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Graves’ Disease: An Overview. Matthew Volk Morning Report November 17 th , 2009. Epidemiology. Prevalence of hyperthyroidism in the general population is 1.2% 0.7% subclinical hyperthyroidism 0.4% Graves’ Disease – most common etiology; note there is overlap with the subclinical group - PowerPoint PPT Presentation
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Graves’ Disease: An Overview
Matthew Volk
Morning Report
November 17th, 2009
Epidemiology
Prevalence of hyperthyroidism in the general population is 1.2% 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)
Pathogenesis
An autoimmune phenomenon – presentation determined by ratio of antibodies
TSHReceptor
Thyroid Stimulating Ab (TSAb)
Thyroid Stimulation Blocking Ab (TSBAb)
Thyroid+
-
Graves’ Disease
AutoimmuneHypothyroidism(Hashimoto’s)Thyroglobulin Ab
Thyroid peroxidase Ab (anti TPO)
The Classic Triad of Graves’ Disease Hyperthyroidism (90%) Ophthalmopathy (20-40%)
proptosis, ophthalmoplegia, conjunctival irritation 3-5% of cases require directed treatment
Dermopathy (0.5-4.3%) 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)
Syndrome of Hyperthyroidism 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
Graves’ Ophthalmopathy
Antibodies to the TSH receptor also target retroorbital tissues T-cell inflammatory infiltrate -> fibroblast growth Severe: exposure keratopathy, diplopia, com-
pressive optic neuropathy Strong link with tobacco
Myxedema of Graves’
Activation of fibroblasts leads to increased hyaluronic acid and chondroitin sulfate
Asymmetric, raised, firm, pink-to-purple, brown plaques of nonpitting edema
Hyperthyroidism Differential
Graves’ Disease Toxic Multinodular Goiter Toxic Adenoma Thyroiditis
silent (Hashimoto’s) – painless, often post partum subacute (de Quervain’s) – painful, post viral drug-induced – amiodarone, lithium, interferon
Thyrotoxicosis factitia
Laboratory Evaluation
Suppressed TSH (<0.05 uU/ml) Elevated Free T4 and/or Free T3
T3:T4 > 20- Graves’ Disease- Toxic MN Goiter
T3:T4 < 20- Non-thyroid illness- Thyroiditis- Exogenous thyroxine
It’s Good to be Free
Thyroxin is 99% bound to thyroid binding globulin (TBG), albumin, and transthyretin Elevated TBG in viral hepatitis, pregnancy, and in
patients taking estrogens and opiates Decreased TBG binding with heparin, dilantin,
valium, NSAIDs, lasix, carbamazepine, ASA Measuring Free T4 instead of total T4 avoids this
problem all together
Laboratory Evaluation
Direct measurement of TSH receptor antibodies (TSAb and TBAb) Can help with Graves diagnosis in confusing
cases (as high as 98% sensitivity) Can predict new-onset Graves’ in the post-partum
period Anti TPO Antibody and anti Tg Antibody
Can be mildly elevated in Graves’ Usually most active in Hashimoto’s
Diagnostic Imaging
Radioactive Iodine Uptake Provides quantitative uptake (nl 5-25% after 24h) Shows distribution of uptake
Technetium-99 Pertechnetate Uptake Distinguishes high-uptake from low-uptake Faster scan – only 30 minutes
Thyroid ultrasonography Identifies nodules Doppler can distinguish high from low-uptake
Immediate Medical Therapy
Thionamides – inhibit central production of T3 and T4; immunosuppressive effect Methimazole – once daily dosing PTU – added peripheral block of T4 to T3
conversion; preferred in pregnancy Side effects: hives, itching; agranulocytosis,
hepatotoxicity, vasculitis Beta-blockade – decrease CV effects High-dose iodine – Wolff-Chaikoff effect
Long-term Therapeutic Options Continued Medical Management
Low dose (5-10mg/day of methimazole) for 12 to 18 months then withdraw therapy
Lasting remission in 50-60% Radioiodine Ablation
Discontinue any thionamides 3-5 days prior Overall 1% chance of thyrotoxicosis exacerbation Hypothyroidism in 10-20% at 1 yr, then 5% per yr Lasting remission in 85%
Long-term Therapeutic Options Total Thyroidectomy
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%
Treatment of Ophthalmopathy Mild Symptoms
Eye shades, artificial tears Progressive symptoms (injection, pain)
Oral steroids – typical dosage from 30-40mg/day for 4 weeks
Impending corneal ulceration, loss of vision Oral versus IV steroids Orbital Decompression surgery
References
Alguire et al. MKSAP14 Endocrinology and Metabolism. 2006. 27-34. Andreoli et al. Cecil Essentials of Medicine. 6th Edition, 2004. 593-7. Nayak, B et al. Hyperthyroidism. Endocrinol Metab Clin N Am. 36
(2007) 617-656. In H et al. Treatment options for Graves disease: a cost-effectiveness
analysis. J Am Coll Surg. 2009 Aug;209(2):170-179.e1-2. Stiebel-Kalish H et al. Treatment modalities for Graves'
ophthalmopathy: systematic review and metaanalysis. J Clin Endocrinol Metab, August 2009, 94(8):2708–2716
Uptodate Online – Disorders that Cause Hyperthyroidism, Diagnosis of Hyperthyroidism, Cardiovascular Effects of Hyperthyroidism, Treatment of Graves Ophthalmopathy
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