Laura Trask, MD FACP Central Maine Endocrinology Lewiston, ME

Transcription

1 Laura Trask, MD FACP Central Maine Endocrinology Lewiston, ME

2 No disclosures

3 Objectives To have an understanding of hyperthyroidism To have an understanding of the management of thyroid nodules To appreciate the effects amiodarone can have on the thyroid

4 A Case 46 yo female felt well until 3-4 months ago, when she developed heat intolerance, new anxiety, palpitations, mild dyspnea on exertion, and oligomenorrhea which she ascribed to being perimenopausal for several months Saw her internist when the anxiety and palpitations were keeping her awake at night, who ordered TFT s

5 Case #1 TSH <0.015 uiu/ml Free T4 5.1 ng/dl ( ) Free T pg/ml ( ) Referred to endocrinologist

6 Relationship between TSH and thyroid hormones Small changes in T4/T3 result in large changes in TSH ATA and AACE guidelines recommend checking all three if pre-test probability is high TSH that is completely suppressed is diagnostic of hyperthyroidism Only cases missed by just doing TSH: TSH-producing pituitary adenoma and thyroid hormone resistance

7 Our Patient s Physical Exam Exam: Thin, anxious appearing, Pulse 112 regular, BP 118/56. Skin warm, no eye signs, thyroid gland twice normal size (about 30 grams) firm texture with right side slightly larger than left, no thyroid bruit, mild weakness of hip flexors and shoulders, fine tremor of hands and tongue

8 Eye signs 30% of patients with Graves show some signs of ophthalmopathy Exophthalmos (bulging eyes) Gritty sensation/redness Pressure/pain in eyes Puffy eyelids Light sensitivity Double vision Stare/lid lag with any thyrotoxic state

9 What is the Likeliest Diagnosis? Causes 10% 3% Graves 4% 1% 7% 75% Silent Thyroiditis Single Nodule Subacute Thyroiditis Multiple Nodules Other Adapted from slide from Peter Singer, MD

10 Hyperthyroidism in the Elderly vs. the Young Signs/Sx Age >70 Age <50 P-value Fatigue 56% 84% 0.01 Weight loss 50% 51% NS Tremor 44% 84% Anorexia 32% 4% Increased appetite 0% 57% Confusion 16% 0% Heat intolerance 15% 92% Nervousness 31% 84% J Am Geriatr Soc 44:50 53, 1996

11 Causes of Thyrotoxicosis Elevated RAIU Graves Toxic multinodular goiter Toxic adenoma TSH secreting pituitary tumor Hydatidaform mole Choriocarcinoma Suppressed RAIU Subacute thyroiditis Silent/painless thyroiditis Iodine induced thyrotoxicosis Radiation thyroiditis Exogeneous T4 or T3 Metastatic follicular thyroid cancer Struma ovarii

12 Role of Other Blood Tests in Diagnosis Ratio of Total T3:Total T4 Relatively more T3 is synthesized in hyperactive gland, so ratio is >20 in GD and TMNG and <20 in painless thyroiditis TSH-receptor antibodies (TRAb) and thyroid stimulating immunoglobulin (TSI) Thyroglobulin released along with thyroid hormone in all thyroiditis whereas release is suppressed in exogenous thyroid hormone administration

13 Role of Ultrasound in Diagnosis Guidelines suggest that ultrasound does not play a role in diagnosis However, most endocrinologists do them to stratify patients as to whether they have nodules that could be culprit RAIU Looking at vascularity that might suggest Graves Overall appearance of thyroid

14 Our patient s ultrasound

15 Further imaging to help define cause Radioiodine uptake and scan should be done if clinical presentation is not consistent with Graves or there are nodules Uptake alone to get number to plan radioiodine dose Graves does not cause nodules!

16 Our Patient s Uptake and Scan

17 Thyroid Nodules Thyroid nodules in patients with Graves disease should be managed per 2009 ATA Guidelines Thyroid cancer occurs in Graves disease with a frequency of 2% or less Solid nodules larger than 1 cm should be evaluated by UGFNAB Smaller nodules should be evaluated if patient is a high risk patient (FH of thyroid cancer in 1 st degree relative, h/o XRT as child, PET positive nodules, MEN syndromes/fmtc)

18 Ultrasonographic features associated with increased risk of malignancy Hypoechoic Irregular borders Increased chaotic vascular flow Microcalcifications Nodule with tall, narrow shape

19 Ultrasonographic features associated with decreased risk of malignancy Hyperechoic Large coarse/eggshell calcifications Peripheral vascularity Spongiform appearance Comet-tail shadowing Pure cyst Halo

20 Cold nodules vs. toxic adenoma Toxic adenomas are almost never cancer and biopsy is not necessary Cold nodules carry a risk of cancer of 5% (95% of thyroid nodules are cold) Ultrasound-guided FNAB is recommended for: cold nodules that would meet criteria for FNAB in the setting of toxic MNG nodules occurring in the setting of Graves if meet criteria

21 Benign nodule Ultrasound-guided FNAB was performed of the nodule and it was benign Recommended followup for benign nodules Follow with serial US exam 6-18 months after initial FNA (due to false negative rate of up to 5% with FNAB) If size is stable (no more than 50% change in volume, or <20% increase in at least 2 dimensions) interval can be increased to 3-5 years Significant growth should prompt re-biopsy No role for TSH suppression with levothyroxine in iodine sufficient populations

22 Therapy for Hyperthyroidism B-blockers Thionamides Radioiodine ablation Thyroidectomy

23 Beta-Blockers Should be used initially in all patients with hyperthyroidism unless contraindications exist Block b-adrenergic activity responsible for palpitations, tremor, anxiety and heat intolerance Propranolol Atenolol/Metoprolol

24 Thionamides Methimazole mg daily PTU 100 mg three times/day Mild disease may require less FDA issued safety alert about PTU Get baseline CBC and liver panel prior to Rx Monitor thyroid function 4 weeks after initiation and then every 4-8 weeks until euthyroid FT4 and/or T3 are best early in disease Once euthyroid, every 2-3 months Treat for months and decrease dose as able Consider getting thyroid receptor antibodies prior to stopping to help predict durability of remission

25 MMI more effective than PTU JCEM 2007: 92:

26 Side Effects of Thionamides SE PTU MMI Minor Reactions (GI, rash, fever) 1-5% 1-5%( dose related Agranulocytosis % % Hepatotoxicity Hepatitis (can be fatal) Vasculitis ANCA + Rare Cholestatic (few deaths)

27 Medical Management of Hyperthyroidism-Factors Affecting Remission Factor Favorable Unfavorable Duration of sx Brief Long Family Hx Negative Positive Thyroid size Small Large Severity Mild Moderate/Severe Response to Tx Rapid Less so TSH response Normalizes Persistently low Smoking status Non-smoker Smoker TRAb Negative Positive

28 Graves Remission Rates Around 30% will have persistent remission after months of thionamide May be as high as 50-75% in those with mild disease Longer treatment with thionamide does not have effect on chances of attaining remission

29 Definitive Therapy- RAI vs. Surgery Toxic multinodular goiter treatment failure Thyroidectomy <1% failure rate RAI 20%risk for need for retreatment Toxic adenoma treatment failure Thyroidectomy <1% RAI 6-18% risk for persistent hyperthyroidism Graves treatment failure Thyroidectomy essentially 0% Most patients hypothyroid by 6 months after RAI, some will need 2 nd treatment

30 Risk of permanent hypothyroidism Toxic multinodular goiter 100% chance of hypothyroidism after total thyroidectomy progressive increase with RAI from 2% at one year posttx and 64% at 20 yrs post-tx Toxic adenoma 2.3% chance after hemithyroidectomy progressive increase with RAI from 7.6% at one year post-tx, 28% at 5 years, 46% at 10 years and 60% at 20 yrs post-tx

31 Back to our patient She opted to treat with methimazole 20 mg per day was prescribed along with Atenolol 2 months later, felt much better, had regained 6 lbs, palpitations, heat intolerance, dyspnea and tremor resolved. Atenolol was stopped TFT s: TSH 0.02, FT4 1.6, FT3 4.0

32 hy is her TSH still suppressed?

33 Our patient Over next 18 months, MMI was able to be weaned and stopped TRAb was negative just prior to stopping Remains in remission 2 years later, nodule has been stable in size

34 Summary Recognize symptoms (particularly atypical ones) of hyperthyroidism Workup nodules independently of Graves Treat with methimazole in most cases Monitor T4/T3 until euthyroid, then TSH Consider definitive treatment with RaI or surgery in appropriate cases

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36 Amiodarone and the Thyroid Amiodarone Class III anti-arrhythmic drug Contains two iodine atoms, equating to 6 mg of iodine in a 200 mg per day dose

37 Intrinsic Drug effects Inhibits outer ring 5 -monoiodination of T4, thus decreasing T3 production, reverse T3 accumulates since not metabolized Metabolite of amiodarone blocks T3-receptor binding to nuclear receptors and decreases expression of some thyroid hormone-related genes May have direct toxic effect on thyroid follicular cells destructive thyroiditis

38 X X Nature Reviews Endocrinology 6, 34-41

39 Iodine effects Iodine is substrate for thyroid hormone synthesis Normal autoregulation (Wolff-Chaikoff effect) When intrathyroidal iodine reaches a critical high, iodine transport and thyroid hormone synthesis are transiently inhibited until intrathyroidal iodine stores return to normal

40 Patients with underlying thyroid disease= defects in autoregulation of iodine Autoimmune thyroid disease Fail to escape from the Wolff- Chaikoff effect Development of goiter and hypothyroidism in Hashimoto s Amelioration of Graves disease Autonomously functioning nodules or latent Graves Do not autoregulate iodine Addition of more substrate can results in excessive thyroid hormone synthesis and thyrotoxicosis (so called Jod-Basedow effect)

41 Amiodarone-Induced Hypothyroidism Transient changes in thyroid function in normal patients Overt hypothyroidism in 5% (TSH>10) Subclinical hypothyroidism in another 25% (TSH ) Patients with underlying Hashimoto s thyroiditis or positive TPO antibodies more likely to develop permanent hypothyroidism Up to 20% of amiodarone-treated patients

42 Monitoring Assess TSH at baseline, can consider checking TPO antibodies as well Assess TSH every 3-4 months thereafter, especially in those with high-normal TSH to begin with or TPO Begin treatment if TSH persistently elevated with low normal or low Free T4 Larger than normal dose may be required Retest patient if amiodarone discontinued

43 HYPERTHYROIDISM 2 types Type I AIT: increased synthesis of T3 and T4 Most have underlying MNG, some have latent Graves Type II AIT: destructive thyroiditis Patients without underlying thyroid disease Lasts several weeks to months Often followed by hypothyroid phase with eventual recovery in most patients

44 Clinical Manifestations Cardiac manifestations often masked due to B- blocking activity of Amiodarone Development/redevelopment of atrial arrhythmias in prior well-treated patient Exacerbation of ischemic heart disease or CHF Unexplained weight loss Restlessness Low grade fever

45 Difficulties with Diagnosis Iodine in amiodarone competes with the tracer used in RAI uptake/scan Therefore the majority of types I (and all II s) have uptakes less than 1% Other criteria Goiter- type I Serum Tg and IL-6 lower in patients with type I TSH-receptor antibodies- Graves Color flow Doppler ultrasound Increased vascularity- type I Decreased vascularity- type II

46 Whether to discontinue Amiodarone Assess necessity of it to control a life-threatening arrythmia Half life is 100 days so no immediate benefit Amio blocks T4 to T3 conversion, B-adrenergic receptors, and possibly T3 receptor so stopping it may worsen hyperthyroid sx and signs

47 Treatment of Type I AIT Thionamides- need higher than normal dose mg due to high intrathyroidal iodine stores Taper dose as able If amiodarone is discontinued, monitor urine iodine until normal, and then can consider cautiously tapering thionamide Radioiodine usually not an option Thyroidectomy for refractory cases

48 Treatment of Type II AIT Glucocorticoids mg of prednisone daily Continue for 1-3 months prior to tapering dose In one study 60% became euthyroid at one month

49 When cause is unclear Combination of methimazole 40 mg daily and prednisone 40 mg daily Rapid response suggests more of a type II AIT Poor response suggests type I

50 Summary Amiodarone can induce hypo or hyperthyroidism Hypothyroidism can be treated the same way one would treat Hashimoto s but often require larger doses Hyperthyroidism can be difficult to distinguish type, often combination Cannot do uptake and scan to determine type due to large iodine load Treatment can be with prednisone, thionamides or both depending on type

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