Grave's Disease

Question 1

What is Grave’s disease?

Answer 1

Graves’ disease is an autoimmune thyroid condition associated with hyperthyroidism.

Question 2

Briefly describe the pathophysiology of Grave’s disease

Answer 2

Graves’ disease is an autoimmune condition.

The aetiology of thyroid hormone overproduction is stimulation of the thyroid by TSH receptor antibodies. Thyroid-stimulating immunoglobin (TSI) antibody binds to TSH and acts as an analogue.

Question 3

Briefly describe Grave’s orbitopathy

Answer 3

Clinically present in around 25% of patients and is usually mild.

Upper eyelid retraction is present in over 90% of cases. The presence of upper eyelid retraction with thyroid dysfunction, exophthalmos/optic neuropathy, and/or extraocular muscle involvement is diagnostic of Graves’ orbitopathy.

Question 4

What risk factors are associated with Grave’s disease?

Answer 4

• Family history
• Female sex

Question 5

What are the signs of Grave’s disease?

Answer 5

• Diffuse goitre
• Orbitopathy
• Moist, velvety skin

Question 6

What are the symptoms of Grave’s disease?

Answer 6

• Heat intolerance
• Sweating
• Weight loss
• Palpitations
• Irritability
• Scalp hair loss
• Muscle weakness

Question 7

What are the clinical features of Grave’s orbitopathy?

Answer 7

• Eye irritation, photophobia or excessive watering of the eyes
• Redness of the eyes or eyelids and/or lid swelling
• Change in the appearance of the eye or eyelids:
  
  • Eyelid retraction
  • Lid lag
  • Proptosis
• Persistent double vision in any direction of gaze
• Unexplained deterioration in visual acuity

Question 8

What investigations should be ordered for Grave’s disease?

Answer 8

• TSH
• Serum free or total T3
• Serum free or total T4
• Calculation of total T3/T4 or T3/T4 ratio
• TSH receptor antibodies (TRAb)

Question 9

Why investigate TSH? And what may this show?

Answer 9

• Initial screening test
• Suppressed

Question 10

Why investigate serum free or total T3? And what may this show?

Answer 10

• Elevated free T3 and suppressed TSH suggest hyperthyroidism, even if the free T4 is normal. Order if TSH suggests hyperthyroidism but free T4 is normal, to differentiate clinical hyperthyroidism (T3 toxicosis) from subclinical hyperthyroidism.
• Elevated

Question 11

Why investigate serum free or total T4? And what may this show?

Answer 11

• A normal level in the presence of low TSH is suggestive of subclinical hyperthyroidism or T3 toxicosis. An elevated level in the presence of a low TSH indicates overt hyperthyroidism. Order the test initially for diagnosis and also along with serum TSH for monitoring therapy.
• Elevated, except in T3 toxicosis or subclinical disease

Question 12

Why investigate calculation of total T3/4 or T3/T4 ratio? And what may this show?

Answer 12

• May be helpful in distinguishing thyroiditis from Graves’ disease and toxic nodular goitre when the radioiodine uptake test is contraindicated (e.g., in pregnancy or lactation). A high T3/T4 ratio is suggestive of Graves’ disease rather than thyroiditis.
• Likely to be high compared with thyroiditis

Question 13

Why investigate TSH receptor antibodies (TRAb)? And what may this show?

Answer 13

• It is used as a diagnostic test for Graves’ disease, particularly in questionable cases. Positive in 95% of patients with Graves’ disease.
• Positive

Question 14

Briefly describe the treatment of Grave’s disease

Answer 14

Antithyroid drugs, radioactive iodine, and surgery are all effective and relatively safe options for treating Graves’ hyperthyroidism.

Beta-adrenergic blockers are used until specific therapy normalises peripheral thyroid hormone levels.

Question 15

Briefly describe the use of antithyroid drugs in Grave’s disease

Answer 15

Antithyroid drugs are used in two ways:

• For a prolonged period of time (typically 12-18 months) to control the hyperthyroidism with the hope that the underlying autoimmune process will go into remission
• As adjunctive therapy to normalise thyroid function before surgery or radioiodine (when necessary)

These drugs block thyroid hormone synthesis. The group includes carbimazole, thiamazole, and propylthiouracil (PTU).

Question 16

Briefly describe the use of radioactive iodine therapy in Grave’s disease

Answer 16

Radioactive iodine is used both as first-line treatment and salvage therapy after failure of antithyroid medications or surgery. The intention is to ablate thyroid tissue and facilitate the start of thyroxine replacement therapy.

Question 17

Briefly describe the role of thyroid surgery in Grave’s disease

Answer 17

Surgery may be preferred in:

• Women planning a pregnancy in <6 months
• Symptomatic compression or large goitres
• Relatively low uptake of radioactive iodine
• Thyroid malignancy is documented or suspected
• Large thyroid nodules
• Coexisting hyperparathyroidism requiring surgery
• Patients with moderate to severe active Graves’ disease

Options include total thyroidectomy or hemithyroidectomy for a single thyroid nodule.

Question 18

Briefly describe the role of beta-blockers in Grave’s disease

Answer 18

Ameliorates adrenergic symptoms such as tachycardia, tremor, and anxiety.

Beta-blockers are not indicated if there is history of asthma, bradycardia, or heart block.

Used early in the course of therapy for symptomatic relief, as well as for preparation for surgery and management of thyroid storm.

Question 19

Briefly describe preoperative medical preparation for thyroid surgery in Grave’s disease

Answer 19

• Prior to surgery, patients are prepared with antithyroid drugs until euthyroidism is achieved
• Some clinics treat patients 7 to 10 days prior to surgery with pharmacological doses of iodine to reduce vascularity of the thyroid gland
• Beta-blockers are usually used for symptomatic therapy

Question 20

Briefly describe postoperative treatment following thyroid surgery in Grave’s disease

Answer 20

Thyroxine therapy (e.g. levothyroxine) is started immediately postoperatively if the patient is euthyroid at the time of surgery.

Question 21

Which thyroid surgery is prefered? Total or bilateral?

And why?

Answer 21

Total or near-total thyroidectomy is preferred over bilateral subtotal thyroidectomy as it prevents recurrent hyperthyroidism.

Question 22

What are the complications of Grave’s disease?

Answer 22

• Bone mineral loss
• Atrial fibrillation
• Congestive heart failure
• Sight-threatening complications of Grave’s orbitopathy

Question 23

What differentials should be considered for Grave’s disease?

Answer 23

1. Toxic nodular goitre
2. Painless and postnatal thyroiditis
3. Gestational hyperthyroidism

Question 24

How does Grave’s disease and toxic nodular goitre differ?

Answer 24

• Differentiating signs and symptoms:
  
  • Hyperthyroidism has gradual onset and is mild in nodular disease. Toxic multinodular goitre usually occurs in an older age group.
  • Nodular goitre is found on physical examination
  • Extrathyroidal manifestations, such as orbitopathy, dermopathy, and acropachy, are absent
• Differentiating investigations:
  
  • Peripheral thyroid hormone levels are not usually as high as in Graves’ disease
  • Thyroid isotope scan and thyroid ultrasound show nodular goitre
  • Radioactive iodine (or technetium-99) uptake is usually normal
  • Thyroid receptor antibodies are absent

Question 25

How does Grave’s disease and painless and postnatal thyroiditis differ?

Answer 25

• Differentiating signs and symptoms:
  
  • Transient hyperthyroid phase is mostly followed by transient hypothyroid phase
  • Fifty percent of patients will ultimately develop permanent hypothyroidism in the following years
• Differentiating investigations:
  
  • Radioactive iodine (or technetium-99) uptake is very low
  • Thyroid receptor antibodies are absent
  • A high T3/T4 ratio is suggestive of Graves’ disease rather than thyroiditis

Question 26

How does Grave’s disease and gestational hyperthyroidism differ?

Answer 26

• Differentiating signs and symptoms:
  
  • High levels of hCG during the first trimester stimulate the TSH receptor
  • Hyperthyroidism is usually subclinical but may be overt, especially if hyperemesis is present
• Differentiating investigations:
  
  • Hyperthyroidism is subclinical or mild and resolves in the second trimester
  • Thyroid receptor antibodies are absent