In hypothyroid replacement (legitimate use): The classic "fog lifting" report — energy, mental clarity, warmth, weight normalization within 2-6 weeks. Often described as "feeling alive again."

In euthyroid (off-label / abuse): Hyperthyroid state — heat intolerance, sweating, tremor (especially fine hand tremor), palpitations, anxiety, insomnia, increased bowel frequency, weight loss, ravenous appetite ("eating everything but losing weight" is the bodybuilding tell). Initial subjective "energy" gives way to fatigue and mood lability as endogenous axis suppresses. Post-cycle: cold intolerance, fatigue, weight regain, depression — symptoms of iatrogenic hypothyroidism that may take months to normalize.

• No tolerance to T3's metabolic effects — receptor downregulation does not occur in the way it does for stimulants. The body responds by suppressing endogenous TSH/T4/T3 production via negative feedback.
• HPT axis suppression is the real concern — exogenous T3 suppresses pituitary TSH within days, which suppresses endogenous T4 production. On discontinuation, axis recovery takes weeks-to-months. During recovery: hypothyroid symptoms (fatigue, cold, weight gain, depression).
• No legitimate "cycling" protocol exists for healthy subjects. The bodybuilding cycle pattern (4-8 weeks on, taper off) is a damage-control attempt to limit suppression duration but does not eliminate it.
• Reset: None needed for legitimate use (continue indefinitely if hypothyroid). For post-abuse: time, supportive care, sometimes T4 bridge while axis recovers; endocrinologist supervision recommended.

Synergistic with

• SSRI / SNRI / TCA (in TRD): T3 augmentation has clinical precedent — but only with depression diagnosis and psychiatrist oversight.
• Levothyroxine (T4): Some hypothyroid patients respond better to T4+T3 combination than T4 alone — controversial, mixed evidence.

Avoid stacking with

• Stimulants (caffeine high-dose, modafinil at supraphysiologic T3 doses, amphetamines): Additive cardiovascular load — tachycardia, BP elevation, arrhythmia risk
• Sympathomimetics (decongestants, clenbuterol, ephedrine): Same — additive CV strain. Bodybuilding "T3 + clenbuterol" stacks are a known cause of cardiac events.
• Anticoagulants (warfarin): T3 increases warfarin sensitivity → ↑ INR → bleeding risk; requires INR monitoring
• Insulin / oral hypoglycemics: T3 alters glucose metabolism; insulin requirement may change
• β-blockers: Not a "don't combine" — actually used clinically to manage hyperthyroid symptoms (propranolol blocks peripheral T4→T3 conversion at high doses). But this is treating, not stacking.

Neutral / safe co-administration

Most non-CV daily compounds (Mg, fish oil, vitamins). But the larger point: there is no euthyroid use case for Dylan's stack.

• CYP enzymes: T3 not heavily CYP-metabolized; primary clearance via deiodinases and conjugation. Limited CYP-based DDIs.
• Absorption interference: Calcium, iron, soy, fiber supplements can reduce thyroid hormone absorption — separate by 4 hours (relevant for T4 more than T3, but applies).
• Bile acid sequestrants (cholestyramine): Bind thyroid hormone, reduce absorption.
• Estrogens (OCPs, HRT): Increase TBG (thyroid-binding globulin) → may increase total T4 dose requirement (less relevant for T3).
• Phenytoin, carbamazepine, rifampin: Induce thyroid hormone metabolism — may need dose increase.
• Warfarin: Above — INR effect.
• SSRIs: Sertraline reported to increase thyroid hormone requirement in some hypothyroid patients.
• Amiodarone: Complex thyroid effects (contains iodine, blocks deiodinase) — separate workup needed.

• DIO2 polymorphisms (Thr92Ala, rs225014): Reduced D2 deiodinase activity → impaired peripheral T4→T3 conversion. Carriers may feel undertreated on T4 monotherapy and respond better to T4+T3 combination. ~12-16% of European populations homozygous. 23andMe raw data does cover this SNP — Dylan's June results may flag this if he eventually has thyroid pathology.
• MCT8 (SLC16A2) mutations: Rare X-linked thyroid hormone transporter defect — Allan-Herndon-Dudley syndrome. Severe.
• TR mutations: Rare resistance-to-thyroid-hormone syndromes.

For a young euthyroid male, pharmacogenomics is moot until/unless thyroid pathology emerges.

For Dylan: no legitimate sourcing question until bloodwork establishes hypothyroidism. If June labs show clinical hypothyroidism, route through a US endocrinologist — this is one of the cleanest US-Rx workflows in medicine, with insurance coverage and standard monitoring.

• Baseline (before starting — for any indication):
  • TSH, free T4, free T3 (full thyroid panel)
  • Reverse T3 (rT3) — useful for non-thyroidal illness assessment
  • Anti-TPO and anti-thyroglobulin antibodies — rule in/out Hashimoto's
  • Resting HR, BP
  • DEXA bone density (baseline if planning chronic supraphysiologic)
  • ECG if any CV history or family history
• During use:
  • TSH at 4-6 weeks after any dose change, then every 6-12 months (replacement)
  • For TSH-suppressive therapy (cancer): target TSH determined by risk stratification
  • Free T3, free T4 to ensure within reference range
  • Resting HR — flag if persistently >85 bpm
  • Annual DEXA if chronic supraphysiologic
• Post-cycle (if discontinuing supraphysiologic use):
  • TSH, fT4, fT3 monthly until axis recovers
  • Symptom monitoring for hypothyroid emergence