Action of Adrenal Steroids and Treatment of Adrenal Disorders

Question 1

What is the function of Mineralocorticoids?

Answer 1

Regulate salt/electrolyte and water balance which is important to maintain blood pressure. Main mineralocorticoid is aldosterone

Question 2

What is the function of glucocorticoids

Answer 2

• Carbohydrate and protein metabolism.
• Immunosuppressive and anti-inflammatory.
• Main one is hydrocortisone (cortisol)

Question 3

Describe the regulation of corticosteroids and some drugs that can be used to mimic effects

Answer 3

• Anterior pituitary hormone releases ACTH which stimulates the synthesis and secretion og glucocorticoids and mineralocorticoids. RAAS aids ACTH to stimulate release of mineralocorticoid secretion.
• Synthetic analogue of ACTH is tetracosactide.
• Fludrocortisone mimics activity of mineralocorticoid effect.
• Prednisolone mimics glucocorticoid effect

Question 4

What drugs can be used in inhibiting synthesis of adrenal hormones

Answer 4

• Aminoglutethimide inhibits the rate limiting step of converting cholesterol to pregnenolone.
• Trilostane blocks 3 beta-dehyd (prevents pregnenolone forming progesterone). Often used in Cushing’s and primary hyperaldosteronism
• Metyrapone prevents beta hydroxylation of C11,
• Carbenoxolone inhibits conversion of hydrocortisone to cortisone in kidney

Question 5

What is the mechanism of action of glucocorticoids?

Answer 5

GCs bind to intracellular receptors. migrate to nucleus, dimerize and regulate gene transcription. Non-genomic effects are mediated through signalling systems in cytosol.

Question 6

What are the regulatory actions of glucocorticoids?

Answer 6

• Negative feed back to hypothalamus (CRF) and pituitary (ACTH) which causes reduced release of endogenous glucocorticoids.
• Cardiovascular effects by causing reduced vasodilation and fluid exudation.
• Decreases osteoblasts and increases osteoclast activity which gives a tendancy for osteoporosis.

Question 7

What are the metabolic actions of glucocorticoids?

Answer 7

• Decreased uptake and utilization of glucose accompanied by increased gluconeogenesis to cause hyperglycaemia. Increases glycogen storage.
• Increased catabolism and reduced anabolism in muscle which can cause muscle wasting.
• Effect on lipolytic hormones and a redistribution of fat

Question 8

What are the anti-inflammatory and immunosuppressive effects of glucocorticoids

Answer 8

Acute inflammation - Decreased influx and activity of leukocytes.
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.

Question 9

What are the actions of glucocorticoids on the mediators of inflammatory and immune responses?

Answer 9

• Decreased production and activity of cytokines.
• Reduced generation of eicosanoids,
• Reduced generation of IgG and complement components in the blood.
• Increased release of anti-inflammatory factors,
• Overall reduction in activity of innate and acquired immune systems

Question 10

What are the clinical uses of glucocorticoids?

Answer 10

• Replacement therapy for patients with adrenal failure (Addison’s disease)
• Anti-inflammatory/immunosuppressive therapy,
• In hypersensitivity states and Asthma,
• Topically in inflammatory conditions of the skin skin, eye, ear or throat (eczema),
• Diseases with inflammatory and immune components (eg, rheumatoid arthritis, IBD),
• To prevent rejection following organ or bone marrow transplant.
• Used in combination with cytotoxic drugs in the treatment of hodgkins disease/acute lymphocytic leukaemia

Question 11

What are the adverse/unwanted side effects of glucocorticoids?

Answer 11

• Suppression of response to infection and injury,
• Opportunistic infections (oral fungal/yeast),
• Wound healing is impaired,
• Osteoporosis
• Risk of fractures,
• Hyperglycaemia,
• Muscle wasting and weakness,
• Inhibition of growth in children,
• CNS effects (depression, psychosis),
• Glaucoma

Question 12

What is Cushing’s Syndrome?

Answer 12

Caused by excessive exposure to glucocorticoids either by disease or prolonged administration of glucocorticoid drugs.
Symptoms include, moon face, buffalo hump, increased abdominal fat, thinning of the skin, thin arms and legs, poor wound healing and easy bruising. Along with other symptoms too

Question 13

Describe the treatment of Cushing’s syndrome

Answer 13

• Surgical removal of tumour.

- Medication which counteracts high cortisol levels

Question 14

What are the clinical uses of mineralocorticoids?

Answer 14

• Mineralocorticoid replacement therapy in Addison’s disease. Common drug used in fludrocortisone which can be taken orally. It increases sodium reabsorption and increases potassium and hydrogen ion efflux

Question 15

What are some causes of Addison’s Disease?

Answer 15

• Autoimmune adrenalitis,
• TB that spreads from lungs to adrenals,
• Atrophy of adrenals

Question 16

What are the symptoms and treatments for Addison’s Disease?

Answer 16

Symptoms - Nausea, vomiting, weight loss, weakness, anorexia, skin pigmentation, hypotension, low sodium/high potassium, chronic dehydration and sexual dysfunction.
Treatment - Corticosteroid replacement (Hydrocortisone, most commonly however prednisolone or dexamethasone can also be used.)

Question 17

Describe causes of primary hyperaldosteronism

Answer 17

• Adrenal adenoma (most common cause),
• Adrenal hyperplasia (most commonly bilateral but can be unilateral and is often congenital),
• Adrenal carcinoma (rare)

Question 18

What is the management of primary hyperaldosteronism?

Answer 18

Medical treatment before surgery is aldosterone antagonists (spironolactone). Surgical treatment is adrenalectomy (laparoscopic is preferred)

Question 19

Describe features of congenital adrenal hyperplasia

Answer 19

Genetic disorder where C-21 hydroxylase enzymes are missing so the resulting non-hydroxylated versions of cortisol, corticosterone and aldosterone are made which lack normal activity. Therefore they do not negatively feedback to HPA axis and so there are high levels of ACTH. Treat with cortisol and mineralocorticoids