Graves Disease Epidemiology n Prevalence of hyperthyroidism in

: Graves’ Disease

Epidemiology n Prevalence of hyperthyroidism in the general population is 1. 2% q q n 0. 7% subclinical hyperthyroidism 0. 4% Graves’ Disease – most common etiology; note there is overlap with the subclinical group Graves’ Disease is more common in females (7: 1 ratio) 12/1/2020 dr yekefallah--phd of nursing 2

Pathogenesis n An autoimmune phenomenon – presentation determined by ratio of antibodies Graves’ Disease + Thyroid - TSH Receptor Thyroglobulin Ab 12/1/2020 Thyroid Stimulating Ab (TSAb) Thyroid Stimulation Blocking Ab (TSBAb) Thyroid peroxidase Ab (anti TPO) dr yekefallah--phd of nursing Autoimmune Hypothyroidism (Hashimoto’s) 3

The Classic Triad of Graves’ Disease n n Hyperthyroidism (90%) Ophthalmopathy (20 -40%) q q n proptosis, ophthalmoplegia, conjunctival irritation 3 -5% of cases require directed treatment Dermopathy (0. 5 -4. 3%) q q localized myxedema, usually pretibial especially common with severe ophthalmopathy There is also a close association with autoimmune findings (e. g. vitiligo) and other autoimmune diseases (e. g. ITP) 12/1/2020 dr yekefallah--phd of nursing 4

Syndrome of Hyperthyroidism n n n n Weight loss, heat intolerance Thinning of hair, softening of nails Stare and eyelid lag Palpitations, symptoms of heart failure Dyspnea, decreased exercise tolerance Diarrhea Frequency, nocturia Psychosis, agitation, depression 12/1/2020 dr yekefallah--phd of nursing 5

Graves’ Ophthalmopathy n Antibodies to the TSH receptor also target retroorbital tissues q q n T-cell inflammatory infiltrate -> fibroblast growth Severe: exposure keratopathy, diplopia, compressive optic neuropathy Strong link with tobacco 12/1/2020 dr yekefallah--phd of nursing 6

Myxedema of Graves’ n Activation of fibroblasts leads to increased hyaluronic acid and chondroitin sulfate Asymmetric, raised, firm, pink-to-purple, brown plaques of nonpitting edema 12/1/2020 dr yekefallah--phd of nursing 7

Hyperthyroidism Differential n n Graves’ Disease Toxic Multinodular Goiter Toxic Adenoma Thyroiditis q q q n silent (Hashimoto’s) – painless, often post partum subacute (de Quervain’s) – painful, post viral drug-induced – amiodarone, lithium, interferon Thyrotoxicosis factitia 12/1/2020 dr yekefallah--phd of nursing 8

Laboratory Evaluation n n Suppressed TSH (<0. 05 u. U/ml) Elevated Free T 4 and/or Free T 3: T 4 > 20 - Graves’ Disease - Toxic MN Goiter T 3: T 4 < 20 - Non-thyroid illness - Thyroiditis - Exogenous thyroxine 12/1/2020 dr yekefallah--phd of nursing 9

Diagnostic Imaging n Radioactive Iodine Uptake q q n Technetium-99 Pertechnetate Uptake q q n Provides quantitative uptake (nl 5 -25% after 24 h) Shows distribution of uptake Distinguishes high-uptake from low-uptake Faster scan – only 30 minutes Thyroid ultrasonography q q 12/1/2020 Identifies nodules Doppler can distinguish high from low-uptake dr yekefallah--phd of nursing 10

Immediate Medical Therapy n Thionamides – inhibit central production of T 3 and T 4; immunosuppressive effect q q q 12/1/2020 Methimazole – once daily dosing PTU – added peripheral block of T 4 to T 3 conversion; preferred in pregnancy Side effects: itching; agranulocytosis, hepatotoxicity, vasculitis dr yekefallah--phd of nursing 11

Long-term Therapeutic Options n Total Thyroidectomy q q q 12/1/2020 Indications: suspicion for malignant nodule, comorbid need for parathyroidectomy, radioactive ablation contraindicated, compressive goiter Recent metaanalysis showed this is the most cost effective if surgery is < $19, 300. Prep with 6 weeks thionamides, 2 weeks iodide Hypoparathyroidism and/or laryngeal nerve damage in <2% Lasting remission in 90% dr yekefallah--phd of nursing 12

Treatment of Ophthalmopathy n Mild Symptoms q n Progressive symptoms (injection, pain) q n Eye shades, artificial tears Oral steroids – typical dosage from 30 -40 mg/day for 4 weeks Impending corneal ulceration, loss of vision q q 12/1/2020 Oral versus IV steroids Orbital Decompression surgery dr yekefallah--phd of nursing 13

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