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31 Cards in this Set
- Front
- Back
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Complete the sentences:
These are the 3 zones of the cortex: (blank), (blank), (blank). Aldosterone is regulated by ACTH and (blank). (Blank) is the only corticosteroid that can turn "off" ACTH. Aldosterone, cortisol, androstenedione are all derived from (blank). Adrenal steroids produce their effects by (name the biochemical mechanism). |
Complete the sentences:
These are the 3 zones of the cortex: glomerulosa (aldosterone), fasciculata (cortisol), reticulans (androgens). Aldosterone is regulated by ACTH and angiotensin. Cortisol is the only corticosteroid that can turn "off" ACTH. Aldosterone, cortisol, androstenedione are all derived from cholesterol. Adrenal steroids produce their effects by direct alteration of gene products (aka: steroids work as transcription factors). |
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Name the enzymes important in the following conversions..
(1) pregnenolone to progesterone (2) pregnenolone to cortisol (3) pregnenolone to aldosterone (4) pregnenolone to 17-alpha-OH-pregnenolone to androstenedione |
(1) pregnenolone to progesterone via 3-beta-hydroxysteroid dehydrogenase
(2) pregnenolone to cortisol via 17-alpha-hydroxylase.. 3-beta-hydroxysteroid dehydrogenase.. 21-hydroxylase... 11-beta-hydroxylase (3) pregnenolone to aldosterone via 3-beta-hydroxysteroid dehydrogenase... 21-hydroxylase.. 11-beta hydroxylase (4) pregnenolone to 17-a-OH pregnenolone via 17-alpha hydroxylase... and 17-a-OH pregnenolone to androstenedione via 3-beta hydroxysteroid dehydrogenase |
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Describe the metabolic effects of glucocorticoids.
Describe the catabolic effects of glucocorticoids. Glucocorticoids result in increased levels of what? Why is this important? |
Metabolic Effects:
Using glycerol and amino acids, GCC stimulates hepatic glucose formation. Catabolic Effects: To get the glycerol and amino acids to the liver, GCC diminishes glucose utilization in periphery by enhancing protein catabolism in muscle and lipolysis in fat. The net result of GCC is to increase levels of plasma glucose which is important in protecting the heart and brain -- the body's glucose dependent tissues. |
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How do glucocorticoids produce anti-inflammatory effects?
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GCC produce anti-inflammatory effects by..
--inhibit synthesis of leukotrienes, PG's --dec content and release of histamine --dec synthesis of interleukins and cytokines --dec release of lytic enzymes --dec release of reactive oxygen products --dec macrophage factors |
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The effects of glucocorticoids on metabolism are most dramatic in the (fasting/fed) state.
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The effects of glucocorticoids on metabolism are most dramatic in the FASTING state.
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A patient's immune system is attacked. Inflammatory factors such as IL-1, IL-6 and TNFalpha are released.
How do these factors affect the hypothalamus/pituitary/adrenal axis? Are any adrenocorticosteroids released? Why is this important? |
Inflammatory factors stimulate the hypothalamus to release CRH and the pituitary to release ACTH.
This leads to the release of cortisol from the adrenals, which has a negative feedback effect on the immune system to decrease the release of inflammatory factors and on the hypothalamus and pituitary to inhibit the release of CRH and ACTH, respectively. |
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Describe the physiologic effects of mineralocorticoids on the kidneys.
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MCC's act on the renal distal tubules and the collecting ducts to..
(1) inc Na reuptake (2) inc K+, H+ excretion (3) create positive Na+ balance (4) inc ECF (5) raise BP |
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Describe the effects of both high and low levels of mineralocorticoids on (1) cardiovascular system (2) electrolyte balance.
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High MCC:
(1) inc BP (2) hypokalemia, hypernatremia (3) alkalosis Low MCC: (1) dec BP (2) hyperkalemia, hyponatremia (3) acidosis |
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TRUE or FALSE
Blocking ACTH release will completely block the release of aldosterone. |
FALSE
Aldosterone is regulated by both ACTH and the renin/angiotensin system. Renin is released in response to low BP, leading to angiotensin synthesis and aldosterone release. |
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Are anti-inflammatory effects produced mainly by glucocorticoids or mineralocorticoids?
What about electrolyte balance and cardiovascular effects? |
GCC's (cortisol) produce anti-inflammatory effects.
MCC's (aldosterone) regulate electrolyte balance and have cardiovascular effects. |
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What is another name for primary adrenal insufficiency?
What is given to a patient for replacement therapy? In what circumstances might the dose of the therapy need to be raised? |
Addison's Disease is primary adrenal insufficiency, and is often an autoimmune disease.
Replacement dose of 30-40mg of cortisol is given to patients with Addison's. (Sometimes MCC supplementation is needed to better regulate blood pressure). Cortisol doses may need to be raised to 2-3x normal in the case of illness or stress. |
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The most common enzyme deficiency in the synthesis of adrenal steroids is of:
(a) 17-alpha hydroxylase (b) 21-hydroxylase (c) 11-beta hydroxylase |
The most common enzyme deficiency in the synthesis of adrenal steroids is of:
(b) 21-hydroxylase |
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In a person with a 21-hydroxylase deficiency, how might her cortisol levels be normal?
Would her androgen secretion be elevated or depressed? How would you treat this patient? |
A 21-hydroxylase deficiency would initally cause decreased cortisol levels. Low cortisol leads to increased ACTH. The elevated ACTH levels would eventually lead to normalized cortisol concentrations at the expense of adrenal hyperplasia.
Androgen secretion would probably be elevated. Treatment would be cortisol 100mg/day initially for 5 days. This would decrease ACTH release and then you would treat the patient with replacement therapy levels of 30-40 mg/day. |
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You discover your patient has a 21-hydroxylase deficiency.
Do you start him on cortisol 30-40mg/day right away? Why or why not? |
Initial treatment would be cortisol 100mg/day for 5 days in order to decrease ACTH release.
After 5 days, you would then put your patient on a replacement therapy of 30-40 mg/day. |
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Exogenous and endogenous GCC can lead to toxicity effects. Describe some of them.
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(1) CNS effects (euphoria)
(2) steroid diabetes (3) osteoporosis (4) ulcers (5) delayed wound healing (6) adrenal atrophy |
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What is another name for having excess ACTH in the blood?
What are the possible causes of this? |
Cushing's syndrome results from excess ACTH release and excess cortisol.
Possible causes: (1) pituitary adenoma = true Cushing's Disease (2) non-endocrine tumor that secretes ACTH (3) abn adrenal gland responses (4) ectopic adrenal tissue |
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Describe the dexamethasone suppression test and the petrosal sinus test for diagnosing Cushing's syndrome.
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Dexamethasone suppression test:
Normally, a low dose of dex would turn off ACTH release. If a patient requires 4x this dose to turn off ACTH, you should suspect Cushing's Disease. If 4x does not turn off ACTH, you should suspect a non-endocrine tumor or ectopic adrenal tissue as the cause of excess ACTH. Petrosal sinus testing: A patient is given CRH and then ACTH levels are measured in the petrosal sinus (veins directly draining the pituitary) and in the peripheral venous blood. High ACTH in the petrosal sinus vs. periphery indicates that the pituitary is causing the excess ACTH. No difference or higher ACTH levels in the periphery vs. petrosal sinus indicates an ectopic source for ACTH. |
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What are the signs and symptoms of GCC, MCC excess?
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(1) truncal obesity
(2) muscle wsting (3) steroid diabetes (4) bone demineralization (5) growth retardation (6) CNS manifestations (7) hypertension (8) delayed wound healing (9) hypokalemic alkalosis |
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What are the signs of androgen excess?
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hirsuitism
amenorrhea (in an adult female) |
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Describe the effects of a 21-hydroxylase deficiency regarding:
(1) aldosterone levels (2) cortisol levels (3) ACTH levels (4) effects in pre-pubescent boy or girl (5) post-pubescent boy |
Describe the effects of a 21-hydroxylase deficiency regarding:
(1) aldosterone levels: low (2) cortisol levels: low (3) ACTH levels: high (4) effects in pre-pubescent boy or girl: masculinization, early puberty, hirsuitism (5) post-pubescent boy: no manifestations |
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Describe the effects of a 17-alpha-hydroxylase deficiency regarding:
(1) cortisol levels (2) androstenedione levels (3) aldosterone levels |
Describe the effects of a 17-alpha-hydroxylase deficiency regarding:
(1) cortisol levels: low (2) androstenedione levels: low (3) aldosterone levels: high |
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Why is pharmacological intervention NOT optimal when it comes to treating Cushing's Disease?
What, then, is the best course of action? |
Pharmacological treatment of Cushing's Disease (pituitary is source of ACTH) focuses on decreasing cortisol production. This leads to an INCREASE in ACTH as well as upregulation of other corticosteroids like aldosterone and androgens.
The best course of treatment is removal of the pituitary adenoma (or in the case of an ectopic ACTH source, aggresive ablation therapy) and using pharmacological treatment as an adjuvant. |
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Compare and contrast mitotane and amphenone B in regards to:
(1) enzymes they block (2) effect on tissue integrity (3) potency (4) availability on US market |
Mitotane and Amphenone B
(1) both block 21, 17alpha, 11beta hydroxylases (2) mitotane destroys adrenal tissues while amphenone B does not (3) amphenone B is a more potent relative of mitotane (4) both have been removed from the US market |
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Metyrapone
(1) What enzyme does it inhibit? (2) What is its primary effect? (3) How is it used? |
Metyrapone
(1) It inhibits 11beta hydroxylase. (2) It blocks 11-deoxycortisol to cortisol (3) It can be used to manage cortisol excess before the cause is known. It is also used to test the pituitary reserve of ACTH (metyrapone administration would decrease cortisol which should result in the release of ACTH). |
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Aminoglutethimide
(1) What steroid synthesis step does it inhibit? (2) Does it only affect the adrenal gland? (3) Can ACTH overcome its effect? (4) How is it used? |
Aminoglutethimide
(1) Inhibits cholesterol to prenenolone conversion (2) Can blunt androgen synthesis in testes (3) ACTH can overcome its effect (4) Used mainly for Cushing's 2ndary to adrenal cancer and can be used w/ dexamethasone to decrease androgen secretion. |
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Ketoconazole
(1) Leads to compensatory increases in what? (2) Effects on estrogen and testosterone? (3) Can lead to these effects in males.. (4) Can lead to this effect in females... |
Ketoconazole
(1) Leads to compensatory increases in ACTH, androgens and aldosterone (2) Increases estrogen:testosterone ratio (3) Males: can cause gynecomastia and oligospermia (4) Females: can alter menstrual cycle |
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Name both the GCC receptor antagonist and the MCC receptor antagonist that can be used to treat Cushing's disease.
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GCC receptor antag = mifepristone
MCC receptor antag = spironolactone |
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Spironolactone can be used to treat excess aldosterone secretion.
What other 2 agents can be used that alter the renin/angiotensin system? |
ACE inhibitor = captopril
AT-1 receptor antag = losartan |
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Identify the specific drug therapy in Cushing's that is described by the following:
(1) increases estrogen:testosterone ratio (2) destroys adrenal tissue and derivative of a pesticide (3) specific inhibitor of 11-beta hydroxylase (4) blocks 21, 17alpha, and 11beta hydroxylases and does not destroy adrenal tissue (5) inhibits cholesterol to pregnenolone conversion (6) blocks cortisol release and used to test pituitary reserve of ACTH (7) used mainly in treatment of Cushing's 2ndary to adrenal cancer (8) both of these drugs have been removed from the US market |
Identify the specific drug therapy in Cushing's that is described by the following:
(1) increases estrogen:testosterone ratio = ketoconazole (2) destroys adrenal tissue and is a derivative of a pesticide = mitotane (3) specific inhibitor of 11-beta hydroxylase = metyrapone (4) blocks 21, 17alpha, and 11beta hydroxylases and does not destroy adrenal tissue = amphenone B (5) inhibits cholesterol to pregnenolone conversion = aminoglutethimide (6) blocks cortisol release and used to test pituitary reserve of ACTH = metyrapone (7) used mainly in treatment of Cushing's 2ndary to adrenal cancer = aminoglutethimide (8) both of these drugs have been removed from the US market = mitotane and amphenone B |
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List the primary uses of synthetic adrenocorticosteroids.
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(1) replacement therapy
(2) anti-inflammatory therapy (3) immunosuppressive therapy (4) diagnostic purposes |
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Natural and synthetic corticosteroids have anti-inflammatory effects and Na retention effects. Usually, one effect is more potent than another. For the following corticosteroids, identify the **relative** potencies of each effect.
(1) cortisol (2) aldosterone (3) double bond derivative (ex: prednisolone, prednisone) (4) flourinated or 16alpha/beta substituted prednisolone (dexamethasone) |
(1) cortisol has a 1:1 anti-inflammatory and Na retention effects
(2) aldosterone's Na retention potency is 300x that of cortisol and its anti-inflamm potency is practically nil (0.35) (3) prednisone's anti-inflammatory effect is 4x that of cortisol and its Na retention effect is slightly less than cortisol's (0.8) (4) dexamethasone's anti-inflammatory potency 30x that of cortisol and it has no Na retention potency |
