What are the treatment options for a patient with a low Thyroid-Stimulating Hormone (TSH) level, indicating hyperthyroidism?

Management of Low TSH (Hyperthyroidism)

Immediate Assessment and Confirmation

For a patient with low TSH, immediately measure free T4 and free T3 to distinguish between overt hyperthyroidism (elevated thyroid hormones) and subclinical hyperthyroidism (normal thyroid hormones). 1, 2

• Grade I subclinical hyperthyroidism: TSH 0.1-0.4 mIU/L with normal free T4 and T3 3
• Grade II subclinical hyperthyroidism: TSH <0.1 mIU/L with normal free T4 and T3 3
• Overt hyperthyroidism: Suppressed TSH with elevated free T4 and/or T3 2, 4

Confirm the diagnosis with repeat testing, as transient TSH suppression can occur with acute illness, medications, or recovery from thyroiditis 1

Determine the Underlying Cause

Measure TSH-receptor antibodies to identify Graves' disease, the most common cause of hyperthyroidism affecting 2% of women and 0.5% of men. 2, 4

• If TSH-receptor antibodies are positive, diagnose Graves' disease 4
• If antibodies are negative or thyroid nodules are present on examination, obtain thyroid scintigraphy to distinguish between toxic nodular goiter, toxic adenoma, and thyroiditis 2, 5
• Thyroiditis shows low or absent uptake on scintigraphy, while Graves' disease shows diffusely increased uptake and toxic nodules show focal uptake 5, 4

Initiate Immediate Symptomatic Management

Start beta-blockers immediately for all symptomatic patients to control tachycardia, tremor, and anxiety while awaiting definitive treatment. 1

• Atenolol 25-50 mg daily or propranolol are preferred agents, titrating to heart rate <90 bpm if blood pressure allows 1
• Beta-blockers provide immediate relief within hours, while antithyroid drugs take weeks to normalize thyroid hormones 1
• Reduce beta-blocker dose once the patient becomes euthyroid, as hyperthyroidism increases clearance of beta-blockers 1, 6, 7

Definitive Treatment Selection Based on Etiology

For Graves' Disease (Most Common)

Methimazole is the preferred first-line antithyroid drug for Graves' disease due to superior efficacy and safety profile. 1, 5

• Starting dose: Methimazole 10-30 mg daily depending on severity 1
• Treatment goal: Maintain free T4 or free T3 in the high-normal range using the lowest effective dose—do NOT target TSH normalization, as TSH may remain suppressed for months even after achieving euthyroidism 1
• Monitoring: Check free T4 or free T3 every 2-4 weeks during initial treatment to guide dose adjustments 1
• Treatment duration: 12-18 months for Graves' disease, with consideration for long-term therapy in selected patients 4

Critical monitoring for methimazole adverse effects:

• Agranulocytosis typically occurs within the first 3 months—instruct patients to report sore throat, fever, or general malaise immediately and obtain CBC 1, 6
• Monitor for vasculitis symptoms including new rash, hematuria, decreased urine output, or hemoptysis 6
• Check prothrombin time before surgical procedures, as methimazole may increase anticoagulation effects 6

For Toxic Nodular Goiter or Toxic Adenoma

Radioactive iodine ablation or thyroidectomy are preferred over antithyroid drugs for toxic nodules. 5, 4

• Antithyroid drugs can be used for initial stabilization but are not curative for nodular disease 5
• Radioactive iodine is contraindicated in pregnancy and breastfeeding, and pregnancy must be avoided for 4 months following administration 1
• Surgery is preferred for patients with compressive symptoms (dysphagia, orthopnea, voice changes) or large goiters 2

For Thyroiditis

Thyroiditis is self-limited and requires only symptomatic management—do NOT use antithyroid drugs. 1

• Beta-blockers provide symptomatic relief during the hyperthyroid phase 1
• Monitor with symptom evaluation and free T4 testing every 2 weeks 1
• Introduce levothyroxine if the patient becomes hypothyroid during the recovery phase (low free T4/T3, even if TSH is not yet elevated) 1

Treatment Recommendations for Subclinical Hyperthyroidism

For patients older than 60-65 years or with TSH <0.1 mIU/L, treatment is recommended due to increased risk of atrial fibrillation, osteoporosis, and cardiovascular mortality. 1, 3, 2, 8

• TSH <0.1 mIU/L carries a 3-fold increased risk of atrial fibrillation over 10 years in patients over 60 years 1
• Treatment is mandatory in older patients or those with comorbidities such as osteoporosis, atrial fibrillation, or heart disease 8
• For TSH 0.1-0.45 mIU/L, routine treatment is not recommended for all patients due to insufficient evidence of adverse outcomes, but consider treatment in high-risk individuals 1, 3

Special Populations

Pregnancy

Propylthiouracil is preferred during the first trimester of pregnancy due to lower risk of congenital malformations compared to methimazole. 1, 6, 7

• Switch to methimazole for the second and third trimesters to avoid maternal hepatotoxicity from propylthiouracil 1, 7
• Both drugs are compatible with breastfeeding 1, 7
• Maintain free T4 or free T3 in the high-normal range using the lowest possible dose 1

Cardiac Disease

Anticoagulation should be guided by CHA₂DS₂-VASc risk factors, not solely by presence of hyperthyroidism. 1

• Atrial fibrillation occurs in 5-15% of hyperthyroid patients, more frequently in those over 60 years 1
• Use intravenous beta-blockers for acute rate control in patients with acute coronary syndrome and new-onset atrial fibrillation 1
• Nondihydropyridine calcium channel antagonists are recommended when beta-blockers cannot be used 1

Critical Pitfalls to Avoid

• Never reduce methimazole based solely on suppressed TSH while free T4 remains elevated or high-normal—this leads to inadequate treatment and recurrent hyperthyroidism 1
• Never use antithyroid drugs for thyroiditis—it is self-limited and requires only symptomatic management 1
• Never start radioactive iodine in pregnancy or breastfeeding—it is absolutely contraindicated 1
• Always monitor for agranulocytosis in the first 3 months of antithyroid drug therapy—instruct patients to report sore throat or fever immediately 1, 6, 7
• Adjust doses of warfarin, digoxin, and theophylline when patients become euthyroid—hyperthyroidism alters clearance of these medications 6, 7