What is the diagnosis if Thyroid Stimulating Hormone (TSH) is low and Thyroxine (T4) is high?

Diagnosis: Primary Hyperthyroidism (Overt Thyrotoxicosis)

Low TSH with high T4 indicates primary hyperthyroidism—the thyroid gland is producing excessive thyroid hormone, which suppresses pituitary TSH secretion through negative feedback. 1

Diagnostic Interpretation

• TSH suppression with elevated T4 is the hallmark of hyperthyroidism, representing autonomous or excessive thyroid hormone production that inhibits anterior pituitary TSH secretion 1
• The combination of suppressed TSH (<0.1 mIU/L typically) with elevated free T4 confirms overt hyperthyroidism rather than subclinical disease 2
• This pattern indicates the thyroid gland is overproducing thyroid hormone independent of normal regulatory mechanisms 1

Essential Next Steps for Diagnosis

Measure free T3 levels immediately, as approximately 5% of hyperthyroid patients have isolated T3 elevation (T3 thyrotoxicosis) with normal T4, though your patient already has elevated T4 1, 3

• Check TSH receptor antibodies (TRAb) to diagnose Graves' disease, the most common cause of primary hyperthyroidism 2
• Obtain thyroid peroxidase antibodies (anti-TPO) to identify autoimmune etiology 2
• Consider radioactive iodine uptake scan if the etiology remains unclear after antibody testing—high uptake indicates Graves' disease or toxic nodular disease, while low uptake suggests thyroiditis 2

Common Causes to Consider

• Graves' disease (most common)—diffuse autoimmune hyperthyroidism with elevated TRAb 3
• Toxic multinodular goiter or toxic adenoma—autonomous thyroid nodules producing excess hormone 2
• Subacute thyroiditis (painful) or silent thyroiditis (painless)—transient hyperthyroidism from thyroid inflammation with low radioiodine uptake 2
• Iatrogenic hyperthyroidism—excessive levothyroxine dosing in patients on thyroid replacement 2
• Iodine-induced hyperthyroidism—recent exposure to iodinated contrast or amiodarone 2

Critical Clinical Assessment

• Evaluate for hyperthyroid symptoms: tachycardia, tremor, heat intolerance, weight loss, anxiety, palpitations, diarrhea 2
• Obtain ECG immediately to screen for atrial fibrillation, which occurs in 10-25% of hyperthyroid patients and carries significant stroke risk 2
• Assess for thyroid storm risk factors in severely symptomatic patients: fever, altered mental status, cardiovascular instability requiring urgent treatment 2

Important Diagnostic Pitfalls

• Do not assume the diagnosis without measuring free T3—some patients have isolated T3 toxicosis with normal T4, and you would miss the diagnosis 1, 3
• Never delay treatment in symptomatic patients while awaiting antibody results—start beta-blockers immediately for symptom control (propranolol 20-40 mg every 6 hours) 2
• Rule out medication-induced causes by reviewing all medications, particularly levothyroxine, amiodarone, and recent iodinated contrast exposure 2
• Distinguish between Graves' disease and thyroiditis before starting antithyroid drugs—thyroiditis is self-limited and does not require methimazole or propylthiouracil 2

Physiological Mechanism

The elevated T4 directly suppresses TSH secretion through negative feedback at the pituitary level, with TSH responding in a logarithmically amplified manner to even minor T4 elevations 4, 5. This explains why TSH becomes undetectable while T4 may be only moderately elevated 5.