Thyroid Flashcards
type 1 (D1) deiodinases
predominantly expressed in liver and kidney. lower expression also occurs in the thyroid. contributes 24% of the circulating T3 converted from T4
type 2 (D2) deiodinases
predominantly expressed in CNS, pituitary, thyroid, heart, brown fat, skeletal muscle. contributes 60% of circulating T3 converted from T4.
intracrine vs. paracrine effects
intracrine affects thyroid signaling inside D2 expressing cells, paracrine effects are when D2 generated T3 also exits the cells to plasma and effects other tissues
type 3 (D3) deiodinase
predominantly expressed in the brain and skin in healthy adults. also in placenta of pregnant women and in tissues in disease states. inactivates T3, converts T3 to T2 and reverse T3. prevents circulating T3 from entering the nucleus.
diseases caused by defective sodium-iodide symporter
symporter gene mutation: causes congenital hypothyroidism.
Autoimmune thyroiditis: autoantibodies against symporter which affects iodide transport
transportation of thyroid hormone into the target cells
- through simple diffusion
- through thyroid hormone transporters
2a. monocarboxylate transporter family
2b. organic anion transporting polypeptides.
the MCT and OATP are important for maintaining intracellular concentrations of thyroid hormones
regulation of thyroid function
hypothal makes TRH, which causes anterior pituitary to make TSH, which causes thyroid to make T4 and T3. T4 and T3 stop production of TSH and TRH.
regulation of gene expression
TR is a heterodimer made of TR and RXR. TR-RXR binds to thyroid hormone response element. T3 then binds to the complex and leads to regulation
hypothyroidism symptoms
fatigue, depression, cold sensitivity, weight gain, goiter, muscle weakness, coarsening of skin, dry hair, muscle cramps, constipation, miscarriage
types of hypothyroidism
iodine deficiency, hashiimoto’s thyroiditis, thyroid ablation. secondary hypothyroidism caused by disorder of pituitary or hypothal. myxedema, cretinism
what are some problems with animal thyroid usage?
contains T3 which acts rapidly, varies in potency, some patients can be allergic.
levothyroxine sodium
synthetic version of T4. preferred drug in treatment of hypothyroidism. longer half life compared with liothyronine. can be converted to T3 in peripheral tissues.
Oral administration, can do IV or IM.
liothyronine sodium
synthetic version of T3. can be used in combo with levothyroxine in hypothyroidism. more rapidly effective. 4x as potent as T4. IV can be used in acute emergency conditions (myxedema coma). leads to transient high levels of T3 in serum if used constantly.
precautions for thyroid hormone drugs
readjust after 4-6 weeks to keep proper levels. perform periodic tests to monitor T3 and T4 and TSH levels if chronic treatment. use with caution in ppl with heart problems. use low doses. give adequate dose to pregnant ladies to prevent fetal brain maldevelopment
goiter
iodine deficiency
hyperthyroidism symptoms
rapid heart beat, weight loss, nervousness and alertness, heat intolerance, fatigue, increased freq of bowel movements, loss of sleep, tremors, excessive sweating, eye changes
graves disease
most common cause of hyperthyroid. autoimmune disease caused by thyroid stimulating antibodies, activate the thyrotropin receptor on thyroid cells.
lab findings for hyperthyroidism
high T3 and T4, low TSH
treatment strats for hyperthyroidism
subtotal thyroidectomy and replacement of T4. irradiate thyroid gland and replace T4. inhibit thyroid peroxidase activity. interfere with thyroid hormone facilitation of sympthetic activity.
what drugs inhibit thyroid peroxidase activity
propylthiouracil, methimazole, carbimazole. inhibit organification of iodide and coupling of iodotyrosine, which prevents thyroid hormone synth.
severe side effects of antithyroid drugs propylthiouracil and methimazole
agranulocytosis, hepatitis, lupus like syndrome. meth is safer than prop with regards to agranulocytosis. prop preferred in pregnancy since it is less likely to go through placenta.
radioactive iodine
thyroid specific I131 isotope to destroy sufficient thyroid tissue to restore euthyroid. effects not seen for over 4 weeks. use in combo with drugz. used if relapse after drug therapy. dont use in pregnancy or breast feeding
