adrenal disorders – Flashcards
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Secondary Hyperaldosteronism
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-Decreased circulating volume is initiating event -Results in increased renin and aldosterone -Results in sodium retention
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Hyperaldosteronism: Physiologic response to Aldosterone Excess
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-Increased renal distal tubular sodium reabsorption -Increased total body sodium content -Increased water retention
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Hyperaldosteronism: Escape phenomenon
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-Compensatory increased ANF secretion -Hypertension may not be solely volume expansion
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Hyperaldosteronism: Physiologic response to Aldosterone Excess
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Increased renal distal tubular sodium reabsorption -Increased total body sodium content -Increased water retention
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Physiologic response to Aldosterone Excess: Escape phenomenon
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-Compensatory increased ANF secretion -Hypertension may not be solely volume expansion
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Physiologic response to Aldosterone Excess: Increased peripheral vascular resistance
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-Hypokalemia: Potassium lost in distal renal tubule -Alkalosis: Ammoniagenesis
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Physiologic response to Aldosterone Excess:
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-Hydrogen ion loss (avid sodium retention) -Polyuria: Decreased renal concentrating ability -Plasma renin suppressed ---Unresponsive to intravascular volume depletion
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Primary Hyperaldosteronism (Conn's Disease): Causes
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-Solitary adrenal adenomas (80-90%) -Bilateral adrenal hyperplasia (10-20%) Idiopathic Hyperaldosteronism Accounts for 50% of cases at some referral centers -Adrenal Carcinoma (rare) -Unilateral Adrenal Hyperplasia (very rare)
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Secondary Hyperaldosteronism: Causes: Hypertensive States
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-Primary Reninism (rare renin producing tumor) -Secondary reninism due to decreased renal perfusion
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Secondary Hyperaldosteronism: Causes: Edematous States
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Cirrhosis Nephrotic Syndrome
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Hyperaldosteronism: Symptoms
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-Often Asymptomatic -Frontal Headache -Muscle Weakness to flaccid paralysis (Hypokalemia) -Polyuria and Polydipsia (carbohydrate intolerance)
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Hyperaldosteronism: Signs
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Hypertension -May be severe -Rarely malignant Motor Exam with decreased muscle strength
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Hyperaldosteronism: Labs
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Serum Electrolytes -Serum Potassium decreased (Hypokalemia) -Serum Sodium increased (Mild) -Metabolic Alkalosis Morning Aldosterone to PRA ratio -Ratio over 20-25 (esp if >100) suggests Hyperaldosteronism -Aldosterone >15 ng/dl and plasma renin low -Saline suppression IVF: 300-500 cc/hour for 4 hours Normal response -Aldosterone usually under 0.28 -Renin usually suppressed
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Differential Diagnosis: Hypertension with Hypokalemia
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Cushing's Disease -Low Aldosterone and Low Plasma Renin Renal Artery Stenosis or other renal cause -High Aldosterone and High Plasma Renin
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Hyperaldosteronism: Management
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Adrenal Adenoma -Surgical excision -Adrenal Hyperplasia First-Line Agents -Spironolactone (Aldactone) -Alternative agents if Gynecomastia develops on Spironolactone ---Eplerenone (Inspra) ---Amiloride (Midamor) Precautions -Follow Serum Potassium and Serum Creatinine every 6 months with these agents
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Cushing's Disease
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Aka: Cushing's Disease, Cushing's Syndrome
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Cushing's Disease: Etiologies
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Iatrogenic -Steroid therapy (most common cause)
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Cushing's Disease: Etiologies: Central Cause
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Pituitary adenoma
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Cushing's Disease: Adrenal Cause
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-Adrenal Adenoma -Adrenal Hyperplasia -Adrenal Malignancy (15%)
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Cushing's Disease: Ectopic Source
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Malignancy (Small Cell Carcinoma of the lung: 15%)
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Cushing's Disease: Symptoms
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-Mood changes (depression and euphoria) -Easy bruising -Weakness -Weight gain -Amenorrhea -Back pain
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Cushing's Disease: Signs
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-Truncal Obesity (90%) -Hypertension (85%) -Glucose Intolerance (80%) -Hirsutism (70%) -Wide, purple abdominal and thigh striae (65%) -Osteoporosis (55%) -Moon facies -Buffalo hump (Thoracic kyphosis) -Myopathy -Plethoric face -Supraclavicular fat pad development -Hypertrichosis -Peripheral Edema -Hypertension
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Cushing's Disease: Labs
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Screening Test -24-hour Urinary free cortisol level (preferred) --Urine 17-Ketosteroid excretion --Urine 17-Hydroxysteroid excretion Serum Cortisol Low dose Dexamethasone Suppression Test -Dexamethasone 1 mg at 11pm -Plasma Cortisol in following 8 AM Night-time Salivary cortisol testing Distinguish between pituitary, adrenal or ectopic cause -Plasma ACTH -High dose Dexamethasone Suppression Test (8 mg)
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Cushing's Disease: Radiology
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CT or MRI Cone down Sella Turcica -Pituitary adenoma -CT abdomen Adrenal tumor
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Cushing's Disease: Management
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Exogenous Cushing's -Stop steroids or decrease dose -Change steroid dosing to qod with drug holiday Endogenous Cushing's -Surgically excise adenoma (in pituitary or adrenal)
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Addison's Disease
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Aka: Addison's Disease, Addisonian Crisis, Adrenal Cortical Insufficiency, Adrenal Insufficiency, Adrenal Hypofunction, Illness Induced Adrenal Insufficiency, Stress Dose Steroid
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Addison's Disease: Pathophysiology
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Hypothalamic-Pituitary-Adrenal Axis (HPA) Dysfunction -Lab features: Cortisol low, ACTH Low -Causes --Severe illness --Exogenous Corticosteroid (suppression lasts months) ---Prednisone >7.5 mg/day for >3 weeks ---Dexamethasone >0.75 mg/day for >3 weeks Pituitary Infarction CNS Infection or tumor invasion Head Injury HIV Infection
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Addison's Disease: Adrenal Insufficiency: Lab features:
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Cortisol low, ACTH high
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Addison's Disease: Causes
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Primary adrenal failure of adrenal glands Idiopathic adrenal hypoplasia or destruction -Granulomatous disease (e.g. Tuberculosis, Fungus) -Amyloidosis -Hemochromatosis -Tumor -Autoimmune process Medication medicated cortisol inhibition -Etomidate -Ketoconazole
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Addison's Disease: Symptoms
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-Weakness -Fatigue or Lethargy -Nausea or Vomiting -Diarrhea -Abdominal Pain -Weight loss -Salt craving -Altered Level of Consciousness (e.g. Delirium)
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Addison's Disease: Signs
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Fever Hyperpigmentation -Skin with mottled areas of increased pigmentation -Pigment at Buccal mucosa (Caucasian) -Increased pigment in lips, vagina, rectum Reduced Hair Growth Postural Hypotension Signs of dehydration
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Addison's Disease: Labs
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Complete Blood Count -Normochromic Normocytic Anemia -Eosinophilia (helps differentiate from other causes) Chemistry Panel -Hyponatremia -Hypochloremia -Hyperkalemia -Hypoglycemia (helps differentiate from other causes) Urine 17-ketosteroids low Urine 17-Hydroxysteroids low
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Addison's Disease: Diagnosis
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Corticotropin Stimulation Test -Failed adrenal response
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Addison's Disease: Management
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Acute -IV Cortisol Chronic Replacement -Hydrocortisone (glucocorticoid) AND -Mineralocorticoid (9-alpha-fluorocortisol) Stress Dose Steroid -Indication: Acute severe illness --Serum Cortisol <15 to 34 mcg/dl --Cortisol <9 after Corticotropin Stimulation Test -Management --Hydrocortisone 50 mg IV or IM q6 hours --Consider adding fludricortisone 50 mcg qd
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Pheochromocytoma
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Aka: Pheochromocytoma, Paroxysmal Hypertension
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Pheochromocytoma: Definition
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Catecholamine secreting tumor of the adrenal gland
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Pheochromocytoma: Epidemiology
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Peak ages: 30-60 years Equal male and female predominance
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Pheochromocytoma: Presentation: Classic Episodes
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Predominant Symptoms -Headache -Diaphoresis or Sweating -Palpitations
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Pheochromocytoma: Associated Symptoms
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Anxiety Tremor Pallor Chest Pain Epigastric Pain Flushing (rare) Painless Hematuria (rare)
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Pheochromocytoma: Timing of episodes
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-Duration: One hour or less -Frequency: daily to once every few months
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Pheochromocytoma: Presentation: Other
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-Resistant Hypertension -Malignant or intra-operative Hypertension -Hypotension episodes (rare)
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Pheochromocytoma: Diagnostic Clues: Six "H's"
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-Hypertension -Headache - throbbing (90%) -Hyperhidrosis or excessive sweating (69%) -Heart consciousness or Palpitations (73%) -Hypermetabolism -Hyperglycemia
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Pheochromocytoma: Diagnostic Clues: Rule of 10
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-Familial (10%) -Malignant (10%) -Multiple or Bilateral (10%) -Extra-adrenal (10%) -Childhood onset (10%) -Recurrence after Surgery (10%)
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Pheochromocytoma: Differential Diagnosis
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-Primary Aldosteronism -Carcinoid -Accelerated or Malignant Hypertension -Illicit, OTC or prescribed Sympathomimetic medications -Chemodectoma -Ganglioneuroma -Thyrotoxicosis -Menopause -Panic Disorder -Antihypertensive withdrawal (e.g. Clonidine withdrawal)
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Pheochromocytoma: Labs: Preparation
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Stop any interfering medications -Labetalol (stop for 1 week) -Tricyclic Antidepressant (stop for 2 weeks) -Psychoactive medications (stop for weeks) -Levodopa or Methyldopa -Decongestants -Benzodiazepines -Muscle relaxants (mephenasin, Methocarbamol) -Avoid Tylenol for 48 hours -Avoid Aspirin
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Pheochromocytoma: Labs: Stop other interfering agents
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-No caffeine, Alcohol or Tobacco for 4 hours -Tomatoes -Walnuts -Pineapple -Banana -Eggplant -Avocado -Plums
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Pheochromocytoma: Labs: Available Tests
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Best studies -Plasma Free Metanephrines --Test Sensitivity: 99% --Test Specificity: 89% Urine Metanephrines (24 hour collections) -Test Sensitivity: 76% -Test Specificity: 94%
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Pheochromocytoma: Labs: Tests with lower efficacy (rarely used now)
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Urinary VMA -Normal value under 6.5 mg/day -Imprecise test -Drugs and food interfere with test -Test Sensitivity: 63% -Test Specificity: 94%
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Pheochromocytoma: Labs: Plasma Catecholamines
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(Norepinephrine, Epinephrine) -Test Sensitivity: 85% -Test Specificity: 80%
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Pheochromocytoma: Labs: Protocol
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-First: 24-hour Urine Metanephrine and Urine VMA -Next: Plasma Free Metanephrines -Next: Plasma Catecholamines (equivocal metanephrines) -Final: Clonidine Suppression (positive Catecholamines)
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Pheochromocytoma: Radiology: Tumor localization
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Adrenal CT or Adrenal MRI -Test Sensitivity: 93 to 100% -Test Specificity: 70% MIGB Scan (metaiodobenzyl-guanidine) -Test Sensitivity: 77 to 90% -Test Specificity: 95 to 100% -Good for looking for tumors in unusual places
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Pheochromocytoma: Management
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Preoperative Medical Management -Alpha Adrenergic Receptor antagonist (2 weeks pre-op) --Phenoxybenzamine PO bid --Phentolamine IV prn Beta Blocker (only start after alpha blockade) -Propranolol PO qid
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Pheochromocytoma: Surgical Management
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Laparoscopic adrenalectomy Indications -Single, small adrenal tumors -Hypertension controlled Open Adrenalectomy -Adrenal tumor size over 7 cm
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Pheochromocytoma: Intra-Operative Management
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-Continuous Arterial-line Blood Pressure Monitoring -Treat Hypotension --Fluid management --Consider pressor support Treat Hypertension -Phentolamine -Nitroprusside Treat Tachycardia or ectopy -Beta Blocker
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Adjunctive treatment for malignant Pheochromocytoma
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Chemotherapy -Cyclophosphamide -Dacarbazine -Vincristine MIGB (metaiodobenzyl-guanidine I-131) Metyrosine 1 gram every 6 hours --Depletes tumor Catecholamine stores
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Pheochromocytoma: Course
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Persistent Hypertension in 25% of treated patients
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Pheochromocytoma: Monitoring
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-Screen Urine Metanephrines annually -Screen Urine Catecholamines annually
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