Glucocorticoids

Question 1

Glucocorticoids

Answer 1

• steroid hormones produced in the adrenal cortex
• influence carbohydrate metabolism and other processes

Question 2

Glucocorticoids: Pharmacologic Effects

Answer 2

• occur at high levels of glucocorticoids
• achieved when administered in large doses required to treat disorders unrelated to adrenocortical function (allergic reactions, asthma, inflammation, cancer)
• can also be reached when production of endogenous glucocorticoids is excessive, as occurs in Cushing’s disease

Question 3

Glucocorticoids: Physiologic Effects

Answer 3

1. carbohydrate metabolism
2. protein metabolism
3. fat metabolism
4. cardiovascular system
5. skeletal muscle
6. CNS
7. Stress
8. Respiratory distress in neonates
9. renal processing of sodium, potassium, and hydrogen

Question 4

Glucocorticoids: Carb metabolism

Answer 4

promotes glucose availability in 4 ways:
1. stimulation of gluconeogenesis
2. reduction of peripheral glucose utilization
3. inhibition of glucose uptake by muscle and adipose tissue
4. promotion of glucose storage in the form of hydrogen

Question 5

Glucocorticoids: Protein metabolism

Answer 5

• opposite action to insulin
• provide amino acids for glucose synthesis
• if present at high levels for a prolonged time, glucocorticoids will cause muscle wasting, thinning of skin, and negative nitrogen balance

Question 6

Glucocorticoids: Fat metabolism

Answer 6

• promote lypolysis
• when present at high levels for extended periods (Cushing’s syndrome), glucocorticoids cause fat redistribution, giving patient a potbelly, moon face, and buffalo hump

Question 7

Glucocorticoids: Cardiovascular system

Answer 7

• Required to maintain functional integrity of vascular system
• When levels are depressed, capillary permeability is increased, the ability of vessels to constrict is reduced, and BP falls
• Multiple effects on blood cells - increase RBC and hemoglobin, polymorphonuclear leukocytes increase; counts of lymphocytes, eosinophils, basophils, and monocytes decrease

Question 8

Glucocorticoids: Skeletal muscle

Answer 8

• support function of striated muscle, primarily by maintaining circulatory competence.
• in the absence of sufficient levels of glucocorticoids, muscle perfusion decreases, causing capacity to decrease as well

Question 9

Glucocorticoids: CNS

Answer 9

• Affect mood, CNS excitability and the electroencephalogram
• Insufficiency associated with depression, lethargy, and irritability; rarely, psychosis occurs
• When present in excess, can produce generalized excitation and euphoria

Question 10

Glucocorticoids: Stress

Answer 10

• Working together, glucocorticoids and epinephrine serve to maintain blood pressure and blood glucose content.
• If glucocorticoid levels are inadequate, hypotension and hypoglycemia can occur.
• If the stress is extreme (e.g., trauma, surgery, severe infection), glucocorticoid deficiency can result in circulatory collapse and death.

Question 11

Glucocorticoids: Respiratory Depression in Neonates

Answer 11

• During labor and delivery, the adrenals of the full-term fetus release a burst of glucocorticoids. Within hours, these steroids act on the lungs to accelerate their maturation.
• In the preterm infant, the adrenals produce only small amounts of glucocorticoids.
• As a result, preterm infants experience a high incidence of respiratory distress syndrome
• Betamethasone or dexamethasone commonly used - injected 24h before baby’s birth

Question 12

mineralocorticoids - aldosterone - physiologic effects

Answer 12

• promotes sodium and potassium hemostasis and helps maintain intravascular volume
• harmful CV effects at high levels

Question 13

Aldosterone: adverse CV effects

Answer 13

1. promotion of myocardial remodelling - impair pumping
2. promotion of myocardial fibrosis - risk for dysrhythmia
3. activation of SNS and suppression of NE - risk for dysrhythmia and ischemia
4. promotion of vascular fibrosis - decrease atrial compliance

Question 14

Adrenal hormone excess causes ____ syndrome

Answer 14

Cushing’s

Question 15

Cushing’s Syndrome: Causes

Answer 15

• hyper-secretion of ACTH by pituitary due to adenoma
• hyper-secretion of glucocorticoids by adrenal adenomas and carcinomas
• administration of glucocorticoids in large doses used to treat arthritis and other non-endocrine disorders

Question 16

Cushing’s Syndrome: Treatment

Answer 16

• for adrenal adenoma and carcinoma: surgical removal of adrenal gland; replacement with gluco- and mineralicorticoids needed
• inoperable carcinoma: anticancer drug that produces selective destruction of adrenocortical cells (mitotane)
• pituitary adenoma: partial removal of pituitary gland lowers ACTH to safe levels; alternative is pituitary radiation
• drug therapy: limited. only employed as adjunct to radiation and surgery; most effective drug = ketoconazole - antifungal drug that blocks glucocorticoid synthesis; can cause significant liver dysfunction

Question 17

Adrenal hormone insufficiency causes ____ disease

Answer 17

Addisons

Question 18

Addison’s Disease: Causes

Answer 18

• most caused by autoimmune destruction of adrenal tissue
• tuberculosis and other infections
• adrenal hemorrhage
• cancers
• certain drugs (ketoconazole, rifampin)

Question 19

Addison’s Disease: Treatment

Answer 19

• replacement therapy with adrenocorticoids required
• hydrocortisone drug of choice
• if additional mineralicorticoid activity needed, fludrocortisone is the only mineralicorticoid available which can be added to the regimen

Question 20

Hydrocortisone: Therapeutic Use

Answer 20

Endocrine Applications
- Replacement therapy for adrenocortical insufficiency; has mineralocorticoid actions and may suffice as sole therapy for adrenal insufficiency, even when salt loss is a sx

Nonendocrine Applications
- broad spectrum: allergic reactions to inflammation to cancer
- doses required significantly higher

Question 21

Hydrocortisone: Adverse Effects

Answer 21

When given in low doses for replacement therapy:
- devoid of adverse effects

Large doses for nonendocrine disorders
- highly toxic
- adrenal suppression
- promotion of Cushing’s syndrome

Question 22

Hydrocortisone: Care planning

Answer 22

• take whole dose PO in morning, immediately after waking
• if fatigued in afternoon, split dose - take 2/3 in morning, and 1/3 around 4:00PM

Question 23

Fludrocortisone: Overview & Therapeutic Use

Answer 23

• Potent mineralocorticoid that also possesses significant glucocorticoid activity
• Preferred drug for treating adrenal insufficiency, primary hypoaldosteronism, and CAH even when salt wasting occurs
• Must be used in combination with glucocorticoid in most cases

Question 24

Fludrocortisone: Adverse Effects

Answer 24

high doses: salt and water retained in excess, while amounts of potassium are lost; results in:
- expansion of blood volume
- hypertension
- edema
- cardiac enlargement
- hypokalemia

Question 25

Fludrocortisone: Care Planning

Answer 25

- Oral tabs for dosing - Monitor patient for weight gain, elevated BP, and hypokalemia - If changes occur, drug should be temporarily withdrawn - If excessive salt retention, dose should be cut in half - Fluid and electrolyte balance resolve spontaneously in a few days

Question 26

Cosyntropin and Dexamethasone: Overview and Therapeutic Use

Answer 26

- Acts like ACTH - Used only for diagnosis of adrenal insufficiency - Acts on adrenal cortex to stimulate synthesis and secretion of cortisol and other glucocorticoids - Plasma cortisol measured before injection and then 30-60 minutes later - If cortisol raises to above 20mcg/dL, adrenal response is considered normal - If cortisol fails to rise significantly, dx of adrenal insufficiency can be made