What is the likely diagnosis and recommended management for a 24‑year‑old woman with a low thyroid‑stimulating hormone (TSH) level and normal free thyroxine (free T4) persisting for more than a year?

Likely Diagnosis and Management of Persistent Low TSH with Normal T4 in a Young Woman

In a 24-year-old woman with suppressed TSH and normal free T4 persisting for over a year, the most likely diagnosis is subclinical hyperthyroidism, and the recommended approach is to confirm persistence with repeat testing, identify the underlying cause through clinical assessment and TSH-receptor antibodies (with thyroid scintigraphy if needed), then treat based on etiology—antithyroid drugs for Graves' disease or observation/definitive therapy for autonomous nodular disease. 1

Diagnostic Confirmation and Assessment

Initial Laboratory Confirmation

• Repeat TSH measurement along with free T4 and free T3 after 3-6 weeks to confirm the pattern persists, as TSH can be transiently suppressed by acute illness, medications, or physiological factors 2
• Measure TSH-receptor antibodies (TRAb) to identify Graves' disease as the underlying cause; positive antibodies confirm autoimmune hyperthyroidism 1
• If TSH is <0.1 mIU/L with normal free T4, this represents grade II subclinical hyperthyroidism and warrants more aggressive evaluation 3
• If TSH is 0.1-0.4 mIU/L with normal free T4, this represents grade I subclinical hyperthyroidism with lower risk 3

Determining the Underlying Cause

• Perform thyroid scintigraphy if TSH-receptor antibodies are negative to distinguish between toxic adenoma, toxic multinodular goiter, or other causes 1, 4
• In a study of undiagnosed hyperthyroidism, among subjects with suppressed TSH (<0.05 mIU/L), the causes were: Graves' disease (40%), toxic adenoma (40%), and multinodular goiter (20%) 4
• For those with TSH 0.05-0.5 mIU/L who had persistent suppression, the distribution was: toxic adenoma (30%), multinodular goiter (35%), Graves' disease (5%), and normal thyroid (30%) 4

Clinical Significance and Risk Stratification

Morbidity and Mortality Risks

• Subclinical hyperthyroidism is associated with significant morbidity and mortality in longitudinal epidemiological surveys, particularly in older adults, including increased risks of atrial fibrillation, dementia, and osteoporosis 3, 2
• In a 24-year-old woman, the immediate cardiovascular and bone risks are lower than in elderly patients, but prolonged TSH suppression still carries long-term consequences 2
• Grade II subclinical hyperthyroidism (TSH <0.1 mIU/L) carries higher risk than grade I and more strongly indicates treatment 3

Progression Risk

• Most subjects with persistently low TSH (0.05-0.5 mIU/L) will have pathological thyroid findings on scintigraphy, indicating underlying thyroid disease rather than transient suppression 4
• The persistence of suppressed TSH for over a year in this patient strongly suggests true thyroid pathology requiring intervention rather than a transient phenomenon 4

Treatment Algorithm Based on Etiology

If Graves' Disease is Confirmed (TRAb Positive)

• First-line treatment is a 12-18 month course of antithyroid drugs (methimazole or propylthiouracil), which is the preferred initial approach for Graves' disease 1
• Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease who relapse after initial therapy 1
• Alternative definitive therapies include radioactive iodine or thyroidectomy, particularly if antithyroid drugs fail or are not tolerated 1

If Toxic Nodular Disease is Confirmed (Scintigraphy Shows Hot Nodule)

• For toxic adenoma or toxic multinodular goiter, radioactive iodine or surgery are preferred as first-line treatments rather than antithyroid drugs 1
• Antithyroid drugs can be used for long-term management in patients who decline or are not candidates for definitive therapy 1

If Thyroiditis is Suspected

• Thyroiditis causes thyrotoxicosis without hyperthyroidism and is managed symptomatically or with glucocorticoid therapy rather than antithyroid drugs 1
• Thyroiditis is typically self-limited, and TSH suppression should resolve over time 1

Special Considerations for Young Women

Fertility and Pregnancy Planning

• If the patient is planning pregnancy, thyroid function must be optimized before conception, as both hyperthyroidism and its treatment can affect pregnancy outcomes 2
• Propylthiouracil is preferred over methimazole in the first trimester of pregnancy due to lower teratogenic risk 1

Long-Term Monitoring

• Even if asymptomatic, persistent TSH suppression requires treatment to prevent long-term cardiovascular and bone complications 3
• After treatment initiation, monitor TSH and free T4 every 4-6 weeks until stable, then every 6-12 months 2

Common Pitfalls to Avoid

Misdiagnosis Risks

• Do not confuse central hypothyroidism with subclinical hyperthyroidism—both can present with low TSH and normal-low free T4, but central hypothyroidism is extremely rare in young adults without pituitary disease 5
• In rare cases, coexistence of central hypothyroidism with autonomous thyroid nodules can lead to misdiagnosis; if clinical suspicion exists, evaluate pituitary function 5
• Do not assume subclinical hyperthyroidism is benign in young patients—the persistence for over a year indicates true pathology requiring intervention 4

Treatment Errors

• Do not delay treatment in patients with TSH <0.1 mIU/L, as this represents grade II subclinical hyperthyroidism with higher risk 3
• Do not use antithyroid drugs as first-line therapy for toxic nodular disease—definitive therapy with radioactive iodine or surgery is preferred 1
• Ensure adequate follow-up after initiating treatment, as both under-treatment and over-treatment carry significant risks 2