What are the recommended initial evaluation and treatment steps for an adult with overt hyperthyroidism and a suppressed thyroid‑stimulating hormone (TSH)?

Evaluation and Management of Hyperthyroidism with Suppressed TSH

Initial Diagnostic Confirmation

Measure free T4 and free T3 immediately to distinguish overt hyperthyroidism (elevated hormones) from subclinical hyperthyroidism (normal hormones), as this fundamentally determines treatment urgency and approach. 1, 2

• A suppressed TSH (<0.1 mIU/L) with elevated free T4 and/or T3 confirms overt hyperthyroidism requiring prompt treatment 1
• A suppressed TSH with normal free T4 and T3 indicates subclinical hyperthyroidism, which may warrant observation or treatment based on age and comorbidities 1
• TSH measurement has approximately 98% sensitivity and 92% specificity for detecting thyroid dysfunction 3

Determine the Underlying Etiology

Establish whether hyperthyroidism is from autonomous thyroid function (Graves' disease, toxic nodules) versus transient thyroiditis, as this dictates definitive treatment strategy. 4, 2

Clinical Assessment

• Graves' disease presents with diffuse goiter, ophthalmopathy (stare, exophthalmos), and systemic symptoms (anxiety, palpitations, weight loss, heat intolerance) 1, 2
• Toxic nodular disease may cause local compressive symptoms (dysphagia, orthopnea, voice changes) and typically occurs in older patients 1
• Thyroiditis often presents with painful thyroid gland and is self-limited, with hyperthyroidism resolving within weeks 4

Laboratory Evaluation

• Measure TSH receptor antibodies if clinical features suggest Graves' disease 4, 2
• Positive TSH receptor antibodies confirm Graves' disease 2
• Obtain thyroid ultrasound to evaluate for nodular disease versus diffuse enlargement 4
• Order thyroid scintigraphy if nodules are present or etiology remains unclear after initial workup 1, 2

Critical Pitfall

• Exclude central hyperthyroidism (TSH-secreting pituitary adenoma or pituitary resistance to thyroid hormone) if TSH is inappropriately normal or elevated despite elevated free T4 and T3, as this requires entirely different management 5
• Low TSH with low free T4 suggests central hypothyroidism from hypophysitis, not hyperthyroidism 4

Immediate Symptomatic Management

Initiate beta-blocker therapy immediately for all symptomatic patients regardless of severity, as this provides rapid relief of adrenergic symptoms while definitive treatment takes effect. 4, 2

• Start propranolol or atenolol as first-line agents 4
• Beta-blockers reduce peripheral conversion of T4 to T3 and block adrenergic symptoms (palpitations, tremor, anxiety) 4
• Adjust dosage based on heart rate and blood pressure response 4
• Continue beta-blockers throughout the treatment course until euthyroidism is achieved 2

Treatment Algorithm Based on Etiology and Severity

For Overt Hyperthyroidism from Graves' Disease

First-line treatment is a 12–18 month course of antithyroid drugs (methimazole or propylthiouracil), with radioactive iodine or thyroidectomy reserved for treatment failures or patient preference. 2

• Antithyroid drugs achieve remission in approximately 50% of patients after 12–18 months 2
• Long-term antithyroid drug therapy is an acceptable alternative for patients who prefer to avoid radioactive iodine or surgery 2
• Radioactive iodine ablation is preferred for patients with large goiters or those who fail antithyroid drug therapy 2
• Thyroidectomy is indicated for compressive symptoms, suspected malignancy, or patient preference 2

For Toxic Nodular Goiter

Radioactive iodine or surgery are preferred first-line treatments, as toxic nodules rarely remit spontaneously and antithyroid drugs provide only temporary control. 2

• Antithyroid drugs may be used for preoperative preparation or in patients who are poor surgical candidates 2
• Long-term antithyroid drug therapy is an option for patients who decline or cannot undergo definitive treatment 2

For Thyroiditis

Observe with symptomatic treatment only, as thyroiditis is self-limited with hyperthyroidism typically resolving within weeks. 4, 2

• Use beta-blockers for symptomatic relief 4
• Painful thyroiditis may benefit from prednisolone 0.5 mg/kg with tapering 4
• Glucocorticoid therapy is reserved for severe inflammation 4, 2
• Monitor thyroid function every 2–3 weeks to detect transition to hypothyroidism 4
• Avoid antithyroid drugs, radioactive iodine, or surgery, as these are ineffective and unnecessary 2

For Subclinical Hyperthyroidism (TSH <0.1 mIU/L, Normal Free T4/T3)

Treat patients older than 65 years or those with persistent TSH <0.1 mIU/L, as they face highest risk of osteoporosis, atrial fibrillation, and cardiovascular mortality. 1

• Treatment is recommended for patients with overt Graves' disease or nodular thyroid disease even if biochemically subclinical 4
• Younger patients without comorbidities may be monitored with thyroid function tests every 3–6 months 1
• Consider treatment for symptomatic patients regardless of age 1

Severity-Based Management Approach

Mild Symptoms (Asymptomatic or Minimal)

• Continue monitoring with thyroid function tests every 2–3 weeks 4
• Beta-blockers for symptomatic relief 4
• Initiate definitive treatment based on etiology as outlined above 2

Moderate Symptoms

• Hydration and supportive care 4
• Beta-blockers for symptomatic control 4
• Consider holding immune checkpoint inhibitor therapy if drug-induced until symptoms return to baseline 4
• Initiate antithyroid drugs for Graves' disease or toxic nodules 2

Severe Symptoms (Thyroid Storm)

• Hospitalize immediately with inpatient endocrine consultation 4
• High-dose beta-blockers (propranolol 60–80 mg every 4 hours) 2
• Antithyroid drugs at maximum doses (methimazole 20 mg every 6 hours or propylthiouracil 200 mg every 4 hours) 2
• Potassium iodide solution for rapid control (given at least 1 hour after antithyroid drugs) 4
• Glucocorticoids (hydrocortisone 100 mg IV every 8 hours) to block peripheral T4 to T3 conversion 2
• Treat precipitating factors (infection, trauma, surgery) 2

Monitoring and Follow-Up

• Check thyroid function tests every 2–3 weeks after diagnosis to detect transition to hypothyroidism 4
• For patients on immune checkpoint inhibitors, monitor TSH every 4–6 weeks as part of routine clinical monitoring 4
• Once euthyroid on treatment, monitor every 6–12 months 1
• Be aware that subclinical hyperthyroidism often precedes overt hypothyroidism, particularly in thyroiditis 4

Critical Pitfalls to Avoid

• Do not assume all suppressed TSH represents primary hyperthyroidism—always measure free T4 and T3 to exclude central hypothyroidism or assay interference 4, 5
• Do not use antithyroid drugs for thyroiditis, as this is ineffective and delays recognition of the self-limited nature of the condition 2
• Do not overlook iodine exposure (CT contrast) as a cause of transient thyroid dysfunction 4
• Do not delay treatment in elderly patients with subclinical hyperthyroidism, as they face substantially elevated cardiovascular and bone risks 1