Free T4 (FT4) - Free thyroxine

Normal values and interpretation of the complete thyroid workup

• FT4 reference values (adult) : 9-25 pmol/L (or 0.7-1.9 ng/dL depending on the unit) + reference values vary between laboratories and enzyme immunoassay methods → always compare with the standards of the laboratory performing the analysis
• Pregnancy - adjusted values : FT4 decreases progressively throughout pregnancy (plasma dilution + estrogen-stimulated increase in TBG → increased T4 protein binding → reduced free FT4) + pregnancy-specific TSH + FT4 targets → FT4 slightly lower than outside pregnancy is normal
• Recommended diagnostic algorithm : TSH in 1st intention (most sensitive screening test) + if TSH abnormal → FT4 + FT3 according to context + if TSH suppressed and FT4 normal → measure FT3 (T3 hyperthyroidism possible) + if TSH high and FT4 normal → subclinical hypothyroidism + if TSH high and FT4 low → frank clinical hypothyroidism

Combined TSH + FT4 interpretation

Low FT4 - causes of hypothyroidism

• Primary hypothyroidism (high TSH + low FT4) - most frequent causes : Hashimoto's thyroiditis (autoimmune - most common in developed countries) + post-thyroidectomy hypothyroidism + post-irtherapy (iodine 131) + De Quervain thyroiditis (transient hypothyroid phase) + drug-induced hypothyroidism (amiodarone + lithium + interferon + anti-PD1/PD-L1 immunotherapy) + iodine deficiency (rare in Canada - fortified foods)
• Central hypothyroidism - secondary (normal or low TSH + low FT4) : pituitary insufficiency (pituitary adenoma + pituitary surgery + cerebral radiotherapy + Sheehan syndrome = post-partum pituitary necrosis + head trauma) + hypothalamic insufficiency (craniopharyngioma + sarcoidosis + histiocytosis) → always consider associated adrenal insufficiency (hypopituitarism)
• Low T4 syndrome (non-thyroid diseases) : FT4 low + FT3 low + TSH normal → prolonged fasting + severe sepsis + advanced heart failure + major surgery → metabolic adaptation → DO NOT treat → treat underlying cause

Elevated FT4 - causes of hyperthyroidism

• Graves' disease (TSH suppressed + FT4 elevated + anti-RTSH positive) : most frequent hyperthyroidism + woman 20-50 years + autoimmunity (anti-RTSH stimulants) + diffuse goiter + exophthalmos (Graves' orbitopathy) + dermopathy (pretibial myxedema) → treatment: synthetic antithyroid drugs (carbimazole + propylthiouracil) + or iodine 131 + or thyroidectomy
• Toxic adenoma + toxic multinodular goiter : TSH suppressed + FT4 elevated + without anti-RTSH + scintigraphy: hyperfixing nodule(s) + treatment: iodine 131 + or surgery
• De Quervain thyroiditis (transient hyperthyroid phase) : TSH suppressed + FT4 elevated + VS very high + CRP elevated + cervical pain + fever + 4-6 weeks hyperthyroidism → euthyroidism → hypothyroidism (20-30 % permanent) → beta-blockers + NSAIDs + no antithyroid drugs (no excess production)
• Iodine overload (amiodarone + contrast media) : amiodarone → very rich in iodine (37 % by weight) → can cause hyperthyroidism (type 1 = exacerbated Basedow + type 2 = destructive thyroiditis) → high FT4 + low FT3 (inhibition of conversion) + variable TSH → complex thyroid profile under amiodarone
• Sham thyrotoxicosis (surreptitious intake of T4 or T3): FT4 very high + TSH suppressed + thyroglobulin collapsed (because thyroid is inhibited without lesion) → diagnosis

Follow-up on levothyroxine - practical rules

• TSH target under treatment : adult: TSH 0.5-2.5 mUI/L (middle of normal range) + pregnancy: TSH < 2.5 mIU/L in the 1st trimester +. < 3.0 mIU/L in 2nd-3rd trimester + post-thyroidectomy differentiated thyroid cancer: TSH < 0.5 mIU/L (mild suppression) or < 0.1 mIU/L (strong suppression) according to risk of recurrence
• Main monitoring parameter : TSH is the reference monitoring parameter under levothyroxine - it reflects the effect of exogenous T4 on the pituitary gland after 4-8 weeks of equilibrium + FT4 is generally not necessary for routine monitoring if TSH is within target + measure FT4 if TSH is discordant or if there is a suspected absorption problem
• Control time : TSH control 4-8 weeks after each levothyroxine dose change (time needed to reach steady state - T4 half-life = 7 days) + once stable: TSH every 6-12 months
• Taking levothyroxine : fasting in the morning 30-60 min before meal + or at bedtime (≥ 3 h after last meal) + absorption reduced by coffee + calcium + iron + antacids + cholestyramine → take at a distance from these substances (≥ 4 h)
• Elevated FT4 on levothyroxine: overdose → TSH suppressed + FT4 high + risk of atrial fibrillation + osteoporosis (in postmenopausal women) + reduce dose + TSH check in 4-8 weeks

Consult at Clinique Omicron

Clinique Omicron's specialized physicians and nurse practitioners (SPNs) prescribe and interpret FT4 in the appropriate clinical context (screening for hypothyroidism + treatment follow-up + pregnancy assessment + evaluation of hyperthyroidism + central hypothyroidism), initiate and adjust levothyroxine to TSH targets according to the clinical context, recognize discordant pictures (normal TSH + low FT4 = central hypothyroidism) requiring pituitary investigation, and refer to endocrinology for complex pictures. Consultations are available at several points of service in Quebec, and via telemedicine. To book an appointment, visit cliniqueomicron.ca.

The contents of this page are provided for information purposes only and do not replace the advice of a physician or endocrinologist. FT4 must always be interpreted in conjunction with TSH and in the patient's clinical context. In central hypothyroidism, TSH may be normal despite low FT4 - FT4 is the main monitoring parameter in this context. Reference values vary from laboratory to laboratory.