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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Hyperthyroidism = suppressed TSH with elevated free T4 and/or T3
- Graves disease: diffuse goiter, ophthalmopathy, pretibial myxedema, positive TSH receptor antibodies
- Radioactive iodine uptake differentiates high-uptake Graves/toxic nodules from low-uptake thyroiditis or exogenous hormone
- Symptom control: beta-blocker; definitive/antithyroid therapy: methimazole, radioactive iodine, or surgery
- PTU is preferred in first trimester pregnancy and thyroid storm; methimazole is otherwise preferred
Overview
Hyperthyroidism is a state of excessive thyroid hormone production or exposure. Thyrotoxicosis refers to the clinical syndrome of excess thyroid hormone from any cause, including destructive thyroiditis or exogenous thyroid hormone. Graves disease is the most common cause in the United States and is mediated by TSH receptor-stimulating antibodies. Toxic multinodular goiter and toxic adenoma cause autonomous hormone production, while thyroiditis causes release of preformed hormone and typically has low radioactive iodine uptake.
Epidemiology
Hyperthyroidism is more common in women and often presents between ages 20 and 50 for Graves disease, while toxic multinodular goiter is more common in older adults. Triggers include iodine exposure, amiodarone, postpartum immune shifts, and autoimmune predisposition. Graves ophthalmopathy is worsened by smoking and may worsen after radioactive iodine therapy without glucocorticoid prophylaxis in high-risk patients.
Clinical Features
Symptoms
Weight loss despite increased appetite, heat intolerance, sweating
Palpitations, anxiety, insomnia, tremor
Frequent bowel movements or diarrhea
Oligomenorrhea, infertility, decreased libido
Eye discomfort, diplopia, photophobia in Graves ophthalmopathy
Chest pain, dyspnea, or syncope from arrhythmia or high-output heart failure
Signs
Tachycardia, widened pulse pressure, systolic hypertension
Fine tremor, hyperreflexia, warm moist skin
Diffuse goiter with bruit in Graves disease
Lid lag, stare, proptosis, ophthalmoplegia in Graves disease
Pretibial myxedema and thyroid acropachy
Atrial fibrillation, especially in older adults
Investigations
First-line
TSHBest initial test; suppressed in primary hyperthyroidism
Free T4 and total/free T3Confirm severity. T3 toxicosis may show high T3 with normal free T4
TSH receptor antibodies / thyroid-stimulating immunoglobulinSupports Graves disease, especially when radioactive iodine uptake is contraindicated
Second-line
Radioactive iodine uptake and scanHigh diffuse uptake = Graves; focal hot nodule = toxic adenoma; patchy uptake = toxic multinodular goiter; low uptake = thyroiditis or exogenous hormone
CBC and liver enzymesBaseline before antithyroid drugs because agranulocytosis and hepatotoxicity are rare but serious adverse effects
ECGAssess atrial fibrillation, tachyarrhythmia, or ischemia
Specialist
Thyroid ultrasoundUseful for nodular goiter, suspicious nodules, or when scan is contraindicated
Ophthalmology evaluationModerate-severe Graves ophthalmopathy, diplopia, corneal exposure, or optic neuropathy
1
Symptom control
- Beta-blocker for adrenergic symptoms: propranolol, atenolol, or metoprolol
- Propranolol at higher doses modestly reduces peripheral T4-to-T3 conversion
2
Antithyroid drugs
- Methimazole is preferred for most nonpregnant patients because it is effective and less hepatotoxic than PTU
- PTU is preferred in first trimester pregnancy and thyroid storm
- Warn about fever/sore throat: stop medication and check CBC urgently for agranulocytosis
- Monitor free T4/T3 initially because TSH may remain suppressed for months
3
Definitive therapy
- Radioactive iodine ablation is common for Graves and toxic nodular disease but avoid in pregnancy and breastfeeding
- Thyroidectomy is preferred for large goiter with compressive symptoms, suspicious nodule/cancer, pregnancy intolerance to medications, or severe ophthalmopathy where RAI is undesirable
- Pretreat severe hyperthyroidism with antithyroid drugs and beta-blocker before surgery
4
Special situations
- Pregnancy: PTU in first trimester, often switch to methimazole after first trimester; avoid radioactive iodine
- Graves ophthalmopathy: stop smoking; consider glucocorticoids if RAI is used in active eye disease
Complications
- Atrial fibrillation and embolic stroke: Common in older adults with thyrotoxicosis
- High-output heart failure: Persistent tachycardia and reduced systemic vascular resistance increase cardiac workload
- Osteoporosis: Excess thyroid hormone accelerates bone turnover
- Thyroid storm: Life-threatening decompensated thyrotoxicosis
- Antithyroid drug toxicity: Agranulocytosis, rash, cholestasis with methimazole, severe hepatotoxicity with PTU
USMLE Step 2 CK Exam Tips
- 1Low TSH is the first clue; then check free T4 and T3
- 2Graves has findings outside the thyroid: ophthalmopathy and pretibial myxedema
- 3Low radioactive iodine uptake in a thyrotoxic patient = thyroiditis or exogenous thyroid hormone, not Graves
- 4PTU in first trimester and thyroid storm; methimazole otherwise
- 5Methimazole adverse effect stem: fever + sore throat = agranulocytosis; stop drug and check CBC
- 6Exogenous thyroid hormone: low thyroglobulin and low uptake
- 7Toxic adenoma is a hot nodule; hot nodules are rarely malignant
- 8Older patient with new atrial fibrillation and weight loss = check TSH
practicetest your knowledge on hyperthyroidism & graves diseaseApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — endocrine and beyond.
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