Endo 5: Thyroid Disorders - Hyperthyroidism Flashcards
What is a key characteristic of Grave’s Disease, and how does it occur?
Key characteristic= autoimmune disease
onset:
- antibodies bind to TSH receptor
- stimulates receptor in the thyroid
–> causes goitre + hyperthyroidism
What are other symptoms of Graves disease?
- antibodies binding to muscles behind eye –> exophthalmos
- pretibial myxoedema
What is pretibial myxoedema ?
Pretibial Myxoedema:
- swelling (growth of soft tissue) that occurs on shin
What are key characteristics of Plummer’s Disease?
Plummer’s disease:
- toxic nodular goitre
- NOT autoimmune
- benign adenoma –> overactive at making thyroxine
- NO pretibial myxoedema
- NO exophthalmos
Explain the effects of thyroxine on the SNS.
- Thyroxine sensitises B-adrenoreceptors to ambient adrenaline/ noradrenaline levels
- so there is apparent Sympathetic activation (but there isn’t - its just more sensitive??? )
- results in tachycardia, palpitations, hand tremor, lid lag
List main symptoms of hyperthyroidism
(EVERYTHING SPEEDS UP)
- weight loss, increased appetite
- breathlessness
- palpitations, tachycardia
- sweating
- heat intolerance
- diarrhea
- lid lag
What are characteristics of a thyroid storm?
- hyprepyrexia >41deg C
- accelerated tachycardia / arrhythmia
- cardiac failure
- delirium / frank psychosis
- hepatocellular dysfunction; jaundice
What are treatment options for thyroid storm?
- thyroidectomy
- radioiodine
- drugs
What are signs + symptoms of Viral Thyroiditis?
- painful dysphagia
- hyperthyroidism
- pyrexia
- raised ESR
What is the mechanism behind viral thyroiditis?
- virus attacks thyroid gland
- causes pain + tenderness
- thyroid stops making thyroxine
- makes virus instead
- so no (ZERO) iodine uptake
- stored thyroxine is released
- so toxic with ZERO uptake
note: by 4 wks later, stored thyroxine = exhausted
- -> hypothyroid
by 1 month –> resolution occurs
patient becomes euthyroid again
What are the 4 classes of drugs used in the treatment of hyperthyroidism?
- thionamides
- propylithiouracil
- carbimazole - potassium iodide
- radioiodine
- B-blockers
Note:
(1+2+3 = reduces thyroid hormone production)
(4 = relieves symptoms of thyrotoxicosis)
How are thionamides used?
What are they used for?
- given as daily treatment of hyperthyroid conditions
(e. g graves, toxic thyroid nodule etc.) - treatment prior to surgery
- reduction of symptoms while waiting for radioactive iodine to act
Briefly describe the process of thyroid hormone synthesis .
- iodine = taken up into follicular cells
- through action of thyroperoxidase + H2O2 –> you get iodination of tyrosine residues (in thyroglobulin)
- then coupling of mono/diiodotyrosine –> T3 + T4
- taken up + released by cells into circulation
Describe the mechanism of action of Thionamides
- Thionamides INHIBIT thyroperoxidase
- so they inhibit iodination of thyroglobulin + coupling of iodotyrosines
- net result = reduction in synthesis + secretion of thyroid hormones
- also suppresses antibody production in Graves disease
- reduced deidination of T4 –> T3 (in peripheral tissue)
How long does it take for clinical effects of thionamides to take place?
- biochemical effect occurs in hours
BUT - it takes WEEKS before clinical effects can be seen.
BECAUSE
- there is a lot of stored thyroid hormone in lumen of thyroid follicles
(doesn’t affect stored hormone)
Why would you want to manage symptoms in the shortterm with non selective beta blockers?
- because there is a delayed clinical effect of thionamides (due to stored hormone)
- takes several weeks for anti thyroid drugs to have clinical effects
What are some unwanted actions of Thionamides?
- agranulocytosis –> reduction in neutrophils
- reversible on withdrawal of drug - rashes
Describe 2 features of pharmacokinetics of thioamides
- orally active
- carbiamazole = pro drug which first has to be converted to methimazole
- crosses placenta –> and is secreted in breastmilk
- metabolized in liver + secreted in urine
How would you follow up with the anti-thyroid drug treatment?
- aim = stop treatment after 18 months
- review patient periodically
thyroid function tests for remission/relapse
What is the role of non selective beta blockers in thyrotoxicosis?
- in short term - deals with problems / clinical features of thyrotoxicosis
e. g tachycardia / tremor
why are the beta blockers used NON SELECTIVE?
- so that it reduces all effects of excess stimulation of B-adrenoreceptors
- cardioselective = only helps with tachycardia - doesn’t help tremor
How is Iodide Potassium Iodide given?
when would you give KI to patients?
- given at doses at least 30 x average daily requirement
given in :
- preparation of surgery of hyperthyroid patients
- severe thyrotoxic crisis (thyroid storm)
Describe the mechanism of action of KI
- by giving lots of KI
- through wolff chaikoff effect
- you inhibit iodination of thyroglobulin + generation of H2O2
- has much quicker effect than giving antithyroid drugs
Describe the Wolff chaikoff effect.
- temporary reduction in thyroid hormones following ingestion of large amounts of iodine
Note: Autoregulatory phenomenon
How is KI useful for pre surgery?
- reduces size + vascularity of thyroid within couple of weeks
What are some unwanted effects of KI?
- allergic reaction
rashes, fever, angio-oedema
Describe the pharmacokinetics of KI administration.
- given orally
- max effects after 10 days (continuous administration)
What is the effect of radioidine? What does it do?
- treats graves disease
- treats plummer’s disease
- treats thyroid cancer
- switches off thyroid completely
What does the effect of radio iodine rely on?
- relies on thyroid gland taking up iodine
- to make thyroid hormone
Describe the mechanism of Radioiodine.
- so thyroid follicular cells take up iodine + accumulates in the colloid.
- from colloid –> emits Beta particles of radiation that destroys follicular cells
Describe the pharmacokinetics of radioiodine
- discontinue anti thyroid drugs 7-10 days prior to radioiodine treatment
- administer as single oral dose
- has radioactive life of 8 days
- radioactivity = negligible after 2 months
NOTE:
- avoid close contact w small children for several weeks
- contra indicated in pregnancy + BREAST FEEDING
