Compare the trophic hormone with the target hormone to localise the lesion
Mnemonic
“Three tiers, and the bottom one switches off the top”:
- Hypothalamus releases a releasing hormone
- Anterior pituitary releases a trophic hormone
- Target gland releases the final hormone, which inhibits both levels above
The pattern reading a result follows directly:
| Trophic hormone | Target hormone | Lesion |
|---|---|---|
| High | Low | Primary target gland failure |
| Low | Low | Secondary, pituitary or hypothalamic |
| Low | High | Primary overactivity of the target gland |
| High | High | Pituitary tumour or resistance |
“High trophic with low target means the gland has failed; low with low means the pituitary has.”
Prolactin is the exception, being under tonic inhibition by dopamine rather than stimulation, so pituitary stalk compression raises it while damaging every other axis.
Positive feedback is rare and always transient: the LH surge before ovulation, and oxytocin in labour and lactation.
Expansion
Take the thyroid axis as the model:
| TSH | Free T4 | Diagnosis |
|---|---|---|
| High | Low | Primary hypothyroidism (opposite directions: gland problem) |
| Low | Low | Secondary hypothyroidism (same direction: pituitary problem) |
| Low | High | Primary hyperthyroidism |
| High | High | TSH-secreting adenoma or thyroid hormone resistance (rare) |
The same logic applies throughout endocrinology:
- Cortisol low with ACTH high means Addison disease; both low means pituitary failure
- Testosterone low with LH and FSH high means primary gonadal failure; all low means hypogonadotrophic hypogonadism
- Calcium high with parathyroid hormone high or inappropriately normal means primary hyperparathyroidism; calcium high with parathyroid hormone suppressed means a non-parathyroid cause such as malignancy
This single principle, that negative feedback should drive the trophic hormone in the opposite direction to the target hormone, resolves most endocrine investigations without memorising individual patterns.