TFTs

When it’s not the thyroid

TFT interpretation pitfalls and clinical pearls

Misinterpreting thyroid function tests in acutely ill patients leads to inappropriate levothyroxine therapy. This guide covers the most important scenarios where TFTs can mislead.

Quick reference: patterns to recognize

Low T3 only, normal TSH NTIS - acute illness Don't treat
Low T3, low T4, low/normal TSH Severe NTIS or central hypothyroidism Investigate cause
Raised TSH (usually below 20) after illness Recovery phase NTIS Recheck in 4-6 weeks
Normal/low TSH with low fT4 Central hypothyroidism Confirm, check cortisol, then MRI
Low TSH on dopamine/high-dose steroids Drug effect, NOT hyperthyroidism Recognize
Raised fT4 with non-suppressed (normal or high) TSH Assay interference, then RTH-beta or TSHoma Exclude artefact, refer

Clinical pearls

critical

Acute illness with low T3, normal/low TSH

PatternLow T3, normal or slightly low fT4, normal TSH

InterpretationNon-thyroidal illness syndrome (NTIS) - NOT hypothyroidism

ActionDo NOT treat with levothyroxine. Repeat tests after recovery. ↗︎ ↗︎

critical

Recovery phase from severe illness

PatternTransiently elevated TSH (up to 20 mU/L)

InterpretationNormal HPT axis recovery, not new hypothyroidism

ActionDo not start levothyroxine. Repeat in 4-6 weeks. ↗︎

critical

Central hypothyroidism (pituitary disease)

PatternLow/normal (occasionally slightly raised) TSH WITH low fT4

InterpretationPituitary failure - missed if relying on TSH alone

ActionRepeat fT4/TSH once acute illness and TSH-lowering drugs are excluded. Check morning cortisol and the other pituitary axes; if cortisol is low or not yet excluded, start glucocorticoid BEFORE levothyroxine. Pituitary MRI once confirmed. ↗︎

critical

Patient on amiodarone with abnormal TFTs

PatternFirst ~3 months: mildly raised TSH, raised fT4, low-normal T3 (expected drug effect; TSH returns to baseline). Any time: suppressed TSH = possible AIT; persistently raised TSH = AIH

InterpretationBoth AIT (hyperthyroidism) and AIH (hypothyroidism) possible

ActionSpecialist referral. Distinguish AIT type 1 vs 2. ↗︎

important

Patient on biotin supplements

PatternOn streptavidin-biotin assays: falsely low TSH with falsely high fT4/fT3 (looks like Graves' disease). Some platforms are unaffected.

InterpretationAssay interference, platform-dependent - ask the laboratory which method is used

ActionStop biotin at least 2 days before retesting; after high-dose biotin (100-300 mg/day) allow up to 5 days. ↗︎ ↗︎ ↗︎

important

Glucocorticoid therapy

PatternLow TSH (dose-dependent; rarely undetectable outside critical illness), normal fT4

InterpretationDirect suppression of TRH/TSH - NOT hyperthyroidism

ActionRecognize as medication effect. ↗︎

important

Iodine contrast for imaging

PatternTSH may rise or fall within 1-4 weeks of contrast

InterpretationIodine load can cause hypo- or hyperthyroidism

ActionCheck TSH in patients with known thyroid disease. Allow 4-8 weeks before radioiodine uptake or scan. ↗︎ ↗︎

important

Pregnancy

PatternSuppressed TSH in 1st trimester

InterpretationhCG cross-stimulation of TSH receptor (normal)

ActionUse trimester-specific reference ranges. ↗︎ ↗︎

important

Checkpoint inhibitor therapy

PatternInitial transient hyperthyroidism, then hypothyroidism

InterpretationImmune-related thyroiditis - common: hypothyroidism in ~7% in trials (4% with ipilimumab alone, 13% with combination therapy); more when TFTs are checked systematically

ActionMonitor TFTs every 4-6 weeks. LT4 if hypothyroid persists. ↗︎ ↗︎

important

Levothyroxine "malabsorption" - rising TSH

PatternRising TSH on stable LT4 dose, good adherence

InterpretationConsider: PPIs, calcium, iron, soy, coffee, celiac, autoimmune gastritis

ActionTake LT4 fasting, ≥30-60 min before food. Test celiac, parietal cell Ab. ↗︎ ↗︎

useful

Older adult (65+) with mildly raised TSH (4.5-10 mU/L)

PatternTSH 4.5-10 mU/L, normal fT4

InterpretationOften age-related shift, NOT pathological

ActionRepeat in 2-3 months, then observe. Levothyroxine showed no benefit in adults 65+ (TRUST); no evidence that TPO+ patients respond better to treatment. ↗︎ ↗︎

useful

Heparin treatment (unfractionated or LMWH)

PatternFalsely elevated fT4

InterpretationIn-tube lipolysis releases fatty acids that displace T4 from binding proteins (artefact)

ActionSample 10+ hours after last heparin dose. Use TSH primarily. ↗︎

Levothyroxine drug interactions

Drugs that affect levothyroxine effectiveness or interpretation

Reduces Absorption 6
Calcium supplements Separate by ≥4 hours ↗︎
Iron supplements Separate by ≥4 hours ↗︎
PPIs Recheck TSH after starting; a higher LT4 dose may be needed (+37% in one omeprazole study) ↗︎
Cholestyramine Separate by ≥4 hours ↗︎
Soy products Separate by 4 hours
Coffee Wait 60 min after LT4 (no effect when coffee was taken 60 min later) ↗︎
Alters Metabolism 3
Phenytoin, carbamazepine Monitor TSH after starting or stopping; raise LT4 only if TSH rises (most patients stay euthyroid) ↗︎
Rifampicin Check TSH after starting; about 1 in 4 on replacement need a higher dose ↗︎
Sertraline Monitor TSH 4-6 weeks ↗︎
Affects Binding 3
Estrogens (oral) Recheck TSH after starting; some women need a higher LT4 dose (TSH rose above 7 mU/L in 7 of 18 on replacement) ↗︎
Tamoxifen Monitor TSH
Androgens May need dose decrease ↗︎
Increases Requirement 2
Pregnancy Increase LT4 by 25-30% as soon as confirmed ↗︎
TKIs (sunitinib) Monitor TSH during treatment; most patients already on LT4 need a higher dose (8 of 11 on sunitinib; median +37.5 µg) ↗︎

Medically reviewed · Last reviewed