Hyperthyroidism (Primary Thyrotoxicosis)
Elevated free T4 and low TSH indicate primary hyperthyroidism, most commonly from Graves disease, toxic nodular disease, or thyroiditis, requiring differentiation through clinical presentation and TRAb testing, with first-line treatment options including antithyroid drugs (methimazole or propylthiouracil), radioactive iodine ablation, or thyroidectomy. 1
Diagnostic Interpretation
- Low (suppressed) TSH with elevated free T4 confirms overt hyperthyroidism, distinguishing it from subclinical hyperthyroidism where free T4 would be normal 1
- This pattern indicates autonomous thyroid hormone production with appropriate negative feedback suppression of pituitary TSH secretion 2
- Free T3 should also be measured, as some patients have isolated T3 toxicosis with normal free T4 2, 1
Differential Diagnosis Algorithm
Step 1: Measure TRAb (TSH receptor antibodies)
- Positive TRAb confirms Graves disease (most common cause: 2% prevalence in women, 0.5% in men) 1
- Negative TRAb suggests toxic nodular disease or thyroiditis 1
Step 2: If TRAb negative, obtain thyroid scintigraphy
- Increased uptake with focal hot nodules indicates toxic adenoma or toxic multinodular goiter 1
- Diffusely increased uptake without TRAb positivity suggests less common Graves disease variant 1
- Low/absent uptake indicates thyroiditis (subacute, silent, or postpartum) - self-limited, requires only supportive care 1
Critical pitfall: Rarely, central hyperthyroidism from TSH-secreting pituitary adenoma presents with elevated free T4 but non-suppressed (normal or elevated) TSH - this requires pituitary imaging 3
Treatment Options for Overt Hyperthyroidism
Antithyroid Drugs (First-Line Medical Therapy)
Methimazole (preferred in most cases)
- Inhibits thyroid hormone synthesis but does not affect stored hormone 4
- Preferred over propylthiouracil except in first trimester pregnancy and thyroid storm 5
- Does not inactivate circulating thyroid hormones, so clinical improvement takes weeks 4
Propylthiouracil (specific indications)
- Inhibits thyroid hormone synthesis AND blocks peripheral T4 to T3 conversion 5
- Preferred in thyroid storm due to peripheral conversion blockade 5
- Preferred in first trimester pregnancy (methimazole associated with rare fetal abnormalities) 5
- Major risk: hepatotoxicity, particularly in first 6 months - requires monitoring for hepatic dysfunction symptoms 5
- Additional risks include agranulocytosis and vasculitis 5
Radioactive Iodine Ablation
- Definitive treatment option for Graves disease and toxic nodular disease 1
- Results in permanent hypothyroidism requiring lifelong levothyroxine replacement 1
Thyroidectomy
- Surgical option for patients with compressive symptoms, large goiters, or contraindications to other therapies 1
- Consider when thyroid nodules cause dysphagia, orthopnea, or voice changes 1
Treatment for Subclinical Hyperthyroidism
If TSH is low but free T4 is normal (not your scenario, but important distinction):
- Treatment recommended for patients >65 years or with persistent TSH <0.1 mIU/L due to increased risk of osteoporosis and cardiovascular disease 1
- Younger patients without risk factors may be observed 1
Monitoring and Complications
Untreated hyperthyroidism consequences:
- Cardiac arrhythmias (especially atrial fibrillation) and heart failure 1
- Osteoporosis and fracture risk 1
- Adverse pregnancy outcomes 1
- Unintentional weight loss and increased mortality 1
Common symptoms to assess:
- Anxiety, insomnia, palpitations, heat intolerance, diarrhea 1
- Graves-specific: diffuse goiter, stare, exophthalmos 1
- Toxic nodular disease: compressive symptoms (dysphagia, orthopnea, voice changes) 1
Treatment should be individualized based on: