glucocorticoids

how is the rate of glucocorticoid synthesis and secretion controlled

controlled by anterior pituitary hormone ACTH under negative feedback control

what is the main glucocorticoid secreted in humans

cortisol

which pituitary hormone controls glucocorticoid release

ACTH

how is cortisol secretion regulated

by negative feedback control via ACTH from anterior pituitary

what trophic effect does ACTH have on adrenal cortex

it maintains normal growth and structure of adrenal cortex

what rhythm does cortisol secretion follow

circadian rhythm (24-hour cycle)

when are cortisol levels the highest

in the morning, before waking

what are the main functions of cortisol

• regulation of carbohydrate, protein and fat metabolism

• anti-inflammatory effects

• immunosuppressive effects

• increased resistance to stress

at what concentrations do anti-inflammatory and immunosuppressive effects occur

high or therapeutic concs

how does cortisol increase blood glucose

by stimulating gluconeogenesis in liver

what effect does cortisol have on liver glycogen

increased synthesis and storage of glycogen

how does cortisol interact with insulin

antagonises insulin’s action on glucose uptake in muscle and adipose tissue

what condition can prolonged cortisol action cause

hyperglycaemia

what effect does cortisol have on protein synthesis

inhibits protein synthesis in peripheral tissue

what tissues undergo protein breakdown due to cortisol

• muscle

• skin

• bone

what clinical effects result from excess cortisol on proteins

• muscle wasting

• easy bruising

• skin thinning

• bone matrix loss

what effect does cortisol have on fat

stimulates lipolysis and inhibits fat synthesis

what fat distribution pattern is seen in excess cortisol

central obesity - face, trunk and between shoulders

how do glucocorticoids reduce inflammation

by inhibiting inflammatory mediator synthesis and leukocyte recruitment

give examples of diseases treated using glucocorticoids for inflammation

• rheumatic diseases

• allergic rhinitis

• eczema

how do glucocorticoids help in severe asthma/anaphylaxis

inhibit histamine synthesis and mast cell release

which immune cells are mainly affected by glucocorticoids

T-lymphocytes

what immune effect results from glucocorticoid therapy

reduced antibody production - immunosuppression

give 2 therapeutic uses of immunosuppression

• autoimmune diseases

• transplant rejection prevention

name stressors that increase cortisol release

• trauma

• surgery

• infection

• pain

• haemorrhage

• hypoglycaemia

• cold, fever

• emotional stress

why is cortisol essential for stress survival

protects body by supressing harmful inflammatory and immune responses

what happens if long term glucocorticoids are stopped suddenly

adrenal insufficiency → inability to handle stress

how should glucocorticoids be stopped safely

gradual dose reduction (tapering)

where is glucocorticoid receptor located

in cytosol (cytoplasm)

what happens after cortisol binds to receptor

complex moves to nucleus and binds to DNA

what is the result of cortisol-DNA binding

gene transcription induction or repression

why are glucocorticoid effects delayed

because they depend on gene transcription and protein synthesis

name the disease due to hyposecretion

Addison’s disease

what causes primary hypoadrenalism (addisons disease)

autoimmune adrenal destruction

what hormone deficiencies occur in Addison’s disease

cortisol and aldosterone

give 5 symptoms of Addison’s disease

• muscle weakness

• weight loss

• hypotension

• hyperpigmentation

• fatigue

• nausea/vomiting

why does hyperpigmentation occur in Addison’s disease

high ACTH has MSH-like (melanocyte-stimulating) activity

how is Addison’s disease treated

hydrocortisone and fludrocortisone replacement therapy

name the condition caused by hypersecretion of cortisol

Cushing’s syndrome

what is Cushing’s syndrome

• excess cortisol (hypercortisolism)

• excess ACTH from pituitary overproduction

name 5 common features of Cushing’s syndrome

• moon face

• buffalo hump

• muscle wasting

• thin limbs

• obesity centrally

what drug inhibits cortisol synthesis

metyrapone

what enzyme does metyrapone inhibit

11β-hydroxylase

what drug inhibits ACTH release in Cushing’s disease

pasireotide

typical hormone levels in Cushing’s syndrome

• high cortisol

• low ACTH

treatment options for Cushing syndrome

• tumour removal

• metyrapone

• pasireotide

• steroid replacement