroid disease. The American Thyroid Association recommends measuring thyroid function in all adults beginning at age 35 years and every 5 years thereafter, noting that more frequent screening may be appropriate in high-risk or symptomatic individuals. The American College of Physicians recommends screening women older than age 50 with 1 or more general symptoms that could be caused by thyroid disease. The American Association of Clinical Endocrinologists recommends TSH measurement in women of childbearing age before pregnancy or during the first trimester. The American College of Obstetricians and Gynecologists recommends that physicians be aware of the symptoms and risk factors for postpartum thyroid dysfunction and evaluate patients when indicated. The American Academy of Family Physicians recommends against routine thyroid screening in asymptomatic patients younger than age 60. Thyroid Testing From: Supit, E.J., & Peiris, A.N. (2002) Interpretation of Laboratory Thyroid Function Tests for the Primary Care Physician. South Med J. 95(5), 481-485. Retrieved from http://wwww.medscape.com/viewartcile/433852_print Serum TSH Level The American Thyroid Association recommends initially checking free-T4 and TSH (thyroid-stimulating hormone) levels to test thyroid function. Serum TSH level remains the single best test of thyroid function. TSH testing is the preferred approach because TSH is central to the negative-feedback system and small changes in serum thyroid function cause logarithmic amplification in TSH secretion. In many situations, a normal TSH level can be sufficient indication to halt further testing of thyroid function; however, it may still be desirable to check a free-T4 level in the setting of possible hypothalamic pituitary disease. Total Serum T4 Level/Free T4 Total serum T4 level has high sensitivity in reflecting the functional state of most patients with thyroid disease. The levels are high in approximately 90% of hyperthyroid patients and low in approximately 85% of hypothyroid patients. Free-T4 level can be estimated by several different methods. Thyroid-stimulating immunoglobulin (TSI) More than 90% of patients with Graves' disease have an immunoglobin G (IgG) antibody, TSI, directed against the thyroid TSH receptor. TSI level determination is unnecessary in most cases, due to characteristic clinical manifestations of Graves' disease. But in patients exhibiting exophthalmos are euthyroid, determining the TSI level may be of value in establishing the diagnosis of euthyroid Graves' disease. Antithyroid antibodies The most common antithyroid antibodies (antimicrosomal/peroxidase and antithyroglobulin) are highly organ-specific and organ-sensitive. The antimicrosomal antibodies, directed primarily against membrane-bound thyroid peroxidase, are most useful in diagnosing Hashimoto's thyroiditis. Tests for these antibodies may also be positive in Graves' disease. Serum thyroglobulin Serum thyroglobulin levels may have utility in distinguishing Graves' disease from factitious thyrotoxicosis from taking too much thyroid hormone medication. In Graves' disease, the level of serum thyroglobulin is increased, whereas in factitious disease the levels are decreased. Algorithm for interpreting thyroid function tests. Iodine Uptake Scan (from http://www.endocrineweb.com/conditions/thyroid/thyroid-gland-function) Cells of the thyroid normally absorb iodine from the bloodstream and use it to make thyroid hormone. A means of measuring thyroid function is to measure how much iodine is taken up by the thyroid gland (RAI uptake). Hypothyroid patients usually take up too little iodine and hyperthyroid patients take up too much iodine. The test is performed by giving a dose of radioactive iodine on an empty stomach. The iodine is concentrated in the thyroid gland or excreted in the urine over the next few hours. Patients who are taking thyroid medication will not take up as much iodine in their thyroid gland because their own thyroid gland is turned off and is not functioning. At other times the gland will concentrate iodine normally but will be unable to convert the iodine into thyroid hormone; therefore, interpretation of the iodine uptake is usually done in conjunction with blood tests. Thyroid Scan (from http://www.endocrineweb.com/conditions/thyroid/thyroid-gland-function) Taking a "picture" of how well the thyroid gland is functioning requires giving a radioisotope to the patient and letting the thyroid gland concentrate the isotope. Therefore, it is usually done at the same time that the iodine uptake test is performed. It has been found that thyroid nodules that concentrate radioactive iodine are rarely cancerous. Use of radioactive iodine is contraindicated in pregnancy. Both of the scans below show normal sized thyroid glands, but the one on the left has a "HOT" nodule in the lower aspect of the right lobe, while the scan on the right has a "COLD" nodule in the lower aspect of the left lobe (outlined in red and yellow). “Hot spot” – caused by hyperfunctioning thyroid nodules which are usually nonmalignant “Cold spot” – caused by nodules that do not take up the radioactive tracer. These areas have hypofunctioning (metabolically inactive) tissue and are more likely to be malignant. However, the majority of cold spots are benign, so need to biopsy. Hyperthyroidism Note: In addition to the following causes of hyperthyroidism, medications such as amiodarone (38% iodine by weight) can cause hyperthyroidism. S/Sx: - goiter (usually) (Thyroid gland enlarges in response to increased TSH secretion) - eye signs (exophthalmos) - unexplained weight loss - tachycardia - tremor and hyperreflexia Palpation: usually do not feel lobes; do feel isthmus (which moves up with swallowing) If find nodule, can put tape over it and measure. Diagnostic Tests Results in Hyperthyroidism: - TSH low - Free T4/Index high (Remember: most T4 is bound to protein, so order Free T4) (Source: http://www.endocrineweb.com/conditions/thyroid/how-your-thyroid-works) Causes (Differential Diagnosis): 1. Graves’ disease – autoimmune disorder; female:male 8:1, 20-40 years of age TSI (autoantibody) - stimulates thyroid to produce T4 and T3 and to enlarge 2. Multinodular gland (also called toxic multinodular goiter; Plummer’s Disease) Seen in older patient; slower onset 3. Autonomously functioning nodule - large, single nodule 4. Subacute thyroiditis - painful; inflammation of thyroid gland, damaged gland; releasing hormone 5. Painless thyroiditis (= lymphocytic thyroiditis) Often seen after pregnancy 6. Iatrogenic (from accidentally or knowingly taking thyroid hormone) All 6 of these causes have decreased TSH and increased free T4. To differentiate, you can get iodine uptake scan/thyroid scan. ________________________________________________________________________ Cause Radioactive Scan iodine uptake Appearance ================================================================ Graves’ disease Increased Multinodular gland Increased Autonomously functioning nodule Increased Treatment options for all of the above: radioactive iodine ablation, antithyroid drug, surgery. [Scan images from http://emedicine.medscape.com/article/383062-overview] Cause Subacute thyroiditis Painless thyroiditis Iatrogenic Radioactive iodine uptake Decreased or 0 Decreased or 0 Decreased or 0 Scan Appearance N/A N/A N/A Treatment Symptomatic treatment: Beta blockers NSAIDs for pain Short course of steroids Iodine Can also do ultrasound; if applicable, fine needle aspiration biopsy. TSI - Usually do not need to order this to diagnose Grave’s disease - Do use in pregnancy, since TSI crosses placenta and can affect baby. Treatments: Propanolol (β-blocker) o Used for symptomatic relief (decrease HR, tremor, diaphoresis, & anxiety) Methimazole (Tapazole)** o Inhibit thyroid hormone synthesis o 5-20 mg up to 60 mg once daily (smaller doses if mild hyperthyroid) o Dosage reduced as manifestations of hyperthyroidism resolve and FT4 levels fall o Rare cases of embryopathy reported with use during pregnancy (Pregnancy Category D)* Propylthiouracil (PTU)** o Safer in pregnancy and breastfeeding o 300-600 mg daily in 4 divided doses o Dosage reduced as manifestations of hyperthyroidism resolve and FT4 levels fall o ** Risk of serious liver damage, including liver failure, or death Monitor closely for s/sx of liver injury, especially during first 6 months of therapy o Considered 2nd-line drug therapy except in patients who are allergic to or intolerance of methimazole o Although Pregnancy Category D, more appropriate for patients with Graves’ disease who are in their first trimester of pregnancy* Iodinated contract agents (Iopanoic acid or ipodate sodium) o Provide temporary treatment of hyperthyroidism of any cause o Block conversion of T4 to T3 o Within 24 hours, serum T3 falls 62% o 500 mg. bid X 3 days then 500 mg daily Radioactive iodine (Treatment of choice for Graves’ disease) o Destroys overactive thyroid tissue (goiter) o Permanent hypothyroidism in 1/3 patients after 8 years of therapy o More commonly used in elderly – gradually reversed, local destruction of thyroid Thyroid surgery o Uncommon unless coexistent thyroid cancer is suspected o Women of child bearing age or pregnant who are intolerant of antithyroid medications o Malignancy o Risks: hypoparathyroidism (check calcium levels), damage to laryngeal nerve) o Permanent hypothyroidism occurs in 14% of patients 6 years post-surgery *From: http://www.medscape.com/viewarticle/703851_print **These meds can cause agranulocytosis (check WBC and differential if any rash, sore throat, or fever). NOTE: Recheck TSH in 6 weeks after starting medications. Special considerations regarding hyperthyroidism in the elderly Cardiac manifestations most common manifestations of hyperthyroidism the elderly o Likely to have heart failure, angina o 27% present with atrial fibrillation Hyperthyroidism can be complicated by depression, myopathy, & osteoporosis Thyroid gland is often shrunken and difficult to palpate in the elderly Iodine-induced hyperthyroidism (Jod-Basedow phenomenon) has been reported in elderly with no know prior thyroid disease who were exposed to iodinated contrast media for cardiac CT imaging. Weight loss was the only clinical manifestation. Complications Cardiac arrhythmias Heart failure Thyroid crisis Hypercalcemia Osteoporosis Decreased libido ED Gynecomastia Ophthalmopathy Dermopathy Hypothyroidism Note: In addition to the following causes of hypothyroidism, medications such as amiodarone can cause hypothyroidism. S/Sx Everything slows down: - hypomentation - hypothermia - hypopnea - hypocardia - hyporeflexia - hyponatremia Demographics: Usually > 40 years old, female:male 5:1-10:1 In US: 0.3% of population o > 65 year olds: increases to 6-10% of women, 2-3% of men o 13.7% with subclinical hypothyroidism Labs TSH Free T4 high low or normal Differential Diagnosis: 1. Post-radioactive iodine ablation 2. Autoimmune thyroiditis (Hashimoto’s thyroiditis) 3. Idiopathic 4. Post-surgical Treatment All are treated the same: give thyroid hormone. levothyroxine 50-150 mcg/day Dosing: Start low and go slow! With levothyroxine (Synthroid, for example), starting dosages: o If young, OK start on 0.1 mg po/day o If > 45 yr. old, no CV disease start on 0.05 mg/day o If elderly, have CV disease, have longstanding hypothyroidism start on 0.025 mg/day If normalizing TSH results in worsening of cardiac symptoms, treatment should aim for the lowest TSH level that avoids cardiac symptoms and may necessitate allowed TSH levels to be above the normal range. o Increase dosage by 0.025 mg every 6 weeks until TSH within normal limits o Iron, calcium, sucralfate, high fiber foods, tofu - all affect absorption (bioavailability) of Synthroid...so take on empty stomach. Elderly patients are much more sensitive to thyroid hormone replacement therapy more liable to suffer more adverse reactions to thyroid hormones than patients in any other age group. Because the symptoms of hypothyroidism may be confused with those of other diseases, nonspecific symptoms such as stumbling, falling, depression, incontinence, cold intolerance, and weight gain should be thoroughly evaluated and documented before a diagnosis of hypothyroidism is rendered. What is the target TSH level in thyroid hormone replacement for primary hypothyroidism? [Reference: Zimmerman, R.S.,(April 2003). What is the target TSH level in thyroid hormone replacement for primary hypothyroidism? Cleveland Clinic Journal of Medicine, 70(4), 329-330.] Recommended to have TSH goal at lower end of the normal range when treating hypothyroidism. This is to avoid driving TSH levels too low, which can produce subclinical hyperthyroidism, which can cause cardiac arrhythmias, osteoporosis, and diastolic dysfunction. The risk of atrial fibrillation is increased in patients with subclinical hyperthyroidism Cholesterol and B/P go up with hypothyroidism, so before treating those conditions, check the thyroid function!!! Re: Why high cholesterol with hypothyroidism? (info found in PubMed) An Association Between Varying Degrees of Hypothyroidism and Hypercholesterolemia in Women: The Thyroid-Cholesterol Connection. By Feld S, Dickey RA, University of Texas-Southwest Medical School, Dallas, TX 75248. Evidence of an association between subclinical hypothyroidism and cardiovascular disease is mounting. The impact of thyroid hormone on lipid levels is primarily mediated through triiodothyronine (T(3))-bound thyroid protein binding and activation of the promoter regions of the low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A-reductase genes, leading to a reduction in serum cholesterol levels. Thus, the decreased T(3) seen in hypothyroidism may result in increased serum cholesterol. Although a clear correlation exists between overt hypothyroidism and clinically significant hypercholesterolemia, there is a logarithmic relationship between thyroidstimulating hormone and cholesterol, and the effects of subclinical hypothyroidism on cardiovascular disease are under debate. However, current data suggest that normalizing even modest thyroid-stimulating hormone elevations may result in improvement in the lipid profile. (c)2001 CHF, Inc. Precautions Patients with DM may need readjustment of hypoglycemia agents with initiation of thyroid replacement therapy. Dosage of oral anticoagulants may need adjustment; monitor PT/INR closely at first Complications If left untreated, hypothyroidism may lead to myxedema coma o Severe, life-threatening form of hypothyroidism o More frequent in winter months o Present with extreme hypothermia, hypoventilation, hyponatremia, hypoglycemia, bradycardia, and hypotension o Cognitive impairments ranging in severity from mild confusion to myxedema coma (confusionstuporcoma) o Treatment: admit to ICU, IV levothyroxine Treatment-induced CHF in people with CAD Increased susceptibility to infection Megacolon (from constipation) Organic psychosis with paranoia Adrenal crisis with vigorous treatment of hypothyroidism Infertility Over-treatment over long periods can lead to bone demineralization (√ DEXA) Subclinical hypothyroidism can cause ischemic heart disease Criteria for possible referral to endocrinologist Age 18 years or younger Unresponsive to treatment Pregnant Cardiac problems Presence of structural changes in the thyroid gland such as goiter or thyroid nodule Presence of concomitant separate endocrine disorder Additional references: Clinical Practice Guidelines For Hypothyroidism In Adults: Cosponsored By The American Association Of Clinical Endocrinologists And The American Thyroid Association at https://www.aace.com/files/final-file-hypo-guidelines.pdf Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists at https://www.aace.com/files/hyperguidelineswithcopyright.pdf Thyroid Nodules What makes you suspicious of cancer? age (young) sex (male) family history of thyroid cancer x-ray treatment/exposure (low dose) physical characteristics of nodule (hard, fixed, larger) Workup for thyroid nodules: Check: - Free T4 - TSH - thyroid microsomal autoantibodies ___________________________|___________________________ |* | |* Increased Free T4 Normal Free T4 Decreased Free T4 Decreased TSH and TSH Increased TSH | | (+) thyroid | | microsomal | | autoantibodies | | | = Autonomously Fine Needle = Autoimmune Functioning Thyroid Aspiration Biopsy thyroiditis with Nodule | hypothyroidism | | Malignant Benign Suspicious | | | Surgery Surveillance Re-biopsy or Surgery *Thyroid scan also performed: if cold nodule, do fine needle aspiration biopsy, if hot nodule, can use radioactive iodine or surgery. Resource for Patient Information on thyroid disorders: http://www.thyroid.org/patient-thyroid-information/ata-patient-education-web-brochures/