Thyroid disease

What is the minimum amount of iodine required per day?

150 micograms/day

Where is excess iodine excreted?

urine and stool

What is the Wolff-Chaikoff effect?

high iodine levels can inhibit further iodine uptake into the thyroid → transient hypothyroid symptoms

Where is T4 converted to T3?

in the periphery

Which form of iodine makes up the bulk of iodine in the body?

T4 - 90%

What form of iodine is considered active thyroid hormone?

T3 - 9%

What form of iodine is biologically inactive?

rT3 - 1%

What is the T 1/2 of T4?

7 days

What is the T 1/2 of T3?

1 day

Which form of iodine has a greater oral bioavalabity?

T3 - 95% oral absorption

How much T4 is naturally made by the body per day?

75 mcg

How much T3 is naturally made by the body per day?

25 mcg

What is the major function of TH?

• regulate growth & development in fetal & childhood

• regulates metabolism

• regulates energy expenditure

What is the condition called with iodine deficiency during fetal development?

Cretinism- PREVENTABLE

What is iodine deficiency in adults called?

myxedema

can cause coma

What is hyperthyroidism?

Thyroid hormone in excess

What is hypothyroidism?

thyroid hormone deficiency

What is the TSH level with hypothyroidism?

High TSH → continually saying need more TH

What is the TSH level in hyperthyroidism?

Low TSH

What is Hashimoto’s disease?

Hypothyroidism

destructive autoantibodies attack thyroid gland

High TSH- signal need more TH

What is Grave’s disease?

Hyperthyroidism

stimulatory autoantibody stimulate TH

low TSH level bc excess

What are S/S of Grave’s disease?

skin: sweating, heat intolerance, thinning hair

ocular: upper eyelid retraction - BUG EYES

CV: elevated HR, Increased CO, arrhythmias, angina

Respiratory: Hypoventilation

GI: Increased peristaltic contractions

CNS: agitation, nervousness

Muscle: weakness, fatigue

Reproductive: Menstrual irregularities, infertility

Metabolic: Increased BMR, Increased drug metabolism

What is a thyroid storm?

acute exacerbation of hyperthyroidism - LIFE THREATENING

What are S/s of a thyroid storm?

palpitations

HF

hyperthermia

What is the treatment for a thyroid storm?

CV symptoms- non-selective beta blockers (propranolol) if BB CI then use diltiazem

TH production: Potassium iodide or PTU

What is the MOA of PTU in removing excess TH during a thyroid storm?

Sequester excess TH w/ bile acid (via cholestyramine) & fecal excretion or plasmapheresis

What are the 4 classes of drugs used to treat hyperthyroidism?

1. Thioamides

2. Uptake inhibitors

3. Radioactive Iodine

4. Surgical resection

What is the MOA of Thioamides?

Inhibit TPO (thyroid peroxidase enzyme)

inhibits T4 → T3 conversion in periphery

When in practice are thioamides used?

Precursor to surgical removal of thyroid

can normalize TSH levels over time

What are commmon AE of thioamides?

Goiter formation (continual thyroid stimulation via TSH)

Maculo-papular rash

arthralgia

What are the rare but severe AE of thioamides?

agranulocytosis

hepatotoxicity

ANCA-+ vasculitis

pancreatitis

How is hyperthyroidism controlled during pregnancy?

1st trimester- PTU is preferred bc higher plasma binding

2nd/3rd trimester- Methimazole preferred bc PTU can cause hepatotoxicity

What is the MOA of Iodine uptake inhibitors (NIS)?

inhibit sodium-Iodine transporter

When are iodine uptake inhibitors used?

hyperthyroidism via other drug interactions (ex amiodarone has iodine and can increase uptake)

Perchlorate rarely used bc risk of aplastic anemia

What drug class does Perchlorate belong to?

Iodine Uptake inhibitors (NIS)

When is radioactive iodine CI and why?

Pregnant and lactating women

risk of fetal thyroid destruction

What is the only form of radioactive iodine?

Iodine 131

What is the MOA of radioactive iodine?

concentrates in thyroid follicle & destroys cells

(epithelial swelling, necrosis, follicle disruption, edema, leukocyte infiltration)

What is Iodide 127 and what is the MOA?

Lugol’s solution

non-radioactive

inhibits TH synthesis via Wolff-Chaikoff effect

What other medications can inhibit peripheral T4 → T3?

Contrast media: Ipodate & Iohexol

Beta-blockers

Corticosteroids

Tyrosine Kinase Inhibitors

Lithium

How do beta-blockers inhibit peripheral T4 → T3?

TH increases expression of B-AR

Hyperthyroidism resembles non-specific SNS stimulation

How do corticosteroids inhibit peripheral T4 → T3?

inhibits 5’-deiodinase, decreases peripheral T3 production

How do TKIs inhibit peripheral T4 → T3?

Sunitinb

causes hypothyroidism as expected ADR

How does Lithium inhibit peripheral T3 → T4?

inhibits coupling of iodotyrosine to decrease T4 production & release

What are 3 primary causes of hypothyroidism?

Hashimoto’s disease

Iatrogenic hypothyroidism

Less common: iodine deficiency, enzyme defects, thyroid hypoplasia, goitrogens

When it is appropriate to treat hypotyroidism?

ELEVATED TSH

w/ normal or low free T4

Why is T4 preferred for hypothyroidism supplementation?

Longer T 1/2 → allows for less dosing throughout day (7 days) → improves adherence

Predictable PK

What is thyroid USP made of and what is its thyroid ratio?

desiccate pork thyroid gland

High T3:T4 (4:1)

inexpensive

What is levothyroxine made of?

Synthetic T4

What is Liothyronine made of and what is is T 1/2?

Synthetic T3

rapid onset

T 1/2 = 1.5 days

What is Liotrix made of and what is the thyroid ratio?

Synthetic T4 & T3 (4:1)

risk of T2 thyrotoxicosis bc high ratio of T3 to T4