Thyroid Disorders Flashcards
Thyroid physiology
- Thyrotropin releasing hormone (TRH) from the hypothalamus stimulates pituitary to release Thyroid stimulating hormone (TSH)
- Thyroid stimulating hormone from the pituitary then stimulates the thyroid to release thyroid hormone
Regulation of TH release
- TH exhibits negative feedback inhibition of TSH
- Similarly TSH inhibits release of TRH
Role of Thyroid Peroxidase
- adds iodine to tyrosine and facilitates coupling of MIT + DIT
- converts iodide into iodine
Monoiodotyrosine (MIT) and Diiodotyrosine (DIT)
MIT and DIT combine to form T3
DIT and DIT combine to form T4
Thyroid Hormone conversions
T4 is converted to T3 in the periphery
T3 is the more active for of the two
Some T3 is converted to reverse T3 (rT3) which is inactive
Thyroid Hormone receptors and effects
- two types of receptors: TRalpha and TRbeta
- Once TH binds, the TR can combine in different ways: combine with each other to form homodimers, combine with other transcription factors to form heterodimers, either way promotes gene expression
TH functions
On growth/development of the CNS: congenital deficiency can result in developmental delays
Excess TH can cause..
Excess energy (anxiety) Heat intolerance Weight loss Tachycardia Sweating
Low TH can cause..
Low energy Cold intolerance Weight gain Bradycardia Dry skin
Thyroid diseases
Graves’ disease
Hashimoto’s Thyroiditis
Grave’s disease
- Thyroid stimulating Immunoglobulin (TsIg) is produced
- TsIg binds to the TSH receptor (TSH-R), stimulates the thyroid
- Result: Hyperthyroidism
- treated with drugs that reduce TH release
Hashimoto’s Thyroiditis
- gradual inflammatory destruction of thyroid gland
- after initial flare of TH hormone release, TH becomes low
- Result: Hypothyroidism
- treated with TH supplementation
Hypothyroidism treatment
Treated with thyroid supplementation
- Levothyroxine
- Liothyronine
Levothyroxine function
- converted to T3 in body
- preferred option for Hypothyroidism
- well established efficacy/safety
- Long half-life (7 days) so less fluctuation in T3 levels
- T4 may provide a ‘reservoir’ of TH that can be converted to T3 when needed
Levothyroxine administration
- a number of substances interfere with T4 absorption
- common: supplements (calcium, magnesium, aluminum)
- best to be taken on an empty stomach
- doses to be taken at a consistent time, once daily
Thyroid supplementation adverse effects
Similar to hyperthyroidism:
- cardiac effects: tachycardia, atrial fibrillation
- tremor
- anxiety
- diarrhea
- reduction in bone mineral density
Liothyronine compared to Levothyroxine
- shorter half life, more fluctuation in levels
- increased risk of cardiovascular adverse effects
- possible alternative to Levothyroxine if patients cannot tolerate that drug
Combining of T3 and T4
Dessicarted thyroid is an older product with T3 and T4 (porcine source)
Problems: quality unreliable (variation)
Anti-thyroid drugs
Thyroid peroxidase inhibitors (thionamides) Radioactive Iodine (I131)
Thyroid peroxidase inhibitors examples (Thionamides)
Methimazole
Propylthiouracil (PTU)
Thyroid peroxidase inhibitors mechanism
- inhibit various stages in Thyroid hormone synthesis
- PTU also inhibits the peripheral conversion of T4 to T3: better for managing thyroid storm (very high TH)
Thionamides mechanism
- inhibit thyroid peroxidase: inhibition of iodinated (adding of Iodine to tyrosine)
- inhibits coupling of MIT and DIT
Thionamides adverse effects
- Caution using in pregnancy (first trimester)
- rash
- hypothyroid- like symptoms
- Serious/rare: Agranulocytosis, Hepatotoxicity
Radioactive Iodine example
Iodine 131
Iodine 131 mechanism
- radioactive Iodine taken up by the thyroid gland
- destroys the gland
- contraindicated in pregnancy
Adverse effects of Iodine 131
- Hypothyroidism: gland is destroyed so patients will likely require supplementation
- damage to salivary glands: results in dry mouth, tooth decay
- altered taste sensation
- Pain
Other options for Antithyroid
Iodide
Iodide based examples
Saturated solution of Potassium Iodide (SSKI)
Lugol’s solution (iodine/potassium iodide)
Iodide based drugs mechanism
- taken up by thyroid, inhibits TH synthesis/release
- Wolf-chaikoff effect
Thyroid drug interactions
- drugs that contain iodine or overuse of iodine may lead to hyper- or hypothyroid-like state
Example: Amiodarone
Adjunctive therapy for Hyperthyroid
Problem: Tachycardia
Solution: Beta-blockers
Problem: inflammation
Solution: anti-inflammatories
Treatment options for thyroid cancer
Surgery
I131
