Adrenal Structure and Function

Question 1

What are the three zones of Adrenal Cortex, and what do they produce? What are they regulated by?

Answer 1

Zona Glomerulosa: Mineralcorticouds i.e. Aldosterone (regulated by Renin)

Zona Fasciculata: Glucocorticouds i.e. Cortisol (regulated by ACTH)

Zona Reticularis: Sex steroids i.e. DHEA (regulated by ACTH)

Question 2

What does the Adrenal Medulla secrete? What is it regulated by?

Answer 2

Catecholaines i.e. Adrenaline / Noradrenaline (regulated by Sympathetic nervous system)

Question 3

What is the initial compound for which all Steroids are synthesised from?

Answer 3

Cholesterol

Question 4

What compound produced from Cholesterol is the rate limiting step in the Steroid synthesis pathway?

Answer 4

Pregnolone

Question 5

Outline the HPA axis to release Cortisol. How is it regulated?

Answer 5

From the Hypothalamus, Corticotropin Releasing Hormone (CRH) is secreted…

Which causes Adrenocorticotropin Releasing Hormone (ACRH) from the Anterior Pituitary…

Which causes Cortisol release from the Adrenal Cortex…

Negative feedback throughout

Question 6

Why do patients with Cushing’s Disease have trouble with sleep?

Answer 6

Cushing’s Disease patients have high levels of Cortisol, which follows circardian rhythm and normally is low at night to facilitate sleep. In Cushing’s patients it is always high.

Question 7

Outline the role of Aldosterone on Na+ and K+ levels

Answer 7

Aldosterone stimulates Na+ (and water reabsorption), and facilitates K+ secretion

This causes increased blood volume and pressure

Question 8

What is the effect of Angiotensin II, Potassium, ACTH and Sodium on Aldosterone?

Answer 8

Angiotensin II: Increases Aldosterone
Potassium: Increases Aldosterone
ACTH: Increases Aldosterone
Sodium: Decreases Aldosterone

Question 9

What is the major androgen secreted by the Adrenal Gland?

Answer 9

DHEA

Question 10

Cortisol is a Glucocorticoid, however can act as a Mineralcorticoid i.e. Aldosterone. In a normal person however, how is this prevented?

Answer 10

Inactivation of Cortisol by 11beta-HSD2

Question 11

What might you see in a patient with Addison’s disease (Primary)?

Answer 11

Primary Adrenal Insufficiency

• High Potassium levels
• Low Sodium / water levels
• Low Blood pressure
• Pigmented skin / buccal (due to ACTH increase)
• Hypoglycaemia

Question 12

What is the main cause of Addison’s disease? Any secondary causes?

Answer 12

• Auto-immune (80%)

- TB / Fungal / CMV

Question 13

What is the best diagnostic test for Addison’s disease (Primary)?

Answer 13

ACTH Stimulation Test

Give patient ACTH and wait 30 mins. In normal patients, Cortisol levels will rise however in Addison’s, will not.

Question 14

What might you see in a patient with Addison’s disease (Secondary)?

Answer 14

Secondary Adrenal Insufficiency

• Normal K+ levels
• Normal Na+ levels
• No hyperpigmentation (due to normal ACTH)
• Hypoglycaemia (due to low levels of Cortisol)

Question 15

Why is ACTH raised in Addison’s disease (Primary)?

Answer 15

There is not enough Cortisol produced by the Adrenal cortex, so this is a feedback loop to stimulate more ACTH

Question 16

What is Conn’s syndrome? What symptoms might a Conn’s patient have?

Answer 16

Hyperaldosteronism, hence high Na+ levels and low K+ levels

Question 17

What is the most common cause of Cushing’s Syndrome?

Answer 17

Exogenous corticosteroid use

Question 18

Difference between Cushing’s Syndrome and Cushing’s Disease?

Answer 18

Cushing’s Syndrome: Increase in Cortisol for any reason

Cushing’s Disease: Increase in Cortisol due to a tumour in the Pituitary Gland raising ACTH levels or due to tumour in the Adrenal Cortex

Question 19

Explain how the Dexamethasone Supression test works

Answer 19

Dexamethasone is a GR receptor agonist. In normal patients, an injection of Dexamethasone will suppress ACTH. In Cushing’s disease however, it will stay high if they have ACTH-dependent Cushing’s disease

Question 20

A tumour affecting the Adrenal medulla is called what? What will it release?

Answer 20

Phaeochromocytoma (i.e. MEN2), releasing Norepinephrine (i.e. Metanephrine in urine)