In a patient with a multinodular goiter, low thyroid‑stimulating hormone and normal free thyroxine and free triiodothyronine, what is the most likely diagnosis and how should it be managed?

Multinodular Goiter with Subclinical Hyperthyroidism

Diagnosis

This patient has subclinical hyperthyroidism secondary to toxic multinodular goiter (Plummer's disease). The combination of low TSH with normal FT3 and FT4 in the setting of multinodular goiter indicates autonomous thyroid hormone production from hyperfunctioning nodules that suppress TSH via negative feedback, even though circulating thyroid hormone levels remain within normal limits 1, 2.

Confirming the Diagnosis

• Repeat TSH measurement within 2-4 weeks along with free T4 and free T3 to confirm persistent suppression, as TSH can be transiently affected by acute illness or medications 1
• Obtain thyroid scintigraphy with radioactive iodine uptake to identify "hot" (autonomously functioning) nodules and assess the degree of extranodular tissue suppression 1, 3, 2
• The scintigraphy will typically show patchy areas of increased uptake corresponding to hyperfunctioning nodules with suppression of surrounding normal thyroid tissue 3, 2

Severity Stratification

This patient has Grade I (mild) subclinical hyperthyroidism if TSH is 0.1-0.45 mIU/L, or Grade II (severe) if TSH is <0.1 mIU/L 1. The distinction is critical because Grade II carries substantially higher cardiovascular and bone risks 1.

Risk Assessment

Cardiovascular Complications

• Patients with TSH <0.1 mIU/L have a 3-fold increased risk of atrial fibrillation over 10 years, particularly those over age 60 1
• All-cause mortality increases up to 2.2-fold and cardiovascular mortality up to 3-fold in individuals older than 60 years with TSH <0.5 mIU/L 1
• Obtain an ECG immediately to screen for atrial fibrillation or other arrhythmias, especially given the patient's age and cardiovascular risk factors 1

Bone Health Risks

• Prolonged subclinical hyperthyroidism causes significant bone mineral density loss, particularly in postmenopausal women 1
• Consider bone density assessment if the patient is postmenopausal or has other osteoporosis risk factors 1

Natural History

• Risk of progression to overt hyperthyroidism is 1-2% per year in patients with TSH <0.1 mIU/L 1, 4
• Spontaneous normalization of TSH may occur but is uncommon in toxic multinodular goiter 1
• Autonomously functioning nodules typically progress slowly over many years, with toxicity rarely developing in nodules <2.5 cm but occurring primarily in nodules ≥3 cm 3

Management Algorithm

For TSH 0.1-0.45 mIU/L (Grade I)

Surveillance without active treatment is recommended for most patients 1:

• Monitor TSH every 3-12 months until normalization or stabilization 1
• Screen for atrial fibrillation with ECG 1
• Educate patient about symptoms of overt hyperthyroidism

For TSH <0.1 mIU/L (Grade II)

Treatment should be strongly considered, especially if the patient 1:

• Has cardiac symptoms or arrhythmias
• Is over 65 years old
• Has osteoporosis or high fracture risk
• Has confirmed toxic multinodular goiter on scintigraphy

Treatment Options

Subtotal thyroidectomy is the preferred treatment for most patients with toxic multinodular goiter because it achieves prompt control of hyperthyroidism and removes the goiter simultaneously 3, 5:

• Surgery provides definitive treatment and rapid resolution of symptoms 3, 5
• Particularly indicated for large goiters causing compressive symptoms 5
• Patients with large goiters and large autonomously functioning nodules become euthyroid more quickly following surgery compared to radioiodine 5

Radioactive iodine (RAI) therapy is an alternative for 3, 5:

• Patients who are poor surgical candidates
• Those who refuse surgery
• Recurrent hyperthyroidism following previous thyroid surgery

Antithyroid drugs (methimazole or propylthiouracil) provide only temporary control and are reserved for 3:

• Preoperative preparation
• Patients who are poor candidates for both surgery and RAI
• Bridge therapy while awaiting definitive treatment

Critical Pitfalls to Avoid

• Do not dismiss suppressed TSH as clinically insignificant—the cardiovascular and bone risks are substantial, particularly in patients over 60 years 1
• Avoid iodine exposure (such as radiographic contrast agents) in patients with nodular goiter and low TSH, as this may precipitate overt hyperthyroidism 1, 2
• Never use levothyroxine suppression therapy in patients with suppressed TSH levels, as this will worsen the hyperthyroidism 5
• Check medications that can affect TSH values (dopamine, glucocorticoids, amiodarone) before making treatment decisions 1

Monitoring Strategy

• Recheck TSH, free T4, and free T3 within 2-4 weeks to confirm persistent suppression 1
• If TSH remains suppressed and treatment is deferred, monitor TSH every 3-12 months 1
• Maintain high suspicion for atrial fibrillation development, especially in patients over 60 years 1
• Assess for progression to overt hyperthyroidism (elevated free T3/T4) at each follow-up 4