Endo E2- Adrenal

What is the adrenal cortex?

Three layers of glandular tissue that synthesize & secrete hormones

What is the adrenal medulla?

nervous tissue; part of the SNS

What is the MCC of Cushing syndrome?

exogenous glucocorticoids

What are sx of Cushing syndrome?

central obesity, muscle wasting, thin skin, hirsutism, purple striae, moon face, buffalo hump

In Cushing syndrome, is K elevated or low?

Low- hypokalemia

What is Pseudo-Cushing state?

some clinical features & biochemical evidence of Cushing syndrome, but resolution of the primary condition results in disappearance of the cushingoid features & biochemical abnormalities

Chronic abuse of what can present w/ findings suggestive of Cushing syndrome?

Alcohol

What lab abnormalities are associated with Cushing syndrome?

elevated white count & hyperglycemia

What acid-base imbalance may occur in patients with markedly elevated cortisol?

Hypokalemic metabolic alkalosis

How do ACTH & cortisol levels change in Cushing syndrome?

elevated

What are the 4 methods used to diagnose Cushing syndrome?

Urinary free cortisol level

Low-dose dexamethasone suppression test

Evening serum & salivary cortisol level

Dexamethasone-corticotropin-releasing hormone test

In healthy individuals, what is the effect of low dose dexamethasone?

Suppression of cortisol

High doses of dexamethasone exert negative feedback on ACTH from the pituitary gland, but NOT on what?

ectopic ACTH producing cells/adenomas

What results following a dexamethasone suppression test would be indicative of Cushing's syndrome?

No change in cortisol on low-dose, but inhibition of cortisol on high-dose

What would the results of a high-dose dexamethasone suppression test show in pts w/ Primary Adrenal Cushing syndrome?

ACTH is low, Cortisol is not suppressed by high or low doses

What would the results of a high-dose dexamethasone suppression test show in pts w/ Ectopic ACTH syndrome?

ACTH is normal/elevated, Cortisol is not suppressed by high or low doses

What would the results of a dexamethasone suppression test show in pts w/ Cushing disease?

ACTH is elevated, Cortisol is NOT suppressed by low doses, but is suppressed by high doses

What medication used for Cushing inhibits endogenous adrenal corticosteroids synthesis?

Metyrapone (Metopirone)

What medication used for Cushing is a broad-spectrum antifungal agent that acts on several P450 enzymes, including the first step in cortisol synthesis?

Ketoconazole (Nizoral)

What medication used for Cushing that inhibits conversion of cholesterol to delta-5-pregnenolone, which in turn, reduces the production of adrenal glucocorticoids, mineralocorticoids?

Aminoglutethimide (Cytadren)

What 3 medications are adrenal steroid inhibitors that can be used in the tx of Cushing syndrome?

Metyrapone (Metopirone), Ketoconazole, Aminoglutethimide (Cytadren)

What are physical findings in a pt in adrenal crisis?

Hypotension, abd pain, vomiting, metal confusion (d/t hyponatremia or hypotension)

What lab findings are seen in an Adrenal crisis?

hypoglycemia, hyperkalemia, hyponatremia, metabolic acidosis

What is Addison disease?

chronic adrenal insufficiency

What is an Adrenal crisis?

acute adrenal insufficiency

What causes Adrenal insufficiency?

destruction/dysfunction of the ENTIRE adrenal cortex (affects cortisol and aldosterone function)

Antibodies to 21-hydroxylase enzyme are highly specific for what condition?

Addison disease

What enzyme is needed for production of cortisol and aldosterone?

21-hydroxylase

Onset of adrenal insufficiency disease occurs when how much of the adrenals has been destroyed?

90+% of both adrenal cortices

What is Schmidt syndrome?

Addison disease + Hashimoto thyroiditis

What is Polyglandular autoimmune syndrome type 1?

Addison disease + Hypoparathyroidism + Mucocutaneous candidiasis

What is Polyglandular autoimmune syndrome type 2?

Addison disease + T1DM + Hashimoto/Graves

What are common sx of Addison disease?

progressive fatigue, weight loss, weakness, poor appetite

What symptom of Addison disease often precedes all other symptoms by months-years?

Hyperpigmentation of skin & mucous membranes

What test is best to evaluate for Addison disease?

Rapid ACTH stimulation test

What is the result seen in patients with Addison disease following the rapid ACTH stimulation test?

Both cortisol & aldosterone show minimal-no change in response to ACTH

How do ACTH & cortisol change in Addison disease?

ACTH inc, cortisol dec

What are lab findings in Addison disease?

dec serum aldosterone, inc TSH, hyponatermia, inc K & Ca

What is a common cause of Addison disease that may be evident on CXR?

TB (used to be MCC)

In a pt with Addison disease, CXR may reveal (enlarged/small) heart

Small

What is the DOC for steroid replacement in acute adrenal crisis & daily maintenance of Addison disease?

Hydrocortisone sodium succinate

*has both glucocorticoid & mineralocorticoid properties

Which drug used for Addison disease is a synthetic adrenocortical steroid with very potent mineralocorticoid activity?

Fludrocortisone (Florinef)

What do patients with Addison disease require for life?

Glucocorticoid & mineralocorticoid replacement

*should also wear an emergency medical alert bracelet

When should pts with Addison disease double or triple their steroid replacement doses?

Stressful situations- ie common cold or tooth extraction

What is the MCC of adrenal crisis?

Stress

How do patients in adrenal crisis present?

fever ~105 F, N/V, vascular collapse, may be comatose; in acute adrenal hemorrhage pt deteriorates w/ sudden collapse, abd pain, nausea

What is the tx for acute adrenal crisis?

ASAP IV isotonic NaCl & IV hydrocortisone sodium succinate

What is one of the MC causes of secondary HTN?

Primary hyperaldosteronism

What is Conn syndrome?

Primary hyperaldosteronism secondary to adrenal aldosteronoma

What is the MCC of primary hyperaldosteronism?

Aldosteronoma

What is the tx of choice for aldosteronoma?

Surgery

What is the tx of choice for idiopathic adrenal hyperplasia?

Aldosterone antagonists- spironolactone

What are 4 common clinical scenarios in which primary hyperaldosteronism should be considered?

Spontaneous hypokalemia, hypokalemia with low-dose K-wasting diuretics, refractory HTN, or FHx of PH

What PE in patients with hyperaldosteronism?

HTN, weakness, abdominal distension, Ileus

What labs are affected in primary hyperaldosteronism?

Hypokalemia, Hypernatremia, inc aldosterone, low renin

What is the tx for primary hyperaldosteronism?

aldosteronomas → surgery

bilateral IAH → spironolactone

What medications are risk factors for developing hypoaldosteronism?

NSAIDs, ACEi, diuretics

Hypoaldosteronism is almost always associated with what?

kidney disease (CRF)

What sx are associated w/ hypoaldosteronism?

postural hypotension, anorexia, wt loss, dizziness

What lab findings are seen in hypoaldosteronism?

Hyperkalemia, Hyponatremia, low aldosterone, inc renin

What is the tx for hypoaldosteronism?

Endo/nephro consult, Fludrocortisone, liberal salt intake

What is a Pheochromocytoma?

rare, catecholamine secreting tumor derived from chromaffin cells most often in the adrenal glands

What are some drugs that inhibit catecholamine uptake, and therefore, can precipitate a hypertensive crisis with a pheochromocytoma?

TCAs, cocaine

What might precipitate a HTN crisis w/ a pheochromocytoma?

anesthesia, opiates, dopamine antagonist, cold meds, radiographic contrast, childbirth

What are sx of a Pheochromocytoma?

Cafe au lait spots, episodes of HA, palpitations, & diaphoresis in association with severe HTN

What is the classic PENTAD of sx of Pheochromocytomas?

HA, palpitations, perspiration, pallor, orthostasis

3 MC sx of pheochromocytoma:

PHEochromocytoma:

Palpitations

Headache

Episodic sweating (diaphoresis)

What is the MC presenting feature of pheochromocytomas?

HTN- systolic may be up to 300 mmHg

What is the tx of choice for pheochromocytoma?

Surgical resection

Which needs to be administered first in a pt with a pheochromocytoma: Alpha blockers or beta blockers? Why?

Alpha blocker THEN BB- if BB is started prematurely, then unopposed alpha stimulation can precipitate HTN crisis

Levels of cortisol & ACTH in Cushing disease:

High cortisol, high ACTH

Levels of cortisol & ACTH in adrenal tumor:

High cortisol, low ACTH

Levels of cortisol & ACTH in ectopic ACTH:

High cortisol, high ACTH

Levels of cortisol & ACTH in Addison disease:

Low cortisol, high ACTH

Levels of cortisol & ACTH in hypopituitarism:

Low cortisol, low ACTH