Overt Hyperthyroidism: Diagnosis and Treatment
Diagnosis
With a TSH of 0.01 mIU/L and free T4 of 1.53 (assuming ng/dL, which equals approximately 19.7 pmol/L), this patient has overt hyperthyroidism requiring immediate evaluation and treatment. 1
The combination of suppressed TSH (<0.1 mIU/L) with elevated free T4 definitively establishes overt hyperthyroidism, not subclinical disease. 1, 2 When TSH is undetectable (<0.04 mIU/L), thyrotoxicosis is present in 97% of cases. 3
Critical Next Steps for Diagnosis
Confirm the diagnosis by repeating TSH with free T4 and free T3 (or total T3) within 4 weeks, as assay interference can rarely cause falsely low TSH readings. 4, 5
Obtain radioactive iodine uptake and scan immediately to distinguish between Graves' disease (diffusely increased uptake), toxic multinodular goiter (patchy uptake), toxic adenoma (single hot nodule), or destructive thyroiditis (low/absent uptake). 4, 6
Measure TSH receptor antibodies (TRAb) if Graves' disease is suspected, as positive antibodies confirm the diagnosis and guide treatment duration. 4
Obtain an ECG to screen for atrial fibrillation, which occurs 3-5 fold more frequently with TSH suppression, especially in patients over 60 years. 7, 4
Treatment Based on Etiology
If Graves' Disease or Toxic Nodular Goiter (High Uptake on Scan)
Initiate antithyroid medication immediately while arranging definitive therapy. 4, 2
Medication Selection
Methimazole is preferred for most patients at 10-30 mg daily in divided doses, as it has once or twice daily dosing and lower hepatotoxicity risk compared to propylthiouracil. 8
Propylthiouracil (PTU) 50-150 mg three times daily is reserved for: first trimester pregnancy (due to methimazole's association with rare fetal abnormalities), thyroid storm, or methimazole allergy. 9, 8
Switch from PTU to methimazole after the first trimester in pregnant patients, as PTU carries significant maternal hepatotoxicity risk. 9, 8
Critical Monitoring Requirements
Obtain baseline complete blood count and liver function tests before starting antithyroid drugs. 9, 8
Instruct patients to immediately report sore throat, fever, rash, or jaundice, as agranulocytosis (potentially fatal) and hepatotoxicity can occur. 9, 8
Check thyroid function tests every 4-6 weeks initially, then every 6-12 months once stable, adjusting medication to maintain normal free T4 while TSH remains suppressed initially. 4
Monitor prothrombin time before surgical procedures, as antithyroid drugs may enhance anticoagulant effects. 9, 8
Definitive Treatment Options
Radioactive iodine (RAI) therapy is commonly used for definitive treatment but may cause hypothyroidism requiring lifelong levothyroxine and can temporarily worsen Graves' eye disease. 4
Thyroidectomy is an alternative for patients who refuse RAI, have large goiters causing compressive symptoms, or have contraindications to medical therapy. 4
A 6-12 month trial of antithyroid medication may induce remission in Graves' disease, though relapse rates are high (50-60%). 2
If Destructive Thyroiditis (Low Uptake on Scan)
Beta-blockers (propranolol 20-40 mg three times daily or atenolol 25-50 mg daily) provide symptomatic relief for palpitations, tremor, and anxiety. 4
Avoid antithyroid medications, as they are ineffective when the thyroid is not actively producing hormone. 4
Recheck thyroid function in 4-6 weeks, as destructive thyroiditis typically resolves spontaneously, though transient hypothyroidism may follow. 7
If Exogenous (Levothyroxine-Induced)
Reduce levothyroxine dose by 25-50 mcg immediately if TSH <0.1 mIU/L with elevated free T4 in a patient taking thyroid hormone replacement. 7, 4
Review the indication for thyroid hormone therapy, as approximately 25% of patients on levothyroxine are unintentionally overtreated. 7
Consult endocrinology if the patient has thyroid cancer, as TSH suppression may be intentional with target levels varying by risk stratification. 7, 4
Cardiovascular and Bone Health Risks Requiring Urgent Attention
Atrial fibrillation risk increases 3-5 fold with TSH <0.1 mIU/L, particularly in patients over 60 years, necessitating cardiac monitoring. 7, 4
Bone mineral density loss accelerates in postmenopausal women with prolonged TSH suppression, increasing fracture risk. 7, 4
Cardiovascular mortality increases up to 3-fold in individuals over 60 with TSH below 0.5 mIU/L. 7
Common Pitfalls to Avoid
Never assume hyperthyroidism based on a single TSH value—confirm with repeat testing and free T4/T3, as assay interference rarely causes false results. 4, 5
Do not delay radioactive iodine uptake scan, as distinguishing between high-uptake (requiring antithyroid drugs) and low-uptake (requiring only symptomatic treatment) conditions fundamentally changes management. 4, 6
Avoid propylthiouracil as first-line therapy except in first trimester pregnancy or specific contraindications, due to severe hepatotoxicity risk. 9, 8
Do not overlook cardiac evaluation, as elderly patients with overt hyperthyroidism have substantially elevated atrial fibrillation and heart failure risks. 7, 4