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53 Cards in this Set
- Front
- Back
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What is produced in the Zona glumerulosa?
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mineralcorticoid production of aldosterone
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What is produced in the Zona fasciculata?
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androgen
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What is produced in the Zona reticularis?
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glucocorticoid production of cortisol
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What is the function of aldosterone?
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facilitates sodium and potassium homeostasis, intravascular volume
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What is the function of glucorticoids?
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Glucocorticoids are required to maintain normal carbohydrate, lipid, and protein metabolism; immune and cardiac function
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Regulation of Hormone Secretion (HPA-axis)
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Hypothalamus releases corticotropin-releasing hormone which acts on the pituitary. The pituitary releases ACTH through the blood stream which acts on the adrenal cortex. The adrenal cortex releases cortisol. Cortisol provides negative feedback to the hypothalamus.
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What are common causes Cushing’s Syndrome?
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Due to hypercortisolism - excess cortisol in plasma
* Pituitary adenoma – Cushing’s disease - Most common 85% - 5 x more common in women * Ectopic ACTH Syndrome * Adrenal tumor (adenoma/carcinoma) |
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Clinical Presentation Cushing’s Syndrome
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* Central obesity
* Hypertension * Facial plethora * Glucose intolerance * Hirsutism * Menstrual dysfunction |
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Cushing’s Disease Diagnosis
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* Presence of hypercortisolism
- Urine cortisol level - Midnight cortisol level - Low dose dexamethasone test * Etiology - ACTH Levels (low levels indicate adrenal tumor while high levels indicate cushing’s or ectopic ACTH syndrome) - High dose dexamethasone (good for differentiating of cushings vs ectopic ACTH syndrome) - Imaging - Exogenous steroids looks like Cushings |
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Cushing’s Disease Treatments
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* Surgery and/or Radiation
* Medications - Inhibitors of Adrenal Steroidogenesis --Amioglutethimide --Ketoconazole --Metyrapone --Etomidate - Adrenolytics --Mitotane - Central Neuromodulators --Cyproheptadine - Peripheral Glucocorticoid antagonist --Mifepristone - Spironolactone |
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Primary Adrenal Insufficiency Etiology
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* Primary (Addison’s Disease)
- most common cause = autoimmune adrenalitis (slow destruction of the adrenal cortex by cytotoxic lymphocytes) - 2nd is tuberculosis and other infections (fungal, bacterial, viral) |
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Secondary Adrenal Insufficiency Etiology
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most common cause = insufficient replacement of exogenous corticosteroids
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Adrenal Insufficiency Clinical Presentation
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* Symptoms of both Primary and Secondary
- Fatigue, malaise, weakness, weight loss, depression, dizziness, nausea, headache, memory impairment * Primary - Hyperpigmentation(– due to high plasma ACTH) , hyponatremia (salt-craving), hyperkalemia (due to adosterone deficiency), possibly other autoimmune conditions |
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Adrenal Insufficiency Diagnosis
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* Cosyntropin Test (synthetic ACTH)
- 250 mcg dose IV, measure cortisol at baseline, 30 and 60 minutes --Cortisol level < 15 mcg/dL = adrenal insufficiency --Cortisol level > 34 mcg/dL = rule out adrenal insufficiency --15-34 range if < 9 mcg/dL change from baseline patient adrenal insufficient * Plasma ACTH level - ACTH Levels 400-2000 pg/mL = primary adrenal insufficiency - ACTH level 0-50 pg/mL = secondary adrenal insufficiency |
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Chronic Adrenal Insufficiency Treatments
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- Initial Dosing: Prednisone 5 mg in the morning and 2.5 mg at bedtime (or 7.5 mg daily at bedtime) or hydrocortisone 15-20 mg in the morning and 5-10 mg in the early afternoon (sometime need tid dosing)
- Hydrocortisone (~67% dose AM & 33% PM) * Mineralocorticoid Replacement (primary only) - Fludrocortisone (Florinef®) 0.05-0.2 mg orally once daily - Minimizes hyperkalemia Use lowest dose that controls symptoms – anorexia, N/V, dizziness – look for signs of excess cortisol – Titrate fludro to BP and electrolyte normalization |
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Acute Adrenal Insufficiency Prevention
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* Wear Medic Alert bracelet
* Carry pre-filled syringes of dexamethasone 4 mg for IM administration * Take an additional 5-10 mg of hydrocortisone or equivalent before stressful activities * If experience febrile illness/trauma: take 2-3 times the normal daily dose for 3 days and follow-up with primary care provider * May need a higher dose for a longer period of time depending on the illness |
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Acute Adrenal Insufficiency Prevention - Surgery
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* Minor (e.g., local anesthetic):
- Usual steroid dose additional 25 mg hydrocortisone equivalent prior to procedure * Moderate (e.g., total joint replacement): - Usual steroid dose + Give 50 mg hydrocortisone IV just before procedure and 25 mg IV q8hrs for 24-48hrs. Resume usual dose thereafter. * Major (e.g., cardiac bypass): - Usual steroid dose + Give 100 mg hydrocortisone IV just prior to procedure and 50 mg q8hrs for 24-48 hrs. Taper dose by ½ per day back down to maintenance. |
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Acute Adrenal Insufficiency
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* Clinical Presentation
- Early --Mylagias, malaise, anoxeria, weakness, wt loss - Late --Vomiting, fever, hypotension, hyponatremia, hypoglycemia and hyperkalemia * Etiology -Acute Stress (infections, trauma, surgery) - Too rapid withdrawal of chronic glucocorticoids |
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Acute Adrenal Insufficiency Diagnosis
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* Hyponatremia not responding to saline but responds to hydrocortisone
* Unexplained catecholamine-resistant hypotension * If no previous diagnosis - ACTH < 15 mcg/dL after rapid Cosyntropin test or < 9 mcg/dl change from baseline |
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Acute Adrenal Insufficiency Treatment
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* 1-3 liters of 5% dextrose and isotonic saline (D5NS) or normal saline (0.9% sodium chloride)
* No previous diagnosis of adrenal insufficiency: - dexamethasone 4mg IV q6hrs for 1-3 days (does not interfere with ACTH test); taper dose by 50% each day until back to maintenance. * Previous diagnosis of adrenal insufficiency: - hydrocortisone 100 mg IV q6hrs for 1-3 days; taper dose by 50% each day until back to maintenance. * When patient stable transition to oral corticosteroids |
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Acute Adrenal Insufficiency in Septic Shock patients
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* Mortality in Septic shock between 20-50%
* Annane et al. 2002 “French Trial” - Corticosteroids failed to reduce 28 day mortality - Subgroup of nonresponders there was a significant reduction in mortality 63% placebo to 53% treatment - Major issue: large number of patients used Etomidate * Corticus 2008 - Corticosteroids failed to reduce 28 day mortality regardless of adrenal responsiveness to cosyntropin - Shock reversed quicker in steroid group there were more superinfections - No benefit to fluid and vasopressor responsive shock - Etomidate was used in same percentage of patients as French trial - Stopped early because loss of funding, slow recuitment * More questions then answers - Who gets steroids? - What dose? - What duration? * International guidelines - Corticosteroids in septic shock to patients who are poorly responding to fluid and vasopressors |
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Glucocorticoid Replacement Equivalence chart
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Glucocorticoids Adverse Effects
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* Similar to Cushing’s Dx symptoms
* Short term - Glucose intolerance, HTN, edema, decreased potassium levels, mood disturbances, myopathy * Long term - HPA suppression, HTN, Hyperlipidemia, cataracts, central obesity, immunosuppression, osteoporosis, mood disturbances, aseptic necrosis |
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Glucocorticoid Replacement HPA-axis Suppression
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* Most likely if …
- 20 mg/day prednisone equivalent for 3 wks * Possible if ….. - >5-20 mg/day prednisone equivalent for 3 wks * Unlikely if ….. - Any dose of glucocorticoids for less than 3 wks - Patients treated with alternate-day glucocorticoid therapy * Risk factors: - Higher dose - Longer duration of therapy - Longer acting agents - PM dosing - Multiple daily dosing * Tapering to prevent adrenal crisis* - decrease dose by 10-20% every 1-3 weeks - can consider checking adrenal function once at a physiological dose# using rapid cosyntropin test -- *various recommendations available; #5 mg/day prednisone equivalent is considered physiological 20-30 mg hydrocortisone or 5-7 mg oral prednisone; glucocorticoid levels peak between 4am and 8am, minimal evening production; synthesis can increase 5-10 fold under conditions of severe stress |
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Define Adverse drug reaction
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Unintended pharmacologic effect of a drug (except failure, overdose, abuse or error)
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Define Drug intolerance
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Undesirable pharmacologic effect causing a patient to alter or discontinue therapy
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Define Drug hypersensitivity
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Immunologically mediated response
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Define Anaphylaxis
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Immediate systemic reaction caused by rapid, IgE-mediated immune response
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When do most skin reactions to drugs occur?
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within 1 week of initial drug exposure
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Who is more likely to have a adverse skin reaction to a medication?
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Women > men (2:1)
Older > younger |
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Most common drugs to cause skin reactions?
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PCNs, sulfonamides, blood products
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Immunologic (Allergic) Drug Reactions
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* Requires activation of host immunologic pathway
* Dependent on molecular size, dose, route of administration, individual sensitivity * Drug or metabolite acts as/forms antigen * Topical > IV > PO * Variable reaction based on exposure * 4 types |
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Immunologic (Allergic) Drug Reactions: Criteria
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* Occurs in a small percentage of patients
* Observed reaction does not resemble the drug’s pharmacologic effect * Manifestation similar to allergic reactions * Lag time between first exposure of drug and apparent reaction * Reaction is reproduced with small doses * Reaction is reproduced by agents with similar chemical structures * Eosinophilia is usually present * Reaction resolves after drug discontinued |
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Type I reaction
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- Immediate hypersensitivity
- IgE mediated - Anaphylaxis, urticaria |
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Type II
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- Cytotoxic reactions
- IgG and IgM mediated - Cytopenias |
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Type III
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- Immune complex
- IgG and IgM mediated - Serum sickness, vasculitis |
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Type IV
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- Cell (Lymphocyte) mediated
- Contact sensitivity |
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Maculopapular Eruptions
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* Most common drug-induced skin reaction
* Type IV hypersensitivity reaction: cell-mediated * Erythematous macules and papules * Appear on trunk, or areas of pressure * Symmetrical eruptions * Pruritis +/- fever * Early: within hours to a few (~3-4) days of initial drug exposure * Late: appear ~ 9-10 days after exposure * “Macular” - Flat, not raised above surrounding skin - Can be seen, based on change in color, but not felt - Usually brown or red if drug-induced * “Papular” - Small, solid elevations of the skin - Easily felt because raised above surrounding skin - Often occur in clusters * Maculopapular = containing both types of lesions |
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Maculopapular Eruptions: Associated Drugs
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Penicillins
Allopurinol Ampicillin Azithromycin Benzodiazepines Carbamazepine Ciprofloxacin Hydantoins NSAIDs Sulfonamides Tetracyline ACE inhibitors |
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Maculopapular Eruptions: Management
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* D/C drug
* Cool water baths/compresses * Mild to moderate reactions: - Topical corticosteroids or antihistamines, or oral antihistamines for pruritis * Severe reactions: - Short-course systemic steroids |
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Urticaria
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* Type I immunologic reaction: IgE mediated
* Non-immunologic reaction: histamine displacement or direct mast cell degranulation * Raised, well-defined, pruritic, erythematous wheals (hives) * Chest or trunk * Size varies from a few mm to large areas * Disappears within hours, but new ones appear * Lasts 12-36 hours and completely resolves in 1-3 days * May progress to angioedema or anaphylaxis |
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Urticaria: Associated Drugs
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* ASA
* NSAIDs * COX-2 inhibitors * Radiocontrast dye * Insulin * H2-blockers * Omeprazole * PCNs * Sulfonamides * ACE inhibitors |
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Urticaria: Management
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* D/C medication
* PO antihistamines * Topical antipruritics not usually effective * Anaphylaxis: - Oxygen and maintain airway - IM or SC epinephrine - IV diphenhydramine - IV hydrocortisone - IV fluids and vasopressors |
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Fixed Drug Eruptions
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* Pathogenesis not exactly known
* Erythematous or hyperpigmented lesions * Round or oval lesions; usually asymptomatic * Sharply demarcated * Few mm to 20 cm in diameter * May change in color over time * Oral mucosa and genitalia common * Recurrence of eruption within 30 minutes to 8 hours of subsequent drug exposure in EXACT same location |
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Fixed-Drug Eruption: Associated Drugs
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Carbamazepine
Sulfonamides NSAIDs Tetracyclines Barbituates Digoxin Diphenhydramine Erythromycin Phenolphthalein |
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Fixed-Drug Eruption: Management
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* D/C medication and do not re-administer
* Cool compresses * Bleaching creams for hyperpigmentation * Antihistamines (+/-) * Corticosteroids (+/-) |
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Photosensitivity Reactions
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* Phototoxic OR photoallergic
* Increased incidence due to tanning bed use and chemicals in cosmetics and drugs * Resembles sunburn (caused by UV-A radiation) * Erythema, edema, papules +/- vesicles * Appears on skin areas exposed to sunlight * May occur with first dose * Phototoxicity: within 30 minutes to few hours * Photoallergy: delayed (1-14 days after exposure) * May take days to weeks to resolve |
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Photosensitivity: Associated Medications
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Tetracycline
Doxycycline Fluoroquinolones Sulfonamides Sulfonylureas Furosemide Thiazides NSAIDs Amiodarone Carbamazepine Oral contraceptives Sulfonylureas Benzodiazepines |
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Photosensitivity: Management
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* D/C Drug
* Cool dressings * Soothing lotions * Topical corticosteroids (photoallergic) * Topical antihistamines (photoallergic) * Oral prednisone for severe reactions ~ 1 mg/kg per day tapered over 3 weeks * Avoidance of sun * If avoidance not poissible, recommend sunscreen use Titanium dioxide and zinc oxide to completely block UV-A radiation |
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Severe Skin Reactions
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* Erythema multiforme
* Stevens-Johnson Syndrome * Toxic Epidermal Necrosis (TEN) |
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Other Potential Skin Reactions
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* Alopecia
* Vasculitis * Hyperpigmentation * Drug-induced SLE |
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Drug Hypersensitivity Syndrome
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* Triad of fever, skin eruption and internal organ involvement
* Occurs in 1/3,000 persons on associated drugs (anticonvulsants, sulfonamide antibiotics, etc.) * Usually occurs during first prolonged course of drug (1-6 weeks up to 2-3 months into therapy) * Prodrome can mimic upper respiratory infection * Skin lesions follow in 85% of patients * Internal organ involvement: lymphadenopathy, hepatitis, nephritis, pneumonitis, and hemotologic involvement * Can cause significant morbidity and mortality |
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Evaluation of Drug Reactions
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* Drug history
* Immunologic status * Tests for IgE for drug allergy * Previous experience * Timing of events * Drug levels * Trial of discontinuation * Rechallenge |
