Term
| Medulla of Adrenal Glands |
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Definition
10% of gland;
secretes catecholamines |
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Term
| Adrenal Cortex - zona glomerulosa |
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Definition
15% of cortex;
mineralocorticoid production: aldosterone - maintains electrolyte & Na balance |
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Term
| Adrenal Cortex - zona fasciculata |
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Definition
60% of cortex;
glucocorticoid production: cortisol - regulates fate, carbs, & protein metabolism; suppresses inflammation; |
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Term
| Adrenal Cortex - zona reticularis |
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Definition
25% of adrenal cortex;
androgen production: testosterone & estradiol --> reproductive system & sex characteristics |
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Term
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Definition
located at base of brain;
regulates release of CRH (corticotropin-releasing hormone) |
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Term
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Definition
lies outside dura behind the eyes;
- stimlated by CRH --> releases ACTH (adrenocorticotropic hormone) |
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Term
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Definition
| stimulated by ACTH to release cortisol; |
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Term
| Normal daily cortisol production |
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Definition
| equivalent to 5-7 mg/day of prednisone |
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Term
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Definition
overrides neg. feedback loop of HPA axis;
- increases level of endogenous cortisol production 5-10x;
Ex:
Minor - fear, hypoglycemia, pain, colonoscopy;
Major - sepsis, infection, burns, major surgery; |
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Term
| Etiology of Primary Adrenal Insufficiency |
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Definition
dysfunction of adrenal gland;
Addison's Dx: 90% of cortex is destroyed before Sx appear, impaired MINERALOCORTICOID AND GLUCOCORTICOID production;
Autoimmune (most), TB (2nd most), Medications (ketoconazole, phenytoin, phenobarb, rifampin) |
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Term
| Symptoms of Primary Adrenal Insufficiency (Addison's Dx) |
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Definition
Specific: salt craving, hypOnatremia, hypERkalemia;
Non-specific Early:
- weakness, weight loss, HA, GI sx, postural dizziness, depression, memory impairment, myalgias, malaise, anorexia, dehydration, elevated BUN;
Progression:
- vomiting, fever, hypotension, shock |
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Term
| Signs of Primary Adrenal Insufficiency |
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Definition
hyperpigmentation of skin;
postural hypotension;
decreased body hair;
vitiligo;
hypopituitarism (amenrrhea, cold intolerance) |
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Term
| Diagnosis of Primary Adrenal Insufficiency |
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Definition
Cosyntropin Stimulation Test:
Normal Response: increased cortisol level of > or = to 18 mcg/dL;
Insufficiency: increased cortisol level < 9 mcg/dL;
Continue further work ups if increased cortisol levels are between 9-18 mcg/dL;
CANNOT use in levels in ACUTELY ILL Pts;
If random levels of cortisol are used:
- <15 mcg/dL indicates INSUFFICIENCY;
- >34 mcg/dL indicates insuffiency UNLIKELY; |
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Term
| Treatment of Primary Adrenal Insufficiency |
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Definition
long-term for irreversible causes;
combination of glucocorticoid & mineralocorticoid may be used;
Hydrocortisone (gluco & mineralo), prednisone (gluco), fludrocortisone acetate (mineralo) - goal to minimize development of hypERkalemia, increase dose of f if hyperkalemic, hyponatremic, or develops postural hypotension; dose is DECREASED if hypOkalemic, hypERtensive, or edema develops;
Monitor Sx every 6-8 wks |
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Term
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Definition
Tx of Primary Adrenal insuffiency & Adrenal Crisis;
Good gluco & mineralocorticoid action;
Doses for Adrenal Crisis:
- 100 mg IV bolus then 100-200 mg IV infusion or bolus q24 hrs for 24-48 hrs, transition to oral dosing: 50 mg q8 for 48 hrs; |
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Term
| prednisone (Sterapred, Intensol) |
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Definition
used in long-term tx of Primary Adrenal Insufficiency;
good glucocorticoid activity; |
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Term
| Etiology of Secondary Adrenal Insufficiency |
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Definition
90% of adrenal cortex destroyed before onset of Sx;
- impaired GLUCOcorticoid production, PRESERVED MINERALOcorticoid production;
due to corticosteroid use (most common), medications (mirtazapine, progestins), hypopituitarism, hypothalamic tumors; |
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Term
| S/Sx of Secondary Adrenal Insufficiency |
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Definition
Early: weakness, HA, memory impairment, depression, postural dizziness, GI symptoms, myalgias, malaise;
Progressive:
- vomiting, fever, hypotension, shock;
Sx: postural hypotension, decreased body hair, hypopituitarism (amenrrhea, cold intolerance) |
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Term
| Tx of Secondary Adrenal Insufficiency |
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Definition
Tx reversible causes: taper corticosteroids, D/C or alter other drug therapy;
Tx of Irreversible Causes:
- glucocorticoids: prednisone or hydrocortisone;
- mineralocorticoids: NOT NECESSARY;
Monitor: assess pt response, Cosyntropin test, S/Sx |
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Term
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Definition
| hypotension, cyanosis, dehydration, hyperpigmentation of skin, HA, N/V/D, abd pain, fever (>40.6 C), increased eosinophils, hypOnatremia, hypERkalemia, hypERcalcemia |
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Term
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Definition
acute onset of S/Sx of adrenal insufficiency;
HAP axis suppression (most common), increased adrenal requirements in pts w/ underlying adrenal insufficiency (surgery, infection, trauma);
Lack of stress-related dose adjustments in pts receiveing corticosteroid-replacement therapy |
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Term
| Ways to avoid Adrenal Crisis in pts receiving corticosteroid-replacement therapy |
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Definition
Add 5-10 mg of hydrocortisone prior to strenuous activity;
Double dose during times of severe physical stress until recovery; |
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Term
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Definition
Hydrocortisone: tx of choice (combinted mineralo & gluco activity), Initial dose: 100 mg IV bolus then 100-200 mg infusion or bolus q24 hrs for 24-48 hrs, once stable transition to oral dosing: hydrocortisone 50 mg q8 for 48 hrs;
Fluid Replacement: D5NS to maintain BP & replete fluids if dehydrated;
Fludrocortisone acetate (mineralo): 0.1 mg PO - use if pt develops hypERkalemia following hydrocortisone maintenance phase |
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Term
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Definition
Tx of Primary Adrenal Insufficiency & Adrenal Crisis;
Dosing in Adrenal Crisis: 0.1 mg PO if pt develops hypERkalemia following hydrocortisone maintenance phase |
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Term
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Definition
excessive circulating levels of glucocoriticoids due to exogenous administration or endogenous overproduction;
Endogenous: ACTH-dependent: pituitary, ectopic ACTH Syndrome;
Exogenous: supraphysiologic doses of glucocorticoids; |
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Term
| S/Sx of Cushing's Syndrome |
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Definition
Sx: myopathies, muscular weakness;
S: peripheral obesity, fat accumulation (buffalo hump), facial plethora (moon face), HTN, psychiatric changes, osteoporosis; |
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Term
| Diagnosis of Cushing's Syndrome |
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Definition
1: Estalish presence of hypercortisolism
- Cortisol levels: 24 hr urine free cortisol level - 20-90 mcg in 24 hrs, values 4x ULN suggest dx; Midnight Serum Cortisol Level - >7.5 mcg/dL are highly sensitive for dx; Dexamethasone Suppression Test - Dx present if AM cortisol level >5 mcg/dL;
Step 2: Determine Etiology - Plasma ACTH - UNDETECTED: adrenal tumor, ELEVATED: use high-dose Dexamethasone Suppression Test - detects dx NOT due to ectopic ACTH production or adrenal tumors |
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Term
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Definition
Surgery is tx of choice for offending tumors;
Use: metyrapone, aminoglutethimide, metyrapone + aminoglutethimide, ketoconazole, mitotane, cyproheptadine, mifepristone |
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Term
| Tx of ectopic ACTH Syndrome Cushing's Syndrome |
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Definition
| metyrapone, aminogluthethimide or combination therapy |
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Term
| Tx of Pituitary Depended Cushing's Syndrome |
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Definition
| mitotane, metyrapone, or cyproheptadine (last line) |
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Term
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Definition
steroidogenic inhibitors;
1st line tx of ectopic ACTH syndrome Cushing's Syndrome & pituitary dependent Cushing's Syndrome;
inhibits 11-hydroxylase activity resulting in inhibition of cortisol synthesis;
cortisol levels return to baseline following D/C;
ADRs:
- N/V, vertigo, HA, dizziness, abd discomfort, allergic rash |
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Term
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Definition
inhibits conversion of cholesterol to pregnenolone;
Indications: monotherapy for short-term use in inoperable Cushing's Syndrome w/ ectopic ACTH syndrome;
- may be used in combination w/ metyrapone;
cortisol levels reduced up to 50%;
ADRs: sedation, N, ataxia, skin rash; |
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Term
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Definition
imidazole derivative anti-fungal;
1st line Tx of Cushing's Syndrome due to adrenal adenoma;
inhibits 11-hydroxylase;
ADRs: increased LFTs, gynecomastia, GI upset; |
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Term
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Definition
adrenolytic;
1st line therapy in Cushing's Syndrome due to pituitary dependence and adrenal carcinoma;
inhibits 11-hydroxylation of 11-desoxycortisol & 11-desoxycorticosterone;
decreases cortisol secretion rate, plasma cortisol conc, & urinary free cortisol;
selectively inhibits adrenocortical fcn without causing cellular destruction;
recommend hospitalizing pt when starting therapy;
ADRs: lethargy, somnolence, CNS effects, N/V; |
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Term
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Definition
neuromodulator of ACTH release;
has NOT demonstrated consistent clinical efficacy;
Reserved for inoperable pts who fail conventional therapy - Last line Therapy |
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Term
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Definition
progesterone, androgen, & glucocorticoid receptor antagonist;
highly effective in reversing manifestations of hypercortisolism;
efficacy & long-term effects need to be determined |
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Term
| Primary Hyperaldosteronism |
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Definition
physiologic abnormality of adrenal cortex;
Caused by: Bilateral Adrenal Hyperplasia (BAH), aldosterone-producing adenoma (APA) |
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Term
| S/Sx of Primary Hyperaldosteronism |
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Definition
More common in women 30-50 yrs old;
Many are ASYMPTOMATIC;
Sx: muscle weakness, fatigue, HA;
S: HTN, paralysis, polysipsia/nocturnal polyuria; |
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Term
| Tx of BAH-induced Primary Hyperaldosteronism |
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Definition
| spironolactone, eplerenone, or amiloride |
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Term
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Definition
inhibits aldosterone biosynthesis within adrenal gland;
1st line tx of BAH-induced Primary Hyperaldosteronism;
ADRs: GI discomfort, impotence, gynecomastia, menstrual irregularities; |
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Term
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Definition
aldosterone antagonist;
2nd line tx of BAH-induced Primary Hyperaldosteronism;
ADRs: GI discomfort, hypertriglyceridemia; |
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Term
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Definition
K-sparing diuretic;
Weak diuretic & antihypertensive properties;
additional antiHTN agent usually required to control BP;
Option in men with BAH-induced Primary Hyperaldosteronism |
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Term
| Tx of APA-induced Primary Hyperaldosteronism |
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Definition
surgical resection of adenoma;
Use spironolactone in pts whom surgery is C/I'd |
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Term
| Secondary Hyperaldosteronism |
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Definition
results from stimulation of zona glomerulosa by an extra-adrenal factor, most commonly RAAS;
Tx of Choice: spironolactone |
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Term
| Length of Corticosteroid Therapy - When to D/C? |
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Definition
Max. disired benefit achieved;
Inadequate benefit after an adequate trial;
Serious or uncontrollable adverse effects;
Steroid-induced psychosis;
Herpes virus-induced corneal ulceration; |
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Term
| Dosing & PKs of Corticosteroids |
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Definition
excellent oral absorption (IV to PO is 1:1);
metabolized in liver;
excreted through kidney;
Alternate Day Therapy (ADT) in stable pts on long-term therapy used to lessen chances of ADRs (HPA-axis suppression) |
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Term
| Dose Tapering of Corticosteroids |
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Definition
used to avoid withdrawal complications when drug-induced HPA-axis suppression exists;
Used when large doses or long-term tx has been used;
If dx relapse occurs during, reinstate previous dose & go slowly; |
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Term
| Drugs that cause Increased clearance of Corticosteroids |
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Definition
phenytoin, phenobarb, rifampin, mitotane, aminoglutethimide;
hyperthyroidism, renal dx; |
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Term
| Drugs/Dx that cause reduced clearance of Corticosteroids |
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Definition
estrogens, oral contraceptives;
Liver dx, age, pregnancy, hypothyroidism, anorexia, malnutrition, renal dx |
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Term
| Acute ADRs of Corticosteroids |
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Definition
| hypOkalemia, hypOmagnesemia, Na & H2O retention, hypERglycemia, weight gain, delirium, HTN |
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Term
| Long-term ADRs of Corticosteroids |
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Definition
| osteoporosis, dyslipidemia, HPA-axis suppression, PUD, increased susc. to infections, cataracts, iatrogenic Cushing's Syndrome, growth suppression in kids, glaucoma, psychosis, pancreatitis; |
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Term
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Definition
greatest bone loss occurs in 1st 6 months;
bisphosphonates +/- Ca + Vit D |
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Term
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Definition
Risk Factos: advanced cancer, hx of PUD, cumulative equivalent dose > prednisone 1000 mg or steroid use >30 days;
Use H2-receptor antagonists or PPIs |
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Term
| Counseling Points for Corticosteroids |
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Definition
Take w/ food to minimize stomach upset;
Increase doses in time of acute illness or stress;
Be aware of possible ADRs (anxiety/insomnia, increased appetite, & weight gain);
Monitor Chem-7, CBC, opthamologic exams, fecal occult blood |
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