Under-active thyroid Flashcards
How is fatigue different from tiredness?
Fatigue is when tiredness that is overwhelming and cannot be easily relieved.
What are some causes of fatigue?
- Anaemia
- Sleep apnoea
- Underactive thyroid
- Coeliac disease
- Chronic fatigue syndrome
- Diabetes
- Glandular fever (mono -> EBV)
- Depression
- Restless Leg syndrome
- Generalised anxiety disorder (GAD)
- Vitamin D deficiency
- Insomnia
- Malignancies
- Chronic Heart failure
- Infections
What relevant investigations can be carried out after history/ physical examination, to find out reason for tiredness?
- FBC
- TFTs
- HbA1c
- Urea and electrolytes
- Vitamin D
- CRP
- Coeliac screen
- Autoimmune screen
- EBV serology (Epstein Barr Virus causes glandular fever)
What are the symptoms of an under active thyroid?
- fatigue
- weight gain
- dry skin
- constipation
- cold intolerance
- bradycardia
What are the normal ranges in TFT?
- TSH: 0.5-5.0 mlU/L
- T3: 0.9-2.8 nmol/L
- T4: 5.0- 12.0 microg/dL
What are the causes of primary hypothyroidism?
- autoimmune (Hashimoto’s)
- iodine deficiency
In Hashimoto’s disease, auto-antibodies against which molecule are produced?
TPO enzyme -> involved in the synthesis of T3/4 (anti-TPO)
What happens to the levels of hormone in Hashimoto’s disease?
- TSH increases (no negative feedback)
- T3/T4 decrease (reduced synthesis of hormones)
Which cells contain MHC I molecules?
All cells in the body
Which cells contain MHC II molecules?
APCs
What receptor in the T cell binds to the MHCII molecule on the APC?
TCR
What cell has the B7 receptor and what does it bind to?
APCs: B7 receptors and they bind to CD28 receptors on T cells
What does the TCR bind to on B cells?
BCR
What cell has the CD40L receptor and what does it bind to?
T cells: CD40L receptor which bind to CD40 receptors on B cells
What cells produce anti-TPO antibodies?
B cells
Describe how T cells recognise non-self antigens.
- APCs present antigen using their MHC II molecules onto the TCRs of T helper cells,
- In order for the T cells to be completely activated, they need to be co-stimulated.
What is T cell co-stimulation?
A secondary signal which activates T cells -> in this case, it is the binding of B7 to CD28 receptors on T cells.
What happens in Hashimoto’s?
- APCs present TPO to T cells which recognise it as an non-self antigen.
- T cells gets co-stimulated (B7 -> CD28)
- Activated T helper cells activate B cells by TCR-BCR binding.
- B cells are co-stimulated.
- B cells differentiate into plasma cells and produce anti-TPO.
What is B cell co-stimulation?
A secondary signal which activates B cells -> in this case, it is the binding of CD40L receptor to CD40 on B cells.
What do the anti-TPO antibodies result in?
They bind to and kill thyrocytes.
What other cells are involved in killing thyrocytes?
Cytotoxic T cells
What is immune tolerance?
Prevention of immune response to self antigens.
How do granulocytes (neutrophils etc.) show immune tolerance?
They only detect
- DAMPs
- PAMPs
so cannot kill self-cells. They are part of the innate immune response.
How do lymphocytes (B + T cells) develop tolerance?
In early development, they are exposed to a microcosm of almost every single protein in the body and are trained not to kill self-proteins.
How do NK cells (part of innate and adaptive immune response) show immune tolerance?
They only become activated in response to an absence of MHC I molecules on their surface.
Why does autoimmunity occur?
Unknown but it could be contributed to…
- genetics
- environment
- molecular mimicry
What is molecular mimicry?
- Pathogens may have a structure which is similar to self-proteins in the body.
- The body may produce antibodies against these pathogenic antigens.
- Due to the self-proteins having a similar shape to the pathogenic antigens, the antibodies may attack them too leading to autoimmunity.
What are some of the different types of tiredness?
- drowsiness
- shortness of breath
- weakness
- exertional tiredness
What are some red flag symptoms you must screen for if someone presents with tiredness?
- lymphadenopathy
- weight loss
- malignancy features (FLAWS)
- joint pains
- focal neurology (problems with nerves/CNS)
- infective symptoms
How is primary hypothyroidism treated?
Levothyroxine (T4) tablets
How is treatment affected by pregnancy?
Dose of Levothyroxine will probably increase because the thyroid hormone is important for the development of the thyroid gland in the foetus.
What can increase absorption of Levothyroxine?
Grapefruit
What are the 2 types of Hashimoto’s?
- Goitrous Hashimoto’s thyroiditis: WBCs attack thyroid and cause inflammation of tissue.
- Atrophic Hashimoto’s thyroiditis: atrophy of thyroid as TSH receptors become blocked by the antibodies.
What is subclinical hypothyroidism/ Mild thyroid failure?
When level of hypothyroidism is so slight that there are no obvious symptoms and it can only be detected by blood tests.
Describe the TSH and T4 levels in subclinical hypothyroidism.
- slightly raised TSH level
- normal FT4 level
