Thyroid, antithyroid

Question 1

How do iodide (I-) levels affect T4 synthesis?

Answer 1

Low I- promotes synthesis, high I- inhibits

Question 2

T4, T3 biosynthesis: How I- enters colloid space

Answer 2

I- uptaken into follicular cells at basolateral membrane via Na/I symport
I- enters colloid space using Pendrin at apical side in exchange for Cl-

Question 3

What happens after I- enters colloid space (how does complex end up in follicular cell)

Answer 3

Thyroid Peroxidase (TPO) oxidises I- into I2, then iodinises thyroglobulin.
Complex endocytosed into follicular cell by binding to Megalin

Question 4

How is T4 secreted into bloodstream after endocytosis into follicular cell

Answer 4

Proteolysis to cleave into T4 and T3 by thiol endopeptidases
Monocarboxylate transporter (MCT) at basolateral membrane release T3 and T4 into bloodstream

Question 5

T4 half life

Answer 5

6-8 days (depends on extent of protein binding)

Question 6

T3 half life

Answer 6

1 day

Question 7

How are T3 and T4 excreted?

Answer 7

Conjugated with glucuronic acid in the liver, excreted in bile

Question 8

Wolff-Chaikoff effect and its significance

Answer 8

Autoregulatory phenomenon that occurs during iodine exposure. Excess iodine transported to thyroid gland by NA/I symport
Transient inhibition of TPO and thyroid synthesis.
Can be used for hyperthyroidism treatment, administering large doses of iodine to suppress thyroid gland

Question 9

Hypothyroidism treatment: Drugs

Answer 9

Levothyroxine (T4), liothyronine (T3) are synthetic preparations of sodium salts of the natural isomers

Question 10

Main differences between levothyroxine and liothyronine

Answer 10

T4 less active. When given orally, levothyroxine requires 3-5 days onset vs 3h for liothyronine. Levothyroxine requires 3-4 months to reach steady state vs 2 wks for liothyronine. Hence, levo is used for chronic thyroid replacement while lio is used when rapid tx is needed (myxedema coma)

Question 11

Levothyroxine: ADR

Answer 11

Long term use associated with increased bone resorption and reduced bone density especially in post-menopausal women
Need to monitor for persistent TSH elevation if dose is inadequate
Risk of MI, angina in elderly, need to administer small doses

Question 12

Liothyronine: ADR

Answer 12

Easy to OD, risk of cardiac carrythmia and MI

Question 13

Levothyroxine: DDI, food

Answer 13

Taken 30-45min before food on empty stomach. Dose needs to increase with estrogen replacement treatment

Question 14

In what special groups does levothyroxine dose need to be lowered?

Answer 14

Elderly, IDH patients

Question 15

In what special group does levothyroxine dose need to be increased?

Answer 15

Pregnant patients w hypothyroidism

Question 16

Hyperthyroidism: Drugs

Answer 16

Thioamides
High doses of I-
Radioactive iodine

Question 17

Thioamides : Class, names, moa, important adr

Answer 17

Hyperthyroidism (anti-thyroid)
Carbimazole, propylthiouracil
Inhibit TPO, inhibit oxidation and iodination. Propylthiouracil further inhibits deiodination of T4 to T3.
Agranulocytosis - watch out for fever within first 3 months
Mild rash
Cholestatic jaundice

Question 18

Carbimazole vs propylthiouracil main differences

Answer 18

Propylthiouracil should be reserved for those who cannot tolerate thioamides, risk of serious liver injury
1st trimester: propylthiouracil (may induce goitre during organogenesis)
2nd-3rd trimester: carbimazole (avoid hepatotoxicity)

Question 19

Iodide: Class, names, moa, adr, contraindications

Answer 19

Hyperthyroidism drugs
Lugol’s solution, KI
*Wolff-Chaikoff effect, inhibit iodine uptake, coupling and release of T4/T3
Iatrogenic thyrotoxicosis - iodine escape
PREGNANCY, BREASTFEEDING -may cause fetal goiter
Chronic intoxication -metallic taste

Question 20

Why is iodide advantageous for thyroidectomy pre-op?

Answer 20

Reduces thyroid synthesis, thyroid size and vascularity

Question 21

Why is iodide advantageous for post-radioactive iodine therapy?

Answer 21

Used to block uptake of radioactive iodine by thyroid, reducing thyroid cancer risk, avoid thyrotoxic crisis

Question 22

Radioactive iodine: Class, names, moa, adr, DDI, contraindication

Answer 22

Hyperthyroidism drugs
131, 123I
Taken up into follicular cells via Na/I symport, release destructive b-particles, spares surrounding tissue, causing pyknosis and necrosis of gland
Cannot use with thioamides, affects efficacy
High incidence of delayed hypothyroidism
Small chance of stomach, kidney, breast cancer (express Na/I symport)
PREGNANT WOMEN