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75 Cards in this Set
- Front
- Back
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What is made in the glomerulosa
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Aldosterone
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What is made in the fasciulata/reticularis
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Cortisol and androgens
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What does the left adrenal vein empty into?
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Left renal vein (can lead to thrombosis and hemorrhage)
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What does the right adrenal vein empty into?
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Posterior aspect of the vena cava (can lead to thrombosis and hemorrhage)
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CRH is from where and stimulates what?
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Hypothalamus; stimulates ACTH in a pulsatile manner; has a diurnal rhythm (peak before awakening)
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What is the main negative feedback for ACTH?
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Cortisol (both long and short feedback)
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What is the precursor molecule for ACTH
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pro-opiomelancortin (POMC)
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StAR protein
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Steroidogenic acute regulator protein-->shuttles cholesterol from the outer to the inner mitochondrial membrane
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P450scc
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Cholesterol--side chain cleavage-->Pregnenolone
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P450c17
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Progesterone--->17-hydroxyprogesterone
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P450c21 and P450c11
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two hydroxylations from 17-hydroxyprogesterone--->active cortisol
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Progesterone-->deoxycorticosterone
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P450c21
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Pregneolone--->androgen
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P450c17
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What is cortisol bound to
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mostly corticosteroid-binding globulin
also albumin |
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11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)
rxn and location? |
Cortisol is metabolized to biologically inert steroid cortisone by the enzyme
In the Kidney It protects cortisol from binding to the same receptor as aldosterone |
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What is the rate limiting step in cortisol production and secretion?
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StAR protein-cholesterol entering the mitochondria
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17a Hydroxylase (P450c17)
If there is a deficiency in the enzyme what are the effects? |
can hydroxylate either pregneolone or progesterone
Increased mineralocorticoids Decreased cortisol and sex hormones HTN, hypokalemia |
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21 Hydroxylase (P450c21)
If there is a deficiency in the enzyme what are the effects? |
Hydroxylates Progesterone to 11-deoxycorticosterone or 17-hydroxyprogesterone to 11-deoxycortisol
decreases mineralcorticoids and cortisol Increases Sex hormones Hypotension, hyperkalemia, incr. renin, masculinization |
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11B Hydroxylase (P450c11)
If there is a deficiency in the enzyme what are the effects? |
11-deoxycorticosterone to corticosterone or 11-deoxycortisol to cortisol
Decrease aldosterone but an increase in 11-deoxycorticosterone; increase in sex hormones Hypertension (d/t 11-deoxycorticosterone) |
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Why is 11B-HSD2 enzyme important?
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It is 100x more effective than aldosterone and therefore would lead to HTN and hyperkalemia if there wasnt 11B-HSD2
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What are the effects of cortisol
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Immune and inflammation
Gluconeogenesis (also increases insulin resistance) Appetite Depression, anxiety Growth and Reproduction Cardiovascular Tone (amplification of adernergic effects) |
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What are the lab values in primary adrenal insufficiency
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High ACTH
High Renin Low Aldosterone Low Cortisol HYPONATREMIA!! |
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What is low in secondary adrenal insufficiency?
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ACTH
Hyponatremia |
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What are the sx of adrenal insufficiency?
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Fatigue, malaise, lack of energy
GI: nausea, vomiting, anorexia, weight loss Hyponatremia, hyperkalemia (primary) Lymphocytosis |
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Causes of 2ndary Adrenal insufficiency
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(Withdrawal from) exogenous corticosteroid therapy
Pituitary/Hypothalamic Disease (Hypophysitis, drug induced (ipilimumab) may cause isolated ACTH deficiency |
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Draw out the tx/dx plan for adrenal insufficiency
Sorry if the pic is small |
after low cortisol is determined...
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What constitutes a normal cortisol response to ACTH
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Peak response at 30 or 60 minutes >18 ug/dL
If it is low you need a ACTC measurement ACTH is ALWAYS elevated in patients with primary adrenal insufficiency |
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In critically sick patients, why is the serum cortisol possibly not reliable?
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May have low binding proteins (need to measure the free cortisol in the saliva)
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What is the effect of estrogen on cortisol levels?
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will have a significant increase in total cortisol levels that reflect an increase in CBG rather than any alteration of adrenal function.
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What is a sensitive measurement of adrenal reserve?
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Adrenal androgen production (DHEAS); rare to see a normal level in any type of adrenal insufficiency
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Causes of PRIMARY adrenal infufficiency
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Autoimmune polyglandular syndromes
Metastatic tumor or primary adrenal lymphoma Adrenal Hemorrhage (bilateral)-b/l adrenal vein thrombosis Tb, fungi, HIV Drugs: Ketoconazole, Metyrapone, mitotane, Etomidate Congenital adrenal hyperplasia, familial glucocorticoid deficiency, adrenoleukodystrophy |
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Tx of primary adrenal insufficiency
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Hydrocortisone (10-15 mg in AM and 5-10 mg in the afternoon) (need additional steroids if you are getting sick)
Monitor overall health; ACTH should remain elevated even with adequate hydrocortisone Solu-cortef-emergency injectable hydrocortisone Give Fludrocortisone daily (monitor electrolyte composition, and plasma renin activity) |
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Treatment for Secondary Adrenal Insufficiency
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Hydrocortisone in daily divided doses; lower doses needed compared to primary adrenal insufficiency
You DONT need mineralocorticoid replacement since renin-angiotensin and zona glomerulosa remain intact) |
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Effects of Cushing's syndrome
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Weight gain, facial fullness, Incr. supraclavicular fat, diabetes, osteoporosis, increase BP, myopathy, neuropsych disorders, edema, hypogonadism, androgen excess; Easy bruising
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High Cortisol: ACTH dependent
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Cushing's disease
or ectopic ACTH secreting tumor |
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High Cortisol: Adrenal Dependent
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Solitary adrenal adenoma
Exogenous glucocorticoid therapy Nodular adrenal hyperplasia |
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Physiological hypercortisolism is d/t
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Stress, alcohol, neuropsych disorders, starvation
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What are the diagnostic tests for cushing syndrome
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Late-night salivary cortisol (very sensitive/specific)
Overnight low dose dexamethasone suppression test (normally cortisol <1.8 in the morning) 24hr urine test: not typically used |
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Write out the flow chart for diagnosing cushings syndrome
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Treatment of Cushings syndrome
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Surgery Always first! (remove the offending tumor)
Bilateral adrenalectomy in patients that have failed other tx (concern for Nelson's syndrome-regrowth of pit tumor) Radiotherapy Pasireotide-->somatostatin analog (where surgery isnt an option) Metyrapone-->11beta hydroxylase inhibitor Mifepristone-->inhibitor of glucocorticoid and progesterone receptor |
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Pasireotide mech and tx
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Somatostatin analog
Tx cushing's disease in patients where surgery isnt an option |
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Metyrapone mech of action
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11-beta hydroxylase inhibitor (stops the cortisol synthesis)
used in adrenal cancer since it is lytic in high doses |
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Mifepristone mech
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potent inhibitor of glucocorticoid and progesterone receptor
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Write out the renin-angiotensin-aldosterone system pathway
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Angiotensinogen--Renin-->Ag I---ACE---->Ag II (neg feedback on renin)--->constricts smooth muscle and releases aldosterone-->renal water and sodium retention
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What channel does aldosterone work on?
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ENaC channels
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Effects of primary hyperaldosteronism
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Adrenal adenoma-->increased aldosterone-->negative feedback shuts renin down
increased aldo leads to HYPOkalemia and increased blood pressure |
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What is the first test to check for primay hyperaldosteronism?
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Plasma aldosterone/Plasma renin ratioq
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Causes of primary hyperaldosteronism
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Aldosterone-secreting adrenocortical adenoma
Bilateral hyperplasia of zona glomerulosa |
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Causes of 2ndary hyperaldosteronism aka high Renin
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Renal ischemia
Decreased intravascular volume CHF Chronic diuretic or laxative use Hypoproteinemic states Chronic Renal failure Sodium wasting disorders |
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Testing for presumed primary hyperaldosteronism
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CT or MRI of adrenals-->if unilateral--> adenalectomy
If bilateral or normal-->selective venous cath-->medical management or unilateral adrenalectomy |
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Medical management of hyperaldosteronism
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Spironolactone
Eplerenone Both mineralocorticoid receptor antagonists Decrease sodium and water retention |
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Apparent mineralocorticoid excess
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11BHSD2 deficiency
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Liddle's syndrome
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mutations in the amiloride sensitive epithelial sodium channel. treated with amiloride and triamterene (potassium sparing diuretics)
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Tumors of the chromaffin cells of the adrenal medulla
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Pheochromocytoma
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Paragangliomas
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tumors that arise from extra-adrenal ganglia of the sympathetic nervous system
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What to pheochromocytomas can secrete what?
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both epinephrine and norepinephrine (primarily norepi)
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What are some of the manifestations of catecholamine excess?
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tachycardia, increased contractility, arrhythmias, HTN, decreased plasma volume (dehydrated); intestinal relaxation, suppression of insulin release (B cells), increased glucose, urinary retention, weight loss
Chest pain, dizziness, circulatory collapase |
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Tests for epi and norepi levels?
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24 hr urinary test for Catecholamines (Norepi and Epi)
Plasma levels of FREE METANPHRINES (metabolites of epi and norepi; Most sensitive) |
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What is the treatment for Pheochromocytoma
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Begin alpha-blockade (phenoxybenzamine)
Next, you can add B-blockers Hydrate Surgical therapy with adrenalectomy |
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What type of cell is in the medulla?
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Chromaffin cells (epinephrine)
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What are the three layers of the adrenal cortex and what is in each layer?
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- Zona glomerulosa (G): Mineralocorticoids (aldosterone) = “Salt”
- Zona fasciculata (F): Glucocorticoids (cortisol) = “Sugar” - Zona reticularis (R): Sex steroids (estrogens and androgens) = “Sex” |
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Bilateral thickening of the adrenal cortex
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Adrenocortical hyperplasia
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What type of cells predominate in adrenocortical hyperplasia?
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Predominantly fasciculata cells; Clear cells
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Characteristics of Adrenocortical adenoma?
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Encapsulated
1-2 cm Usually Non-functional Predominantly zona fasciculata cells (like hyperplasia) |
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Characteristics of Adrenocortical Carcinoma
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Rare
>200-300 grams; 5 cm in diameter Invasive Necrosis/hemorrhage invade adrenal vein and vena cava If poorly differentiated it will have more color in cytoplasm, large nuclei, and a lot of irregularity |
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exogenous glucocorticoids leads to what change in the adrenal gland?
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Cortical atrophy
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Increased ACTH leads to what change in the adrenal gland?
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Bilateral hyperplasia
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ACTH independent hypercortisol leads to what change in the adrenal gland?
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Adrenocortical adenoma or carcinoma
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Hyperaldosteronism leads to what change in the adrenal gland?
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Adrenal cortical adenoma (Conn Syndrome)
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What is the indicator for malignancy for pheochromocytoma?
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METASTASIS
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What is the microscopic appearance of pheochromocytoma?
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Zellballen: nests of cells within a rich vascular network; abundant cytoplasm that is granular (basophilic)
Stain with neuroendocrine markers (chromogranin, synaptophysin) |
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Adrenal Pheochromocytoma
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Extra adrenal pheochromocytoma
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Paraganglioma
Common sites-->jugulotypanic, carotid body, vagal, aorticopulmonary |
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What is the most common finding associated with endogenous Cushings
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Bilateral hyperplasia
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What is the pheochromocytoma rule of 10?
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Pheochromocytoma 'rule of 10': 10% bilateral, 10% malignant (higher in familial cases), 10% extra-adrenal, 10% familial
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