Week 4 - Adrenal Flashcards by Chelsea V

What is the action of Amiloride?

Blocks ENaC channels –> K+ sparing diuretic

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What is the action of Spironolactone?

Antagonist of mineralocorticoid (aldosterone) and androgen receptors –> K+ sparing diuretic

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What is the screening test for Cushing’s Syndrome?

ACTH level

- Overnight dexamethasone suppression test

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What is the test for differentiating Cushing’s Disease from other causes of Cushing’s syndrome?

Petrosal sinus sampling

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What lab tests are required to rule out Pheochromocytoma?

Urine catecholamines and catecholamine metabolites (ex. metanephrine)

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What is Conn’s syndrome?

Primary hyperaldosteronism due to aldosterone-secreting adenoma

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What test is useful to rule out Conn’s syndrome?

Aldosterone:renin ratio

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What is the first investigation for adrenal insufficiency?

Rapid ACTH stimulation test (with baseline ACTH and cortisol measurements)

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For ACTH stimulation test, what does it mean if there is blunted cortisol response with high ACTH?

with low ACTH?
what about normal ACTH and normal cortisol response?

High ACTH, Low cortisol response ==> Primary Adrenal Insufficiency (Addison’s disease)

Low ACTH, Low cortisol response ==> Secondary Adrenal Insufficiency or Chronic Steroid Use

Normal ACTH, Normal cortisol response ==> Not Addison’’s

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What are the cells in the adrenal medulla called?

- what do they secrete?

Chromaffin cells

- secrete catecholamines

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What does MEN stand for?

Multiple Endocrine Neoplasia

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What are the types and subtypes of MEN?

MEN-1

MEN-2: subclassified to

MEN-2a
MEN-2b
MCT (Medullary carcinoma of the thyroid)

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What are the main symptoms associated with MEN-2?

Medullary carcinoma of the thyroid (>95%)

2. Pheochromocytoma (50%)

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What are the main symptoms associated with MEN-1?

“P-P-P triad”

Parathyroid
Pancreatic Islet cell (usually insulin or gastrin secreting)
Pituitary (anterior)

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What’s the difference in clinical presentation between MEN-2a & MEN-2b?

MEN-2a has hyperparathyroidism.

MEN-2a is more common than 2b.

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How is the presentation of medullary carcinoma of the thyroid different than other MEN-2 presentations?

MCT is not a/w pheos.
MCT and MEN-2b do not have hyperPTH, but Men-2a does.

ie. the only symptom a/w MCT is MCT.

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How is dx of MEN-2 confirmed?

Bx of mass in neck (most important early finding).

- Measure for elevated calcitonin

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What is a marker for MCT?

elevated calcitonin

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What is the rate of secretion of cortisol under physiological conditions?

10mg/day

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What is the normal range for K+ in the blood?

3.5-5mmol/L

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List the types of corticosteroids and state their main function.

Glucocorticoids - regulate carbohydrate metabolism (& anti-inflammatory)
Mineralocorticoids - regulate electrolyte balance (mainly Na+ retention)

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What is the transport protein for cortisol in the blood?

CBG (Corticosteroid binding globulin)

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Name a short-acting glucocorticoid.

- what is the approximate half life of this?

Hydrocortisone (cortisol) or cortisone

- t(1/2) = 8-12 hrs

Name a intermediate-acting glucocorticoid.

- what is the approximate half life of this?

Prednisone

- t(1/2) = 12-36 hrs

Name a long-acting glucocorticoid. | - what is the approximate half life of this?

Dexamethasone | - t(1/2) = 36-72 hrs

What synthetic corticosteroid has much more potent mineralocorticoid action (as opposed to glucocorticoid action)

Fludrocortisone

What is the benefit of taking steroids in the inhaled form?

Prevents systemic effects of the drug

What are the pharmacokinetics of ingested cortisol (ADME)?

A: well absorbed via GI D: binds to CBG or albumin in blood M: hepatic metabolism E: excreted by kidneys

Of the alpha and beta type catecholamine receptors, which one has a much higher affinity for Epi over NE?

beta-2 receptors

How does cortisol act in catecholamine production?

Induces PNMT (enzyme that converts NE --> Epi

What is the rate-limiting step in catecholamine synthesis?

Tyrosine --> DOPA | enzyme = Tyrosine hydroxylase

What is the enzyme that catalyzes the rate-limiting step in cholesterol synthesis?

HMG-CoA reductase

Why does the adrenal medulla get stained dark brown?

Due to conversion of catechols to melanin (occurs in granules)

Is the adrenal medulla necessary for life?

no.

What are the pathways for the metabolism of Epi & NE? | (include enzymes)

Epi --(COMT)--> metanephrine --(MAO)--> VMT NE --(COMT)--> normetanephrine --(MAO)--> VMT

Why is dexamethasone given after surgery?

To prevent nausea/vomiting

What are some of the main complications of long-term glucocorticoid tx?

Adrenal atrophy --> iatrogenic Cushing's (due to too much synthetic glucocorticoid action) Glucocorticoid withdrawal --> acute adrenal insufficiency

What is the similarity between the following drugs? - Aminoglutethimide - Metyrapone - Ketoconazole - Etomidate

CYP 450 inhibitors - affect the production of corticosteroids and androgens

What is the molecular action of finasteride?

- 5-alpha-reductase inhibitor | - prevents conversion of T --> DHT

What is the action of Mifepristone?

Progesterone receptor blocker

What cells are in the adrenal medulla to support the spindle cells?

Sustentacular cells

Where are the spindle cells?

At periphery of the nests of chromaffin cells.

What is the most common adrenal mass in children?

Neuroblastoma

What is the DDx for bilateral adrenal masses?

- pheo - cushing's disease (excess ACTH stimulation) - ectopic ACTH/CRH production - mets - hemorrhage - adrenal nodular hyperplasia - lymphoma

In Addison's disease, what percent of the adrenal cortex has to be destroyed before symptoms present?

90% compromised

What are some causes of Addison's disease?

- autoimmune - infections (TB, histoplasmosis, coccidiodes) - mets/lymphomas - hemorrhage - HH (hemochromatosis)

What virus is common in adrenal glands of AIDS patients?

CMV

Where are steroid receptors when not activated?

In cytoplasm, bound to HSD (heat shock protein)

What are fibrates used to treat? | - what receptor do they bind to?

Treat dyslipidemia | - bind PPAR-alpha receptor

What is Vit D used to prevent? | - which receptor does it bind?

Prevents rickets & ostemalacia, diabetes, CA | - binds VDR (Vit D receptor)

What are thiazolidinediones used to treat? | - what receptor does it bind?

Diabetes | - binds PPAR-gamma receptor

How are blood glucose levels related to serum K+?

Hypokalemia causes inhibition of insulin secretion, thus leading to hyperglycemia

How does cortisol affect GFR?

Cortisol increases GFR --> increases free water clearance

What's associated with mutations in the RET proto oncogene?

MEN-2a MEN-2b MCT Hirschprung's syndrome

What happens in Addisonian Crisis?

hypotension, hyperkalemia, hyponatremia