Thyroid, Parathyroid & Adrenals Flashcards
What cells make thyroid hormone?
Follicular cells of the thyroid gland
What is the source of iodine in our body and how is it absorbed?
Diet, ionic form called iodide
How is iodide taken up and where does it concentrate?
Via Na-iodide symporter at the follicular cells, it concentrates as a result in the follicular cells
What are the 2 forms of thyroid hormone
Triiodothyronine (T3) and Tetraiodothyronine (T4)
Explain the synthesis of thyroid hormone
- Thyroid Peroxidase (TPO) oxidises iodide to iodine2. TPO couples iodine to tyrosine, this makes thyroglobulin. This process is called organification3. A diiodo and a monoiodo tyrosine residue gives you T3, while two diiodo tyrosine residues coupled together gives you T4; both T3 and T4 are stored as thyroglobulin in the follicular lumen.4. Follicular cells cleave T3 and T4 from follicular lumen
What is more potent? T3 or T4?
T3
What converts T4 to T3 in the peripheral tissue?
5’-deiodinase (it is deiodinized)
What is one effect of thyroid hormones on the peripheral tissues and as a result what drugs can we use for hyperthyroidism?
One of the effects of thyroid hormone is to increase the sensitivity of peripheral tissues to sympathetic stimulation by causing increased transcription of beta-receptors, which increases the body’s sensitivity to circulating catecholamines.As a result we can use beta blockers for symptomatic treatment of hyperthyroidism
What is the most common cause of hyperthyroidism?
Graves disease
Explain exophthalamous associated with Grave’s disease.Why does this exactly happen?
Grave’s ophthalmopathy = increased volume of retroorbital connective tissue, due to cellular proliferation, inflammation, and the accumulation of glycosaminoglycans.Happens due to auto antibodies associated with Grave’s disease.
Explain radioactive iodine treatment and what potential adverse effect can it lead to?
Radioactive iodine becomes concentrated inside the follicular cells via the Na+/Iodine symporter, it can potentially lead to hypothyroidism
What are the adverse effects of radioactive iodine treatment?In what condition is this therapy contraindicated?
It has a small risk of thyroiditis that causes severe thyroid pain and can exacerbate hyperthyroidism and Grave’s disease, worsening its symptoms (e.g. palpitations, tremors, exophthalmos). Ironically it is contraindicated in patients with exophthalmos due to risk of exacerbation of Grave’s disease
What drugs can be used to avoid exacerbation of Grave’s disease
Thionomides, they deplete iodine stores before being given ablative iodine treatment - that way, when the follicular cells are being destroyed, you won’t get too much T3/T4 leaking out
Give examples of thionomides
Propylthiouracil, Methimazole
Explain propylthiouracil and Methimazole MOA.How do they differ?
Propylthiouracil and Methimazole treat hyperthyroidism by directly inhibiting TPO - prevents the oxidation of iodine into iodide. Methimazole is 10x more potent than PTU but PTU also treats hyperthyroidism by inhibiting 5’ deiodinase -> leading to decreased conversion of T4 into T3.
Explain MOA of beta blockers in treating hyperthyroidism
Antagonizes adrenergic receptors AND inhibits 5’ deiodinase enzyme
Compare and contrast glucocorticoids and beta blockers use in treating Grave’s disease
Glucocorticoids don’t treat sympathetic symptoms but can reduce inflammation associated with Grave’s disease
Explain thyroid storm
Acute exacerbation of all the hypermetabolic and hyperadrenergic symptoms of thyrotoxicosis, presenting as a life-threatening syndrome. Thyroid storm (thyrotoxic crisis) can occur due to chronic untreated hyperthyroidism or can occur due to an acute event such as surgery, trauma, or infection.
Explain treatment of thyroid storm
1) blocking sympathetic effects (beta-blockers) and 2) blocking thyroid hormone synthesis (PTU), and 3) blocking conversion of T4 into T3 (beta-blockers, PTU, glucocorticoids).
How can we use anions to treat hyperthyroidism
Since I- requires a Na+/I- symporter to enter follicular cells, anions can be used as competitive inhibitors of I- transport
Name anions that are used for hyperthyroidism
perchlorate, pertechnetate, and thiocyanate
What are the adverse effects of PTU?
- Hepatoxicity and even liver failure2. Agranulocytosis (irregular bleeding)3. Causes maculopapular pruritic rash4. Aplastic anemia5. Lupus like syndrome6. ANCA associated vasculitisSafe to use in pregnancy!
What are the adverse effects of Methimazole?
agranulocytosis, aplastic anemia, drug induced lupus, teratogenic!
What is the most common cause of hypothyroidism
Hashimoto’s Thyroiditis
Whats the outcome of untreated hypothyroidism?
Untreated hypothyroidism can lead to myxedema coma (progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, death)
Levothyroxine
Synthetic T4