Toxic MNG Thyroiditis 5-15

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1 Hyperthyroidism Facts Prevalence %, more common in women Thyrotoxicosis is excess thyroid hormones from endogenous or exogenous sources Hyperthyroidism is excess thyroid hormones from thyroid gland Common causes include Graves disease, TMNG, thyroiditis Diagnosis established by low TSH, high FT4, high T3, and RAIU CP Hyperthyroidism Etiology Autonomous overactivity Pituitary TSH hypersecretion Graves disease Inappropriate TSH Hashimoto s secretion thyroiditis Thyrotrophic Plummer s disease pituitary adenoma Toxic nodule Ectopic thyroid Hormonal discharge stimulators, eg, HCG Granulomatous Metastatic follicular thyroiditis carcinoma Lymphocytic thyroiditis Struma ovarii CP Hyperthyroidism Common Causes % Graves disease Toxic MNG 5-15 Thyroiditis 5-15 CP

2 Graves Disease Symptoms Nervousness sweating Heat intolerance Palpitations Fatigue Weakness Weight loss Eye Signs Goiter Exophthalmos Tremor Tachycardia Atrial fibrillation CP Toxic Multinodular Goiter Elderly patient Longstanding goiter Heart disease: HR, AF, CHF Unexplained weight loss Depression Anxiety CP Comparison of Graves Disease and Toxic MNG GD TMNG Goiter Diffuse Nodular Size Small Large Growth Rapid Slow Age (yr) <45 >50 Symptoms Rapid onset Slow onset Histology Parenchymatous, Variable follicular hyperplasia, uniform size and intensity intense iodine meta- of iodine bolism in follicles metabolism CP

3 CP CP Symptoms and Signs of Hyperthyroidism Less common than younger pt Goiter and ophthalmopathy Heat intolerance Tachycardia, plapitations Muscular weakness More common than younger pt Tremor Anorexia CHF, AF Muscular wasting CP

4 CP CP CP

5 CP CP CP

6 Fatourechi et al Manifestations of Autoimmune Thyroid Disease. AITD Graves or Hashimoto 0.04%? %? Hyp o 5 % % Hype r 95% 4-13% 20% Onset of Dermopathy and Ophthalmopathy 50 Dermopathy (n=136) 50 Ophthalmopathy (n=373) n time interval (%) Pt in > >6-41 Years Diagnosis Years before hyper- after diagnosis thyroidism diagnosis Years Diagnosis before hyper- diagnosis thyroidism Years after diagnosis CP Fatourechi V, Garrity JA, Gorman CA et al. J Endocr Invest 16: Graves Ophthalmopathy The Clinical Spectrum

7 Enlargement... of muscles and adipose tissues in the confines of the bony orbit leads to. proptosis, venous congestion, chemosis, injection, periorbital edema, and optic neuropathy Pathophysiology of GO Pathophysiology of GO Fibrotic restriction of extraocular muscles leads to... diplopia, increased intraocular tension Histopathology of GO (Band C)

8 Schwarts,Fatourechi et al, % 28% 18% Non-pitting Edema Plaque Type Nodular Thyroid Dermopathy Thyroid Dermopathy 5 % Elephantiasis Dermopathy in scar tissue Dermopathy on the shoulder Thyroid Acropachy Clubbing in Thyroid Dermopathy 20% of Dermopaty

9 Thyroid Acropachy Severe Acropachy with severe Dermopathy Hyperthyroidism Treatment Options Thionamides Radioiodine ( 131 I) Stable iodine ( 127 I) Thyroidectomy Miscellaneous Lithium, beta-adrenergic blockers, oral cholecystographic agents CP Thionamides Main- Serum Incidence of Initial tenance half- side effects dose dose life (%) (mg/d) (mg/d) (hr) Major Minor Carbimazole Methimazole Propylthiouracil CP

10 ATD Comparisons Parameter PTU MMI Response Slower Faster time Toxicity Dose related Dose related Compliance Worse Better Effect on 131 I Decrease None CP Q ATD FAQs A Optimal duration of therapy? mo Dose influences remission? Probably not Higher dose causes more rapid Yes control? Predictors of remission? Small goiter, mild disease, low TRAb titer Prevents post RAI exacerbation? Maybe Does T4 enhance remission? No Cooper DS: JCEM 88:3474, 2003 CP ATD Remission? Sign goiter size ATD dose RAIU thyroid autonomy Test Palpation FT4 RAIU TSH CP

11 Why Not Antithyroid Drugs? Prolonged therapy At least 50% relapse after discontinuation of treatment Side effects CP I Treatment Treatment of choice for Hyperthyroid, nonpregnant adult pt with diffuse goiter and adequate 131 I uptake Complications Persistent hyperthyroidism Permanent hypothyroidism CP Simple 131 I Treatment Effective Economical Complications depend on 131 I dose used Recurrent hyperthyroidism Permanent hypothyroidism CP

12 Calculation of 131 I Dose Dose est thyroid wt x uci/est gm x 100 = (mci) RAIU % CP Thyroiditis Hyperthyroidism Low RAIU Graves disease with I overload IIT Exogenous thyrotoxicosis Ectopic tissue, eg, struma ovarii CP Painless Thyroiditis vs Graves Disease PT GD Onset Abrupt Insidious Clinical hyperthyroidism Common Universal Goiter Common Universal Exophthalmos Absent Common Duration Wk to mo Mo to yr Thyroid hormone (TSH, T3, FT4),,,, 131 I uptake Absent Elevated TPO Infrequent Common CP

13 Factors Limiting Usefulness of 131 I Therapy Low thyroid uptake of 131 I Toxic nodular goiter Pregnancy Childhood? CP Hyperthyroidism Surgery Choose an experienced surgeon Decreased experience with surgical treatment of hyperthyroid y patient Bilateral subtotal thyroidectomy is preferred Complications include hemorrhage, hypopara, VC paralysis and hypothyroidism CP Surgery Complications % Mortality 0 Persistent or recurrent < hyperthyroidism Vocal cord paralysis 0-4 Hypoparathyroidism Hypothyroidism 4-30 CP

14 Surgery Preop preparation Need for Lugol s solution Cord check Discussion of general and specific risks Incidence of hypoparathyroidism Incidence of cord paralysis Possibility of hypothyroidism Eye problem Need for follow-up CP Indicated Surgery Plummer s disease (toxic nodular goiter) Pregnancy Children Graves disease with large goiter When coexisting neoplasm suspected CP Surgery Contraindicated in Poor surgical risk pt Pt with recurrent thyrotoxicosis who is postop thyroidectomy with vocal cord paralysis CP

15 Surgery Recommend for Toxic nodular goiter Solitary nodules Pregnancy Children CP Why Not Surgery? Why operate when there are acceptable alternatives? Hypoparathyroidism 1% at best Hypothyroidism Approximately 40% at 5 years Recurrent hyperthyroidism Varies inversely with postop hypothyroidism CP Beta-Adrenegic Antagonists Popranolol (Inderal) mg qid Metoprolol (Lopressor) mg bid Atenolol (Tenormin) Nadolol (Corgard) mg qd mg qd CP

16 Beta-Adrenegic Antagonists Thyroid crisis or near-crisis During interval prior to therapy Preoperative therapy, preferably with iodine Prepares pt for surgery in 1 wk Possibly as sole therapy in mild cases CP Pregnancy Potential complications Maternal Miscarriage, preterm delivery, HTN, thyroid storm Fetal Hyperthyroidism, prematurity, stillbirth, IU growth retardation CP Pregnancy Antithyroid drugs or surgery equally effective Radioiodine contraindicated ATD cross the placenta With ATD maintain T4 in the upper normal range for pregnancy Surgery favored in second trimester Preoperative preparation with iodine and/or PTU CP

17 Pregnancy Postpartum hyperthyroidism Autoimmune basis Has low RAIU Hypothyroidism may follow hyperthyroidism May spontaneously resolve Treat symptomatic patients CP CP Hyperthyroidism Children Graves disease is most common cause MMI mg/kg/day or PTU 5-10 mg/kg/day is treatment of choice Remission occurs in 30-60% in 2 years Subtotal thyroidectomy for those with large goiters 131 I appears to be safe CP

18 Hyperthyroidism Choice of Treatment Toxic adenoma Toxic nodular goiter Graves disease in children Graves disease in pregnancy Recurrent Graves disease Graves disease in middle- aged or elderly patients Increased surgical risk 131 I or surgery Surgery Drugs or surgery Drugs or surgery 131 I 131 I 131 I or drugs CP Hyperthyroidism Therapy Personal comments ATD are accompanied by side effects and high relapse Surgical complications may be increasing as the numbers of trained surgeons decline 131 I is the preferred initial Rx for most patient with Graves disease Surgery is preferred for large hot nodules Genetic hazards of 131 I have been overstated younger patients can be safely treated Current findings do not support the contention that 131 I therapy is an important initiator of ophthalmopathy CP CP

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