Lecture 6: The Adrenal Gland

Question 1

the adrenal gland is composed of which two endocrine glands (rolled into one structure)?

Answer 1

• adrenal medulla (25%) is a modified sympathetic ganglion (neuroendocrine gland).
• adrenal cortex (75%), is a true endocrine gland.

Question 2

what does the adrenal medulla secrete?

Answer 2

catecholamines from the post-ganglionic cell, mainly epinephrine (adrenaline) but also norepinephrine and dopamine.

Question 3

what does the adrenal cortex secrete?

Answer 3

3 classes of steroid hormones:
1. mineralocorticoids e.g. aldosterone: involved in regulation of Na+ and K+.
2. glucocorticoids e.g. cortisol: involved in maintaining plasma glucose.
3. sex steroids e.g. testosterone

aldosterone and cortisol are essential for survival

Question 4

which zone of the adrenal cortex secretes sex hormones?

Answer 4

zona reticularis

Question 5

which zone of the adrenal cortex secretes glucocorticoids e.g. cortisol?

Answer 5

zona fasciculata

Question 6

which zone of the adrenal cortex secretes aldosterone?

Answer 6

zona glomerulosa

Question 7

defects in 21-hydroxylase is a common cause of?

Answer 7

• congenital adrenal hyperplasia resulting in deficiency of aldosterone and cortisol and associated disruption of salt and glucose balance.
• androgen biosynthesis is unaffected so accumulating steroid precursors are channeled into excessive adrenal androgen production. increased ACTH secretion responsible for enlargement

Question 8

what is the peak time for plasma cortisol levels?

Answer 8

6-9am

Question 9

why is cortisol essential for life?

Answer 9

• loss of cortisol means animals cannot deal with stress, particularly in terms of maintaining blood glucose levels.
• cortisol is crucial in helping to protect the brain from hypoglycaemia.
• it has a permissicve action on glucagon, which is vital al glucagon alone is inadequate in responding to hypoglycaemic challenge.

Question 10

list the actions of cortisol on glucose metabolism (glucocorticoid actions)

Answer 10

1. gluconeogenesis: cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis.
2. proteolysis
3. lipolysis: creates an increase [FFA plasma] creating an alternative fuel supply that allows [BG] to be protected whilst also creating a substrate (glycerol) for gluconeogenesis.
4. decreases insulin sensitivity of muscles and adfipose tissue.

Question 11

list the additional (non-glucocorticoid) actions of cortisol

Answer 11

1. negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption > osteoporosis.
2. impairment of mood and cognition
3. permissive effects on norepinephrine: particularly in vascular smooth muscle (alpha-receptor effect = vasoconstrictive). Cushing’s disease (hypercortisolaemia) is strongly associated with hypertension.
4. suppression of the immune system: can be useful clinically e.g. asthma, UC, organ transplant.

Question 12

what are side effects of glucocorticoid (e.g. cortisol) therapy?

Answer 12

• increased severity and frequency of infection due to immune system suppression.
• muscle wastage due to proteolysis.
• loss of percutaneous fat stores gives appearance of ‘thinning skin’ making it more fragile due to lipolysis.

Question 13

what can happen when withdrawing chronic glucocorticoid treatment too quickly?

Answer 13

• exogenous cortisol has enhanced negative feedback effects on ACTH and CRH.
• loss of trophic action of ACTH on adrenal gland > atrophy of gland > adrenal insufficiency.

Question 14

what is the function of aldosterone?

Answer 14

• aldosterone is a mineralocorticoid, which acts on the kidney to determine the levels of minerals reabsorbed/excreted.
• aldosterone increases the reabsorption of sodium ions and promotes the excretion of potassium ions.
• aldosterone is essential for life.

Question 15

what are the effects of increased aldosterone release?

Answer 15

• stimulates Na+ (and H2O) retention and K+ depletion, resulting in increased blood volume and **increased blood pressure. **

Question 16

what are the effects of decreased aldosterone release?

Answer 16

• leads to Na+ (and H2O) loss and increased plasma [K+], resulting in diminished blood volume and **decreased blood pressure. **

Question 17

list the causes of Cushing’s syndrome/disease

Answer 17

Hypersecretion is most commonly due to a tumour in:
- adrenal cortex (primary hypercortisolism = Cushing’s syndrome) or
- pituitary gland (secondary hypercortisolism = Cushing’s disease, most common, excess ACTH)

• Iatrogenic: too much cortisol administered therapeutically.

Question 18

what is the appearance of Cushing’s disease characterised by?

Answer 18

• wasting of extremities (due to catabolic action of cortisol)
• for unknown reason, fat is redistributed to the face (‘moon face’) and trunk.

Question 19

describe Addison’s disease

Answer 19

• hyposecretion of all adrenal steroid hormones (hyposecretion of cortisol).
• due to immune destruction of adrenal cortex.

Question 20

what is an Addisonian crisis/adrenal crisis?

Answer 20

• life threatening hypotension and hypoglycaemia.
• medical emergency.

Question 21

how does stress increase vulnerability to infection?

Answer 21

• CRH and ACTH release is promoted by stress
• alcohol, caffeine and lack of sleep all ‘disinhibit’ the hypothalamo-pituitary-adrenal axis (HPA). Alcohol in particular depresses the neurons involved in negative feedback further enhancing stres effect and increasing levels of CRH and ACTH.
• subsequent elevation of cortisol levels > immune suppression > increased vulnerability to infection.

Question 22

describe the adrenal medulla

Answer 22

• modified sympathetic ganglion, not true endocrine tissue.
• preganglionic sympathetic fibres terminate on specialised postganglionic cells in the adrenal medulla. These postganglionic fibres do not have axons - instead they release their neurohormones (adrenaline) directly into the blood.

Question 23

describe pheochromocytoma

Answer 23

• a rare neuroendocrine tumour, found in the adrenal medulla which results in excess catecholamines (e.g. epinephrine, norepinephrine).
• this causes increased heart rate, increased cardiac output, increased blood pressure.
• diabetogenic due to adrenergic effect on glucose metabolism.
• responds well to surgery.

Question 24

what are the levels of CRH, ACTH and cortisol when there is secondary hypersecretion in due to pathology in hypothalamus?

Answer 24

CRH - high
ACTH - high
cortisol - high

Question 25

what are the levels of CRH, ACTH and cortisol when there is secondary hypersecretion due to pathology in the anterior pituitary?

Answer 25

CRH- low
ACTH- high
cortisol- high

Question 26

what are the levels of CRH, ACTH and cortisol when their is primary hypersecretion due to pathology in adrenal cortex?

Answer 26

CRH > low
ACTH > low
cortisol > high