Treatment of Adrenal Disorders

Question 1

What drug would you administer if you wanted to assess adrenal gland function?

Answer 1

Tetracosactide (synthetic analogue) - stimulates release of cortisol from adrenal gland

Question 2

What first line drug is selected if we want to isolatedly stimulate mineralcorticoid activity from the adrenal glands?

Answer 2

Fludrocortisone

Question 3

What first line drug is selected if we wanted to isolatedly stimulate glucocorticoid activity in the adrenal glands?

Answer 3

Prednisolone

Question 4

What drugs block the biosynthesis of corticosteroids?

Answer 4

• aminoglutethimide: blocks RLS - cholesterol conversion to pregnenolone
• trilostane blocks 3-beta-dehydrogenase (inhibiting all downstream processes)
• metyrapone inhibits production of hydrocortisone and corticosterone by blocking the enzyme
• carbenoxolone inhibits conversion of active hydrocortisone to inactive cortisone in the kidney

Question 5

What conditions is trilostane used to treat?

Answer 5

• Cushing’s syndrome

- primary hyperaldosteronism

Question 6

What is cabenoxolone used to treat?

Answer 6

• ulcers and inflammation

due to the fact that it increases the amount of active hydrocortisone

Question 7

Describe the regulatory actions of the glucocorticoids

Answer 7

• HPA: negative feedback on CRH and ACTH
• CV: reduced vasodilation and fluid exudation
• MSK: decreased osteoblast activity and increased osteoclast activity (risk of osteoporosis)

Question 8

Describe the metabolic actions of glucocorticoids

Answer 8

• carbs: decreased uptake and utilisation of glucose - increased gluconeogenesis (hyperglycaemia) and glucose storage
• proteins: increased catabolism and reduced anabolism esp in muscle (muscle wasting)
• lipids: allows secretion of lipid hormones and redistribution of fat (seen in Cushing’s)

Question 9

Describe the anti-inflammatory and immunosuppressive effects of the glucocorticoids

Answer 9

• acute inflammation: decreased influx and activity of leucocytes
• chronic inflammation: decreased activity of mononuclear cells, decreased angiogenesis and fibrosis
• lymphoid tissue: decreased clonal expansion of T and B cells and decreased activation of cytokine-secreting T cells. Th1 switched to Th2 responses

Question 10

Describe the effect of glucocorticoids on mediators of immune/inflammatory responses of the body

Answer 10

• decreased production and action of cytokines (IL, TNF-alpha, cell adhesion factors and NO)
• decreased generation of eicosanoids due to decreased COX-2
• decreased generation of IgG and complement components of blood
• increased release of anti-inflammatory factors (IL-10 and annexin-1)
• reduced activity of innate and acquired immune systems

Question 11

What clinical conditions can be treated with glucocorticoids?

Answer 11

• replacement therapy (Addison’s): hydrocortisone
• anti-inflammatory/immunosuppressive therapy
• severe allergic reactions and asthma
• topically in inflammatory conditions of eye/skin/ear/throat (eg. eczema, conjunctivitis, rhinitis)
• other inflammatory/immune conditions (eg. RA, IBD, some haemolytic anaemias etc.)
• prevent rejection following transplantation
• cancer (in combo with other cytotoxic drugs in Hodgkin’s/acute lymphocytic anaemia)
• dexamethasone decreases oedema in tumours

Question 12

What is a good systemic anti-inflammatory/immunosuppressive glucocorticoid drug?

Answer 12

• prednisolone

- dexamethasone (where water retention is undesirable)

Question 13

What are some adverse effects of glucocorticoids?

Answer 13

• suppression of response to infection/injury
• opportunistic infections (eg. yeast/fungal)
• impaired wound healing
• osteoporosis/fracture hazard
• hyperglycaemia
• muscle wasting and weakness (inhibits growth in children)
• CNS effects
• glaucoma (increased ICP)

Question 14

What are the causes of Cushing’s Syndrome?

Answer 14

Endogenous causes (overproduction of cortisol):

• pituitary tumour
• adrenal tumour
• idiopathic

Exogenous causes:
- taking too much glucocorticoids such as hydrocortisone

Question 15

Describe the cellular actions of spironolactone

Answer 15

• blocks actions of aldosterone in collecting tubule in the kidney
• decreases Na+ reabsorption if aldosterone levels are too high

Question 16

Describe the clinical uses of mineralcorticoids

Answer 16

• replacement therapy (Addison’s): fludrocortisone used to increase Na+ reabsorption and K+ and H+ efflux in distal tubules in kidney
• hyperaldosteronism
• resistant hypertension (spironolacting - K+ sparing diuretic)
• heart failure
• oedema

Question 17

What are the causes of Addison’s disease?

Answer 17

• autoimmune
• TB that spreads from the lungs
• metastatic cancers that spread to adrenals
• atrophy from prolonged steroid therapy
• global metabolic disorders and fluid imbalance

Question 18

What are the symptoms of Addison’s Disease?

Answer 18

• nausea/vomiting
• weightloss/weakess
• anorexia
• hypotension
• skin pigmentation
• low sodium/high potassium
• chronic dehydration
• sexual dysfunction

Question 19

What is the main cause and treatment of Conn’s Syndrome?

Answer 19

• main cause is adrenal adenoma
• medical management is used prior to surgery - spironolactone for 4 weeks
• then surgical adrenalectomy

Question 20

What are the different types of primary hyperaldosteronism?

Answer 20

• Conn’s Syndrome
• adrenal hyperplasia
• adrenal carcinoma (rare)

Question 21

Describe the mechanism behind congenital adrenal hyperplasia and treatment

Answer 21

• c-21 hydroxylase enzyme is missing meaning non-hydroxylated versions of hormones are made that lack normal activity
• they do not negatively feedback on to the HPA axis
• results in constant stimulation from ACTH and constant production of c-19 androgens
• treated with replacement therapy