S9) The Adrenal Glands & Disorders

Question 1

Describe the macroscopic and microscopic structure of the adrenal glands

Answer 1

Question 2

What are the three areas in the adrenal cortex?

Answer 2

• Zona glomerulosa
• Zona fasiculata
• Zona reticularis

Question 3

Identify and describe the hormones in the different regions of the adrenal cortex

Answer 3

Question 4

Steroid hormones are lipid soluble.

Describe their formation and function

Answer 4

• Formation: synthesised from cholesterol in adrenal glands and gonads
• Function: bind to receptors of the nuclear receptor family to modulate gene transcription

Question 5

Provide five examples of steroid hormones

Answer 5

• Glucocorticoids
• Mineralocorticoids
• Androgens
• Oestrogens
• Progestins

Question 6

Corticosteroids exert their actions by regulating gene transcription.

In six steps, outline this process

Answer 6

⇒ Corticosteroids readily diffuse across plasma membrane

⇒ Bind to glucocorticoid receptors

⇒ Binding dissociates chaperone proteins

⇒ Receptor-ligand complex translocates to nucleus

⇒ Dimerisation with other receptors can occur

⇒ Receptors bind to GREs / other transcription factors

Question 7

Aldosterone is the most abundant mineralocorticoid.

Describe its function and transport

Answer 7

• Transport: carrier protein (mainly serum albumin or transcortin)
• Function: central role in regulation of plasma Na⁺, K⁺ and arterial blood pressure

Question 8

Aldosterone is a central component of renin-angiotensin-aldosterone system.

In light of this, explain its specific actions

Answer 8

• Promotes expression of Na⁺/K⁺ pump increasing reabsorption in distal tubules and collecting ducts of nephron
• This influences water retention, blood volume & therefore blood pressure

Question 9

Outline all the cellular and hormonal mechanisms involved in RAAS

Answer 9

Question 10

What is hyperaldosteronism?

Answer 10

Hyperaldosteronism is a physiological state/condition wherein there is an excessive production of aldosterone

Question 11

Distinguish between the two forms of hyperaldosteronism

Answer 11

• Primary – defect in adrenal cortex (high aldosterone:renin ratio)
• Secondary – over-activation of RAAS (low aldosterone:renin ratio)

Question 12

Identify two causes of primary hyperaldosteronism

Answer 12

• Bilateral idiopathic adrenal hyperplasia (most common)
• Aldosterone-secreting adrenal adenoma (Conn’s syndrome)

Question 13

Identify two causes of secondary hyperaldosteronism

Answer 13

• Renin producing tumour e.g. juxtaglomerular tumour (rare)
• Renal artery stenosis

Question 14

Identify 5 clinical signs of hyperaldosteronism

Answer 14

• High blood pressure
• Left ventricular hypertrophy
• Stroke
• Hypernatraemia
• Hypokalaemia

Question 15

The treatment for hyperaldosteronism depends on its form.

Describe the possible options

Answer 15

• Aldosterone-producing adenomas removed by surgery
• Spironolactone (mineralocorticoid receptor antagonist)

Question 16

Cortisol is the most abundant corticosteroid & accounts for ~95% of glucocorticoid activity.

Describe its formation and transport

Answer 16

• Formation: synthesised and released by zona fasiculata in response to ACTH
• Transport: carrier protein in plasma (transcortin)

Question 17

Cortisol is the most abundant corticosteroid & accounts for ~95% of glucocorticoid activity.

Describe its function and regulation

Answer 17

• Function: cortisol receptor exerts its actions by regulating gene transcription
• Regulation: negative feedback to hypothalamus inhibits CRH & ACTH release

Question 18

Cortisol can act in 6 different ways.

Identify these

Answer 18

• Increased proteolysis in muscle
• Increased lipolysis in fat
• Increased gluconeogenesis in liver
• Resistance to stress
• Anti-inflammatory effects
• Depression of immune response

Question 19

Cortisol is useful medication for allergic reactions

Describe its anti-inflammatory effects

Answer 19

• Inhibits macrophage activity
• Mast cell degranulation

Question 20

Explain the resistance of cortisol to stress

Answer 20

• Increased supply of glucose
• Raise BP by making vessels more sensitive to vasoconstrictors

Question 21

Identify one use of cortisol due to its ability to depress the immune response

Answer 21

Cortisol is prescribed to organ transplant patients

Question 22

Outline the HPA axis

Answer 22

Question 23

Explain how the glucocorticoid actions on metabolism lead to the following:

• Increased glucose production
• Breakdown of protein
• Redistribution of fat

Answer 23

Question 24

What is Cushing’s syndrome?

Answer 24

• Cushing’s Syndrome is a clinical condition arising due to chronic excessive exposure to cortisol
• It leads to the re-distribution of fat especially in abdomen, supraclavicular fat pads, dorso-cervical fat pad, (buffalo hump), & on face (moon face)

Question 25

Describe the aetiology of Cushing's syndrome in terms of its endogenous and exogenous causes

Answer 25

Question 26

Identify some signs and symptoms of Cushing's syndrome

Answer 26

- Plethoric moon-shaped face - Buffalo hump - Abdominal obesity - Purple striae - Acute weight gain - Hyperglycaemia - Hypertension

Question 27

Identify two examples of steroid drugs

Answer 27

- Prednisolone - Dexamethasone

Question 28

Steroid drugs have anti-inflammatory & immunomodulatory effects, thus are used to treat inflammatory disorders. Provide some examples of these conditions

Answer 28

- Asthma - Inflammatory bowel disease - Rheumatoid arthritis - Other auto-immune conditions

Question 29

Describe the possible side effects due to steroid drugs

Answer 29

Side-effects are the same as the **effects of higher levels of cortisol**, plus can also have mineralocorticoid effects

Question 30

How might one stop steroid drug usage?

Answer 30

Steroid dosage should be **reduced gradually** and not stopped suddenly

Question 31

What is Addison's disease?

Answer 31

- **Addison’s disease** is a clinical condition due to chronic adrenal insufficiency, commonly due to the destructive atrophy from autoimmune response - Affects more women than men and the exact reason for autoimmunity is unknown

Question 32

Identify some rare causes of Addison's disease

Answer 32

- Fungal infection - Adrenal cancer - Adrenal haemorrhage *e.g. following trauma*

Question 33

Identify some signs and symptoms of Addison's disease

Answer 33

- Postural hypotension - Lethargy - Weight loss - Anorexia - Increased skin pigmentation - Hypoglycaemia

Question 34

What is the reason for the hyperpigmentation presenting in Addison's disease?

Answer 34

- Increased melanin synthesis due to increased MSH & increased POMC - ACTH can also directly activate melanocortin receptors on melanocytes

Question 35

What is Addisonian Crisis?

Answer 35

- **Addisonian Crisis** is a life threatening emergency due to adrenal insufficiency - It is often precipitated by severe stress, salt depravation, infection, trauma or abrupt steroid drug withdrawal

Question 36

How does Addisonian Crisis present?

Answer 36

- Nausea - Vomiting - Pyrexia - Hypotension - Vascular collapse

Question 37

What is the treatment for Addisonian Crisis?

Answer 37

- Fluid replacement - Cortisol

Question 38

Identify the two types of androgens

Answer 38

- Dehydroepiandrosterone (DHEA) - Androstenedione

Question 39

Describe the role of androgens in males and females respectively

Answer 39

- **Male** – DHEA converted to testosterone in testes (insignificant after puberty) - **Female** – adrenal androgens promote libido and are converted to oestrogens by other tissues (only source of oestrogens after menopause)

Question 40

Describe the role of androgens in both sexes

Answer 40

Promote axillary and pubic hair growth

Question 41

The adrenal medulla is a modified sympathetic ganglion of autonomic nervous system. Describe the role of is chromaffin cells

Answer 41

**Chromaffin cells** in adrenal medulla lack axons but act as postganglionic nerve fibres that release hormones into blood – adrenaline (~80%), noradrenaline (~20%)

Question 42

Explain why adrenaline is the dominant hormone produced by the adrenal medulla

Answer 42

Question 43

Outline, in detail, the biological signalling pathway induced at adrenergic receptors

Answer 43

Question 44

Outline the various hormonal actions of adrenaline

Answer 44

Question 45

Outline the cellular mechanism by which adrenaline increases heart rate

Answer 45

Question 46

What is a phaeochromocytoma?

Answer 46

- A **phaeochromocytoma** is a chromaffin cell tumour which secretes catecholamines (mainly adrenaline) - It may precipitate life-threatening hypertension

Question 47

How do phaeochromocytomas present?

Answer 47

- Severe hypertension - Headaches - Palpitations - Diaphoresis (excessive sweating) - Weight loss - Elevated blood glucose

Question 48

Compare and contrast adrenal hormones in terms of the following: - Synthesis - Precursor - Mode - Storage - Solubility - Receptors - Typical effect on enzymes - Speed of response - Effect of bilateral adrenalectomy

Answer 48

Question 49

What are the clinical tests of adrenocortical function used in the differential diagnosis of adrenocortical disease?

Answer 49

- Plasma cortisol levels - ACTH level - 24hr urinary excretion of cortisol and its breakdown products (17-hydroxysteroids) - Dynamic function tests *e.g. dexamethasone suppression tests and ACTH stimulation tests*

Question 50

Describe the action of dexamethasone

Answer 50

**Dexamethasone** is a potent synthetic steroid that, when given orally would normally suppress (by feedback inhibition) the secretion of ACTH and thus cortisol

Question 51

Describe the role of dynamic function tests in diagnosing adrenocortical diseases

Answer 51

- **Dexamethasone suppression** of plasma cortisol by \>50% is characteristic of Cushing’s disease - A normal response to, **Synacthen**, a synthetic analogue of ACTH which normally increases plasma cortisol by \>200 nmol/L, indicates Addison’s disease