PharmacologyTier 1Medical Sciences concept

Thyroid drug mechanisms (thionamides vs iodine - synthesis vs release blockade)

Core concept

Thyroid hormone is made slowly and stored in colloid - roughly 2-3 months of hormone sits in the gland
- Any drug blocking synthesis therefore takes weeks to work
Thionamides block synthesis. Iodine blocks release. That is the whole distinction

Thionamides - carbimazole (-> methimazole), propylthiouracil

Inhibit thyroid peroxidase (TPO) -> dec iodide oxidation, dec organification of tyrosine, dec coupling of MIT/DIT
No effect on stored hormone -> clinical response takes 4-6 weeks
PTU additionally inhibits peripheral 5'-deiodinase -> dec T4 to T3 conversion (an acute advantage in storm)

Iodine - Lugol's solution, potassium iodide

High-dose iodide acutely inhibits release of preformed hormone from colloid, and transiently inhibits organification (Wolff-Chaikoff effect)
Acts within hours, but escape occurs at 7-14 days
Must be given at least 1 hour AFTER a thionamide - given first it is substrate for new hormone synthesis

	Carbimazole	Propylthiouracil
Potency	~10-15x	Lower
Dosing	Once daily	2-3x daily
Peripheral T4->T3	No	Yes
Placental transfer	Higher	Lower, highly protein bound
Signature toxicity	Aplasia cutis, choanal atresia (embryopathy)	Fulminant hepatic necrosis, ANCA vasculitis
Use in pregnancy	2nd/3rd trimester	First trimester

Agranulocytosis - both agents, ~0.3%, usually within 90 days, idiosyncratic and not predicted by routine FBC
- Warn every patient: fever or sore throat -> stop the drug and get an urgent FBC
Both cause a mild transient leucopenia, rash, arthralgia, cholestasis
Thyroid storm combination therapy
- PTU loading (blocks synthesis and conversion), then
- Lugol's iodine 1 h later (blocks release), plus
- Propranolol (symptoms, and dec T4->T3 at high dose), plus
- Hydrocortisone (dec conversion, treats relative adrenal insufficiency), plus treat the precipitant
Pre-operative Lugol's for 10-14 days before thyroidectomy - dec gland vascularity and friability
Radioiodine (I-131) - a different mechanism again: beta emission destroying follicular cells; withhold thionamides 3-7 days either side, worsens Graves ophthalmopathy (steroid cover)

Slow response to carbimazole is expected, not failure - do not escalate on a 2-week TSH
- TSH stays suppressed for months - titrate on free T4, not TSH
Amiodarone-induced thyrotoxicosis
- Type 1 (iodine-induced excess synthesis, pre-existing nodular gland) -> thionamide
- Type 2 (destructive thyroiditis) -> prednisolone; low uptake, low vascularity on Doppler
Block-and-replace vs titration - equivalent remission, titration has fewer adverse effects
Iodine is contraindicated before planned radioiodine - saturates the gland and blocks I-131 uptake for weeks
Radiological contrast, amiodarone and kelp are all large iodine loads

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