Graves' disease Flashcards
1
Q
What is Grave’s disease?
A
Autoimmune thyroid condition associated with hyperthyroidism
Graves-specific stigmata:
- Extrathyroidal manifestations include orbitopathy
- pretibial myxoedema (thyroid dermopathy)
- acropachy
- which do not occur with other causes of hyperthyroidism.
2
Q
What is the aetiology of Grave’s disease?
A
-
- Autoimmune
- Stimulation of thyroid by TSH receptor antibodies causing thyroid hormone overproduction
- Although other thyroid antibodies occur in people with Graves’ disease (namely, antithyroglobulin [Tg], antithyroid peroxidase [TPO], and antibodies to the sodium iodide transporter), they do not play a part in the development of hyperthyroidism
- The fundamental cause of autoimmunity is not clear
- Genetic (80%) and environmental (20%) factors
3
Q
What are the risk factors for Graves’ disease?
A
- female
- family history
- Tobacco use is an important risk factor for orbitopathy
weak
-
high iodine intake
- presumably through stimulation of the autoimmune process
-
lithium therapy
- Lithium use is associated with an increased risk of hypothyroidism.
- Long-term use has been associated with a possible increased risk of hyperthyroidism due to painless thyroiditis or Graves’ disease.
- Lithium increases thyroid autoimmunity if present before therapy
-
biological agent and cytokine therapies
- Biological agent therapy (e.g., alemtuzumab, ipilimumab, nivolumab, pembrolizumab)
- cytokine therapy (e.g., interferon)
- are associated with autoimmune thyroid disease, including painless thyroiditis and Graves’ hyperthyroidism
-
radiation
- There have been cases of Graves’ disease following neck radiation for lymphoma.
- However, hypothyroidism is the common outcome
-
radioiodine therapy for benign nodular goitre
- Patients with benign multinodular goitres have been reported to develop Graves’ hyperthyroidism after radioiodine therapy, presumably because of release of thyroid antigens
-
stress
- severe psychological trauma
- However, there is no proven evidence for a causative relationship.
4
Q
What is the epidemiology of Grave’s disease?
A
- Most common form of hyperthyroidism in most areas of world
- In iodine-sufficient parts of the world, the prevalence of overt hyperthyroidism is 0.2% to 1.3%
- In areas of iodine deficiency and endemic goitre, particularly in the older age group, toxic multinodular goitre is more common
5
Q
What are the presenting symptoms of Grave’s disease?
A
- Heat intolerance
- Irritability
Physical
- Neck lump
- Weight loss
- Increased appetite
- Sweating
- Palpitations
- Tremor
6
Q
What are the signs of Grave’s disease on examination?
A
Obs
-
Wide pulse pressure
- Relates to decreased peripheral vascular resistance. Non-specific.
- Tachycardia
O/A
-
Cardiac flow murmur
- Is due to the increased flow of blood through the heart valves
- Thyroid bruit
O/E
- Diffuse goitre
-
Orbitopathy
- Upper eyelid retraction, exophthalmos/optic neuropathy, extraocular muscle involvement
- Scalp hair loss
- Moist, velvety skin
Uncommon
-
Oncholysis
- Detachment of nail from nail bed, when present, is a good diagnostic physical finding.
-
Vitiligo
- Associated autoimmune process that is not directly related to Graves’ disease but suggests an autoimmune diathesis
-
Pretibial myxoedema
- Almost always associated with orbitopathy. The combination of Graves’ orbitopathy and dermopathy is highly diagnostic
-
Acropachy
- = nail clubbing + soft tissue changes of hands
- Due to sub-periosteal new bone formation. Manifests as clubbing of the fingers and toes with soft-tissue swelling. Almost always associated with orbitopathy
7
Q
What is the histological meaning of a diffuse goitre?
A
uniform follicular epithelial hyperplasia
8
Q
Which triad of symptoms/signs if diagnostic of Grave’s disease?
A
The combination of :
- diffuse goitre
- recent onset of orbitopathy
- symptoms of hyperthyroidism
9
Q
What does this image show?
A
pretibial myxoedema
10
Q
What are the investigations for Grave’s disease?
A
-
TSH
- = Suppressed
- (Normal range may differ among assays, but is usually 0.4-4.0 mIU/L)
-
Serum free T4
- = Elevated
- if normal, in presence of supressed TSH, suspect T3 toxicosis (clinical hyperthyroidism) or subclinical hyperthyroid disease
-
Serum free or total T3
- = Elevated
- Elevated free T3 and suppressed TSH suggest hyperthyroidism, even if the free T4 is normal
- if normal, in presence of supressed TSH, suspect in subclinical disease
11
Q
What are some secondary investigations for ?Grave’s disease
A
-
T3 resin uptake (T3RU), free T4 index
- = elevated
- T3RU is an indirect measure of hormone binding to thyroxine-binding globulin. This test and the free T4 index are proportional to free T4. However, free T4 index and T3RU are not widely used investigations.
-
radioactive iodine (I-131 or I-123) or technetium-99 (Tc-99) uptake
- = elevated
- Radioactive iodine (I-123 preferred) or Tc-99 uptake of the thyroid test can be used for diagnosis of Graves’ hyperthyroidism and exclusion of low-uptake hyperthyroid states such as painless thyroiditis.
- It may be ordered for calculating the dose of radioactive iodine therapy.
- This test is used less since the advent of TSH receptor antibody measurement
-
thyroid isotope scan
- = diffuse uptake
- A thyroid isotope scan can differentiate diffuse enlargement of Graves’ disease from patchy uptake of multinodular goitre.
-
TSH receptor antibodies (TRAb)
- = positive
- It is used as a diagnostic test for Graves’ disease, particularly in questionable cases.
- It is also helpful in pregnant patients with active Graves’ disease or a history of the disease, to assess the possibility of transplacental transfer.
- It may be helpful during therapy with antithyroid medications for prediction of remission
-
thyroid ultrasound
- = highly vascular, diffuse, enlarged
- order if nodules suspected on examination or on thyroid isotope scan.
- Colour-flow Doppler may help to distinguish Graves’ from painless thyroiditis, and amiodarone-induced thyroiditis similarly shows low blood flow.
- May also be used for thyroid volume estimation for calculation of dose of radioactive iodine.
-
CT or MRI scan of orbit
- = may show muscle thickening
- May be needed to confirm euthyroid orbitopathy, or exclude other processes when proptosis is asymmetrical or if presentation is atypical (e.g., no previous or present evidence of thyroid dysfunction, absence of upper eyelid retraction, divergent strabismus, diplopia sole manifestation, history of diplopia worsening towards the end of the day).
-
skin biopsy
- = may confirm thyroid dermopathy
- Occasionally needed (e.g., when orbitopathy is absent).
12
Q
What are the differentials for:
- serum TSH is normal or even (slightly) elevated
- presence of hyperthyroid symptoms
- elevated free T4 level
A
consider other causes of hyperthyroidism such as
- TSH-producing pituitary tumour
- Partial resistance to thyroid hormone (on thyroid gland receptors)
- However, in the latter group, patients may clinically be hypothyroid, euthyroid, or hyperthyroid, depending on the type of resistance.
- heterophile antibodies (other causes of inappropriate TSH level)
- presence of these Abs causes false high TSH reading
- lab error
13
Q
a) What are heterophile antibodies?
b) Name 1 form of the heterophile antibody test
c) What is the heterophile antibody test used to test for?
A
a) Heterophile antibodies are antibodies induced by external antigens. Some cross-react with self-antigens. For example, in rheumatic fever, antibodies against group A streptococcal cell walls can also react with human heart tissues. These are considered heterophile antibodies.
b) mononuclear spot test or monospot test
c) The test is specific for heterophile antibodies produced by the human immune system in response to EBV infection
14
Q
What is subclinial hyperthyroidism?
A
- Low TSH
- normal T3/T4
15
Q
What is a thyroid storm?
A
Thyroid storm is a rare but severe and potentially life-threatening complication of hyperthyroidism (overactivity of the thyroid gland). It is characterized by:
- high fever (temperatures often above 40 °C/104 °F)
- fast and often irregular heart beat
- HTN
- vomiting
- diarrhea
- agitation
can cause heart failure & MI
