STEPTRACKERPHARMACOLOGY + ENDOCRINOLOGY | ENDOCRINE | HIGH-YIELD REVIEW

Thyroid Drugs

Replace thyroid hormone when it's missing; when there's too much, block its synthesis, release, peripheral effects or the gland itself.

FOCUS ON
Levothyroxine (T4): hypothyroidism; monitor TSH (6 weeks after a change); overdose → AF, osteoporosis; absorption ↓ by iron, calcium, PPIs, bile resins; dose ↑ in pregnancy (↑ TBG). Liothyronine (T3): myxedema coma adjunct. Thionamides — methimazole and propylthiouracil: inhibit thyroid peroxidase (oxidation, organification, coupling); PTU also blocks peripheral 5′-deiodinase (T4 → T3). Adverse: agranulocytosis (fever, sore throat → stop, check ANC), rash, ANCA vasculitis; PTU hepatotoxicity; methimazole first-trimester teratogen (aplasia cutis). PTU in first trimester and thyroid storm. Radioactive iodine: Graves, toxic nodule; contraindicated in pregnancy; may worsen ophthalmopathy. Iodide (SSKI, Lugol): Wolff-Chaikoff — preoperative and storm (after thionamide). β-blockers (propranolol): symptoms. Thyroid storm: β-blocker + PTU + iodide (1 h later) + steroids.
DRUG
MECHANISM
USE
ADVERSE · NOTES
Levothyroxine (T4)
Synthetic T4, converted to T3 peripherally
Hypothyroidism, TSH suppression after thyroid cancer
Over-replacement: AF, bone loss, anxiety; take on empty stomach
Liothyronine (T3)
Active hormone, short half-life
Myxedema coma (with T4), thyroid cancer imaging prep
Arrhythmias, angina
Methimazole
Blocks thyroid peroxidase
Graves disease (first-line), toxic nodules
Agranulocytosis, cholestatic hepatitis, aplasia cutis (1st trimester)
Propylthiouracil
Blocks peroxidase + 5′-deiodinase
1st-trimester pregnancy, thyroid storm
Fulminant hepatitis, agranulocytosis, ANCA vasculitis
Radioactive iodine (¹³¹I)
Concentrated by NIS → destroys follicular cells
Graves, toxic multinodular goiter, thyroid cancer ablation
Hypothyroidism (expected), worsens Graves eye disease; contraindicated in pregnancy/lactation
Potassium iodide · Lugol solution
High iodide → ↓ organification and release (Wolff-Chaikoff)
Thyroid storm, before thyroidectomy (↓ vascularity), radiation emergency
Give ≥ 1 h after thionamide (else fuels synthesis)
Propranolol
β block + ↓ T4 → T3
Symptoms of thyrotoxicosis, storm
Use atenolol/metoprolol if asthma concern
Glucocorticoids
↓ T4 → T3, treat relative adrenal insufficiency
Thyroid storm, Graves ophthalmopathy, subacute thyroiditis
—
Teprotumumab
IGF-1 receptor antibody
Thyroid eye disease
Hearing loss, hyperglycemia
Drugs that cause hypothyroidism
Lithium, amiodarone, interferon-α, immune checkpoint inhibitors, tyrosine kinase inhibitors
—
Check TSH
Drugs that raise T4 binding
Estrogens, pregnancy, tamoxifen → ↑ TBG
Total T4 ↑, free T4 normal
Hypothyroid patients need more levothyroxine

Mechanism — where antithyroid drugs act

Iodide uptake (NIS)Perchlorate, ¹³¹I enters here
→
Peroxidase: oxidation, organification, couplingMethimazole, PTU
→
Release of T4/T3Iodide blocks
→
T4 → T3 in tissuesPTU, propranolol, steroids

Choosing the antithyroid drug

SITUATION
DRUG
REASON
Most Graves
Methimazole
Once daily, safer liver
1st trimester
PTU
Methimazole teratogenic
2nd–3rd trimester
Methimazole
Avoid PTU liver risk
Thyroid storm
PTU
Also blocks T4 → T3

How it's tested

COMMON CONFUSIONThionamides don't affect stored hormone — symptoms take weeks to settle, so β-blockers bridge the gap.
THE TRAPFever and sore throat on methimazole → stop the drug and check a neutrophil count (agranulocytosis), don't just treat as pharyngitis.
YOUR APPROACHHypo → levothyroxine, follow TSH. Hyper → symptoms (β-blocker) + synthesis (thionamide) ± definitive (RAI or surgery).

If you see… think…

Fever, sore throat on Graves therapy → agranulocytosis
Liver failure on an antithyroid drug → PTU
Scalp defect in newborn, mother treated for Graves → methimazole (aplasia cutis)
Antithyroid drug that blocks peripheral conversion → PTU
Pre-thyroidectomy to shrink vascularity → potassium iodide
Graves eye disease worsening after treatment → radioactive iodine
AF and osteoporosis in a hypothyroid patient → levothyroxine overdose
Higher levothyroxine need in pregnancy or on OCPs → ↑ TBG
Hypothyroidism and nephrogenic DI → lithium
Thyroid storm regimen → propranolol, PTU, iodide, steroids