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Long-loop negative feedback and how it localises a lesion

Effect and feedback · Long loop Short loop Set point

Each end hormone suppresses both its pituitary cell and the hypothalamic neurone above it, while pituitary hormones feed back short-loop on the hypothalamus. Measuring the trophic hormone beside its end hormone is what tells you which floor of the axis has failed.

Traced from the start

  1. Corticotrophin-releasing hormone (paraventricular nucleus)
  2. Corticotroph — ACTH cleaved from pro-opiomelanocortin
  3. Adrenal cortex — zona fasciculata and zona reticularis
  4. Thyrotrophin-releasing hormone (paraventricular nucleus)
  5. Thyrotroph — thyroid-stimulating hormone
  6. Thyroid follicular cell
  7. Gonadotrophin-releasing hormone pulse generator (arcuate nucleus)
  8. Gonadotroph — luteinising hormone and follicle-stimulating hormone
  9. Leydig cells and ovarian theca cells (the LH target)Sertoli cells and ovarian granulosa cells (the FSH target)
  10. GHRH and somatostatin (arcuate and periventricular nuclei)
  11. Somatotroph — growth hormone
  12. Hepatocyte — GH receptor and IGF-1 synthesis
  13. CortisolThyroxine (T4) and triiodothyronine (T3)Testosterone and oestradiolInsulin-like growth factor 1
  14. Long-loop negative feedback and how it localises a lesion

Detail

Primary gland failure
End hormone low with a high trophic hormone: TSH high with low free T4, ACTH high with low cortisol, LH and FSH high with low testosterone or oestradiol
Secondary failure
Both low, or the trophic hormone inappropriately normal — the pituitary or hypothalamus is at fault
Autonomous excess
End hormone high with a suppressed trophic hormone means the gland (Graves disease, adrenal adenoma); if the trophic hormone is not suppressed the source is pituitary or ectopic
Titrating replacement
Use the trophic hormone in primary disease (TSH for thyroxine) but the end hormone in secondary disease (free T4), because the feedback signal is the broken part

When it goes wrong

Long-term prednisolone

CRH and ACTH suppressed with adrenal atrophy: recovery takes 6-12 months, so taper slowly and give stress cover for illness and surgery

Over-replacement with levothyroxine

Suppressed TSH with atrial fibrillation and accelerated bone loss, particularly in older people

Practise this structure

2 questions in the bank tagged Feedback Axis.

A 35-year-old woman has palpitations and a 9 kg weight loss over 3 months. Her free thyroxine is 48 pmol/L (reference 10–22 pmol/L), TSH is less than 0.01 mIU/L…

Mechanisms of disease · common

A 41-year-old woman has progressive weight gain, proximal muscle weakness and easy bruising. Her 24-hour urinary free cortisol is 780 nmol/day (reference less t…

Mechanisms of disease · middle twist