Graves' Disease

Question 1

what is the definition of graves disease?

Answer 1

Autoimmune induced excess production of thyroid hormone

Question 2

what is the epidemiology of graves disease?

Answer 2

This is the MOST COMMON CAUSE of hyperthyroidism (2/3rds of
cases)
- More common in FEMALES than males
- Typically presents at 40-60yrs (appear earlier if maternal family
history)

Question 3

what is the aetiology of graves disease?

Answer 3

• Genetic - association with HLA-B8, DR3 & DR2,
• E.coli and other gram-NEGATIVE organisms contain TSH-binding sites so may initiate pathogenesis via ‘molecular mimicry’,
• autoimmune diseases such as vitiligo, Addison’s, pernicious anaemia, MG and T1DM

Question 4

what are the risk factors of graves disease?

Answer 4

Female
family history
smoking
postpartum, genetic, bacteria, smoking, stress, high iodine intake, autoimmune diseases

Question 5

what is the brief pathophysiology of graves disease?

Answer 5

• Serum IgG antibodies, specific for Graves’ disease, known as TSH receptor stimulating antibodies (TSHR-Ab) bind to TSH receptors in the thyroid
• Thereby stimulating thyroid hormone production (T3 & T4) - essentially they behave like TSH
• Resulting in excess secretion of thyroid hormones and hyperplasia of thyroid follicular cells resulting in hyperthyroidism and diffuse goitre
• Persistent high levels predict a relapse when drug treatment is stopped
• Similar auto antigen can also result in retro-orbital inflammation - graves ophthalmopathy

Question 6

what are the key presentations of graves disease?

Answer 6

presence of risk factors 
heat intolerance
sweating
weight loss
palpitations
tremor
diffuse goitre
orbitopathy

Question 7

what are the signs of graves disease?

Answer 7

presence of risk factors 
diffuse goitre 
orbitopathy
cardiac flow murmur
thyroid burit
onycholysis 
vitiligo

Question 8

what are the symptoms of graves disease?

Answer 8

• Palpitations
• Diarrhoea
• Weight loss & increase appetite
• Oligomenorrhea (infrequent periods) +/- infertility
• Heat intolerance i.e. sweating a lot
• Irritability/behavioural change
• Tremor
• Hyperkinesis - muscle spasm
• Warm moist velvety skin - vasodilator peripheries
• Proximal myopathy & muscle wasting
• Lymphadenopathy and splenomegaly can occur
• Anxiety
• Hands: Palmar erythema, warm moist skin and fine tremor
• Diffuse goitre
• Lid lag & ‘stare’

Question 9

what are the 1st line investigations for graves disease?

Answer 9

Thyroid function tests (TFTs) - test serum TSH and T4&T3 levels (raised T4 and T3 levels are diagnostic of hyperthyroidism)
Serum TSH suppressed, T4 and T3 raised , thyroid peroxidase and thyroglobulin antibodies present in 80% of graves’, TSH receptor stimulating antibodies (TSHR-Ab) raised, mild neutropenia

Question 10

what are the gold standard investigations for graves disease?

Answer 10

Test for TSH receptor stimulating antibodies (TSHR-Ab) (raised = diagnostic)

Question 11

what other investigations could be done for graves disease?

Answer 11

• Thyroid peroxidase (TPO) and thyroglobulin antibodies are present in 80% of Graves’ but are all found in normal hyperthyroidism
• Ultrasound of thyroid: Helps to differentiate Graves’ from toxic adenoma

Question 12

what are the differential diagnoses of graves disease?

Answer 12

Thyroiditis, exogenous and ectopic hyperthyroidism, hashitoxicosis, toxic adenoma and toxic multi nodular goitre. (other causes of hyperthyroidism)

Question 13

how is graves disease managed?

Answer 13

• Beta blockers for rapid control of symptoms
• antithyroid drugs (propylthiouracil)
• radioactive iodine
• surgery

Question 14

how is graves disease monitored?

Answer 14

Regular blood tests to monitor thyroid function

Question 15

what are the complications of graves disease?

Answer 15

• Antithyroid drugs - Main side effect is AGRANULOCYTOSIS - results in a severely low white blood cell count (leukopenia) - most commonly neutropenia: If they get sore throat, mouth ulcers and fevers then STOP DRUG ASAP,Other S/E; rash (common), arthralgia, hepatitis and vasculitis (in bold less common)
• Surgery - Complications: Tracheal compression from postoperative bleeding, Laryngeal nerve palsy resulting in hoarse voice, Transient hypocalcaemia - due to removal of parathyroid gland
• Thyroid crisis or thyroid storm: MEDICAL EMERGENCY! Rare, life threatening condition in which there is a rapid deterioration of thyrotoxicosis (RAPID T4 INCREASE) Features include hyperpyrexia, tachycardia, extreme restlessness and eventually delirium, coma and death. Usually precipitated by stress, infection, surgery or radioactive iodine therapy in an unprepared patient. Treated with LARGE DOSES of:
• ORAL CARBIMAZOLE
• ORAL PROPRANOLOL
• ORAL POTASSIUM IODIDE (to block acutely the release of thyroid hormone from gland)
• IV HYDROCORTISONE (to inhibits peripheral conversion of T4 to T3)

Question 16

what is the prognosis of graves disease?

Answer 16

Prognosis generally good, if patients suffer a thyroid storm = 20-50% death rate