Thyroid Agents

Thyroid function runs on a feedback loop, the hypothalamic–pituitary–thyroid (HPT) axis. The hypothalamus releases TRH, which tells the pituitary to release TSH (thyroid-stimulating hormone), which tells the thyroid to make T4 and T3. T4 is the main circulating hormone; tissues convert about half of it into the more active T3. When thyroid hormone is plentiful, it feeds back to shut off TRH and TSH — a self-regulating thermostat.

That feedback is why TSH is the lab you titrate to, and it moves in the *opposite* direction of thyroid status. A high TSH means the pituitary is "shouting" for more hormone — the patient is under-replaced / hypothyroid. A low TSH means feedback has switched it off — the patient is over-replaced / hyperthyroid. Thyroid hormone itself sets the basal metabolic rate of nearly every tissue, so it acts like the body’s metabolic accelerator: heart rate, heat production, gut motility, and mental speed all rise and fall with it.

Hypothyroidism — too little hormone — slows everything: fatigue, cold intolerance, weight gain, bradycardia, constipation, dry skin. The fix is replacement with levothyroxine, synthetic T4 that the body converts to T3 and uses to restore a normal metabolic rate. Because it has a long half-life and a narrow therapeutic index, the dose is fine-tuned to the TSH over weeks.

Hyperthyroidism (often Graves disease) — too much hormone — speeds everything up: heat intolerance, weight loss despite a good appetite, tachycardia and palpitations (even atrial fibrillation), tremor, anxiety. The fix is an antithyroid drug — methimazole (first-line) or propylthiouracil (PTU) — which block thyroid peroxidase, the enzyme that builds thyroid hormone. PTU has a second action: it also blocks the peripheral conversion of T4 to T3, which is why it’s favored in thyroid storm. A key teaching point: antithyroid drugs stop new synthesis but don’t remove hormone already stored in the gland, so the clinical effect takes weeks as the reserve is used up.

Because these drugs move the metabolic thermostat, the main adverse effects are simply overshoot. Too much levothyroxine produces iatrogenic hyperthyroidism: palpitations, insomnia, tremor, heat intolerance, and weight loss — and, most dangerously in the elderly or in coronary artery disease, angina, arrhythmia, and atrial fibrillation, because the faster, harder heart demands more oxygen. Chronic over-replacement also accelerates bone loss. Conversely, too much antithyroid drug tips the patient back into hypothyroidism.

Two *idiosyncratic* dangers of the antithyroid drugs are dose-independent and immune-mediated: agranulocytosis (a sudden loss of infection-fighting white cells — the reason patients must report a sore throat or fever at once) and hepatotoxicity, severe enough that PTU carries a boxed warning for liver failure. Levothyroxine’s own boxed warning is different — it warns that thyroid hormone must never be used for weight loss, because in a euthyroid person the doses needed to affect weight are toxic.