Adrenal Steroids - Cushing Syndrome

Question 1

What is the overall cause of Cushing’s Syndrome?

Answer 1

Too much cortisol

Question 2

What are the 4 specific causes of Cushing’s Syndrome?

Answer 2

1 - Excess cortisol secretion by diverse lesions of the adrenal gland =ADRENAL CUSHING’S SYNDROME
2 - ACTH suppression by neoplasm (small lung cell carcinoma) = ECTOPIC CUSHING’S SYNDROME
3 - Excess pituitary ACTH secretion (pituitary tumors) = PITUITARY CUSHING’S SYNDROME (Cushing’s Disease)
4 - Excess administration of exogenous corticosteroids = IATROGENIC CUSHING’S SYNDROME

Question 3

What are the symptoms of Cushing’s Syndrome?

Answer 3

1 - Excess protein catabolism: thin skin, poor muscle development, poor wound healing, thin hair
2 - Elevated AA levels + increased gluconeogenesis gives hyperglycemia
3 - Redistribution of body fat: Moon face, buffalo hump, pendulous abdomen and straite (bloody stretch marks)
4 - Sodium retention and hypertension
5 - Inhibition of bone formation and excessive calcium excretion causes osteoporosis

Question 4

What is the treatment of Cushing’s Syndrome?

Answer 4

1 - Pituitary: External irradiation, radioactive implants, hypohysectomy, microsurgery
2 - Adrenal: Unilateral or bilateral adrenalectomy
3 - Ectopic tumors: Resection
4 - Drug therapy

Question 5

What drugs are used in the treatment of Cushing’s Syndrome?

Answer 5

1 - Mitotane (Lysodren): Atrophy of the zone fasciculata and reticularis reducing cortisol levels (for adrenal carcinomas) (said he won’t test on this one)
2 - Aminoglutethamide (Cytadren): Blocks the synthesis of all steroids (blocks the first step in steroid synthesis)
3 - Metyrapone (Metopirone): Reduces aldosterone production. Used diagnostically.
4 - Trilostane (Modrastane): Not in the US. Teratogenic. Also inhibits all the steroids. For Cushing’s and Hyperaldosteronism
5 - Ketoconazole (Nizoral): Antifungal that blocks multiple P450 steps in steroidogenesis.
6 - Etomidate: An induction anesthetic to put a person under for surgery, at sub hypnotic doses it inhibits cortisol. Used in Severe Cushing’s Disease. Given IV. Prevents you from putting a hydroxy group in position 11 so you don’t get cortisone and aldosterone.
7 - Mitopristone (RU486): Blocks progesterone receptors. At higher doses blocks the cortisol receptor (the only drug that blocks the cortisol receptor (GR, glucocorticoid receptor)

Question 6

What is another name for Primary Hyperaldosteronism?

Answer 6

Conn’s Syndrome

Question 7

What causes Primary Hyperaldosteronism (Conn’s Syndrome)?

Answer 7

Caused by aldosterone secreting tumor of the adrenal cortex

Question 8

What are the symptoms of Primary Hyperaldosteronism (Conn’s Syndrome)?

Answer 8

Severe K+ depletion which leads to muscle weakness, sodium retention (which leads to hypertension and metabolic alkalosis because you excrete H+ in the urine). You also get interference with Digitalis.

Question 9

What is the treatment of Primary Hyperaldosteronism (Conn’s Syndrome)?

Answer 9

Surgical removal of tumor
- Some relief with use of Aldosterone Antagonists (Spironolactone(blocks mineralcorticoid and aldosterone receptors), Aldactone, Drospirenone (3rd Gen))

Question 10

What is of Secondary Hyperaldosteronism?

Answer 10

Excess aldosterone secondary to elevated circulating levels of renin and agiontensin II. Treat with ACE or ARB’s.

Question 11

What is Congenital Adrenal Hyperplasia?

Answer 11

Steroid 21-hydroxylase deficiency. Impaired synthesis of aldosterone and cortisol(feedback inhibition so more ACTH) = increased production of sex steroids. Fix by administering cortisol.

Question 12

What is Adrenogenital Syndrome

Answer 12

Masculinization of females