Makindo Medical Notes

Related Subjects: |Adrenal Physiology |Addison's Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

Adrenocorticotropic hormone (ACTH) is a peptide hormone produced by the anterior pituitary gland. It plays a critical role in regulating the adrenal cortex's secretion of glucocorticoids, mainly cortisol, which are essential for stress response, metabolism, and immune function.

Synthesis and Secretion

• Production:
  • ACTH is synthesized from a precursor protein called pro-opiomelanocortin (POMC).
  • POMC is cleaved into several peptides, including ACTH, in the corticotroph cells of the anterior pituitary.
• Regulation:
  • ACTH secretion is regulated by corticotropin-releasing hormone (CRH) from the hypothalamus.
  • CRH release is stimulated by various factors, including stress, low blood cortisol levels, and circadian rhythms.
  • Negative feedback: Elevated cortisol levels inhibit CRH and ACTH secretion.

Function of ACTH

• Stimulation of Adrenal Cortex:
  • ACTH binds to specific receptors on the adrenal cortex, particularly in the zona fasciculata and zona reticularis.
  • Stimulates the production and release of glucocorticoids (mainly cortisol) and androgens.
• Cortisol Release:
  • Cortisol has several vital functions, including regulation of metabolism, immune response, and stress adaptation.
  • Increases blood glucose levels by promoting gluconeogenesis and inhibiting glucose uptake by tissues.
  • Enhances the breakdown of proteins and lipids.
  • Suppresses the immune system and reduces inflammation.
• Androgen Production:
  • ACTH stimulates the adrenal cortex to produce androgens, which are precursors for sex hormones.

Clinical Significance

• ACTH Stimulation Test:
  • Used to assess adrenal gland function by measuring cortisol response to synthetic ACTH.
  • Helps diagnose conditions such as Addison's disease (adrenal insufficiency) and secondary adrenal insufficiency (pituitary dysfunction).
• Disorders of ACTH Secretion:
  • Cushing's Syndrome:
    • Caused by prolonged exposure to high levels of cortisol.
    • Can result from ACTH-secreting pituitary adenomas (Cushing's disease) or ectopic ACTH production (e.g., from lung tumours).
  • Addison's Disease:
    • Characterized by adrenal insufficiency and low cortisol production.
    • Can be primary (due to adrenal damage) or secondary (due to insufficient ACTH production).
  • Congenital Adrenal Hyperplasia (CAH):
    • A group of genetic disorders affecting cortisol synthesis, leading to increased ACTH levels and adrenal hyperplasia.

ACTH and Circadian Rhythm

• ACTH secretion follows a diurnal pattern, with peak levels in the early morning and lowest levels at night.
• This circadian rhythm is crucial for maintaining appropriate cortisol levels and metabolic functions throughout the day.

Summary

Adrenocorticotropic hormone (ACTH) is a vital hormone produced by the anterior pituitary gland, regulating the adrenal cortex's production of glucocorticoids and androgens. Its secretion is controlled by CRH from the hypothalamus and follows a circadian rhythm. ACTH plays a critical role in stress response, metabolism, and immune function. Understanding its functions and regulation is essential for diagnosing and managing disorders related to adrenal and pituitary function.

Values

• Reference ranges 0 – 47 ng/L (sample taken at 9am)
• Ideally take samples between 9am and 10am.
• Consider Short synacthen test if the 30 min cortisol is less than 500 nmol/L