What is the appropriate work‑up for a suppressed serum TSH?

Work-Up for Suppressed TSH

When you encounter a low TSH, immediately measure free T4 and free T3 to distinguish between subclinical hyperthyroidism (normal thyroid hormones) and overt hyperthyroidism (elevated thyroid hormones), then systematically exclude non-thyroidal causes before pursuing definitive thyroid imaging. 1

Initial Laboratory Assessment

Measure the following tests simultaneously:

• Free T4 (FT4) – to determine if thyroid hormone is elevated 1, 2
• Free T3 (FT3) – particularly important because T3 toxicosis can occur with normal T4 3
• Repeat TSH in 3-6 weeks if the initial value is borderline (0.1-0.4 mIU/L), as TSH can be transiently suppressed 1, 2

The combination of these tests allows you to categorize the patient into one of three groups:

1. Overt hyperthyroidism: TSH <0.1 mIU/L + elevated FT4 and/or FT3 2, 3
2. Subclinical hyperthyroidism: TSH <0.1 mIU/L (or 0.1-0.4 mIU/L) + normal FT4 and FT3 1, 4
3. Non-thyroidal TSH suppression: Low TSH with normal thyroid hormones due to other causes 2, 5

Exclude Non-Thyroidal Causes of TSH Suppression

Before attributing a low TSH to intrinsic thyroid disease, systematically rule out the following:

Medication-Related Causes

• Levothyroxine overtreatment – the most common cause of iatrogenic TSH suppression; approximately 25% of patients on levothyroxine are unintentionally overtreated 1
• Glucocorticoids (prednisone, dexamethasone) – suppress TSH via central mechanisms 2, 5
• Dopamine or dopamine agonists – suppress pituitary TSH secretion 5
• Methimazole overtreatment – in patients being treated for hyperthyroidism, excessive antithyroid medication can suppress TSH while normalizing thyroid hormones 6

Acute Illness and Hospitalization

• Non-thyroidal illness syndrome – acute illness, hospitalization, or critical illness can transiently suppress TSH 1, 5
• TSH typically normalizes 3-6 weeks after recovery from acute illness 1

Psychiatric Conditions

• Acute psychiatric illness – can transiently suppress TSH independent of thyroid hormone levels 5

Central Hypothyroidism

• Pituitary or hypothalamic disease – low TSH with low (not elevated) FT4 indicates central hypothyroidism, not hyperthyroidism 1, 5
• This requires a completely different diagnostic approach focused on pituitary imaging and assessment of other pituitary hormones 1

Confirm Persistent TSH Suppression

If the initial TSH is between 0.1-0.4 mIU/L (low but detectable) and thyroid hormones are normal:

• Repeat TSH, FT4, and FT3 in 3-6 weeks to confirm persistence 1, 2
• Transient TSH suppression is common and does not require further work-up if it normalizes 2, 5
• Day-to-day TSH variability can be substantial, with fluctuations up to 50% 1

If TSH remains suppressed on repeat testing, proceed with thyroid imaging.

Thyroid Imaging to Identify Etiology

Once you have confirmed persistent TSH suppression with normal or elevated thyroid hormones and excluded non-thyroidal causes, obtain thyroid imaging:

Technetium-99m or Radioiodine Uptake Scan

• Toxic adenoma (hot nodule) – focal area of increased uptake with suppression of surrounding thyroid tissue 4
• Toxic multinodular goiter – multiple areas of increased uptake 4
• Graves' disease – diffusely increased uptake throughout the gland 4
• Thyroiditis (subacute, silent, or postpartum) – low or absent uptake despite hyperthyroidism 1

A low but detectable TSH (0.1-0.4 mIU/L) in an ambulant patient frequently indicates underlying autonomous thyroid function, with isotope scanning revealing hot nodules in 36% and multinodular goiter in 40% of cases 4.

Thyroid Ultrasound

• Useful adjunct when isotope scanning is normal – can identify early multinodular goiter or structural abnormalities 4
• In one study, ultrasound identified definite or early multinodular goiter in 50% of patients with low TSH but normal isotope scans 4

Measure Thyroid Antibodies

Check anti-thyroid peroxidase (anti-TPO) antibodies and TSH receptor antibodies (TRAb) when appropriate:

• Anti-TPO antibodies – elevated in Hashimoto's thyroiditis, which can have a transient hyperthyroid phase 1
• TSH receptor antibodies (TRAb) – positive in Graves' disease, confirming autoimmune hyperthyroidism 1

Thyroid antibodies were negative in 96% of patients with low TSH due to autonomous nodular disease, helping distinguish this from autoimmune causes 4.

Risk Stratification Based on Degree of TSH Suppression

The degree of TSH suppression determines urgency and risk:

TSH <0.1 mIU/L (Fully Suppressed)

• Higher risk of complications – 3-5 fold increased risk of atrial fibrillation, especially in patients >60 years 1, 6
• Increased cardiovascular mortality – up to 3-fold in elderly patients 6
• Accelerated bone loss – particularly in postmenopausal women 6
• Consider treatment even if asymptomatic, especially in high-risk patients 1

TSH 0.1-0.4 mIU/L (Low but Detectable)

• Intermediate risk – still associated with increased atrial fibrillation and bone loss, but lower magnitude 1, 6
• Monitor every 3-12 months – treat if symptomatic or high-risk features present 1

Special Populations Requiring Modified Approach

Patients on Levothyroxine

• First step: Review indication for thyroid hormone therapy 1
• If for hypothyroidism without thyroid cancer – reduce dose by 12.5-25 mcg (TSH 0.1-0.45 mIU/L) or 25-50 mcg (TSH <0.1 mIU/L) 1
• If for thyroid cancer – consult endocrinology, as intentional TSH suppression may be appropriate depending on risk stratification 1, 6

Patients on Methimazole

• TSH suppression with normal thyroid hormones indicates overtreatment 6
• If TSH <0.1 mIU/L – discontinue methimazole and recheck in 2-4 weeks 6
• If TSH 0.1-0.45 mIU/L – reduce methimazole dose by 50% and recheck in 4-6 weeks 6

Elderly Patients (>60 Years)

• Higher risk of atrial fibrillation – obtain ECG to screen for subclinical arrhythmias 6
• More aggressive management warranted due to cardiovascular risks 6

Postmenopausal Women

• Consider bone density assessment if TSH has been suppressed for >6 months 6
• Ensure adequate calcium (1200 mg/day) and vitamin D (1000 units/day) 1, 6

Common Pitfalls to Avoid

Do not assume hyperthyroidism based on a single low TSH value – 17% of suppressed TSH values in one study were due to non-thyroidal causes 5. Always confirm with repeat testing and measure thyroid hormones 2, 5.

Do not overlook medication history – particularly levothyroxine, glucocorticoids, dopamine, and methimazole, which are common causes of iatrogenic TSH suppression 1, 6, 5.

Do not miss central hypothyroidism – if TSH is low with low (not elevated) FT4, this indicates pituitary or hypothalamic disease, not hyperthyroidism 1, 5.

Do not delay imaging in persistent subclinical hyperthyroidism – a low but detectable TSH in an ambulant patient frequently indicates underlying autonomous thyroid disease requiring definitive imaging 4.