steroids of the adrenal cortex Flashcards
what are the steroids of the adrenal cortex ?
glucocorticoids - cortisol in mammals
mineralocorticoids - aldosterone
androgens
what are the layers of the adrenal cortex ?
- blood flows from outer cortex to inner medulla
- steroid synthesis in 1 layer can inhibit different enzymes in other layers
- functional zonation of the cortex with different hormones made in each layer
what are the actions of adrenal steroids ?
mineralocorticoids - salt and water balance
glucocorticoids - metabolism and immune function
why doesn’t cortisol stimulate salt and water retention if it has similar affinity to aldosterone for the aldosterone receptor ?
cortisol is rapidly metabolized to inactive cortisone in the kidney
what are the major actions of cortisol on metabolism ?
General Effects
✅ Affects brain, bone, cardiovascular system, immune system, kidney, skin/connective tissue, and fetus.
✅ Plays a key role in metabolism and glucose regulation.
Metabolic Effects
🟠 Muscle → Breaks down protein, releases amino acids, inhibits GLUT4 (reduces glucose uptake).
🟣 Liver → Stimulates gluconeogenesis (amino acids → glucose), raises blood sugar.
⚪ Adipose Tissue → Promotes lipolysis, releases free fatty acids (FFAs).
📈 Insulin Regulation → Increases glucose, triggers insulin, but reduces glucose uptake in muscle & fat.
Other Effects
🛡️ Immune System → Suppresses immunity.
❤️ Cardiovascular System → Affects heart & blood pressure.
🦴 Bone → Reduces bone formation (risk of osteoporosis).
🧠 Brain → Impacts stress response & cognition.
🚰 Kidney → Influences fluid balance & BP.
🩹 Skin/Connective Tissue → Affects healing & skin integrity.
👶 Fetus → Plays a role in fetal development.
what are the functions of glucocorticoids ?
- Decreased glucose utilization (glucose
sparing)
· Lipolysis
· Gluconeogenesis (maintain plasma glucose
concentration)
· Proteolysis (supply AA substrates for
. gluconeogenesis)
Overall: maintenance of blood glucose -
essential for survival during fasting - Cardiovascular
· Required for vascular integrity
· hypocortisolism: inappropriate
vasodilation, hypotension
· hypercortisolism: hypertension - Anti-inflammatory, immunosuppresive
· 60 years of GC therapy
· Highly profitable industry
· Extremely effective drugs
How do glucocorticoids affect inflammatory mediators derived from arachidonic acid?
- Inhibit Phospholipase A₂ (PLA₂): Decrease arachidonic acid release via lipocortin-1.
- Suppress COX-2 Expression: Reduce prostaglandin (PGE₂, PGI₂) synthesis.
- Inhibit 5-Lipoxygenase (5-LOX): Decrease leukotriene (LTB₄, LTC₄) production.
- Promote Anti-Inflammatory Lipid Mediators: Increase lipoxins for inflammation resolution.
➡️ Result: Reduced inflammation, pain, fever, and immune response.
explain how the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol and androgen production acts in response to circadian rhythms and stress
Inputs:
Circadian rhythm and stress trigger the hypothalamus.
Hypothalamus:
Releases Corticotropin-Releasing Hormone (CRH) and Vasopressin (VP).
Anterior Pituitary:
CRH and VP stimulate the release of Adrenocorticotropic Hormone (ACTH).
Adrenal Cortex:
ACTH stimulates the adrenal glands to produce cortisol and androgens.
Effects of Cortisol:
Regulates metabolism, cardiovascular function, immune response, and fetal development.
Negative Feedback:
High cortisol levels inhibit the hypothalamus and anterior pituitary, reducing CRH and ACTH release, preventing excessive cortisol production.
what is Adrenocorticotropic Hormone (ACTH) ?
- ACTH receptor is member of the melanocortin group of receptors
- Different forms of melanocyte-stimulating hormones bind to melanocortin receptors
- ACTH can also bind to other melanocortin receptors
- Excess circulating ACTH may cause skin pigmentation - sign of addisons disease
what are the clinical features of Addisons ?
Primary adrenal insufficiency
· Low circulating adrenal
steroids
· High ACTH
· Plasma [Na+]: normal to low
· Plasma [K+]: normal to high
· Elevated plasma renin
May be unmasked by significant stress or illness -
shock, hypotension, volume depletion (adrenal crisis)
what are causes of adrenal insufficiency ?
· Addison’s disease: primary adrenal insufficiency
· Secondary
· Hypopituitarism: secondary hypocortisolism
· Failure in RAAS: secondary hypoaldosteronism
· Enzyme defect in steroid synthesis pathways
what is hypercortisolism ?
Cushing’s syndrome: excess glucocorticoid:
· ACTH-dependent
· Cushing’s disease: due to increased ACTH
secretion (typically due to pituitary adenoma:
secondary)
· Ectopic ACTH-secreting tumor
· ACTH-independent
· Adrenal adenoma or carcinoma (primary)
. latrogenic; effect of GC therapy
clinical features:
· Hypertension
· Hyperglycaemia
· Truncal obesity
· Fatigue, muscle weakness
· Virilization (hirsutism in females)
· Depression, mood or psychiatric disturbance
how is hypercortisolism diagnosed ?
First step: confirm
hypersecretion of cortisol
· 24-hour urinary cortisol
· Cortisol at nadir of secretion (around midnight)
Next, determine the cause
· Plasma ACTH dependent or not
· Dexamethosone suppression test
what is the most common cause of Cushings ?
- iatrogenic - excess glucocorticoids due to therapy
- Exogenous glucocorticoids activate cortisol receptor
- At high doses will shut down HPA
- Adrenal cortex atrophies with lack of ACTH stimulation
- Several days may be required for adrenal to become
responsive to ACTH again
What is the difference between Cushing’s Disease and Cushing’s Syndrome?
Cushing’s Disease: Caused by a pituitary tumor overproducing ACTH, leading to high cortisol.
Cushing’s Syndrome: A broader term for excess cortisol from any cause (e.g., pituitary tumor, adrenal tumor, or long-term steroid use).
Key Difference: Cushing’s Disease is a specific type of Cushing’s Syndrome caused by pituitary overproduction of ACTH.
describe the dexamethasone suppression test
Dexamethasone: exogenous steroid
- Low doses will normally supress ACTH secretion via
negative feedback - Low dose fails to supress ACTH secretion with pituitary disease (Cushing’s)
- Higher dose will supress ACTH secretion in Cushing’s
- No supresssion with low or high dose: suggests ectopic source of ACTH (e.g., tumour
elsewhere
