CH 63 Drugs for Disorders of the Adrenal Cortex

Question 1

Drug: Hydrocortisone (Cortef, Solu-Cortef)

Answer 1

Class: Glucocorticoid
MOA: Mimics endogenous cortisol; binds to glucocorticoid and mineralocorticoid receptors to regulate metabolism, inflammation, and immune responses.
Note: Has a structure identical to natural cortisol.

Question 2

Drug: Prednisone (Deltasone, Rayos)

Answer 2

Class: Glucocorticoid
MOA: Mimics glucocorticoid effects; suppresses inflammation and immune responses by altering gene expression.
Note: Preferred oral therapy for chronic adrenal insufficiency.

Question 3

Drug: Dexamethasone (Decadron)

Answer 3

Class: Glucocorticoid
MOA: Binds selectively to glucocorticoid receptors; minimal mineralocorticoid activity.
Note: Used in the overnight diagnostic test for Cushing’s syndrome.

Question 4

Drug: Cortisone

Answer 4

Class: Glucocorticoid
MOA: Prodrug that is converted to hydrocortisone (cortisol) in the liver.
Note: Requires metabolic activation to become effective.

Question 5

Drug: Fludrocortisone (Florinef)

Answer 5

Class: Mineralocorticoid
MOA: Promotes sodium reabsorption and potassium/hydrogen excretion by acting on renal distal tubules.
Note: The only mineralocorticoid commonly available for therapeutic use.

Question 6

Drug: Ketoconazole (Nizoral)

Answer 6

Class: Steroid synthesis inhibitor
MOA: Inhibits steroid hormone biosynthesis by blocking enzymes involved in cortisol production.
Note: Used as adjunctive therapy in Cushing’s syndrome.

Question 7

Drug: Pasireotide (Signifor)

Answer 7

Class: Corticotropin-release inhibitor
MOA: Inhibits ACTH secretion from the pituitary by activating somatostatin receptors.
Note: Targets pituitary origin of excess cortisol.

Question 8

Drug: Osilodrostat (Isturisa)

Answer 8

Class: Steroid synthesis inhibitor
MOA: Inhibits 11β-hydroxylase, an enzyme necessary for cortisol synthesis in the adrenal gland.
Note: Newer drug (approved in 2020); monitor for adrenal insufficiency.

Question 9

Drug: Cosyntropin (Cortrosyn)

Answer 9

Class: Synthetic ACTH
MOA: Stimulates adrenal cortex to produce and release cortisol.
Note: Used as a diagnostic tool for adrenal insufficiency.

Question 10

Drug: Spironolactone (Aldactone)

Answer 10

Class: Aldosterone antagonist (potassium-sparing diuretic)
MOA: Competitively inhibits aldosterone at receptor sites in the distal renal tubules.
Note: Used to treat primary hyperaldosteronism and also has antiandrogenic effects.

Question 11

Classes of steroid hormones

Answer 11

Glucocorticoids (e.g. cortisol)
* regulate metabolism
* reduce inflammation
* suppress immune response
* assist with stress response

Mineralocorticoids (e.g. aldosterone)
* regulate Na+/K+ balance
* increase blood volume/pressure w/ Na+ retention and K+ excretion

Question 12

Cushing’s Syndrome

Answer 12

Causes:
* hypersecretion ACTH
* hypersecretion glucocorticoids
* admin of lage dose glucocorticoids

Signs/Symptoms:
* Moon face
* truncal obesity
* buffalo hump
* muscle wasting
* hypertension
* hyperglycemia & glycosuria
* purple striae
* osteoporosis

Treatment:
* gradual tapering of corticosteroids
* surgery/radiation for tumors
* medications
– ketoconazole (Nizoral) - blocks steroid synthesis
– pasireotide - inhibits secretion of corticotropin from pituitary
– osilodrostat - blocks cortisol synthesis in adrenal gland

Question 13

Addison’s Disease

Answer 13

Causes:
* Autoimmune destruction of adrenal cortex
* infections (e.g., TB)
* adrenal hemorrhage
* congenital adrenal hyperplasia

Signs/Symptoms:
* Fatigue
* weight loss
* hypotension
* hyperpigmentation
* hyponatremia
* hyperkalemia
* hypoglycemia

Treatment: Lifelong hormone replacement
– glucocorticoids - hydrocortisone & prednisone
– mineralocorticoids - fludrocortisone

Question 14

Split glucocorticoid dosing

Answer 14

2/3 in morning; 1/3 in afternoon
mimics normal cortiosteroid secretion

Dosage increased in times of stress

Question 15

AEs of steroid therapy

Answer 15

Glucocorticoids: Weight gain, osteoporosis, hyperglycemia, immunosuppression, mood changes, peptic ulcers.

Mineralocorticoids: Hypertension, edema, hypokalemia, fluid retention.

Question 16

ACTH Stimulation Test

Answer 16

• Evaluates adrenal response to synthetic ACTH
• used to diagnose adrenal insufficiency

Normal: Increased cortisol levels
Addison’s: No or minimal increase

Question 17

Dexamethasone Suppression Test

Answer 17

• Evaluates cortisol suppression
• used to diagnose Cushing’s syndrome

Normal: Decreased cortisol
Cushing’s Syndrome: No suppression
Cushing’s Disease (pituitary): Partial suppression with high-dose test
Ectopic ACTH or adrenal tumor: No suppression with low or high dose