What is the appropriate management for an adult with overt hyperthyroidism (thyroid‑stimulating hormone <0.01 µIU/mL, free thyroxine ≈1.5 ng/dL)?

Overt Hyperthyroidism Requires Immediate Antithyroid Treatment

With a TSH <0.01 µIU/mL and free T4 of 1.53 ng/dL (elevated), you have overt hyperthyroidism that requires prompt treatment to prevent serious cardiovascular, bone, and metabolic complications.

Immediate Management Approach

First-Line Treatment Options

You must choose one of three definitive therapies 1, 2:

• Antithyroid drugs (methimazole or propylthiouracil) – typically first-line for 12-18 months
• Radioactive iodine ablation – definitive therapy, especially for toxic nodular disease
• Thyroidectomy – surgical option for large goitres, compressive symptoms, or patient preference

Methimazole is the preferred antithyroid drug in most cases due to once-daily dosing and lower hepatotoxicity risk compared to propylthiouracil 3, 1, 2.

Determining the Underlying Cause

Before selecting treatment, establish the etiology 1, 2:

• Measure TSH-receptor antibodies (TRAb) – positive in Graves disease (most common cause: 2% of women, 0.5% of men globally) 1
• Perform thyroid scintigraphy if nodules are palpable or etiology unclear – diffuse uptake suggests Graves disease, focal uptake indicates toxic nodular goitre, low/absent uptake suggests thyroiditis 1, 2
• Clinical examination – look for diffuse goitre, exophthalmos, or pretibial myxedema (Graves disease) versus solitary/multiple nodules (toxic nodular goitre) 1

Critical Safety Monitoring with Methimazole

If starting methimazole, patients require close surveillance 3:

• Obtain baseline complete blood count and liver function tests before initiation
• Instruct patients to report immediately: sore throat, fever, rash, jaundice, or general malaise – these may signal agranulocytosis (rare but life-threatening) 3
• Check CBC with differential if any signs of infection develop 3
• Monitor prothrombin time, especially before surgical procedures, as methimazole may cause hypoprothrombinemia 3
• Warn about vasculitis risk – patients should report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 3

Monitoring Thyroid Function During Treatment

• Recheck TSH, free T4, and total T3 every 4-6 weeks during initial treatment phase 3, 2
• Once TSH begins to rise, reduce methimazole dose to prevent iatrogenic hypothyroidism 3
• Target euthyroid state: TSH 0.5-4.5 mIU/L, normal free T4 4

Why Treatment Cannot Be Delayed

Untreated overt hyperthyroidism causes 1, 2:

• Cardiac complications – atrial fibrillation (3-5 fold increased risk), heart failure, increased cardiovascular mortality 1, 5
• Bone loss – accelerated osteoporosis and fracture risk, especially in postmenopausal women 1, 5
• Metabolic effects – unintentional weight loss, muscle wasting, increased mortality 1
• Pregnancy risks – if applicable: spontaneous abortion, preterm birth, stillbirth, fetal hyperthyroidism 3

Special Considerations

If Graves Disease is Confirmed

• 12-18 month course of methimazole is first-line 2
• Long-term antithyroid drug therapy is an acceptable alternative if remission is not achieved 2
• Radioactive iodine or surgery are preferred if large goitre, compressive symptoms, or patient preference 2

If Toxic Nodular Goitre is Confirmed

• Radioactive iodine or surgery are preferred over antithyroid drugs for definitive cure 2
• Long-term methimazole is an option if radioactive iodine/surgery are contraindicated 2

If Thyroiditis is the Cause

• Thyrotoxicosis from thyroiditis may be observed or treated symptomatically (beta-blockers for palpitations/tremor) 1
• Glucocorticoids may be needed for painful subacute thyroiditis 2
• Antithyroid drugs are NOT effective because thyroiditis does not involve increased thyroid hormone synthesis 2

Common Pitfalls to Avoid

• Do not delay treatment while awaiting antibody or scintigraphy results – start methimazole empirically if overt hyperthyroidism is confirmed and the patient is symptomatic 1, 2
• Do not miss agranulocytosis – approximately 0.3% of patients on methimazole develop this complication, which can be fatal if unrecognized 3
• Do not use methimazole in first trimester of pregnancy – switch to propylthiouracil due to teratogenicity risk (though methimazole is preferred in second/third trimesters) 3
• Do not assume falsely low TSH – while rare TSH variants can cause falsely undetectable TSH in certain assays, elevated free T4 confirms true hyperthyroidism 6
• Adjust doses of other medications – beta-blockers, digoxin, and theophylline may require dose reduction as the patient becomes euthyroid due to altered drug clearance 3