Thyroid hormone replacements

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Thyroid Physiology - Hormone Factory HQ

  • Axis: Hypothalamus (TRH) → Anterior Pituitary (TSH) → Thyroid Gland.
  • Key Enzyme: Thyroid Peroxidase (TPO) drives oxidation & organification of iodide.
  • Products: Thyroxine ($T_4$) and Triiodothyronine ($T_3$) are synthesized and stored in colloid, bound to thyroglobulin.
  • Ratio: Thyroid secretes $T_4$ to $T_3$ in a ~20:1 ratio.

High-Yield: The vast majority (~80%) of active $T_3$ is generated from the peripheral deiodination of $T_4$, primarily in the liver and kidneys.

Thyroid Hormone Synthesis, Storage, and Secretion

The Replacements - Drug Lineup

  • Levothyroxine (Synthroid, Levoxyl): Synthetic T4.

    • Drug of choice for hypothyroidism.
    • Metabolized to T3 peripherally; long half-life (~7 days) allows for stable, once-daily dosing.
    • Take on an empty stomach, 30-60 minutes before breakfast.
    • Steady state achieved in 6-8 weeks.
  • Liothyronine (Cytomel): Synthetic T3.

    • Faster onset, shorter half-life (~1 day).
    • Primarily used for myxedema coma (IV) or short-term TSH suppression.
    • Associated with ↑ cardiotoxicity risk.
  • Liotrix: Synthetic T4:T3 in a 4:1 ratio.

  • Desiccated Thyroid Extract (Armour Thyroid): Porcine-derived.

    • Contains T4 & T3; inconsistent potency and antigenicity concerns.

DTE vs T4 on Thyroid Hormones and Heart Rate

⭐ Levothyroxine's long half-life is a key clinical advantage. It ensures a stable reservoir, meaning a missed dose doesn't cause significant fluctuation, making it forgiving for patients and reliable for maintaining euthyroid states.

Dosing & Monitoring - The Titration Game

  • Initial Dose (Levothyroxine):
    • Standard: ~$1.6$ mcg/kg/day (ideal body weight).
    • Elderly / Cardiac Disease: Start low, go slow. Initial dose 12.5-25 mcg/day to avoid cardiac stress.
  • Titration & Monitoring:
    • Primary Goal: Normalize TSH to 0.4-4.0 mIU/L.
    • Check TSH 4-6 weeks after any dose change.
    • Adjust dose by 12.5-25 mcg increments.
      • High TSH (Hypo): ↑ Levothyroxine dose.
      • Low TSH (Hyper): ↓ Levothyroxine dose.
  • Special Considerations:
    • Pregnancy: Often requires a dose ↑ of 30-50%.

⭐ Levothyroxine's long half-life (~7 days) means steady state takes over a month. This is why TSH is re-checked 4-6 weeks post-dose adjustment, not earlier.

Levothyroxine Dosing and TSH Monitoring by Patient Type

Adverse Effects & Interactions - Too Much of a Good Thing

Essentially iatrogenic hyperthyroidism. Symptoms mirror thyrotoxicosis.

ECG: Atrial Fibrillation in Thyrotoxicosis

  • Cardiovascular: Tachycardia, palpitations, angina, arrhythmias (esp. atrial fibrillation in elderly).
  • Neurological: Nervousness, anxiety, tremor, insomnia.
  • Metabolic/General: ↑ aBMR, weight loss despite ↑ appetite, heat intolerance, sweating.
  • Musculoskeletal: Muscle weakness, ↑ bone turnover leading to osteoporosis with long-term overuse.

⭐> High-Yield: Over-replacement, especially in older adults, significantly increases the risk of atrial fibrillation and accelerated osteoporosis.

Drug Interactions:

  • ↓ Absorption: Bile acid sequestrants (cholestyramine), iron, calcium supplements, PPIs.
  • ↑ Metabolism: Rifampin, Phenytoin, Carbamazepine induce CYP450 enzymes.

High‑Yield Points - ⚡ Biggest Takeaways

  • Levothyroxine (T4) is the mainstay treatment for hypothyroidism, acting as a prodrug converted to active T3 peripherally.
  • Liothyronine (T3) has a faster onset and is reserved for severe, acute conditions like myxedema coma.
  • Monitor therapy with TSH levels; the goal is to bring TSH into the normal range.
  • Adverse effects are symptoms of iatrogenic hyperthyroidism: palpitations, anxiety, and weight loss.
  • Take on an empty stomach; absorption is impaired by food, iron, and calcium.
  • Increases warfarin's anticoagulant effect.

Practice Questions: Thyroid hormone replacements

Test your understanding with these related questions

A 39-year-old female presents to the clinic with the complaints of dry skin for a few months. She adds that she also has constipation for which she started eating vegetables and fruits but with no improvement. She lives with her husband and children who often complain when she turns the air conditioning to high as she cannot tolerate low temperatures. She has gained 5 kgs (11.2 lb) since her last visit 2 months back although her diet has not changed much. Her past medical history is relevant for cardiac arrhythmias and diabetes. She is on several medications currently. Her temperature is 98.6° F (37° C), respirations are 15/min, pulse is 57/min and blood pressure is 132/98 mm Hg. A physical examination is within normal limits. Thyroid function test results are given below: Serum TSH: 13.0 μU/mL Thyroxine (T4): 3.0 μg/dL Triiodothyronine (T3): 100 ng/dL Which of the following medications is most likely to be responsible for her symptoms?

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Flashcards: Thyroid hormone replacements

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Which thyroid medications are associated with aplastic anemia?_____

TAP TO REVEAL ANSWER

Which thyroid medications are associated with aplastic anemia?_____

Propylthiouracil (PTU) and methimazole

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