ChemPath: Thyroid Flashcards
What controls the uptake of iodide by thyroid follicular cells?
TSH
Which channel is important for the transport of iodine across the cell membrane?
Na+/K+ ATPase
Which enzyme converts iodide to iodine?
Thyroid peroxidase - happens in thyroid follicular cells
happens in thyroid gland
How is thyroxine produced?
Iodination of tyrosine residues in thyroglobulin generates MIT and DIT which leads to the formation T3 and T4
happens in the colloid
what percentage of thyroxine is free active T4?
0.03%
What does thyroxine bind to in the blood?
- 75% - Thyroxine binding globulin (TBG)
- 20% - Thyroxine-binding prealbumin (TBPA)
- 5% - Albumin
Outline the hypothalamo-pituitary-thyroid axis.
- The hypothalamus produces TRH which stimulates the release of TSH from the anterior pituitary
- TSH stimulates T3/T4 production
- T3 is active hormone and produced in perpipheries
- T4 -ve feedback to the hypothalamus and pituitary
List some causes of hypothyroidism.
- Hashimoto’s thyroiditis (autoimmune)
- Atrophic thyroid gland
- Iatrogenic - Post-Graves’ disease (after treatment e.g. radioiodine, thionamides, surgery)
- Post-thyroiditis
- Drugs (e.g. amiodarone, lithium)
- Iodine deficiency
- Pituitary disease - secondary
- Peripheral thyroid hormone resistance
Outline the investigation findings that may be seen in hypothyroidism.
- High TSH
- Low T4
- Thyroid peroxidase antibodies
- Other autoimmune conditions - coeliac, pernicious anaemia, addison’s
- ECG
Why is it important to do an ECG in patients with suspected hypothryoidism?
If someone with hypothyroidism has underlying cardiovascular disease, giving them thyroxine may induce ischaemia
NOTE: so you would start on a low dose of thyroxine and then escalate if they have CV
Symptoms of hypothyroidism
Metabolic - gain weight
GI - constipation
Reproductive - amenorrhea
Depression
Cold intolerance
Fatigue
How is hypothyroidism treated?
Thyroxine (50-150-200 µg/day titrated to a normal TSH)
NOTE: you replace with T4, giving T3 has no clinical benefit
dose is adjusted to weight
What are some risks of overtreatment with thyroxine?
- Osteopaenia
- Atrial fibrillation
What is a subclinical hypothyroidism?
- Normal T4 with high TSH
- Sometimes referred to as compensated hypothyroidism
NOTE: if TPO antibodies are positive, the patient may go on to develop hypothyroidism
Why might there be some benefit to treating subclinical hypothyroidism?
- Hypothyroidism is associated with hypercholesterolaemia
Outline how thyroid function changes in pregnancy.
- hCG has a similar structure to TSH so high hCG levels can cause hyperthyroidism in 1st trimester
- Free T4 levels rise slightly
- TSH levels decrease slightly
- Clinically they are not hyperthyroid - it is normal, different reference ranges
- TBG level increase dramatically due to estrogen increase (but this cant be measured in serum)
NOTE: hCG level drops later on in pregnancy
How is neonatal hypothyroidism diagnosed?
Guthrie test - measures TSH
Why is the timing of the Guthrie test important?
It needs to be done at least 48-72 hours after birth to make sure maternal TSH is no longer in the baby
Later would cause brain damage due to congenital hypothyroidism
What is sick euthyroid?
- Alteration in the pituitary thyroid axis in non-thyroidal illness
- In other words, when you are very sick, your thyroid will shut down to try and reduce your basal metabolic rate
What are the TFT findings in sick euthyroid?
- Low T4 and T3
- Normal/high TSH
NOTE: these patients do not have symptoms of hypothyroidism
normal physiology
What are the three main causes of hyperthyroidism?
- Graves’ disease - anti-TSH antibodies
- Toxic multinodular goitre
- Single toxic adenoma
Others: subacute/viral thyroiditis, post-partum thyroiditis
Explain varying results of technetium uptake scan for causes of hyperthyroidism
increased uptake:
graves, toxic multinodular goitre, single toxic adenoma - thyroxtoxicosis is due to increased production of thyroxine
decreased uptake
subacute/viral thyroididts, post-partum thyroiditis - thyrotoxicosis is due to release of PRE-FORMED thyroxine, not increased production, eventually become hypothyroid
key distinguishing symptom of viral thyroiditis
painful goitre
What is post-partum thyroiditis?
During pregnancy, the body may produce antibodies that stimulat the thyroid gland
What is struma ovarii?
A rare form of ovarian tumour (usually a teratoma) that contains mostly thyroid tissue and produces thyroxine
List some investigation findings of hyperthyroidism.
- Low TSH
- High T4 and T3
- Technetium scan
- Thyroid antibodies (thyroid microsomal)
metabolic - weight loss, increased appetitie
cardiac - tachycardia, palpitations
GI - diarrhoea
respiratory - tahcypnoea
skeletal - osteopenia/osteoporosis
reproductive - irregular periods, infertility
heat intolerance, anxiety
Outline the management of hyperthyroidism.
- symptomatic - Beta-blocker
- ECG - check for AF
- Bone mineral density - to look for ostepenia/osteoporosis
- Radioiodine
- Thionamides
What is a major risk of radioiodine treatment for hyperthyroidism?
- Can precipitate thyroid storm
- results in hypothyroidism –> give thyroxine
Also not if they have graves eye disease
List some features of Graves’ disease.
- Diffuse goitre
- Thyroid-associated ophthalmopathy
- Pretibial myxoedema
- Thyroid acropachy
NOTE: radioiodine can make Graves’ eye disease worse
What is the mechanism of action of thionamides?
Inhibit thyroid peroxidase - Prevents the conversion of I- to I2 and iodination of tyrosine residues on thyroglobulin
Carbimazole, PTU
What is a rare but important side-effect of thionamides?
Agranulocytosis
NOTE: patients should be advised to stop treatment if they develop a sore throat or fever
What kind of dosing regimes can be used for thionamides?
- Can be titrated to achieve normal T4
or - Block and replace - high dose is given to block the thyroid gland and then given thyroxine replacement
Which drug can be given to hyperthyroid patients prior to surgery to block uptake of iodide?
Potassium perchlorate
What is the long-term treatment of thyroiditis?
Thyroid hormone replacement
What are the two most common forms of thyroid cancer?
- Papillary thyroid cancer
- Follicular thyroid cancer
Medullary is very rare
How is thyroid cancer treated?
- Total thyroidectomy
NOTE: radioiodine treatment may also be given afterwards to kill remaining cells
NOTE: high dose thyroxine may be given to suppress TSH levels to prevent TSH from stimulating any remaining thyroid cells
What is tumour marker for thyroid cancer recurrence
thyroglobulin
Which cells do medullary thyroid cancer arise from?
- Calcitonin-producing C cells
NOTE: it is part of MEN2
Name two tumour markers used for medullary thyroid cancer?
Calcitonin
CEA
