Physiology of the adrenal glands, hyper/hypoadrenocorticism

Question 1

What are the broad areas within the adrenal glands and which hormones do they produce?

Answer 1

• Medulla - catecholamines
• Cortex
  
  • Zone glomerulosa - mineralocorticoids
  • Zone fasciculata - glucocorticoids
  • Zone reticularis - androgens

Question 2

What is the most peripheral zone within the adrenal cortex and which hormones does it produce?

Answer 2

Zone glomerulosa - mineralocorticoids

Question 3

Which hormones does the Zone fasciculata produce?

Answer 3

Glucocorticoids

Question 4

Which hormones does the Zone reticularis produce?

Answer 4

Androgens

Question 5

Which area consists of 80-90% of the adrenal gland?

Answer 5

Cortex

Medulla is only 10-20%

Question 6

The synthesises of steroid hormones always begins with which molecule?

Answer 6

Cholesterol

Question 7

Give an example of a glucocorticoid and explain the origin of the name ‘glucocorticoid’

Answer 7

Cortisol

‘Glucocorticoid’ = has a role in regulation glucose

Question 8

Describe the control of glucocorticoid release within reference to the HPA axis

Answer 8

• Hypothalamic-pituitary axis
• CRH is transported from hypothalamus down axons to the portal capillary bed
• CRH causes corticotrophin cells in the anterior pituitary to release ACTH
• ACTH travels through systemic circulation to the adrenal glands where it stimulates the synthesis of glucocorticoids, predominantly cortisol.

Question 9

Glucocorticoids are _______-soluble hormones. This means that…

Answer 9

Glucocorticoids are lipid-soluble hormones. This means that when transported in the blood, 90% are bound to plasma proteins. They bind to specific cell membrane/cytosolic receptors at their target, and this complex is then transported to the nucleus where it results in altered gene expression.

Question 10

What are the actions of glucocorticoids in the body?

Answer 10

Stress hormone - variety of roles in different areas of the body

• Stimulate gluconeogenesis
• Stimulate glycogenolysis
• Causes proteolysis
• Promote lipolysis

Question 11

What effect do glucocorticoids have on fat?

Answer 11

They cause fat mobilisation from peripheral stores

Question 12

What effect do glucocorticoids have on muscle?

Answer 12

They cause muscle catabolism

Question 13

What effect does glucocorticoids have on the liver?

Answer 13

Antagonise insulin

Stimulate gluconeogenesis

Question 14

What effect do glucocorticoids have on the kidney?

Answer 14

Increase GFR

Block the action of ADH

Question 15

What effect do glucocorticoids have on skin?

Answer 15

Follicular atrophy

Sebaceous gland atrophy

Question 16

What effect do glucocorticoids have on bone?

Answer 16

Reduce calcium levels

Osteopenia

Question 17

What effect do glucocorticoids have on the brain?

Answer 17

increased hunger and thirst

Question 18

What effect do glucocorticoids have on the immune system?

Answer 18

Release neutrophils from the marginated pool

Down-regulates the immune response such as T cell function and recruitment, and B cell activation

Question 19

Mineralocorticoid

Answer 19

class of steroid hormone characterised by their effects on salt and water balance e.g. aldosterone

Question 20

Describe the control of mineralocorticoid release

Answer 20

• The main stimulus for aldosterone release is low blood pressure (think RAAS!)
• High serum potassium also stimulates aldosterone release
• The role of ACTH is only minor

Question 21

Function of aldosterone

Answer 21

• Plays a central role in the regulation of blood pressure
• Acts on the cells of the distal tubule and collecting duct to increase reabsorption of Na+, Cl-, and hence water
• Stimulates the secretion of K+ into the tubule lumen so that it is lost into urine

Question 22

Androgens

Answer 22

type of steroid hormone that stimulates/controls the development and maintenance of male characteristics by binding to androgen receptors. Females do have some androgens too.

Androgens are precursors for all oestrogens.

e.g. testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione

Question 23

Hyperadrenocorticism

Answer 23

a condition characterised by excessive production of steroid hormones esp. glucocorticoids from the adrenal cortex.

a.k.a. Cushing’s

Question 24

Causes of canine HAC

Answer 24

• Can be spontaneous or iatrogenic
• Iatrogenic: dog on excessive steroid therapy
• Spontaneous: may be pituitary-dependent or adrenal-dependent.

Question 25

Differentiate between adrenal- and pituitary-dependent HAC

Answer 25

* **Pituitary-dependent (PDH):** 80-90% cases. Excess ACTH secretion results in bilateral adrenal hyperplasia. * **Adrenal-dependent (ADH):** 10-20% cases. Adenomas or carcinomas. These are independent of pituitary control so there is low circulating ACTH.

Question 26

Which is usually harder to control - PDH or ADH?

Answer 26

ADH

Question 27

Of canine PDH, where do the majority of tumours arise from?

Answer 27

* 70% pars distalis * 30% pars intermedia

Question 28

Which type of canine HAC does this diagram depict?

Answer 28

Pituitary-dependent HAC In this type of HAC, normal negative feedback mechanisms fail

Question 29

Which type of canine HAC does this diagram depict?

Answer 29

**Adrenal-dependent HAC** Unilateral adrenal enlargement which causes atrophy of the contralateral side. This is independent of ACTH control (ACTH is low or undetectable because the pituitary gland is normal and responds to negative feedback).

Question 30

Signalment for canine PDH

Answer 30

* Generally seen in middle-aged dogs (7-9 years) * Poodles, dachshunds and small dogs more predisposed to PDH * No sex predispositions

Question 31

Signalment for canine ADH

Answer 31

* Generally seen in older dogs (11-12 years) * Larger breed dogs appear more at risk * Females slightly more at risk

Question 32

Describe the classic canine HAC presentation

Answer 32

* Small, terrier-type dog with pot-bellied appearance and hairloss * Signs develop over time and may be dismissed as “just ageing" * Signs may be intermittent and may take a while for client to notice

Question 33

Clinical signs of canine HAC

Answer 33

* PUPD * Polyphagia * Abdominal enlargement * Hepatomegaly * Skin changes * Muscle wasting/weakness * Lethargy/exercise intolerance/panting * Repro changes if entire

Question 34

Give the thresholds for PUPD in canine HAC and explain with PUPD is seen with this disease

Answer 34

Polydipsia (PD) \>100ml/kg/day Polyuria (PU) \>50ml/kg/day Polydipsia occurs secondary to polyuria. Polyuria mechanism not fully known but likely due to antagonism of ADH and increased GFR stimulated by cortisol.

Question 35

Why does abdominal enlargement occur in a dog with HAC?

Answer 35

* Redistribution of fat into the abdomen + hepatic enlargement + wasting/weakness of abdominal muscles

Question 36

Why does polyphagia occur in a dog with HAC?

Answer 36

* Assumed to be a direct effect of the glucocorticoids * May progress to scavenging → dog often treated for worms prior to diagnosis

Question 37

Describe the skin changes seen with canine HAC and why they occur

Answer 37

* Bilaterally symmetrical alopecia → caused by inhibitory effect of steroids on anlagen phase * Thin skin and reduced elasticity with prominent abdominal veins → caused by protein catabolism (e.g. of collagen) and loss of subcutaneous fat * Excessive scale and comedomes * Slow wound healing → caused by inhibition of fibroblast proliferation and collagen synthesis * Secondary pyoderma common → immune system is largely suppressed so infections are more common * May see calcinonsis cutis (calcification of soft tissue inc. skin; evident on biopsy)

Question 38

What are the treatment options for canine HAC?

Answer 38

* Surgery: adrenalectomy or hypophysectomy. Cannot survive with adrenals so will need replacement therapy. * Drugs: * Trilostane (licensed): reversal enzyme inhibitor that blocks cortisol production * Mitotane: causes chemical ablation of adrenal cortex but spares medulla

Question 39

Describe the characteristics of feline HAC

Answer 39

* Rare: cats are resistant to the effects of most glucocorticoids * Signalment: middle-aged to older cats * 75-80% cases PDH, 20-25% ADH * Clinical signs: PUPD, polyphagia, pendulous abdomen, weight loss, extreme skin fragility, UTIs.