Steroids of the adrenal cortex

Question 1

What are the steroids of the adrenal cortex?

Answer 1

Glucocorticoids: Oruncupally cortisol in mammals
Mineralcorticoids: aldosterone
Androgens

Question 2

Cortisol

Answer 2

The stress hormone, but essential to life

Metabolic, cardiovascular and immune functions

Question 3

Aldosterone

Answer 3

Maintains blood volume by regulating amount of body sodium

Question 4

Adrenal blood flow and functional zonation

Answer 4

• 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

Question 5

Sodium retention

Answer 5

Active reabsorption of sodium (with associated passive reabsorption of water)
Active secretion of potassium

Question 6

Volume regulation

Answer 6

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

Question 7

Circulating concentrations of cortisol much higher than aldosterone so why doesn’t cortisol stimulate salt and water retention?

Answer 7

Cortisol is rapidly metabolized to inactive cortisone in the kidney

Question 8

What is the enzyme inactivates cortisol?

Answer 8

11 beta-hydroxysteroid dehydrogenase type 2

Question 9

What happens when cortisol isn’t active?

Answer 9

Rare mutation of 11 B-HSD2 leads to a syndrome of apparent mineralocorticoid excess (AME)

Question 10

What food can affect 11B-HSD2?

Answer 10

A compound in liquorice blocks the enzyme

Question 11

The glucocorticoid receptor

Answer 11

Nuclear receptor superfamily
A 3-domain structure
-Ligand-binding,
-DNA binding (binds to HRE on genomic DNA)
- N-terminal transcription co-factor-binding

Question 12

Functions of glucocorticoids

Answer 12

Decreased glucose utilization

• Proteolysis
• Gluconeogenesis
• Lipolysis

Question 13

Part 2 Glucocorticoids

Answer 13

Cardiovascular

• Required for vascular integrity and maintenance of blood
• Hypocorisolism: inappropriate vasodilation, hypotension
• Hypercortisolism: hypertension

Question 14

Part 3 glucocorticoids

Answer 14

Anti-inflammatory, immunosuppresiv
- 60 years of GC therapy 
- Highly profitable industry
- Extremely effective drugs
DOUBLE EDGED SWORD

Question 15

Adrenal insufficiency

Answer 15

Addison’s disease: primary adrenal insufficiency
Secondary (hypopituitarism; secondary to failure in RAAS)
-Enzyme defect in steroid synthesis pathways

Question 16

Clinical features of Addison’s

Answer 16

Low circulating adrenal steroids

• High ACTH
• Plasma [Na+]: normal to low
• Plasma [K+]: normal to high
• Elevated plasma renin

Question 17

What can mask Addison’s ?

Answer 17

Significant stress or illness - shock, hypotension, volume depletion (adrenal crisis)

Question 18

Excess circulating ACTH

Answer 18

Leads to Skin pigmentation

Question 19

What is Cushing’s syndrome

Answer 19

Excess glucocorticoid

Question 20

What causes Cushing’s?

Answer 20

ACTH - dependent
Increased ACTH secretion
Ectopic ACTH - secreting tumour
ACTH- Independent
- Adrenal adenoma or carcinoma 
-Latrogenic; effect of GC therapy

Question 21

Clinical features of Cushing’s

Answer 21

Hypertension
Hyperglycaemia 
Truncal obesity
Fatigue, muscle weakness
Virilization (hirsutism in females)
Depression, mood or psychiatric disturbances

Question 22

What is hirsutism?

Answer 22

Excessive hair growth where the hair is normally minimal or absent

Question 23

What is virilization

Answer 23

Exaggerated male feature in females

Question 24

Diagnosis of Cushing’s

Answer 24

First, confirm hypersecretion of cortisol
24-hour urinary cortisol
Cortisol at nadir of secretion (around midnight)

Question 25

How to determine the cause of hypersecretion of cortisol

Answer 25

Plasma ACTH

Dexamethosone suppression test

Question 26

Dexamethasone suppression test

Answer 26

An exogenous steroid
Low doses will normally suppress ACTH secretion via negative feedback
Low dose fails to suppress ACTH secretion with the pituitary disease - CUSHING’S
A higher dose will suppress ACTH secretion in Cushing’s
No Depression with low or high dose: suggests the ectopic source of ACTH (e.g. tumor elsewhere)