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© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View.

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Presentation on theme: "© Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View."— Presentation transcript:

1 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

2 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. in the clinic Hyperthyroidism

3 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Terms of Use  The In the Clinic ® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for- profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets constitutes copyright infringement.

4 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Who has an elevated risk for hyperthyroidism? Individuals with:  Diffuse or nodular goiters  Type 1 diabetes, other endocrine/ nonendocrine AI diseases  Family histories of hyperthyroidism or hypothyroidism Medications that increase risk:  Amiodarone  Alpha-interferon  Interleukin-2  Lithium  Iodide  Iodinated contrast agents in those with preexisting autoimmune or nodular thyroid disease

5 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Should clinicians screen for hyperthyroidism?  Screen: Individuals with risk factors  High risk comorbid conditions, family Hx, medication use  Consider screening: those with other medical conditions caused or aggravated by hyperthyroidism  e.g., osteoporosis, supraventricular tachycardia, A-Fib  Screen: Women >50 years  1 in 71 have unsuspected but symptomatic hyperthyroidism or hypothyroidism responsive to Rx

6 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. If clinicians screen for hyperthyroidism, which test should they use?  Serum TSH levels  Low in both overt and subclinical hyperthyroidism (due to negative feedback by  thyroid hormone levels on pituitary gland)  Screens for both hyperthyroidism & hypothyroidism  TSH assays: standardized, accurate, widely available

7 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. CLINICAL BOTTOM LINE: Screening…  Don’t screen: general population (not cost-effective)  Do screen: those with…  Diffuse or nodular goiters  Type 1 diabetes, other endocrine/ nonendocrine AI diseases  Osteoporosis, supraventricular tachycardia, or A-Fib  Family Hx hyperthyroidism or hypothyroidism  Amiodarone, α-interferon, interleukin-2, lithium, iodide use  Women > 50 years of age  Use serum TSH test

8 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What symptoms should prompt clinicians to consider hyperthyroidism?  Nervousness (frequency: 99%)  Increased sweating (91%)  Palpitations (89%) or tachycardia (82%)  Heat intolerance (89%)  Fatigue (88%)  Weight loss (85%)  Shortness of breath (75%), weakness (70%)  Leg swelling (65%)  Eye symptoms (54%)  Hyperdefecation (33%)  Menstrual irregularity (22%)  Emotional lability (30–60%)

9 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What physical examination findings indicate possible hyperthyroidism?  Tachycardia (100% frequency)  Goiter (100%)  Skin changes (97%)  Tremor (97%)  Bruit (77%)  Eye signs (30-45%)  Atrial fibrillation (10%)  Splenomegaly (10%)  Gynecomastia (10%)

10 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What lab tests should be used for diagnosis?  Serum TSH measurement  If low: order free T4 or free T4 index (FT4I)  If free T4 or FT4I not elevated: order total T3 or free T3  Radioiodine uptake (RAIU): helps determine cause  Thyroid scan: helps distinguish Graves disease, toxic multinodular goiter, toxic adenoma  If radioisotope studies contraindicated…  Blood tests: TSH-receptor antibodies; thyroid-stimulating immunoglobulins; thyroid-peroxidase antibodies; thyroglobulin; human chorionic gonadotropin; sed rate  Color Doppler US (thyroid)  Whole-body radioiodine scan

11 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Differential Diagnosis (with radioiodine uptake ) High or Normal Graves disease Toxic multinodular goiter Toxic adenoma HCG-induced hyperthyroidism TSH-producing pituitary tumor Low Silent thyroiditis Postpartum thyroiditis Subacute (granulomatous) thyroiditis Iodine-induced hyperthyroidism Amiodarone-induced hyperthyroidism Iatrogenic hyperthyroidism Metastatic follicular thyroid cancer Struma ovarii

12 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Lab and Other Studies for Hyperthyroidism (plus indication)  TSH (suspected hyperthyroidism)  Free thyroxine FT4 (suppressed TSH)  Free triiodothyronine FT3 (suppressed TSH, normal FT4)  Thyroglobulin (suspected thyroiditis)  Erythrocyte sed rate ESR (suspected subacute thyroiditis)  TSH-receptor antibodies (euthyroid Graves ophthalmopathy; assess remission with antithyroid drug Rx in Graves disease; assess neonatal risk in pregnant patients with Graves disease)  Thyroid peroxidase antibodies (confirm Hashimoto thyroiditis and autoimmune thyroid disease; assess risk for Rx-induced thyroid dysfunction and postpartum thyroiditis  RAIU (confirmed biochemical thyrotoxicosis, if cause unclear)  Thyroid scan (confirmed biochemical thyrotoxicosis, if cause unclear)  Whole body scan (suspected struma ovarii)  Color Doppler US (type I vs. type II amiodarone-induced thyrotoxicosis)  Human chorionic gonadotropin HCG (choriocarcinoma)

13 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What alternative explanations should clinicians consider?  Infection  Sepsis  Anxiety  Depression  Chronic fatigue syndrome  Atrial fibrillation of other causes  Pheochromocytoma  TSH testing usually distinguishes these from hyperthyroidism  But serum TSH levels often low in pregnancy; hyperemesis gravidarum; euthyroid sick syndrome; central hypothyroidism; with some medications (glucocorticoids, dopamine, heparin)

14 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should clinicians consult an endocrinologist?  Presence of hyperthyroidism uncertain  Serum TSH level low, but T4 and T3 within reference range  TSH level normal, but T4 or T3 above reference range  Cause unclear  RAIU low or undetectable (Dx usually clear when elevated)  Uncertain or suspicious about risk for or presence of thyroid storm or Graves orbitopathy

15 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. CLINICAL BOTTOM LINE: Diagnosis…  To make diagnosis, use:  History and physical exam  Low serum TSH level with elevated serum levels for free T4, FT4 I, total T3, or free T3  To identify cause, use:  Clinical features  RAIU and thyroid scan  Additional tests (TRAb, TSI, TPO antibodies, thyroglobulin, ESR, HCG, color Doppler US, whole-body scanning)

16 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What nondrug therapies should clinicians recommend? Until thyroid disease adequately controlled…  Avoid heavy physical exertion  Reduce or eliminate caffeine intake  Avoid OTC decongestants and cold remedies  Discontinue smoking  Avoid exogenous sources of iodine

17 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. How should clinicians choose and prescribe drug therapy?  Beta-adrenergic blockade  Propranolol, atenolol, metoprolol, nadolol  For symptomatic hyperthyroidism of any cause  Side effects: CHF, asthma exacerbation  Antithyroid medications  Methimazole: preferred  Propylthiouracil: alternative (in 1 st trimester pregnancy, if methimazole allergy, thyroid storm); beware liver failure  Inhibit thyroid hormone synthesis, lower thyroid hormone  Use for: Graves, toxic multinodular goiter, toxic adenoma  Don’t use for: low RAIU hyperthyroidism  Agranulocytosis occurs in 0.2%-0.4%

18 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Ancillary Therapy  Potassium iodine  Acutely reduces thyroid hormone release  Use before thyroidectomy for Graves  Don’t use before radioactive iodine therapy  Lithium  Reduces thyroid hormone release  Cholestyramine  Binds thyroid hormone in intestines  Nonsteroidal anti-inflammatory  Treats subacute thyroiditis  Glucocorticoids  For severe subacute thyroiditis

19 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should clinicians consider I-131 as primary therapy for hyperthyroidism?  Graves disease  Achieves remission in ≈90%  Good choice if no remission with antithyroid medications Side effects  Hypothyroidism: in almost all patients within 3–6 months  Sialadenitis (due uptake by salivary glands)  Worsening of Graves orbitopathy  Possible small increase in thyroid cancer

20 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should clinicians consider I-131 as primary therapy for hyperthyroidism?  Toxic multinodular goiters & toxic adenomas Note: Contraindicated in pregnancy! Side effects  Hypothyroidism: 50%-75%  Worse symptoms from thyroid hormone  in first 2 weeks  Thyroid storm, if severely hyperthyroid  Pretreat with β-adrenergic blockade &/or methimazole: if very symptomatic or free T4 or FT4I levels exceed upper limit of reference range more than 2-fold  Discontinue methimazole 7 days before I-13

21 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should clinicians consider thyroidectomy as primary therapy?  High RAIU hyperthyroidism (primary therapy)  Refractory amiodarone-induced cases (primary therapy)  Most often recommended for…  Those with thyroid nodules and suspected cancer  Those who can’t tolerate or refuse alternative forms Rx  Pregnancy  Patients who don’t achieve remission with antithyroid Rx

22 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. How should clinicians monitor patients who are being treated for hyperthyroidism?  At baseline: Perform CBC w/ differential WBC count, liver panel  Once euthyroid: Assess clinically Measure serum TSH every 6 to 12 months for lifetime  Monitoring differs depending on chosen treatment…

23 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1.  Antithyroid medications  Agranulocytosis, liver injury, vasculitis: discontinue  Fever or pharyngitis: repeat CBC with differential WBC  Symptoms of liver injury: order liver profile Once symptoms resolved + results in reference range…  Discontinue β-adrenergic blocker + reduce antithyroid Rx  Continue clinical and lab assessments every 3–6 months After months reduced dose + normal TSH: ? remission  Taper or stop antithyroid Rx  Measure TRAb: normal = greater likelihood remission  No remission: consider I-131 or surgery

24 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1.  Radioactive iodine (I-131)  Repeat clinical and lab assessments at 1-2 months  Measure TSH and free T4 in first 1-3 months  TSH suppression may last up to 6 wks after T4 and T3 fall to normal range  Start thyroid hormone-replacement when free T4 level low or TSH elevated  Adjust dose every 6-8-weeks until TSH in desired range  Thyroidectomy  Start levothyroxine before hospital discharge  Adjust dose every 6-8 weeks until TSH in desired range

25 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. What is subclinical hyperthyroidism, and what are the indications for treatment?  Definition: Low serum TSH levels + T4 and T3 levels within reference ranges  Asymptomatic or mild symptoms  RAIU typically in reference range  Thyroid scan findings consistent with underlying cause  TSH levels often normalize w/o treatment  Treat: if TSH <0.1 mU/L or symptomatic  Consider treating: if TSH ≥0.1 mU/L but still lower than reference range

26 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. How does a clinician recognize thyroid storm?  “Thyroid crisis”  exaggerated manifestations of thyrotoxicosis  Unrecognized or inadequately treated thyrotoxicosis + precipitating event (infection, trauma)  Radioiodine therapy may precipitate  Dx often based on suspicious, nonspecific clinical findings  Cardinal manifestation: fever >102° F  Other features: Tachycardia, tachypnea; nausea/vomiting, diarrhea, CNS manifestations, anemia, hyperglycemia  Elevated serum total, free T4 and T3 levels; undetectable serum TSH level Use Thyroid Storm Scoring System 

27 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. Fever ° FScore 99– – >10430 CNS agitation Absent 00 Mild10 Moderate20 Severe30 Cardiac–pulse, bpm 99– – – –13920 ≥14025 Atrial fibrillation10 Cardiac–CHF Absent0 Mild (edema)5 Moderate (rales)10 Severe (pulm edema) 15 Thyroid Storm Scoring System (feature, score) GI signs Absent0 N, V, D, Pain10 Jaundice20 Precipitant history Absent0 Present10 Total Score <25 = unlikely = suggestive >45 = likely

28 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. How does a clinician treat thyroid storm? 1. Decrease thyroid hormone synthesis  Propylthiouracil or methimazole 2. Inhibit thyroid hormone release  Sodium iodide (IV) or potassium iodide (oral) 3. Reduce heart rate  β-blocker (esmolol, metoprolol, propranolol) or diltiazem 4. Support circulation  Glucocorticoids in stress doses  Fluids (IV), oxygen, cooling 5. Treat precipitating cause

29 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should patients be hospitalized?  When thyroid storm present, impending, or suspected  Prognosis with aggressive therapy  ≈20% mortality (was once 100%)  Dx usually based on suspicious, nonspecific findings  Do not wait for test results on serum TSH levels: delays potentially lifesaving therapy  Also, TSH levels don’t reliably distinguish thyroid storm from uncomplicated thyrotoxicosis

30 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. When should clinicians consult an endocrinologist or ophthalmologist? Endocrinologist  Help developing optimal management plan  Unexpected events or Rx complications  Significant Graves eye disease present  Patient is pregnant  Thyroid storm present, impending, or suspected  Some guidelines suggest co-management in all cases Ophthalmologist  Double vision or impaired visual acuity, visual fields, color vision  Significant eye discomfort  Proptosis >22 mm or extraocular muscle dysfunction

31 © Copyright Annals of Internal Medicine, 2012 Ann Int Med. 157 (1): ITC1-1. CLINICAL BOTTOM LINE: Treatment…  If RAIU high or normal: Rx usually required  Inform patients on benefits and risks and jointly decide on preferred treatment  Graves disease: antithyroid meds, I-131, thyroidectomy  Toxic multinodular goiter: I-131 or thyroidectomy  Toxic adenoma:I-131 or thyroidectomy  Before definitive treatment, use antithyroid medications to improve thyroid hormone levels  If RAIU low: treat underlying cause or monitor  Condition may be transient


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