Adrenal Glands

Question 1

State the regions of the adrenal gland

Answer 1

Capsule on outside, cortex in middle and medulla on inside

Question 2

State the hormones produced in the adrenal gland and its location

Answer 2

• Cortex has 3 layers - salt, sugar, sex, excitement
  
  • Zona glomerulosa - mineralocorticoids (aldosterone)
  • Zona fasiculata - glucocorticoids (cortisol)
  • Zona reticularis - glucocorticoids + androgens
• Medulla - chromaffin cells synthesise and release catecholamines into blood

Question 3

State the 3 layers of the adrenal cortex

Answer 3

• Zona glomerulosa - outermost
• Zona fasiculata
• Zona reticularis - innermost

Question 4

Explain the mechanism of action of cortisol in target cells

Answer 4

• Bind to receptors of nuclear receptor family to modulate gene transcription - intracellular
  
  • Diffuses across plasma membrane and binds to glucocorticoid receptors
  • Binding causes dissociation of chaperone protein (heat shock protein 90), allowing receptor-ligand complex to enter nucleus
  • Receptors bind to glucocorticoid response elements (GRE) or other transcription factors

Question 5

Describe the effects of aldosterone

Answer 5

• Carrier protein - serum albumin and sometimes transcortin
• Regulates gene transcription - intracellular
• Regulates plasma Na, K and arterial blood pressure
• Promotes expression of Na/K pump in nephron to promote reabsorption of Na and excretion of K
  
  • Influences water retention, blood volume and therefore blood pressure
• Component of renin-angiotensin-aldosterone system

Question 6

Explain how cortisol secretion is regulated

Answer 6

• Cortisol regulated by a negative feedback loop
• Cortisol inhibits CRH release in hypothalamus
• Also inhibits ACTH release in anterior pituitary
• CRH increased in response to physical (temperature, pain), chemical (hypoglycaemia) and emotional stressors

Question 7

Explain how ACTH can lead to hyperpigmentation

Answer 7

• Decreased cortisol leads to negative feedback on anterior pituitary leading to ACTH synthesis
• More POMC required to synthesize ACTH
  
  • Produces both ACTH and MSH along with other peptides
  • ACTH itself can also activate melanocortin receptors on melanocytes
• Melanin stimulating hormone (MSH) overproduction leads to hyperpigmentation due to increased melanin synthesis
• Hyperpigmentation common in Addison’s disease

Question 8

How are cortisol and aldosterone carried in the blood

Answer 8

• Aldosterone - serum albumin and sometimes transcortin

- Cortisol - transcortin and sometimes serum albumin

Question 9

Describe the main physiological actions of cortisol

Answer 9

• Increase gluconeogenesis in liver which increase glucose
  
  • Stimulates insulin to store glycogen
• Increase protein breakdown in muscle
  
  • Inhibits GLUT-4 to prevent glucose uptake in muscles so relies on protein for energy
• Increased lipolysis in adipose tissue - decreases sensitivity of adipose cells to insulin
  
  • Redistribution of fat to abdomen
• Resistance to stress - increase glucose supply, raise blood pressure by making vessels more sensitive to vasoconstrictors
• Anti-inflammatory effects - mast cell degranulation useful medication against allergies
• Depression of immune response - organ transplant patients

Question 10

Explain the actions of chromaffin cell

Answer 10

• Chromaffin cells lack axons but act as postganglionic nerve fibres that release adrenaline and noradrenaline into the blood
  
  • Convert tyrosine into dopamine and then into noradrenaline
  • 20% chromaffin cells lack N-methyl transferase enzyme needed to convert noradrenaline to adrenaline
    
    • Adrenaline - 80%, noradrenaline 20%

Question 11

What are the actions of androgens

Answer 11

• DHEA and androstenedione secreted
• Partially regulated by ACTH and CRH
• In male, DHEA converted to testosterone in testes
  
  • Insignificant after puberty as testes release far more testosterone
• In female, adrenal androgens promote libido and are converted to oestrogen by other tissues
  
  • After menopause, only sources of oestrogen
• Promote axillary and public hair growth in both sexes

Question 12

Explain the actions of adrenaline on adrenergic receptors

Answer 12

• Activate GPCRs
• Binds to alpha 1,2 and beta 1,2 receptors
  
  • Alpha 1 receptors activate Gq which stimulates phospholipase C to produce DAG and IP3
    
    • PKC and calcium release via IP3 receptor on SR/ER
  • Alpha 2 receptor activate Gi which inhibits adenylyl cyclase
  • Beta 1,2 receptors activate Gs which stimulate adenylyl cyclase to produce cAMP and then protein kinase A
    
    • Can phosphorylate and open VOCC

Question 13

Describe how adrenaline can increase heart rate

Answer 13

• Adrenaline binds to ß-1 receptors which activate Gs and stimulate adenylyl cyclase to produce cAMP
  
  • cAMP activates HCN channels - responsible for funny current
  • Increase slope and shortens duration
• cAMP activates protein kinase A
  
  • PKA phosphorylation of HCN channels modulates function
  • PKA phosphorylation of L-type Ca channels - potentiates opening
    
    • Increase slope of upstroke of SA action potential

Question 14

Explain how the RAAS system works and state its effects

Answer 14

• Stimulated by hypovolaemia or hypotension
• Decrease in renal perfusion, drop in blood pressure and increased sympathetic tone from baroreceptor activation leads to more renin release from kidney
• Angiotensinogen produced in the liver cleaved into angiotensin I
• Angiotensin converting enzyme (ACE) produced in lung endothelial cells convert angiotensin I to angiotensin II
• Angiotensin II has many effects
  
  • Causes arterial vasoconstriction
  • Stimulates aldosterone production in adrenal glands which increases expression of Na/K pump leading to water retention
    
    • Stimulates ADH production from posterior pituitary which moves and opens aquaporin channels to aid water reabsorption

Question 15

What are the causes of Cushing’s Syndrome

Answer 15

• Chronic excessive exposure to cortisol
• Most commonly caused by prescribed glucocorticoid drugs
  
  • Used to treat inflammatory disorders - asthma, inflammatory bowel disease, rheumatoid arthritis
  • Steroid dosage should be reduced gradually and not stopped suddenly
• Cushing’s disease - adenoma in pituitary gland secreting ACTH
• Adrenal Cushing’s - excess cortisol produced by adrenal tumour
  
  • Secrete glucocorticoids but may also secrete androgens
  • Treatment - adrenalectomy
• Small cell lung cancer - non pituitary adrenal tumours producing ACTH

Question 16

What are the signs and symptoms of Cushing’s syndrome

Answer 16

• Abdominal obesity - increased lipogenesis
• Skinny and weak arms and legs - increased muscle proteolysis
• ‘Buffalo hump’
• Plethoric moon-shaped face
• Purple striae - proteolysis leading to easy bruising because if thin skin
• Red stretch marks on abdomen
• High blood pressure and diabetes - sodium and fluid retention
• Osteoporosis

Question 17

How to test to distinguish between Cushing’s disease and adrenal Cushing’s

Answer 17

• Suppression test used to differentiate between Cushing’s disease and adrenal Cushing’s
• Use dexamethoasone - synthetic steroid
  
  • If positive (cortisol suppressed), Cushing’s disease as ACTH will still be inhibited in a pituitary tumour
    
    • If negative (cortisol not suppressed), adrenal Cushing’s as cortisol produced from adrenal gland regardless of ACTH concentration

Question 18

State the causes of Addison’s disease

Answer 18

• Chronic adrenal insufficiency
• Caused by destructive atrophy of adrenal glands from autoimmune response
• Disorders in pituitary or hypothalamus that lead to decreased secretion of ACTH or CRF

Question 19

State the signs and symptoms of Addison’s disease

Answer 19

• Postural hypotension - fluid depletion
• Lethargy
• Weight loss
• Anorexia
• Abdominal pain
• Dizziness
• Hyperpigmentation
• Hypoglycaemia - sodium and fluid depletion

Question 20

What is Addisonian crisis and its causes

Answer 20

• Life threatening emergency due to adrenal insufficiency (loss of both cortisol and mineralocorticoids)
  
  • Precipitated by - severe stress, salt depravation, infection, trauma, cold exposure, abrupt steroid drug withdrawal

Question 21

What are the symptoms and treatment of Addisonian crisis

Answer 21

• Symptoms - nausea, vomiting, pyrexia, hypotension, vascular collapse
• Treatment - fluid replacement (dextrose in normal saline), IV hydrocortisone

Question 22

How would you test for Addison’s disease

Answer 22

• Stimulation test using synthacthen (synthetic analogue of ACTH)
• If normal, should increase plasma cortisol

Question 23

Discuss the cause, presentation and treatment of Congenital adrenal hyperplasia

Answer 23

• Autosomal recessive
• Block in adrenal cortex pathway
• 21 hydroxylase deficiency - less glucocorticoid and mineralocorticoid production
  
  • Precursor of 21 hydroxylase diverted to produce more androgen - high sex steroid level
  • Result in genital ambiguity in female infants
• Leads to large amounts of ACTH synthesis - hyperplasia of adrenal cortex
• Presentation - hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia
• Treatment - treat adrenal crisis, determine sex of baby

Question 24

Explain primary and secondary hyperaldosteronism and distinguish between the two

Answer 24

• Excess aldosterone produced from adrenal glands
• Primary - defect in adrenal cortex
  
  • Bilateral idiopathic adrenal hyperplasia
  • Conn’s syndrome - aldosterone secreting adrenal adenoma
  • Low renin levels (high aldosterone: renin ratio)
    
    • Low renin does not cause decrease in aldosterone in Conn’s syndrome
• Secondary - due to over activity of the RAAS
  
  • Renin producing tumour
  • Renal artery stenosis
  • High renin levels (low aldosterone: renin ratio)
    
    • Aldosterone increase water retention -> increase blood volume -> increase arterial pressure -> decrease renin production -> decrease aldosterone

Question 25

What are the signs and treatment of hyperaldosteronism

Answer 25

• Signs - high blood pressure
  
  • Left ventricular hypertrophy
  • Stroke
  • Hypernatraemia
  • Hypokalaemia
• Treatment - dependent on type
  
  • Aldosterone-producing adenomas removed by surgery (adrenalectomy)
  • Spironolactone (mineralocorticoid receptor antagonist)

Question 26

What are the symptoms if high androgen levels

Answer 26

• Female - excessive body hair growth, acne, menstrual problems, virilisation (development of male characteristics such as low voice), increased muscle bulk
• High oestrogen - breast development, broad hips, accumulation of fat in breast and buttocks, body hair distribution

Question 27

Describe the cause and symptoms of phaeochromocytoma

Answer 27

• Genetic inheritance common
• Tumour of adrenal medulla
• Symptoms
  
  • Hypertension
  • Anxiety
  • Palpitations
  • Pallor
  • Sweating
  • Glucose intolerance
  • Headaches
  • Panic attacks
  • Diaphoresis - excessive sweating
  • Weight loss
    
    • Collapse