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Human Body Study

HPT Axis — Hypothalamic–Pituitary–Thyroid

The HPT axis The hypothalamus releases TRH, which stimulates the anterior pituitary to release TSH, which stimulates the thyroid gland to release T4 (and a smaller amount of T3). T4 is converted to T3 by peripheral deiodinase enzymes. Circulating thyroid hormones exert negative feedback on both the pituitary and the hypothalamus. Hypothalamus paraventricular nucleus Anterior pituitary thyrotrophs Thyroid gland follicular cells Nearly every tissue ↑ basal metabolic rate · thermogenesis cardiac output · neurodevelopment TRH TSH T4 (T3) T4 → T3 (deiodinases) T3/T4 − − Solid arrows: stimulation. Dashed red: negative feedback.

Signaling chain

Section titled “Signaling chain”

TRH (hypothalamus) → TSH (anterior pituitary thyrotrophs) → T4 and T3 (thyroid follicular cells). T4 is the predominant secreted hormone; it is converted peripherally to the more active T3 by deiodinase enzymes.

Function

Section titled “Function”

Sets basal metabolic rate and influences nearly every tissue. Thyroid hormone regulates thermogenesis, cardiac output and heart rate, gut motility, lipid and carbohydrate metabolism, and is essential for fetal/neonatal neurodevelopment and skeletal growth.

Feedback

Section titled “Feedback”

Negative feedback: circulating T3/T4 suppress TRH and TSH. TSH is the most sensitive marker of axis status — it moves logarithmically against small changes in free T4.

Clinical relevance

Section titled “Clinical relevance”
  • Hyperthyroidism — low TSH, high T4/T3 (Graves’ disease, toxic nodule); weight loss, tachycardia, heat intolerance, tremor.
  • Hypothyroidism — high TSH, low T4 (Hashimoto’s thyroiditis, iodine deficiency); fatigue, weight gain, cold intolerance, bradycardia.
  • Central dysfunction — TSH inappropriately normal/low despite abnormal T4.
  • Sick euthyroid syndrome — axis is downregulated during severe illness.

Key labs

Section titled “Key labs”

TSH (first-line screen), free T4, free T3, thyroid antibodies (TPO, TRAb), thyroglobulin.