Session 9 (2) - Disorders of Adrenal cortical function

Question 1

What is the name for hypoactivity of the adrenal cortex?

Answer 1

Addison’s disease

Question 2

What two factors can cause hypoactivity of adrenal cortex, and what do they cause?

Answer 2

Autoimmune destruction of the adrenal cortex - Reduces glucocorticoids and meneralocorticoids

Disorders in pituitary or hypothalamus that lead to decreased secretion of ACTH or CRF - only affects glucocorticoids

Question 3

What is the name for hyperactivity of adrenal cortex?

Answer 3

Cushing’s syndrome

Question 4

What two biological factors can cause Cushing’s syndrome?

Answer 4

Increased activity of the adrenal cortex due to adenoma

Disorders in secretion of ACTH caused by pituitary adenoma or ectopic secretions.

Question 5

What is congenital adrenal hyperplasia?

Answer 5

Genetic defect in enzyme involved in production of cortisol. Lack of cortisol means no feedback control to pituitary, therefore large amounts of ACTH secreted. Results in adrenal hyperplasia, with various effects.

Question 6

Give clinical effects of cushing’s syndrome (remember the acronym)

Answer 6

Pissed Lions Break Into Cash Machines

Muscle proteolysis resulting in

• Hepatic gluconeogenesis + Hyperglycaemia (steroid diabetes)
• Wasting of arm and leg muscles, weakness

Lipogenesis in adipose tissue
- Fat gain in abdomen and face, resulting in central obesity and moon shaped face

Purple stria in low abdomen
- Destruction of muscle tissue under skin results in thinning and easy bruising

Immunosupressive effects of cortisol
- Increased bacterial infections and acne

Disturbances of calcium metabolism
-Osteoperosis, causing back pain and collapse or ribs

Mineralocorticoid effects of excess cortisol
- Hypertension due to sodiuma and fluid retention

Question 7

What is cushing’s disease?

Answer 7

Pituitary adenoma, causing excess ACTH production

Question 8

In what two ways would too little cortisol present?

Answer 8

Addisonian crisis or Addison’s disease

Question 9

When would addison’s disease be complicated by mineralocorticoid defiency?

Answer 9

When there is autoimmune destruction of adrenal gland NOT when it is caused by disorders in pituitary or hypothalamus secretion

Question 10

Give symptoms of addisons disease

Answer 10

Tiredness
Extreme muscular weakness
Increased pigmentation on exposed areas of body, due to ACTH mediated melanocyte stimulation
Decreased blood pressure due to sodium and fluid retention (mineralocorticoid)
Postural hypotension due to fluid depletion
Hypglycaemic episodes on fasting

Question 11

What happens if person suffering from addisons disease under goes stress such as trauma or infection? What are the symptoms?

Answer 11

Addisonian crisis

Nausea, vomiting, dehydration, hypotension, confusion, fever, coma

Question 12

How is addisonian crisis treated?

Answer 12

Intra-venous cortisol and dextrose in normal saline

Question 13

What are intitial steps for investigation adrenocortical function?

Answer 13

Measurement of plasma cortisol and ACTH levels
Measure 24h urinary excretion of cortisol and breakdown products
Dynamic function tests (Dexamethasone supression test and Synacthen)

Question 14

Outline dexamethasonn supression tests

Answer 14

Dexamethasone potent synthetic steroid
Would normally suppress secretion of ACTH and cortisol
Dexamethasone supression of cortisol by >50% is characteristic of Cushing’s disease (diseased pituitary disease)

Question 15

Why is a reading of >50% in a dexamethasone supression test characteristic of Cushing’s disease?

Answer 15

Because for the diseased pituitary, even though it is relatively insensitive to cortisol it will still respond to potent synthetic steroid. Supression not evident in adrenal tumours or ectopic ACTH production

Question 16

What does Synacthen do?

Answer 16

Analogue of ACTH, would normally increase plasma cortisol. Normal response usually excludes addisons disease. (but what about addisons disease caused by disorders of pituitary?)

Question 17

What artificial devices can induce Cushing’s syndrome

Answer 17

Long-term glucocorticoid steroid treatment in patients with chronic inflammatory conditions

Question 18

What are the three regions of steroid receptor?

Answer 18

Hydrophobic hormone binding region, DNA-binding region rich in cysteine and basic amino acids and a variable region.

Question 19

Why does excess cortisol have mineralocorticoid effects?

Answer 19

Because their is sequence homology in the hormone binding regions of the receptors. Thus, cortisol will bind to mineralocorticoid receptors with low afinity. This becomes significan when high levels of hormone present.