T4 (Levothyroxine)

Structure: Synthetic sodium salt of L-thyroxine (3,5,3',5'-tetraiodo-L-thyronine), chemically identical to endogenous T4. It is a prohormone: type 1 and type 2 deiodinases in liver, kidney, muscle, and brain strip one iodine to produce active T3. That conversion step is the whole reason T4 behaves differently from T3 (Cytomel).

Dosage:

• Full replacement (primary hypothyroidism): roughly 1.6mcg/kg/day, commonly 100-150mcg/day for an adult male
• Cautious start (older users, cardiac history): 25-50mcg/day, titrate every 6 weeks
• Subclinical hypothyroidism: 25-75mcg/day, titrated to symptoms and TSH
• T4/T3 combination: typically 88-100mcg T4 plus 5-12.5mcg T3, used when symptoms persist on adequate T4 alone
• Fat loss: not what T4 is for. At supraphysiological doses in a euthyroid person it mostly feeds the reverse T3 pathway. Users chasing thermogenesis reach for T3 instead, and both carry a cardiac and muscle-loss cost.

Administration:

• Oral tablet, once daily, fasted, 30-60 minutes before food. Consistency matters more than the exact time.
• Separate by at least 4 hours from calcium, iron, magnesium, zinc, multivitamins, and proton pump inhibitors. These bind levothyroxine in the gut and cut absorption substantially. This trips up a lot of lifters who take ZMA, iron, or a greens powder near their dose.
• Bedtime dosing (at least 3 hours after the last food) is a validated alternative with equal or slightly better absorption.
• Steady state takes about 6 weeks because of the 7-day half-life. Do not retest or adjust before then.
• Brand-to-brand and generic-to-generic switches can shift absorption. If you change manufacturer, retest at 6 weeks.

Key Notes:

• The long half-life is the main practical difference from T3: levels are stable, a missed dose is not a crisis, and there is no midday crash. It also means dose changes take weeks to show up, so patience is mandatory.
• AAS lower thyroxine-binding globulin (TBG). Total T4 and total T3 drop while the free fractions stay normal. Reading a low total T4 on cycle as hypothyroidism leads to levothyroxine being started in someone who does not need it. Interpret Free T4 and Free T3, not Total T4.
• Aggressive dieting, very low body fat, and high training volume shift T4 conversion toward Reverse T3 instead of active T3, the euthyroid sick syndrome pattern. Adding T4 in that state largely feeds the inactive pathway. Restoring energy availability fixes it; more thyroxine usually does not.
• Growth Hormone increases T4-to-T3 conversion. Starting GH can make an existing levothyroxine dose feel stronger, or unmask an inadequate one.
• Oestrogen raises TBG and increases levothyroxine requirement. Relevant for women on oral oestrogen and for men aromatising heavily on cycle.
• Over-replacement is not benign. A suppressed TSH with a high Free T4 carries a measurable increase in atrial fibrillation risk and accelerated bone mineral density loss. Deliberately pushing TSH to zero for metabolic effect is buying those risks.
• Discontinuation is gentler than T3: no acute rebound, but TSH and symptoms take 4-6 weeks to settle.
• Untreated hypothyroidism raises LDL and total cholesterol. If lipids are poor and TSH is high, treat the thyroid before blaming the cycle.

Bloodwork Monitoring:

• Baseline: TSH, Free T4, Free T3, and TPO antibodies to identify Hashimoto's. Reverse T3 is optional and mostly useful in the dieting athlete.
• Titration marker: TSH in primary hypothyroidism, targeting roughly 0.5-2.5 mIU/L for most people. In central (pituitary) hypothyroidism TSH is useless and Free T4 is the target.
• Timing: retest 6 weeks after any dose change. Anything earlier is not steady state and will mislead you.
• Draw before the morning dose. Taking levothyroxine 1-3 hours before a blood draw transiently raises Free T4 by around 20% and makes an adequate dose look excessive.
• On cycle: rely on the free hormones. Expect Total T4 and total T3 to read low from TBG suppression while Free T4 and Free T3 sit normal.
• Over-replacement signs to catch early: suppressed TSH with high-normal or high Free T4, resting heart rate up 10+ bpm, tremor, insomnia, unintended weight loss.
• If Free T4 is comfortably mid-range but Free T3 is low and symptoms persist, look at conversion inputs (calorie deficit, selenium, zinc, iron, cortisol) before adding T3.