Physiology: adrenal glands

Question 1

ADRENAL CORTEX
- The group of hormones (as a whole) secreted by the adreanl cortex?

Answer 1

Corticosteroids

Question 2

ADRENAL CORTEX
- The three layers?
- The group of hormones they secrete?
- How to remember?

Answer 2

Zona glomerulosa: mineralocorticoids

Zona fasciculata: glucocorticoids

Zona reticularis: androgens

–>Salt, sugar, sex

Question 3

ADRENAL CORTEX
What germ layer contributes to the adrenal cortex?

Answer 3

Mesoderm

Question 4

ADRENAL CORTEX
Describe the generalised HPA axis for corticosteroid secretion

Answer 4

Question 5

ADRENAL CORTEX
Describe the pattern of CRH release
Factors impacting CRH/ACTH release?

Answer 5

CRH is released by the hypothalamus in a pulsatile and diurnal manner (peak before waking, decline over the day, lowest before midnight)

Stress - mental, fever, hypoglycemia

Question 6

ADRENAL CORTEX
Describe the synthesis of corticosteroids

Answer 6

Question 7

ADRENAL MEDULLA
Name of the cells?
What do they release?
Embryonic origin?

Answer 7

Medullar chromaffin cells - modified postganglionic sympathetic neurons
Synthesise catecholamines - 80% adrenaline, 20% NA
Neural crest cells

Question 8

MINERALOCORTICOIDS (zona glomerulosa)
- What is the most potent mineralocorticoid?

Answer 8

Aldosterone

Question 9

MINERALOCORTICOIDS (zona glomerulosa)
Pharmacokinetics
- Describe protein binding
- Half life?
- Where is it metabolised?
- Where is it excreted?

Answer 9

50-70% is bound to corticosteroid binding globulin (weakly) and albumin in circulation; the rest is free

Short half life of ~15-20 minutes

Largely metabolised in the liver

Metabolites are excreted in the urine

Question 10

MINERALOCORTICOIDS (zona glomerulosa)
Triggers for aldosterone secretion?

Answer 10

• Decreased BV/BP
• Increased K+ in the blood
• Extreme stress
  - Mass secretion of ACTH
• Note: increased BV/BP leads to ANP secretion –> decreases aldosterone secretion

Question 11

MINERALOCORTICOIDS (zona glomerulosa)
- Impact of cortisol on mineralocorticoid receptor?

Answer 11

Cortisol can act on the mineralocorticoid receptor (MR) in renal tubule cells

However, these cells contain an enzyme that converts cortisol to a product with low affinity for the MR

Question 12

MINERALOCORTICOIDS (zona glomerulosa)
Effects of aldosterone?

Answer 12

Question 13

GLUCOCORTICOIDS (zona fasciculata)
What is the most potent glucocorticoid?

Answer 13

Cortisol

Question 14

GLUCOCORTICOIDS (zona fasciculata)
- What kind of receptor does cortisol bind to?
- Describe pattern of cortisol secretion over the day

Answer 14

• Cytoplasmic glucocorticoid receptor
• Like CRH/ACTH, it peaks in the morning before waking, lowest around midnight

Question 15

GLUCOCORTICOIDS (zona fasciculata)
Functions of glucocorticoids

Answer 15

Question 16

GLUCOCORTICOIDS (zona fasciculata)
- Describe protein binding
- Where is it metabolised/inactivated?
- Where is it excreted?

Answer 16

Question 17

GONADOCORTICOIDS/ANDROENS (zona reticularis)
They are stimulated by ACTH release.
- Do the androgens provide any feedback inhibition to the hypothalamus/pituitary gland?

Answer 17

No

Question 18

GONADOCORTICOIDS/ANDROENS (zona reticularis)
- What are the androgens that are made within the zona reticularis? Are these strong or weak androgens?
- Where are these converted to more potent hormones (testosterone and estradiol)?

Answer 18

DHEA and androstenedione
Weak androgens

In peripheral tissues

Question 19

GONADOCORTICOIDS/ANDROENS (zona reticularis)
Do adrenal androgens or gonadal (testes/ovaries) androgens play the major role in:
- Males?
- Females?

In menopausal women, what is the main source of estrogen?

Answer 19

Males: testes androgens play the major role
Females: adrenal androgens play the major role

Menopausal women: adrenal estronges

Question 20

CUSHING’S DISEASE/SYNDROME
- Differentiate Cushing’s disease vs syndrome

Answer 20

Cushing’s disease: anterior pituitary adenoma –> excess ACTH (hence excess cortisol)

Cushing’s syndrome: any other cause leading to excess cortsiol

Question 21

CUSHING’S DISEASE/SYNDROME
Symptoms

Answer 21

Question 22

CUSHING’S DISEASE/SYNDROME
- Differentiate ACTH dependent and ACTH independent Cushing’s

Answer 22

ACTH dependent
- ACTH must be rised; this is what causes increase in cortisol

ACTH independent
- Cortisol is rised; leads to feedback suppresion of ACTH

Question 23

CUSHING’S DISEASE/SYNDROME
How can dexamethasone suppression tests help distinguish between ACTH dependent/independent Cushing’s?

Answer 23

Dexamethasone is a synthetic glucocorticoid; given in high doses in this test

In Cushing’s disease: high dose dexamethasone can suppress ACTH

Primary adrenal overproduction of cortisol: has little effect (already has low levels of ACTH)

Question 24

ADDISON’S DISEASE
- What is it?
- Differentiate primary vs secondary

Answer 24

Adrenal insufficiency: the adrenal cortex produces insufficient corticosteroids

Primary failure of the entire adrenal cortex - autoimmune/infection destruction, cancer

Secondary failure - deficiency of ACTH

Question 25

ADDISON'S DISEASE - Symptoms

Answer 25

Question 26

ADDISON'S DISEASE What is an ACTH stimulation test? What is the result in healthy people versus those with adrenocortical insufficiency (primary)?

Answer 26

Administration of ACTH analogue, look at serum cortisol levels Healthy: ACTH analogue administration usually leads to increased serum cortisol levels Primary adrenocortical insufficiency: ACTH analogue administration does not impact serum cortisol levels

Question 27

PHAECHROMOCYTOMA What is it? Symptoms relate to:

Answer 27

Chromaffin cell tumour --> excessive secretion of NA (common) Excessive SNS stimulation