Thyroid - Antithyroid

Question 1

What are the steps in thyroid hormone biosynthesis, secretion, and transport?

Answer 1

Iodide uptake into gland by NIS transporter - Thyroglobin molecule iodination - makes MIT and DIT - rearrangement of these makes the actual molecule - t3 t4
molecule is phagocytized into cell - most in t4 form/bound - secreted.

Question 2

What is the cellular mechanism by which thyroid hormone mediates its effects?

Answer 2

In Absence of Thyroid hormone: T3 receptor has ligand binding domain and DNA binding domain. LBD and DBD, bound to corepressors

In Presence of Thyroid hormone: Hormone transported into cell, T3 binds to T3 Receptor in nucleus while T4 needs to be coverted to T3. Co repressor and TR monomer dissociates and increases gene transcription.

Question 3

What are the activators and inhibitors that regulate the Hypothalamic/Pituitary/Thyroid axis?

Answer 3

Activators: TRH, TSH, Low Iodine levels, in some diseases high iodine

Inhibitors: T3, T4, High Iodine level,

Question 4

What are the key physiologic effects of thyroid hormone?

Answer 4

Sympathetic NS: increase Beta, Dec alpha
Growth/Develop: Neurogenesis, bone maturation
Thermogenic: heat production
Respiratory: inc O2 consumption
CNS: reasoning, muscle tone
GI: inc secretions
Skin and Hair: growth
Cardiovascular: Inc heart rate, contraction, decreased vasc resistance, inc volume
Metabolic: Fat down, Carb absorp up, Prot synth up, Vit need up, overall increase

Question 5

What is the impact of
Hyperthyroidism?
Hypothyroidism?

Answer 5

Hyperthyroidism:
Could be Graves disease
Thyroid adenoma/carcinoma
Autoimmune thyroiditis (initial hashimoto)
Thyroid storm
Excess iodide (more likely with underlying thyroid disease)
OR secondarily Dysfunction of hypothalamus/pituitary

Hypothyroidism:
Could be Congenital (cretinism), Autoimmune (Hashimotos), Iodine deficiency, or sx, radiation, meds.
OR secondarily - Impaired TSH production from head trauma, tumor, infection.
Causes Slow heart, wt gain, constipation

Question 6

Levothyroxine (T4)

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 6

Use: Hypothyroidism, DRUG OF CHOICE
Target: conversion then T3 Receptors
MOA: Converted then activates T3 R
Pharmacokinetics: 80% absorption, half life of 7 days, small potency
Interactions: Dont give if CORONARY ARTERY DISEASE

Question 7

Liothyronine (T3)
Liotrix ( T3 and T4)

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 7

Use: Hypothyroidism
Target: T3 Receptors
MOA: Activates T3 receptors
Pharmacokinetics: 95% absorption, much more potent than Levothyroxine
Interactions: Dont give if CORONARY ARTERY DISEASE

Question 8

Methimazole
Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 8

Use: Hyperthyroidism, #1 NORMALLY
Target:
MOA: Inhibit peroxidase rxn, iodination and coupling to tyrosines - Inhibit the first steps of biosynthesis
Pharmacokinetics: Much MORE POTENT than PTU
Drug - Nutrient/Drug Interactions: Rash, altered TASTE AND SMELL

Question 9

Propylthiouracil
Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 9

Use: Hyperthyroidism (preferred one in FIRST TRIMESTER b/c it binds with PLASMA PROTEINS, also Preferred for THYROID STORM b/c absorbed faster)
Target:
MOA: Inhibit peroxidase rxn, iodination and coupling to tyrosines - inhibit first steps of biosynthesis
Pharmacokinetics:
Drug - Nutrient/Drug Interactions: severe HEPATITIS

Question 10

Potassium Iodide
Lugol’s Solution

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 10

Use: Hyperthyroidism, THYROID STORM bc fast onset
Target:
MOA: Inhibit Proteolysis of Tgb (increasing Iodide stores in gland), at high dose can also inhibit organification
Pharmacokinetics: Used in combo bc will only inhibit for 2-8 weeks - withdrawal produces thyrotoxicosis
Drug - Nutrient/Drug Interactions: good pre surgery if hyperplastic thyroid
Fetal goiter if pregnant

Question 11

Radioactive Iodide

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 11

Use: Hyperthyroidism
Target:
MOA: Beta gamma emitter, Beta destroys tissue, ablate gland with this. dont want to fully destroy the gland. if over ablate, have hypothyroidism,
Pharmacokinetics: takes 2-3 months
Drug - Nutrient/Drug Interactions: induce thyroid storm by ablating tissue, concern if development of other cancers, crosses placenta
After treatement: give Beta blockers and Iodide

Question 12

Perchlorate
Pertechnetate
Thiocyanate

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 12

Use: Iodide-Induced Hyperthyroidism 
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions: example is iodine containing AMIODARONE. could produce hyper or hypo thyroidism.  can use this for amiodarone induced hyperthyroidism. 
Perchlorate can cause APLASTIC ANEMIA

Question 13

Propranolol

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 13

Use: Hyperthyroidsm adjunct KEY DRUG
Target:
MOA: inhibits conversion of T4 to T3. 
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Question 14

Diltiazem

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 14

Use: Hyperthyroid adjunct
Target:
MOA: control tachycardia in asthmatic
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Question 15

Barbiturates

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 15

Use: Hyperthyroid adjunct
Target:
MOA: Increased T4 metabolism
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Question 16

Bile Acid Sequestrants

Use:
Target:
MOA:
Pharmacokinetics:
Drug - Nutrient/Drug Interactions:

Answer 16

Use: Hyperthyroidism adjunct
Target:
MOA: Inc biliary T4 excretion
Pharmacokinetics:
Drug - Nutrient/Drug Interactions: