This document provides an overview of Graves' disease. It discusses the epidemiology, pathophysiology, clinical manifestations, diagnostic evaluation and treatment options. The key points are: - Graves' disease is the most common cause of hyperthyroidism and is an autoimmune disorder causing the thyroid to produce too much hormone. - It commonly affects women ages 30-50 and presents as thyrotoxicosis with or without a goiter. - Clinical manifestations include hyperthyroidism, ophthalmopathy in 20-40% of cases, and dermopathy in rare cases. - Diagnosis involves lab tests showing suppressed TSH and elevated T3/T4, and imaging may include ultrasound

1. Graves’ Disease:
An Overview
Done by
Kulanthaivel Shanmugaraj,141B
Crimean Federal University, Russia.
Presented to
Assoc. Prof. Divinskaya Valentina Alexandrovna,
Ph. D. in Medicine

2. Thyrotoxicosis
n Thyrotoxicosis describes a constellation of
clinical features arising from elevated circulating
levels of thyroid hormone. The most common
causes are Graves’ disease, multinodular goitre
and autonomously functioning thyroid nodules
(toxic adenoma)

3. Epidemiology
n Prevalence of hyperthyroidism in the general
population is 1.2%
q 0.7% subclinical hyperthyroidism
q 0.4% Graves’ Disease – most common etiology;
note there is overlap with the subclinical group
n Graves’ Disease is more common in females
(7:1 ratio)

4. The Thyroid &
Grave’s
n Thyroid hormone is critical for regulating mood, weight, and
mental and physical energy levels.
n If the body makes too much thyroid hormone, the condition is
called hyperthyroidism. (An underactive thyroid leads to
hypothyroidism.)
n Graves disease is the most common cause of hyperthyroidism.
n Caused by an abnormal immune system response that causes the
thyroid gland to produce too much thyroid hormones.
n Body actually produces antibodies that activate thyroid hormone
production

5. Graves’ disease
n Graves’ disease can occur at any age but is
unusual before puberty and most commonly
affects women aged 30–50 years. The most
common manifestation is thyrotoxicosis with or
without a diffuse goitre.

6. Pathophysiology
n The thyrotoxicosis results from the production of IgG antibodies
directed against the TSH receptor on the thyroid follicular cell,
which stimulate thyroid hormone production and proliferation of
follicular cells, leading to goitre in the majority of patients.
n These antibodies are termed thyroid-stimulating
immunoglobulins or TSH receptor antibodies (TRAb) and can
be detected in the serum of 80–95% of patients with Graves’
disease. The concentration of TRAb in the serum is presumed
to fluctuate to account for the natural history of Graves’
thyrotoxicosis.
n The thyroid failure seen in some patients may result from the
presence of blocking antibodies against the TSH receptor, and
from tissue destruction by cytotoxic antibodies and cell-
mediated immunity.

8. Pathogenesis
n An autoimmune phenomenon – presentation
determined by ratio of antibodies
TSH
Receptor
Thyroid Stimulating
Ab (TSAb)
Thyroid Stimulation
Blocking Ab (TSBAb)
Thyroid
+
-
Graves’ Disease
Autoimmune
Hypothyroidism
(Hashimoto’s)Thyroglobulin Ab
Thyroid peroxidase
Ab (anti TPO)

9. The Classic Triad of Graves’ Disease
n Hyperthyroidism (90%)
n Ophthalmopathy (20-40%)
q proptosis, ophthalmoplegia, conjunctival irritation
q 3-5% of cases require directed treatment
n Dermopathy (0.5-4.3%)
q localized myxedema, usually pretibial
q especially common with severe ophthalmopathy
There is also a close association with autoimmune findings
(e.g. vitiligo) and other autoimmune diseases (e.g. ITP)

10. Syndrome of Hyperthyroidism
n Weight loss, heat intolerance
n Thinning of hair, softening of nails
n Stare and eyelid lag
n Palpitations, symptoms of heart failure
n Dyspnea, decreased exercise tolerance
n Diarrhea
n Frequency, nocturia
n Psychosis, agitation, depression

11. Graves’ Ophthalmopathy
n Antibodies to the TSH receptor also target
retroorbital tissues
q T-cell inflammatory infiltrate -> fibroblast growth
q Severe: exposure keratopathy, diplopia, com-
pressive optic neuropathy
n Strong link with tobacco

12. Grave’s Eye Disease - Inflammation

13. 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

14. Hyperthyroidism Differential
n Graves’ Disease
n Toxic Multinodular Goiter
n Toxic Adenoma
n Thyroiditis
q silent (Hashimoto’s) – painless, often post partum
q subacute (de Quervain’s) – painful, post viral
q drug-induced – amiodarone, lithium, interferon
n Thyrotoxicosis factitia

15. Laboratory Evaluation
n Suppressed TSH (<0.05 uU/ml)
n Elevated Free T4 and/or Free T3
T3:T4 > 20
- Graves’ Disease
- Toxic MN Goiter
T3:T4 < 20
- Non-thyroid illness
- Thyroiditis
- Exogenous thyroxine

16. Non-specific laboratory abnormalities in
thyroid dysfunction
Thyrotoxicosis
•
Serum enzymes: raised alanine aminotransferase, γ-glutamyl
transferase (GGT), and alkaline phosphatase from liver and bone
•
Raised bilirubin
•
Mild hypercalcaemia
•
Glycosuria: associated diabetes mellitus, ‘lag storage’ glycosuria

17. Laboratory Evaluation
n Direct measurement of TSH receptor
antibodies (TSAb and TBAb)
q Can help with Graves diagnosis in confusing
cases (as high as 98% sensitivity)
q Can predict new-onset Graves’ in the post-partum
period
n Anti TPO Antibody and anti Tg Antibody
q Can be mildly elevated in Graves’
q Usually most active in Hashimoto’s

18. Diagnostic Imaging
n Radioactive Iodine Uptake
q Provides quantitative uptake (nl 5-25% after 24h)
q Shows distribution of uptake
n Technetium-99 Pertechnetate Uptake
q Distinguishes high-uptake from low-uptake
q Faster scan – only 30 minutes
n Thyroid ultrasonography
q Identifies nodules
q Doppler can distinguish high from low-uptake

19. Immediate Medical Therapy
n Thionamides – inhibit central production of
T3 and T4; immunosuppressive effect
q Methimazole – once daily dosing
q PTU – added peripheral block of T4 to T3
conversion; preferred in pregnancy
q Side effects: hives, itching; agranulocytosis,
hepatotoxicity, vasculitis
n Beta-blockade – decrease CV effects
n High-dose iodine – Wolff-Chaikoff effect

20. Long-term Therapeutic Options
n Continued Medical Management
q Low dose (5-10mg/day of methimazole) for 12 to
18 months then withdraw therapy
q Lasting remission in 50-60%
n Radioiodine Ablation
q Discontinue any thionamides 3-5 days prior
q Overall 1% chance of thyrotoxicosis exacerbation
q Hypothyroidism in 10-20% at 1 yr, then 5% per yr
q Lasting remission in 85%

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

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

25. Droopy eyelid repaired

28. DDX