Steroids of the adrenal cortex Flashcards
What are the steroids of the adrenal cortex?
Glucocorticoids: Oruncupally cortisol in mammals
Mineralcorticoids: aldosterone
Androgens
Cortisol
The stress hormone, but essential to life
Metabolic, cardiovascular and immune functions
Aldosterone
Maintains blood volume by regulating amount of body sodium
Adrenal blood flow and functional zonation
- Blood flows from outer cortex to inner medulla
- Layer specific enzymes; steroid synthesis in or layer can inhibit different enzymes in subsequent layers
- Results in functional donation of cortex with different hormones made in each layer
Sodium retention
Active reabsorption of sodium (with associated passive reabsorption of water)
Active secretion of potassium
Volume regulation
Increased MC activity increases the amount of sodium retained in the body, not the concentration. This is because an osmotically - equivalent amount of water is retained with the sodium, so the concentration doesn’t change
Circulating concentrations of cortisol much higher than aldosterone so why doesn’t cortisol stimulate salt and water retention?
Cortisol is rapidly metabolized to inactive cortisone in the kidney
What is the enzyme inactivates cortisol?
11 beta-hydroxysteroid dehydrogenase type 2
What happens when cortisol isn’t active?
Rare mutation of 11 B-HSD2 leads to a syndrome of apparent mineralocorticoid excess (AME)
What food can affect 11B-HSD2?
A compound in liquorice blocks the enzyme
The glucocorticoid receptor
Nuclear receptor superfamily
A 3-domain structure
-Ligand-binding,
-DNA binding (binds to HRE on genomic DNA)
- N-terminal transcription co-factor-binding
Functions of glucocorticoids
Decreased glucose utilization
- Proteolysis
- Gluconeogenesis
- Lipolysis
Part 2 Glucocorticoids
Cardiovascular
- Required for vascular integrity and maintenance of blood
- Hypocorisolism: inappropriate vasodilation, hypotension
- Hypercortisolism: hypertension
Part 3 glucocorticoids
Anti-inflammatory, immunosuppresiv - 60 years of GC therapy - Highly profitable industry - Extremely effective drugs DOUBLE EDGED SWORD
Adrenal insufficiency
Addison’s disease: primary adrenal insufficiency
Secondary (hypopituitarism; secondary to failure in RAAS)
-Enzyme defect in steroid synthesis pathways
Clinical features of Addison’s
Low circulating adrenal steroids
- High ACTH
- Plasma [Na+]: normal to low
- Plasma [K+]: normal to high
- Elevated plasma renin
What can mask Addison’s ?
Significant stress or illness - shock, hypotension, volume depletion (adrenal crisis)
Excess circulating ACTH
Leads to Skin pigmentation
What is Cushing’s syndrome
Excess glucocorticoid
What causes Cushing’s?
ACTH - dependent Increased ACTH secretion Ectopic ACTH - secreting tumour ACTH- Independent - Adrenal adenoma or carcinoma -Latrogenic; effect of GC therapy
Clinical features of Cushing’s
Hypertension Hyperglycaemia Truncal obesity Fatigue, muscle weakness Virilization (hirsutism in females) Depression, mood or psychiatric disturbances
What is hirsutism?
Excessive hair growth where the hair is normally minimal or absent
What is virilization
Exaggerated male feature in females
Diagnosis of Cushing’s
First, confirm hypersecretion of cortisol
24-hour urinary cortisol
Cortisol at nadir of secretion (around midnight)
