Hyper/hypothyroidism Flashcards
What is the thyroid gland made up of (anterior)?
Pyramidal lobe (sometimes absent)
Right lobe
Isthmus
Left lobe
What is the thyroid gland made up of (posterior)?
Superior parathyroid glands
Inferior parathyroid glands
What is main function of the thyroid gland?
Synthesis thyroid hormones (T3 and T4), thyroxine.
Secretion of calcitonin
Where is the thyroid gland found?
At the base of the neck
What is the functions of parathyroid?
Maintenance of serum calcium and phosphate levels through secretin of parathyroid hormone (PTH)
What effects to T3 and T4 have one the body? (4)
1) Cardiovascular
2) Metabolic
3) Developmental
4) Other
What produces T3 and T4?
Iodine (Mono and Di)
Thyroid hormones mechanism?
- Hypothalamus = TRH
- Pituitary = TSH
- Thyroid = T4 and T3 to go and work peripherally (T2 excreted)
- Then feedback to pituitary and hypothalamus to turn off.
What is ratio of T4 and T3 produced?
10:1 (more T4)
Types of hypothyroidism
Primary
Secondary
Peripheral
What is primary hypothyroidism?
Disfunction in the thyroid itself.
What is secondary hypothyroidism?
Reduced thyroid stimulation (TSH or TRH)
What is peripheral hypothyroidism?
Circulating levels are enough but the body cannot use them
Causes of hypothyroidism (5)
- Autoimmune thyroiditis
- Iodine deficiency
- Post thyroidectomy or radioactive iodine treatment
- Drug induced (lithium)
- Peripheral resistance to thyroid hormone
- Congenital diseases e.g., thyroid agenesis
Diagnosis of hypothyroidism
- Sympotoms
2. Biochemical testing – Thyroid function and TSH and Free T4
Why does a high TSH indicate hypothyroidism?
Because they body if not producing enough thyroxine, so the body is indicating the need for more via TSH
High TSH and normal T4 =
Subclinical hypothyroidism (just about able to manage)
Low TSH and normal T4
Subclinical hyperthyroidism (just about able to manage)
High TSH and low T4 =
Primary hypothyroidism (likely autoimmune thyroiditis)
Low TSH and high T4 =
Primary hyperthyroidism (likely Graves’ disease)
Aim for treatment for hypothyroidism
- Effectivly replace thyroid hormone
2. Correct TSH levels and resolve clinical symptoms
1st line drug for hypothyroidism
Levothyroxine (T4 replacement)
What do you do with people with glucocorticoid deficiency before starting thyroxine?
Glucocorticoid replacement
What is monitored in use of thyroxine?
TFTs every 3 months until stable then annually
How long can it take for TSH to stabiles with use of thyroxine?
6 months. Most adults stabiles at does between 100-200 micrograms. (do not really go over)
In what doses is thyroxine titrated?
25 micrograms
How is thyroxine dose decided?
Based on weight (1.6/kg rounded to nearest 25 microgram)
Why are drug interaction important for thyroxine?
It get absorbed and bounds reduces its use.
Thyroxine main interactions
Calcium and iron should not be taken at the same time as they bind. Also PPIs.
Milk
How may IBD or coeliac impact levothyroxine dose?
May need higher doses due to absorption issues.
How to take levothyroxine?
In the morning 30-60 mins before food.
Side effects of levothyroxine
Flushing Restlessness Palpitations Insomnia Angina Thyroid crisis
Liothyronine
Synthetic form of T3
IV and rarely used not non-oral usage
Usually switch everyone to levothyroxine
What happens to levothyroxine dose when pregnant?
Increase by 20-25 micrograms immediately and have TSH levels checked. Monitoring every 4-6 weeks.
Go back to normal dose after birth
Can use while breastfeeding
TSH target levels pregnancy
First trimester <2.5 mU/L
Third trimester <3.0 mU/L
Myxedema crisis
Extreme manifestation of hypothyroidism.
Rare but potentially fatal
Graves’ disease (hyperthyroid) symptoms
Bulding eyes
Eyelids retracts
Redness
Nodular disease (hyperthyroid)
Can be single or multiple goiter
Actively release T3/T4
Images using radioactive iodine
Thyroiditis (hyperthyroid)
Inflammation of the thyroid follicles (usually painful and tender)
Causes by infection, trauma, drug induced or autoimmune medicated.
T3 and T4 leaked from inflamed cells
-Can go or cause lots of damage
Diagnosis for hyperthyroidism
Thyroid function tests TSH , Free T4 and T3 and TRABs
Low TSH but high FT4 and FT3 =
Hyperthyroidism of thyroidal region
High TSH and high FT4 and FT3 (RARE) =
Hyperthyroidism of external origin indicating pituitary or hypothalamic disease .
What is required for definitive diagnosis of hyperthyroidism?
2 sets of TFTs taken at least 6 weeks apart. Thyrotoxicosis usually used until further investigation.
Hyperthyroidism treatment aim
Acute: manage symptoms
Chronic: Effectively suppress thyroid hormone back do euthyroid levels.
Treatment options (3)
Antithyroid drugs
Radioactive iodine
Thyroidectomy
Graves disease If patients are likely to go into remission: treatment
First line: Thionamides; carbimazole unless contraindicated.
Graves disease If unlikely to go into remission: treatment
First line: Radioactive iodine
Graves disease If concerns regarding possible compression or malignancy: treatment
First line: Thyroidectomy
Multinodular goitre treatment
First line: Radioactive iodine
Second line: Either thionamides or thyroidectomy
Single nodular adenoma treatment
First line: Either radioactive iodine or surgical intervention of total- or hemi-thyroidectomy
Second line: Thionamides
Hyperthyroidism treatment pregnancy
1) Thionamides; propylthiouracil
2) Thyroidectomy
Radioactive iodine is contraindicated in both pregnancy and breastfeeding, as rarely can potentiate thyroid hormone release and even precipitate thyroid crisis which could be teratogenic.
Graves’ Disease Children treatment
First line: Thionamides; carbimazole unless contraindicated.
If remission not achieved review for possible radioactive iodine or consider long-term therapy.
MNG or SNA Children treatment
Initially commenced thionamides. Long-term will need to discuss risks and benefits of radioactive iodine or thyroidectomy
Thionamides (Anti-thyroid Drugs) e.g.
Carbimazole and Propylthiouracil
Thionamides (Anti-thyroid Drugs) uses
6-8 weeks to show benefit
Can titrate up
Or block and replace (loss in thyroid as it has been blocked)
Carbimazole MOA
Mechanism of action: Inhibition of the organification of iodide and thyroglobulin and the coupling of iodothyronine residues which in turn
suppress the synthesis of thyroid hormones.
What is Carbimazole
Pro-drug which undergoes metabolism by hepatic enzymes to the active metabolite, thiamazole, also known as methimazole.
Carbimazole uses
First line choice due to quick thyroid hormone correction (4-8 weeks)
20-60mg in divided doses
Carbimazole monitoring
TFTs checked every 6-8 weeks
Once thyroid levels are within range, can either block and replace or titrate for 12-18 months.
Titration of Carbimazole (Thionamides Anti-thyroid Drugs)
5-15mg once daily. Regular TFT checks at hospital and dose adjusted to response
Block and replace of Carbimazole (Thionamides Anti-thyroid Drugs)
remains on high starting dose to ensure endogenous T3/T4 production completely suppressed but levothyroxine is started alongside to supplement. Thyroxine is then titrated until TSH, T3 and T4 are within reference range.
Carbimazole Contraindications
- Severe hepatic impairment (unable to be metabolised to active methimazole)
- Pre-existing blood disorders (risk of dyscrasias)
- History of pancreatitis (may exacerbate)
Carbimazole Side effects
- Macropapular rash – can be treated with a generic antihistamine
- Bone marrow suppression and some fatal cases of agranulocytosis have occurred in patients treated with carbimazole
- On initiation patients need to be counselled on the signs and symptoms of blood dyscrasias – sore throat, bruising, bleeding, mouth ulcers, fevers and malaise
- Full blood count to be checked as a baseline and 6 monthly during treatment
Carbimazole Counselling
- Advise on dose to be taken during initial dosing then dependent on regimen elected for and monitoring as appropriate to that regimen
- Need for additional medications i.e. beta blockers for symptom management
- May take six to eight weeks to have an observable effect as do not alter existing levels of T3 and T4.
- Advised on the urgency of reporting onset of severe sore throats, bruising or bleeding, mouth ulcers, fever and malaise
- Women of childbearing age advised for need for contraception due to teratogenic effects of carbimazole and previous cases of foetal malformation
Carbimazole is a vitamin K antagonist
S o may intensify or potentiate effects of warfarin. Advise for closer INR monitoring when initiated and on dose changes if relevant to patient case
Propylthiouracil MOA
Propylthiouracil achieves these actions by the inhibition of the enzyme peroxidase.
-Its effects are only begin to manifest after a latent period of up to 3 or 4 weeks because
all the preformed hormone has to be used up before circulatory concentrations will fall.
-Inhibits organification of iodide and the coupling of iodothyronine residues suppressing thyroid hormone production
-Inhibits conversion of T4 to T3 in peripheral tissues supressing thyroid hormone action
Propylthiouracil uses
Most commonly second line for patients who have contraindications to or suffer
adverse reactions with carbimazole and in pregnancy
Propylthiouracil monitoring
TFTs to be checked every 6-8 weeks
Once thyroid hormone levels are within reference range patients choose either ‘titration’
or ‘block and replace’ and continue for 12-18 months
Titration of Propylthiouracil (Thionamides Anti-thyroid Drugs)
50-150mg once daily. Regular TFT checks at hospital and dose adjusted to
response
Block and replace of Propylthiouracil (Thionamides Anti-thyroid Drugs)
remains on high starting dose to ensure endogenous T3/T4 production completely suppressed but levothyroxine is started alongside to supplement. Thyroxine is then titrated until TSH, T3 and T4 are within reference range.
Propylthiouracil Contraindications
- Severe hepatic impairment (unable to be metabolised to active methimazole)
- Pre-existing blood disorders (risk of dyscrasias)
- History of pancreatitis (may exacerbate)
Propylthiouracil Side effects
-Macropapular rash – can be treated with a generic antihistamine
-Severe hepatic reaction causing acute liver injury; some cases of which were fatal and
some requiring liver transplant
-Bone marrow suppression, thrombocytopenia and risk of agranulocytosis
-On initiation patients need to be counselled on the signs and symptoms of blood
dyscrasias – sore throat, bruising, bleeding, mouth ulcers, fevers and malaise
-Full blood count to be checked as a baseline and 6 monthly during treatment
Propylthiouracil Counselling
Advise on dose to be taken during initial dosing then dependent on regimen elected
for and monitoring as appropriate to that regimen
-Need for additional medications i.e. beta blockers for symptom management
-May take six to eight weeks to have an observable effect as do not alter existing
levels of T3 and T4.
-Advised on the urgency of reporting onset of severe sore throats, bruising or
bleeding, mouth ulcers, fever and malaise
-Some cases of severe hepatic reactions, both in adults and children, including fatal
cases and cases requiring a liver transplant have been reported with
propylthiouracil. Patients should be advised to report any jaundice, dark urine,
abdomen pain, pruritis, nausea and vomiting,
-Time to onset has varied but in most cases the liver reaction occurred within 6 months
-If significant hepatic enzyme abnormalities develop STOP treatment
When switching from Carbimazole to Propylthiouracil
- 1mg of carbimazole is roughly equivalent to 10mg of
propylthiouracil
Post thyroidectomy
- Start levothyroxine at standard 1.6microgram/kg dose immediately post-op total thyroidectomy
- Post hemithyroidectomy monitor TSH at 2- and 6-months post surgery and start levothyroxine when/if indicated
Thyroid Crisis aka Thyrotoxic Storm Treatment mechanism (4)
- Inhibition of thyroid hormone synthesis
- Inhibition of thyroid hormone release
- Inhibition of peripheral action of excess thyroid hormone
- Supplementary management
Thyroid Crisis aka Thyrotoxic Storm Inhibition of hormone synthesis Treatment drugs (2)
-Carbimazole: 20-30mg every 4 to 6 hours
-Propylthiouracil: 600mg loading followed by 200-250mg every 4 to 6 hours
Oral, NG or rectal
Lots and quick
Thyroid Crisis aka Thyrotoxic Storm Inhibition of peripheral hormone action Treatment drugs
Propranolol
If pre-existing asthma or COPD consider more Cardioselective beta blocker
e.g. metoprolol
If beta blockers contraindicated completely – rate limiting calcium channel blocker
Diltiazem
Glucorticosteroids inhibit peripheral T4 to T3 conversion.
Thyroid Crisis aka Thyrotoxic Storm Additional symptom control and supplementary management Treatment drugs
Paracetamol for high temperature
Cholestyramine
-Enhances thyroid hormone excretion by increasing enterohepatic circulation
which is increased in thyroid storm
-Cholestyramine bile sequestrant binds free thyroid hormone to facilitate excretion
through faeces
