Adrenal #L3 Therapy I

Hypercortisolism is also known as

Cushing’s syndrome

What is hypercortisolism? condition in which…

too much cortisol is produced

What are 4 symptoms of hypercortisolism?

weakness, back pain, myopathies, depression

What are 4 common signs of hypercortisolism?

Moon face, central obesity, htn, glucose intolerance

What are some laboratory test you can get to test for hypercortisolism?

midnight plasma cortisol, 24 hour urinary free cortisol, low dose dexamethasone suppression test

What are the challenges of diagnosing hypercortisolism?

difficult to measure bc cortisol is found all over the body

What is the first-line treatment of Cushing’s disease?

surgery

What is Cushing’s disease also known as?

pituitary adenoma

What is the most common type of hypercortisolism? (category)

ACTH dependent

What are the two main causes of ACTH-independent hypercortisolism?

adrenal cortical adenoma and carcinoma

What is the cause of iatrogenic hypercortisolism?

prolonged glucocorticoid use

What are the two main causes of ACTH dependent hypercortisolism?

pituitary adenoma, ectopic ACTH syndrome

What is the role of pharmacotherapy in hypercortisolism?

Adjunctive, not curative

What happens after discontinuation of medications treating hypercortisolism?

disease relapse

What is the most commonly used class of pharmacologic agents for hypercortisolism?

Adrenal enzyme inhibitors

What is a major concern with prolonged pharmacotherapy for hypercortisolism?

Serious side effects (increase with time/dose)

Why might higher doses of pharmacotherapy be needed over time to treat hypercortisolism?

ACTH rises with tumor progression

Examples of adrenal enzyme inhibitors used to treat hypercortisolism (5)

ketoconazole, metyrapone, mitotane, pasireotide, mifepristone

Major drug interactions of ketoconazole?

Strong CYP3A4, 2C9, P-gp inhibitor

In a patient with classic Cushing's disease (caused by an adrenal adenoma), the preferred treatment is:​

1. Mitotane 3g three times daily​

2. Pasireotide 0.5mg twice daily​

3. Mifepristone 300mg daily​

4. Resection of adrenal tumor

4

Which medication might cause iatrogenic Cushing's syndrome?​

1. Mitotane 3g three times daily​

2. Prednisone 40mg daily​

3. Spironolactone 50mg daily​

4. Estradiol 1mg daily​

2

What is hyprealdosteronism? condition where you have…

high levels of aldosterone

What are the symptoms of hyperaldosteronism?

Paresthesias, weakness, polydipsia/polyuria

What are the signs of hyperaldosteronism?

resistant htn, hypokalemia, arrhythmias

Expected laboratory result of hyperaldosteronism?

increased aldosterone:renin ratio

What drug class is used to treat hyperaldosteronism?

Aldosterone antagonists

Examples of aldosterone antagonists?

Spironolactone, eplerenone, amiloride

What are the first line medications used to treat hyperaldosteronism?

spironolactone, eplerenone

Side effects of spironolactone (not the most common one)

sex steroid side effects

What is the key difference between spironolactone and eplerenone?

eplerenone has less sex steroid side effects

Why is amiloride less preferred out of the aldosterone antagonist?

less effective for bp control

Treatment adjustment for hyperaldosteronism? Adjust dose every —?

4-8 weeks

When treating hyperaldosteronism, if BP remains high after max dose, add another?

antihypertensive

In which patient should hyperaldosteronism be suspected?​

1. Patient with moon face, hypertension, and impaired fasting glucose​

2. Patient with weight loss, skin pigmentation, and low blood pressure​

3. Patient with tachycardia, hypertension, and heat intolerance​

4. Patient with treatment resistant hypertension and hypokalemia

4

What are the most common side effects of aldosterone antagonist?​

1. Edema​

2. Dehydration​

3. Renal/electrolyte abnormalities​

4. Gymecomastia

3

Key sign of adrenal insufficiency?

Skin pigmentation

Adrenal insufficiency symptoms?

weakness, nv, salt craving, cold tolerance

What laboratory test is used to diagnose adrenal insufficiency?

Positive cosyntropin test

What laboratory results will you see in Addison’s disease?

Elevated ACTH

Addison’s disease is also known as

primary adrenal insufficiency

What lab result will you see in secondary adrenal insufficiency?

low ACTH levels

What are the two drug classes used to treat adrenal insufficiency?

mineralocorticoids, corticosteroids

Example of mineralocorticoid drug used to treat adrenal insufficiency

fludrocortisone acetate

What is the drug of choice in treating adrenal insufficiency?

hydrocortisone

Examples of corticosteroid drugs used to treat adrenal insufficiency?

Hydrocortisone, cortisone acetate, prednisolone

Counseling point for patients taking corticosteroids to treat adrenal insufficiency?

give 2/3 of dose in morning and 1/3 6-8 hr later to mimic circadian rhythm

Why is hydrocortisone preferred for treatment of adrenal insufficiency despite the need for BID (or TID) dosing​

1. Hydrocortisone possess both mineralocorticoid and glucocorticoid properties​

2. BID or TID dosing more closely mimics the normal diurnal adrenal rhythm​

3. Hydrocortisone is associated with less side effects that prednisolone​

4. ACTH levels normalize sooner when hydrocortisone is used compared to prednisolone

1, 2

What are common precipitating factors of acute adrenal insufficiency?

Glucocorticoid dose reduction, lack of stress-dose steroids, surgery, infection, trauma

How does acute adrenal insufficiency present?

Flu-like symptoms that rapidly progress to fever, hypotension, and shock

What is the initial treatment of acute adrenal insufficiency?

hydrocortisone 100 mg IV STAT

How is hydrocortisone administered after the initial dose when treating acute adrenal insufficiency?

IV continuous (Q6H bolus) 200 mg/day, taper 20-30% daily