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63 Cards in this Set
- Front
- Back
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IS cortisol required for the synthesis of epinephrine?
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yes
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what is the role of 11B-HSD?
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a set of isoenzymes that is involved in regulating cortisol activity in different tissues.
In the kidney, colon, and salivary gland: it works to INACTIVATE cortisol (to cortisone) IN the liver, adipose tissue, bone and eye, 11B-HSD favours the conversion of cortisone into the active form (cortisol) |
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what is cortisol's effect on gonadal function?
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it inhibits response of pituitary to GnRH (thus decreased gonadotropins and gonadal steroids)
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what is cortisol's effect on teh CNS? initially? Later?
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initially: euphoria
later: irritability, memory loss, etc. |
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cortisol's effect on the thyroid?
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inhibits TSH secretion
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where in the kidney does aldosterone act?
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distal tubules
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aldosterone is a (strong/weak) glucocorticoid?
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weak
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of DHEAS, DHEA and androstenedione, which has the longest t1/2?
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DHEAS
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Explain how ADRENAL ANDROGEN production varies throughout life? What changes does cortisol production undergo throughout life?
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Adrenarche - age 6-10
peaks - age 30 adrenopause - production decreases as we age (corresponds to atrophy of ZR) Cortisol production does not change with age |
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when we say adrenal steroids, what are we talking about?
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all the hormones made by the ZG, ZF, ZR
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all adrenal steroids synthesis begins with...
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cholesterol
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what is the rate limiting step in the synthesis of adrenal androgens? What stimulates this reactino in teh ZG? What stimulates this reaction in teh ZF and ZR?
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cholesterol --> pregnenolone
ZG: AII ZF and ZR: ACTH |
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What is the role of P450 enzymes in the synthesis of adrenal steroids?
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they hydroxylate the steroid molecules
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what drug will interfere with the synthesis of adrenal androgens through its actuion of inhibiting p450 enzymes?
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ketoconazole
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why will does hi ACTH often correspond with increased pigmentation?
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ACTH is a spliced product of the POMC gene protein. Another product is MSH. Thus a high ACTH means that MSH is also being produced.
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what is the immediate precursor to cortisol? Why do I care about the precursor?
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11-deoxycortisol
IT will accumulate in 11-B-hydroxylate deficiency (testing for increased levels of this is the DIAGNOSTIC TEST for 11-hydroxylate deficiency) |
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after cholesterol is made into pregnenolone, what is the next step?
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pregnenolone --> progesterone
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what percentage of cortisol is bound to CBG (cortisol binding globulin)
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90% (only 10% is free in teh circulation)
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what are the two SCREENING tests for cushings?
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Urine free cortisol
Low-dose dexamethasone |
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what is the main blood carrier for adrenal androgens? Testosterone?
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adrenal androgens= albumin. Testosterone = SHBG (sex hormone binding globulin)
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what are the 2 fates of cortisol in teh circulation?
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1. either metabolised in the liver to glucuronide OR
2. passed into the urine |
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what are 2 things that can override the negative feedback of cortisol on the hypothal & pituitary? (i.e. what will determine cortisol levels more that cortisol itself?) What is the MOA?
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1. stress
-physical (trauma) -emotional (e.g. depression) -hypoglycemia -severe illness (via cytokines: IL-1, TNF-alpha, IL-6) 2. circadian rhythm (diurnal) Both of these act via stimulating CRH secretion |
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what are estrogen's (via BCPs, pregnancy.) effects on cortisol concentration in the blood?
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estrogen will increase CBG (made by liver), and therefore cortisol in the blood. However, the amount of free cortisol will stay the same.
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Illness or malnutrition will (increase/decrease) CBG in the blood?
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decrease
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3 main factors that control aldosterone release from the ZG:
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1. REnin - RAS
2. K+ 3.ACTH (minor short-term effects) |
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what does renin do?
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catalyses conversino of angiotensinogen to angiotensin I
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what changes angiotensin I to angiotensin II?
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ACE
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how will postural change affect renin secretion?
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renin will increase in an upright position
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ANP,BNP,and CNP are relased by the atria, ventricles and vascular endothelium in response to (hi/low) filling pressure and volume. They (stimulate/suppress) the RAS system
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hi
Suppress (causing natriuresis) |
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with illness, adrenal androgens (increase/decrease) while cortisol (increase/decreases)
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androgens - decrease (think, less sex drive when sick)
cortisol - increases (ahhh! body is stressed!) |
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has DHEA been shown to have anti-aging effects?
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no!
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can DHEA supplementation be important for women with adrenal insufficiency?
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YES!
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what are the 4 primary causes of adrenal insufficiency?
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1. Autoimmune adrenalitis (m/c cause of Addison's disease)
2. Granulomatous disease (e.g. TB) 3. Congenital adrenal hyperplasia (21 or 11 hydroxylase deficiency) 4.Adrenoleukodystrophy (accumulation of VLCFAs) |
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what is the m/c secondary cause of hypocortisolism?
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iatrogen (i.e. long term glucocorticoid Tx)
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what will you see in Primary hypocortisolism in terms of
a. ACTH levels b. Cortisol levels c. aldosterone levels? |
In primary hypocortisolism
a. ACTH levels will be up b. cortisol levels will be down c. aldosterone levels will be down |
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what is Type II Autoimmune Polyglandular Syndrome (APS-11)= Schmidt's Syndrome?
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It's when Addisons' disease is part of a syndrome (i.e the autoimmune aspect of it affects other glands suchas :
-thyroid -pancreatic B cells --> insulin dependent DM -ovaries -melanocytes -parathyroid recall Mrs. Addison picture |
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what 2 symptoms of addisons disease are important features that can lead to an addisonian crisis?
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hyperkalemia
low blood pressure leading to cirdculatory collapse |
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what enzyme is deficient in adrenoleukodystrophy?
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a peroxisomal enzyme that catabolizes VLCFAs
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what is the presentation of adrenoleukodystrophy?
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neurological +/- adrenal symptoms
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Adrenoleukodystrophy shoudl be considered a cause of Addison's disease in (males/females_
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males (it is x-linked)
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the rapid ACTH stimulation test is used for?
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to test for adrenal insufficiency (primary or secondary)
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If the result of a rapid ACTH stimulation test are as follows, what is the diagnosis?
-normal baseline ACTH -increase in cortisol after injection |
Not Addison's disease
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if the result of the rapid ACTH stimulation test is as follows, what is your diagnosis:
-low baseline ACTH -blunted cortisol response after injection |
secondary cause or atrophy due to chronic glucocorticoid Tx
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if the result of the rapid ACTH stimulation test is as follows, what is your diagnosis:
-hi baseline ACTH -blunted cortisol response after injection |
primary cause of adrenal insufficiency (e.g. Addison's disease)
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If you determine the cause of adrenal insufficiency to be due to a secondary cause in the rapid ACTH stimulation test, what should you do next?
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Confirm that it really is a secondary cause by testing the whole axis via an insulin-induced hypoglycemia test. If the patient cannot recover, then this confirms that their problem is due to the pituitary or hypothalamus
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Treatment for primary adrenal insufficiency?
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glucocorticoid AND mineralocorticoid
+ DHEA in females |
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Treatment for a secondary adrenal insufficiency?
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glucocorticoid only (AII will take care of the aldosterone)
+ DHEA in females |
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what is the main cause of Conn's syndrome?
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an aldosterone secreting adenoma (70%)...the other 30% are idiopathic
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what will you see in Conn's syndrome in terms of:
a. aldosterone level? b. renin level? c. blood pressure? d. potassium status? |
1. increased aldo
2. low renin 3. hi BP 4. hypokalemia |
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what are teh 4 symptoms of HYPOkalemia
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1. muscle weakness
2. abnormal glucose tolerance 3. polyuria (due to nephrogenic DI) 4. ECG changes |
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is hypokalemia a/w acidosis or alkalosis?
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alkalosis. Low serum K will result in cells pumping K out from their insides. This is a K/H pump that is going this. So H+ ions are going to move INTO cells, causing alkalosis
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Secondary hyperaldosteronism is due to things that cause increased renin. What are 3 examples of things that will cause an increase in renin?
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1. renal artery stenosis
2. renin secreting tumor 3. coarctation of the aorta |
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How do you diagnose hyperaldosteronism?
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RENIN:ALDOSTERONE ratio.
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Summary:
1. Diagnosis of adrenal insuffiency? 2. Diagnosis of hyperaldosteronism 3. SCREENING of Cushing's |
1. rapid ACTH stimulation test
2. renin:aldosterone ratio 3. urine free cortisol, low-dose dexamethasone supression test |
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when would you run a bilateral adrenal venous sampling of aldosterone?
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when you suspect a primary cause of hyperaldosteronism (Conn's syndrome).
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what is the Tx for primary hyperaldosteronism?
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surgical resection
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What 2 diseases do Congenital Adrenal Hyperplasia refer to?
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Diseases that will increase ACTH secretion, therefore accounting for the adrenal hyperplasia: Namely:
1. 21 hydroxylase deficiency 2. 11 hydroxylase deficiency |
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What is the definitive dx test for 21 hydroxylase deficiency? What is the definitive dx test for 11 hydroxylase deficiency?
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17-hydroxyprogesterone
11-deoxycortisol |
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what is the Tx for 21-hydroxylase deficiency?
what is the tx for 11-hydroxylase deficiency? |
21: glucocorticoid and mineralocorticoid
11: glucocorticoid only. |
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Drugs and hormones that act via nuclear receptors can be remembered by "GREAT Football Game". What do the letters stand for?
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Glucocorticoids
Retinoids (acne) Estrogen(HRT) Androgens (HRT) Thyroid hormone Fibrates Glitazones |
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The nuclear receptors that glucocorticoids bind to form (hetero/homo) dimers
the nuclear receptors that Thyroid hormone binds to form (hetero/homo) dimers |
glucocorticoids: homo
TH: hetero |
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the anti-inflammatory effect of glucocorticoids is primarily due to the (shutting off/switching on) of genes
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shutting off (3 mechs)
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what are the 3 mechs by which glucocorticoids work to shut off genes?
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1. stimulates production of IkB, which binds to NFkB interfering with the production of cytokines
2. interferes with AP-1 (normally involved in regulating expression of collagenase) 3. interferes with CBP/P300 - needed for transcription of many genes |
