Thyroid diseases

Question 1

What are the agents available for hypothyroidism?

Answer 1

Levothyroxine
Liothyronine

Question 2

What are the agents available for hyperthyroidism?

Answer 2

Thionamides: Carbimazole, Propylthiouracil (PTU)
Iodides
Non-selective BB

Question 3

Describe the MOA of levothyroxine.

Answer 3

Exogenous, optically active levo isomer of thyroxine (T4)

Question 4

Describe the MOA of liothyronine.

Answer 4

Exogenous suppl of T3

Question 5

Describe the MOA of carbimazole.

Answer 5

Competitively inhib thyroperoxidase –> inhib iodination of TH
Decreased TH synth

Question 6

Describe the MOA of PTU.

Answer 6

Competitively inhib thyroperoxidase –> inhib iodination of TH
Decreased TH synth
Inhib conversion of T4 –> T3 in periphery at high dose

Question 7

Describe the MOA of iodides.

Answer 7

At low doses iodides stim uptake
At high doses inhib TH release
Minimal effect on hormone synth
Decrease vascularity and size of thyroid gland

Question 8

Describe the MOA of non-selective BB.

Answer 8

Blocks beta adrenergic rece –> bradycardia
Blocks conversion of T4 –> T3 at high doses

Question 9

Describe the PK of levothyroxine.

Answer 9

A:
- Good PO F, 70-80%
- Onset: 3-5d (6-8h IV)
- Mainly absorbed in duodenum and jejunum but affected by gastric pH

D:
- t1/2: 7h
- Highly plasma protein bound (>99%)

M:
- Hepatic (glucuronidation and sulfation)
- Renally (deiodinated thyroid hormones)

E:
- Primarily renally cleared
- Metabolites excre in urine and faeces

Question 10

Describe the PK of liothyronine.

Answer 10

t1/2: 1-2.5d

Question 11

Describe the PK of carbimazole.

Answer 11

A:
- Good PO F
- Meta to methimazole in serum upon absorption
- Onset quicker than methimazole

D:
- t1/2 longer than methimazole
- t1/2 (methimazole): 4-6h (effects last whole day as it concentrates in thyroid gland)
- Methimazole does NOT bind to plasma protein (>90% inhib of thyroid organification of iodine within 12h)

M:
- CYP450 and FMO enzymes

E:
- >90% PO admin carbimazole excre as methimazole and its metabolites
- Rest in faeces (enterohepatic circ)

Question 12

What are the S/E of levothyroxine and liothyronine?

Answer 12

Cardiac abonormalities (tachyarrhythmias, MI, angina)
Seizures
Tremors
Anxiety
Insomnia
Decreased mineral bone density –> increased fracture risk
Alopecia
Diarrhoea
Liothyronine > levothyroxine

Question 13

What are the S/E of carbimazole?

Answer 13

Rash, risk of SJS
Agranulocytosis (RARE, early on in thera, usually within first 3mo)
Fever
Joint pains
NV
Congenital malformations

Question 14

What are the S/E of PTU?

Answer 14

Rash, risk of SJS
Agranulocytosis (RARE, early on in thera, usually within first 3mo)
Fever
Joint pains
NV
Hepatotoxicity

Question 15

How do we monitor hypothyroidism?

Answer 15

4-8 weeks after ini or titration

TSH:
- Target 0.4-4.0 mIU/L
- Elderly up to 6.9 mIU/L ( age related increase in TSH, controversial)

FT4 in central hypothyroidism

After euthyroid, Q6mo-1y in non-pregnant adult pt

Question 16

How do we monitor hyperthyroidism?

Answer 16

4-6mo after ini or titration

FT4

T3 may be a better marker of effectiveness in early stages of treatment

TSH may remain suppressed for months after thera begins

Question 17

What is the recommended dosing regimen for levothyroxine?

Answer 17

Ini: 100 mcg once daily
50-60y with no cardiac risk: 50 mcg once daily
W CVD: 12.5-25 mcg once daily

Titration:
Increase or decrease by 12.5-25 mcg daily or 10-15% of total weekly dose

Question 18

What is the recommended dosing regimen for carbimazole?

Answer 18

Ini: 15-60 mg daily in two or three divided doses
Once euthyroid: reduce to 5-15 mg once daily

Question 19

What is the recommended dosing regimen for liothyronine?

Answer 19

Normal: 25 mcg
Elderly and CVD: 5 mcg

Question 20

When is non-selective BB indicated?

Answer 20

Symptomatic relief of hyperthyroidism
Bridging therapy
- Waiting for surgery, ablation
- Waiting for effects of thionamides
Treatment of thyroiditis
PRN for high risk pts e.g. elderly w CVD

Question 21

When is carbimazole indicated?

Answer 21

Hyperthyroidism, preferred for Graves

2nd-3rd trimester of pregnancy
(Avoid in 1st trimester)

Question 22

What are the pregnancy considerations for thionamides?

Answer 22

Carbimazole
1st trimester: CI
2nd-3rd trimester: > PTU

PTU
1st trimester: > carbimazole
2nd-3rd trimester: CI

Question 23

When are iodides indicated?

Answer 23

Before surgery (7-10d): to shrink thyroid gland
After ablative thera (3-7d): to inhib thyroiditis mediated release of stored TH
Thyroid storm

Question 24

When is liothyronine indicated?

Answer 24

When T4 and T3 combi considered (TSH normalised but still symptomatic for hypothyroidism)
Myxedema coma (more potent)

Question 25

What are the special counselling points for thionamides?

Answer 25

Slow onset, maximal effect may take 4-6mo
No effect on existing thyroid hormone stores –> wait for them to deplete

May not req lifelong treatment after resetting thyroid
- Remission rate low: 20-30%
- Remission = Normal TSH & T4 for 1y after discontinuing antithyroid - feedback loop normal

Question 26

What are the special counselling points for levothyroxine?

Answer 26

Take 30-60min before breakfast or 4h after dinner or other medications
Pay special attention to polyvalent ions: space at least 2h apart (otherwised decreased absorption). Dietary fibre can also cause erratic absorption.

Takes 2-3 weeks for symptomatic relief (-ve feedback)
Takes time for FT4 to normalise (-ve feedback)