In a 45‑year‑old woman not taking any medication, TSH is <0.01 µIU/mL and free T4 is 4.8 µg/dL; what is the most likely diagnosis and what work‑up and initial management should be pursued?

Overt Hyperthyroidism (Graves' Disease or Toxic Nodular Goiter)

This 45-year-old woman has overt hyperthyroidism with a suppressed TSH <0.01 µIU/mL and markedly elevated free T4 of 4.8 µg/dL (approximately 62 pmol/L, well above the normal range of 9-19 pmol/L). This is not subclinical hyperthyroidism—this is frank thyrotoxicosis requiring urgent evaluation and treatment 1.

Immediate Diagnostic Work-Up

Confirm the diagnosis and establish etiology:

• Measure free T3 (or total T3) to assess the full extent of thyroid hormone excess, as T3 is the more metabolically active hormone and may be disproportionately elevated 2, 3.

• Obtain TSH receptor antibodies (TRAb) to diagnose Graves' disease, the most common cause of overt hyperthyroidism in this age group 1.

• Measure thyroid peroxidase antibodies (anti-TPO) to identify autoimmune thyroid disease, which is present in the majority of Graves' disease cases 4.

• Perform a radioactive iodine uptake (RAIU) scan if the etiology remains unclear after antibody testing—this will distinguish between Graves' disease (diffusely increased uptake), toxic multinodular goiter (patchy uptake), toxic adenoma (single hot nodule), or thyroiditis (low/absent uptake) 5, 6.

• Obtain a thyroid ultrasound if nodules are suspected clinically or if RAIU shows focal uptake, to evaluate nodule characteristics and guide further management 5.

Critical Clinical Assessment

Evaluate for life-threatening complications:

• Assess for thyroid storm by checking for fever >38.5°C, tachycardia >140 bpm, altered mental status, or cardiovascular decompensation—this is a medical emergency requiring immediate hospitalization 1.

• Screen for atrial fibrillation with an ECG, as hyperthyroidism dramatically increases risk, especially with TSH <0.1 mIU/L 1, 5.

• Evaluate for heart failure by assessing for dyspnea, peripheral edema, and elevated jugular venous pressure, as thyrotoxicosis increases cardiac output and can precipitate decompensation 1.

• Check for ophthalmopathy (proptosis, lid lag, diplopia) if Graves' disease is suspected, as this may influence treatment decisions 1.

Immediate Management

Initiate pharmacologic therapy without delay:

• Start methimazole 15-30 mg daily (or propylthiouracil 100-150 mg three times daily if methimazole is contraindicated) to block new thyroid hormone synthesis 1, 5.

• Add a beta-blocker (propranolol 20-40 mg three to four times daily or atenolol 25-50 mg daily) to control tachycardia, tremor, and other adrenergic symptoms while awaiting thyroid hormone normalization 1, 5.

• Consider iodine therapy (saturated solution of potassium iodide, 1-2 drops three times daily) if thyroid storm is suspected, but only after starting methimazole, as iodine given first can paradoxically worsen hyperthyroidism 1.

Monitoring and Follow-Up

Recheck thyroid function tests (TSH, free T4, free T3) in 4-6 weeks after initiating antithyroid drug therapy to assess response 1, 5.

Monitor for antithyroid drug side effects:

• Obtain baseline complete blood count (CBC) and liver function tests before starting methimazole, and repeat if symptoms of agranulocytosis (fever, sore throat) or hepatotoxicity (jaundice, abdominal pain) develop 1.

• Warn the patient to stop methimazole immediately and seek urgent medical attention if fever, sore throat, or mouth sores develop, as agranulocytosis occurs in 0.2-0.5% of patients and can be fatal 1.

Definitive Treatment Planning

Once the patient is biochemically euthyroid (typically 4-8 weeks), discuss definitive therapy:

• Radioactive iodine ablation is the preferred definitive treatment for Graves' disease in non-pregnant adults, with a single dose achieving cure in 80-90% of patients 1, 5.

• Thyroidectomy is an alternative for patients who decline radioactive iodine, have large goiters with compressive symptoms, or have coexisting suspicious thyroid nodules 1.

• Long-term antithyroid drug therapy (12-18 months) can be considered for Graves' disease, but remission rates are only 30-50%, and relapse is common after discontinuation 1.

Critical Pitfalls to Avoid

• Never delay treatment while awaiting RAIU results—start methimazole and beta-blocker immediately based on the biochemical diagnosis of overt hyperthyroidism 1, 5.

• Do not start iodine before methimazole in suspected Graves' disease, as this can worsen thyrotoxicosis by providing substrate for additional hormone synthesis 1.

• Do not assume this is subclinical hyperthyroidism—a free T4 of 4.8 µg/dL is profoundly elevated and indicates overt disease requiring urgent treatment 1, 2.

• Do not miss thyroid storm—fever, tachycardia >140 bpm, altered mental status, or cardiovascular instability require immediate hospitalization and aggressive treatment with high-dose antithyroid drugs, beta-blockers, iodine, corticosteroids, and supportive care 1.

• Do not overlook cardiac complications—obtain an ECG to screen for atrial fibrillation, which occurs in 10-25% of patients with overt hyperthyroidism and requires anticoagulation if present 1, 5.