What is cortisol permissive for?
For glucagon & catecholamine actions
When are the peaks and troughs of the diurnal rhythm?
- Peaks morning
- Low night
What does cortisol promote in the liver?
Gluconeogenesis
What does cortisol cause in the muscle?
Breakdown of skeletal muscle proteins - substrate for gluconeogenesis.
What effect does cortisol have on adipose tissue?
Enhances lipolysis – FA for energy
What effect does cortisol have on the immune system?
Suppresses the immune system
What effect does cortisol have on calcium?
- Causes negative calcium balance
- ↓absorption, ↑excretion, bone breakdown
- ↓absorption, ↑excretion, bone breakdown
What effect does cortisol have on the brain?
Influences brain function –mood, memory, learning
What are the effects of cortisol being used as a therapeutic drug?
- Suppresses the immune system
- Inhibits the inflammatory response
- Some specific uses
- Bee stings, poison ivy, and pollen allergies
- Prevents rejection of transplanted organs
- Bee stings, poison ivy, and pollen allergies
- Prevents rejection of transplanted organs
What does long-term use of cortisol result in?
Inhibition of ACTH secretion and atrophy of cortisol‐secreting cells - taper doses gradually.
Is cholesterol made on demand or stored?
Made on demand.
What is the half-life of cortisol?
60-90 minutes
What factors affect the release of cortisol?
Circadian rhythm of tonic secretion; stress enhances release
Where is the receptor for cortisol located?
Intracellularly
What is the action of cortisol at the molecular level?
Initiates transcription, translation and new protein synthesis.
What are the 3 major adrenal cortex disorders resulting from hypersecretion?
- Hyperaldosteronism
- Excess Cortisol (Cushing’s syndrome)
- Excess Androgen & Estrogen (adrenogenital syndrome)
What are the 2 types of hyperaldosteronism?
- Primary hyperaldosteronism (Conn’s syndrome)
- Secondary hyperaldosteronism (RAS)
What do the 2 types of hyperaldosteronism cause?
Cause hypernatremia, hypokalaemia, hypertension
What are the different causes of excess cortisol (Cushing's syndrome)?
- Primary adrenal cortex tumors that autonomously secretes cortisol
- Secondary pituitary tumor that autonomously secretes ACTH (Cushing’s disease)
- Hyperstimulation (CRH, ACTH)
- Iatrogenic (physcian caused) hypercortisolism – treat with cortisol therapy
What does excess cortisol (Cushing's syndrome) cause?
Glucose excess, protein shortage, abnormal fat distribution
What causes excess Androgen & Estrogen (adrenogenital syndrome)?
- Lack enzyme in cortisol steroidogenic pathway
- Inappropriate masculinisation in all but adult males
How is excess Androgen & Estrogen (adrenogenital syndrome) treated?
With glucorticoids - repairs glucorticoid deficit and inhibits ACTH (reducing steroid secretion)
What are the signs and symptoms of Cushing's syndrome (hypercortisolism)?
- Excess gluconeogenesis causes hyperglycemia; mimics diabetes
- Muscle protein breakdown, lipolysis causes wasting
- Paradoxical fat deposits in trunk & face due to ↑appetite
- Thin arms & legs, trunk obesity, “moon face”
- Stretched skin due to fat depots causes reddish purple striae
- Mineralocortocoid action of excess glucocorticoid
- Salt & water retention, “moon face”, weakness, hypertension
- Osteoporosis
- Mood elevation then depression, difficult learning & memory
- Thin arms & legs, trunk obesity, “moon face”
- Stretched skin due to fat depots causes reddish purple striae
- Salt & water retention, “moon face”, weakness, hypertension
What is the primary pathology that can lead to hypercortisolism (Cushing's syndrome)?
Primary secretion due to problem with adrenal cortex: CRH and ACTH low (due to cortisol inhibitory feedback) Cortisol levels high.
What are the secondary pathologies that can lead to hypercortisolism (Cushing's syndrome)?
- Secondary secretion due to hypothalamic or pituitary problem.
- Hypothalamic: high CRH, ACTH and cortisol.
- Pituitary: low CRH, high ACTH and cortisol.
What is cortisol hyposecretion due to?
Adrenocortical insufficiency
What is Addison's disease?
Primary adrenal insufficiency - autoimmune destruction of adrenal cortex.
What happens in Addison's disease?
- Autoimmune destruction of adrenal cortex
- Hyposecretion of all adrenal steroid hormones
- ↓Aldosterone
- K+ retention → Cardiac arrhythmias
- Na+ depletion → hypotension
- ↓Cortisol
- ↓stress response & hypoglycaemia
What hereditary problems can cause cortisol hyposecretion?
Adrenal steroid enzyme defects - lack of cortisol & aldosterone causes ↑ androgens & adrenogenital syndrome
What happens in secondary cortisol hyposecretion?
- Deficient cortisol only:
- Abnormal hypothalamus or pituitary
- ↓ACTH & ↓cortisol only (normal aldosterone)
- Abnormal hypothalamus or pituitary
- ↓ACTH & ↓cortisol only (normal aldosterone)
