Thyroid and Anti-Thyroid Agents Flashcards
What is the primary sensor / controller of the body’s metabolic rate, and what does this do?
Hypothalamus. When BMR / temp are too low, more thyroid hormone is needed -> releases TRH
What is the feedback loop utilized by T3/T4?
T3/T4 feed back on the pituitary to inhibit the release of TSH.
Elevated TSH will be found in hypothyroidism because TSH is unable to prompt sufficient release of thyroxine
What receptor does thyroid hormone utilize, and what is its relative potency for T3/T4?
A nuclear receptor of the steroid receptor class (transcription factor)
T3 is 10x more active than T4
What is the primary storage / transport /synthesis form of thyroid hormone? How is T3 made?
T4 is the primary product of the thyroid gland, which has a longer halflife due to its preferential binding to thyroid-binding globulin (TBG). It can be thought of as a pro-hormone.
T3 is end-organ more potent, made via deiodinase enzyme which can make T4 into T3 or reverse T3 (inactive)
What is the uptake form of iodine and why can this be a problem?
Iodide, I-, rapidly and efficiently uptake at 250x blood concentration. A problem during nuclear catastrophe with radioactive iodide, which tends to concentrate iodide in thyroid follicular cells
What is the main dietary source of iodide and what can it cause?
Salt-water seafood, but is generally given as sodium iodide in table salt as well.
Frequent cause of hypothyroidism / goiter / congenital cretinism
What is iodine attached to in the thyroid follicular cell and by what enzyme?
Attached to thyroglobulin via thyroperoxidase (tyrosine residues). This forms MIT and DIT, still within the protein
These are stored in the colloid within the follicule
What does TSH do? How does this affect size of thyroid gland?
Stimulates uptake of colloid from extracellular lumen of the colloid follicle into the follicular cell
-> uptake stimulates lysosomal digestion and subsequent release of T3 / T4
TSH causes growth of the gland -> goiter. This can happen in both hypo and hyperthyroidism due to excessively high TSH levels in both (in hyper, often due to molecular mimicry antibody)
What are the two main thyroid function tests utilized and why?
- Free thyroxine index (FTI) - based on total T4 measured, and percent bound to TBG
- TSH level -> most accurate and easily measured by ELISA or RIA, very sensitive because small changes in T4 will lead to log-scale changes in TSH
What do anti-thyroid antibodies check for?
Anti-thyroperoxidase (hypo)
Anti-thyroglobulin (hypo)
Anti-TSH receptor (hyper / Graves)
What are the symptoms of hypothyroidism?
- Lack of facial affect / depression
- Cold, dry skin
- Lowered cardiac output
- Husky, low-pitched voice
- Weakness / diminished appetite / still gaining weight
What is cretinism and how is it prevented?
Congenital hypothyroidism which stunts neural development, can result from maternal hypothyroidism so T4 does not cross placenta
Thyroid levels must be monitored throughout pregnancy
What are the three main etologies of hypothyroidism? Who is it common in?
- Hashimoto’s - autoimmune to thyroid
- Deficiency of iodine - with goiter
- Destruction of thyroid - surgical or radioactive therapy for treatment of Graves’ disease
Both Graves’ and Hashimoto’s are more common in women
What are the two thyroid replacement therapies and which one is typically used?
- Levothyroxine - T4
- Liothyronin sodium - T3
T4 is used because it is cheaper and has a long half-life for easy treatment.
T3 is only used to treat acute symptoms
What are the symptoms of thyrotoxicosis?
This is caused by hyperthyroidism / Graves disease:
- Exophthalmus
- Goiter
- Warm, flushed, and moist skin
- Tachycardia
- Muscle tremor
- Anxiety, insomnia, paranoia
- Osteoporosis - increased bone turnover in longstanding disease
