The Adrenal gland

Question 1

How much does an adrenal gland weigh?

Answer 1

4g

Question 2

Describe the venous drainage of the adrenal veins

Answer 2

Left adrenal vein - left renal vein

Right adrenal vein - inferior vena cava

Question 3

What does the adrenal medulla produce?

Answer 3

Catecholamines e.g. norepinephrine and epinephrine

Question 4

What are the 3 layers of the adrenal cortex (outermost to innermost) and what do they each produce?

Answer 4

Zona glomerulosa - mineralocorticoids e.g. aldosterone
Zona fasciculata - glucocorticoids e.g. cortisol
Zone reticularis - androgens e.g. sex hormones

Question 5

What are the main products of the cortex?

Answer 5

Aldosterone and cortisol

Question 6

What type of hormones are produced in the adrenal gland, and what are they derived from?

Answer 6

Steroid hormones, all derived from cholesterol

Question 7

What is the pre-hormone of the sex hormones which declines with age?

Answer 7

DHEA

Question 8

What is a common cause of congenital adrenal hyperplasia?

Answer 8

Defects in 21-hydroxylase

Question 9

What are some feedback loops in the hypothalamic-pituitary-adrenal pathway?

Answer 9

Cortisol inhibits corticotrophin releasing hormone (CRH) via long loop feedback

Also short-loop feedback by ACTH on CRH.

Question 10

How much of cortisol is protein bound in plasma, and what to?

Answer 10

~95% of plasma cortisol is bound to a carrier protein, cortisol binding globulin (CBG).

Question 11

What cells express cortisol receptors?

Answer 11

ALL nucleated cells

Question 12

What are the functions of glucocorticoids?

Answer 12

Glucocorticoids, such as cortisol, respond to signs of stress and play a role in the regulation of glucose metabolism and turn off pro-inflammatory genes to act as a feedback mechanism for the immune system e.g. COX enzymes, NO etc

Question 13

When is there typically high levels of cortisol in the blood?

Answer 13

Highest peak in the morning when we wake up

Question 14

Why is cortisol important for survival?

Answer 14

Cortisol as a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia. It has a permissive action on glucagon, which is vital as glucagon alone is inadequate in responding to a hypoglycaemic challenge.

Removal of adrenal glands also renders animals incapable of maintaining their extracellular fluid volume, an effect mediated by aldosterone

Question 15

Describe the actions of cortisol on glucose metabolism

Answer 15

Gluconeogenesis: Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle

Proteolysis: cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver.

Lipolysis: similarly, cortisol stimulates lipolysis in adipose tissue, which increases [FFA] plasma creating an alternative fuel supply that allows [BG] to be protected to maintain brain supply while also creating a substrate (glycerol) for gluconeogenesis.

Decreases insulin sensitivity of muscles and adipose tissue.

Question 16

What are the non-glucocorticoid actions of cortisol?

Answer 16

Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption → osteoporosis e.g. following long term glucocorticoid therapy

Impairment of mood and cognition: depression and impaired cognitive function are strongly associated with hypercortisolaemia.

Permissive effects on norepinephrine: particularly in vascular smooth muscle (α-receptor effect = vasoconstrictive). Cushing’s Disease (hypercortisolaemia) is strongly associated with hypertension. Likewise, low levels of cortisol are associated with hypotension.

Suppression of the Immune System: Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response. Latter effect can be useful clinically e.g. use of glucocorticoids for asthma/organ transplant patients, avoid LT though!

Question 17

What are the side effects of glucocorticoid therapy?

Answer 17

Frequent infections with increased severity
Muscle wasting
Thinned skin

Question 18

What is the function of aldosterone?

Answer 18

Aldosterone increases the reabsorption of Na+ ions and promotes the secretion of K+ ions.

Question 19

What is the result of increased aldosterone?

Answer 19

Increased aldosterone release stimulates Na+ (and H2O) retention and K+ depletion, resulting increased blood volume and increased blood pressure.

Question 20

What is the result of decreased aldosterone?

Answer 20

Decreased aldosterone leads to Na+ (and H2O) loss and ↑[K+]plasma, resulting in diminished blood volume and decreased blood pressure.

Question 21

What stimulates aldosterone production by the adrenal glands?

Answer 21

Production of aldosterone (in adult humans, about 20–200 micrograms per day) in the zona glomerulosa of the adrenal cortex is regulated by the renin-angiotensin system. Renin is secreted from the kidneys in response to variations in blood pressure and volume and plasma sodium and potassium levels.

Question 22

What can cause hypersecretion of cortisol?

Answer 22

Cushing’s syndrome/disease: Hypersecretion is most commonly due to a tumour either in:
• Adrenal cortex (1o hypercortisolism = Cushings’s syndrome)
• Pituitary gland (2o hypercortisolism = Cushing’s disease) Most common. Excess ACTH due to pituitary tumour

Iatrogenic - Too much cortisol administered therapeutically (prednisone)

Question 23

What can cause hyposecretion of cortisol?

Answer 23

Addison’s disease - Hyposecretion of all adrenal steroid hormones due to AI destruction of adrenal cortex

Question 24

What are some signs of Cushings?

Answer 24

Red moon face
Thin arms - muscle and fat wastage
Abdominal fat gain

Question 25

What hormones are released in response to stress, and is further aggravated by caffeine, alcohol and lack of sleep?

Answer 25

Corticotropin-releasing hormone (CRH)
Adrenocorticotropic hormone (ACTH)

Question 26

Describe the sympathetic outflow in the adrenal glands form the medulla

Answer 26

Modified sympathetic ganglion, not true endocrine tissue. Similar to posterior pituitary in having neuroendocrine role.

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 27

Describe pheochromocytoma

Answer 27

Pheochromocytoma is a rare neuroendocrine tumour, found in adrenal medulla which results in XS catecholamines: ↑HR→↑CO →↑↑BP

Diabetogenic due to adrenergic effect on glucose metabolism.

Question 28

Why must you wean people off long term glucocorticoid therapy?

Answer 28

Therapeutic cortisol enhances the negative feedback on hypothalamus and pituitary, reducing release of CRH and ACTH.

Loss of trophic action of ACTH on adrenal gland causes atrophy of adrenal gland.

Risk of adrenal insufficiency if withdrawal is too fast.

Question 29

What are the signs of adrenal insufficiency, and why must it be treated quickly?

Answer 29

If not treated, adrenal insufficiency may result in severe abdominal pains, vomiting, profound muscle weakness and fatigue, depression, extremely low blood pressure (hypotension), hypoglycaemia, weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis). An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow