Rosen & Barkin's 5-Minute Emergency Medicine Consult (184 page)

• IV rehydration
  
• Glucose-lowering agents for hyperglycemia
  
• Appropriate cultures and antibiotics for suspected infection
  
• Antihypertensive agents for uncontrolled BP
  
• Administer steroids (hydrocortisone) with iatrogenic Cushing if patient under stress to prevent addisonian crisis.
  
• Medications to lower cortisol levels (bromocriptine, ketoconazole, aminoglutethimide, metyrapone):
  
  • Used rarely with severe symptoms in patients awaiting surgery
    
  • Institute under the direction of an endocrinologist.
    
  • Definitive therapy:
    
• Iatrogenic:
  
  • Taper steroids as rapidly as possible
    
  • Calcium, vitamin D, and estrogen supplementation if possible
    
• Pituitary Cushing:
  
  • Transsphenoidal surgery
    
  • Radiation for surgical failures and a few select patients
    
• Adrenal adenoma/carcinoma:
  
  • Adrenal resection with medical therapy for metastatic lesions not resectable
    
• Ectopic ACTH:
  
  • Tumor resection (if possible) with medical therapy for metastatic lesions not resectable
    

ONLY if in adrenal crisis: Hydrocortisone: 100 mg (peds: 1–2 mg/kg) IV q6h

• In consultation with an endocrinologist
  
• SYMPTOMATIC TREATMENT ONLY as adjunctive therapy in patients awaiting surgery or refractory to other treatment
  
• Steroidogenic inhibitors:
  
  • Ketoconazole 200 mg PO BID
    
  • Methyrapone 0.5–1 g/d PO in 4 div. doses
    
  • Aminoglutethimide 250 mg PO q6h
    
  • Mifepristone 300 mg PO daily
    
• Adrenolytics:
  
  • Mitotane 500 mg PO daily
    
• ACTH release inhibitors:
  
  • Cyproheptadine 4 mg PO BID
    
  • Bromocriptine 2.5–30 mg/d
    
• Other:
  
  • Pasireotide 0.6 mg SQ initial
    
  • Spironolactone for symptomatic relief of HTN or hypokalemia
    

FOLLOW-UP

• Complications that require admission such as:
  
  • MI
    
  • Stroke
    
  • Sepsis
    
  • Pathologic fracture
    
  • Uncontrolled DM
    
  • Psychiatric emergency
    
• Impending addisonian (adrenal) crisis
  

Well-appearing, stable patient without admission criteria

• Any patient suspected of Cushing syndrome for further evaluation
  
• Conditions secondary to Cushing requiring treatment
  

Follow-up testing to confirm diagnosis

• Keep a high index of suspicion in the physiologically stressed patient by history or from body habitus and for the need to prevent against addisonian crisis
  
• Suspect Cushing disease when there are supraclavicular fat pads
  

• Andreoli T, Carpenter C.
  Cecil Essentials of Medicine
  . 8th ed. Philadelphia, PA: Saunders-Elsevier; 2010.
  
• Gilbert R, Lim EM. The diagnosis of Cushing syndrome: An endocrine society clinical practice guideline.
  Clin Biochem Rev.
  2008;29:103–106.
  
• Goldman L, Bennett JC, eds.
  Cecil’s Textbook of Medicine
  . 23rd ed. Philadelphia, PA: Saunders-Elsevier; 2008.
  
• Guaraldi F, Salvatori R. Cushing syndrome: Maybe not so uncommon of an endocrine disease.
  J Am Board Fam Med.
  2012;25(2):199–208.
  

CODES

255.0 Cushing’s syndrome

BASICS

• Toxicity through inhalation, or GI tract absorption
  
• Intracellular toxin that inhibits aerobic metabolism through interruption of oxidative phosphorylation:
  
  • Leads to decreased O
    ₂
    utilization and ATP production
    
• Detoxification:
  
  • Rhodanese: Hepatic mitochondrial enzyme responsible for the metabolism:
    
    • Combines cyanide (CN) with sulfur (rate-limiting step) covalently (irreversible) to form less toxic and water-soluble thiocyanate (T-CN)
      
    • Forms less toxic reversible cyanhemoglobin when combined with hemoglobin (Fe 3+)
      
    • Forms nontoxic cyanocobalamin (B
      ₁₂
      ) when combined with hydroxocobalamin (B
      ₁₂
      a)
      
    • Rate of CN removal requires adequate bioavailability of sulfur compounds (thiosulfate [TS]).
      

• Fires:
  
  • Combustion by-product of natural and synthetic products
    
• Industry:
  
  • Metal plating, microchip manufacturing
    
  • Chemical synthesis
    
  • Plastic manufacturing
    
  • Pesticides
    
• Solvents:
  
  • Artificial nail remover
    
  • Metal polishes
    
• By-product of nitroprusside metabolism (nonenzymatic)
  
• By-product of
  Pseudomonas aeruginosa
  and pyocyaneus infections
  
• Amygdalin (converted by intestinal flora to CN), CN-containing plants (apricot and peach pits, apple and pear seeds, and cassava)
  
• Jewelry making
  

DIAGNOSIS

• Heart and brain—most sensitive organs—1st to show manifestation of toxicity
  
• CNS:
  
  • Headache
    
  • Confusion
    
  • Syncope
    
  • Seizures
    
  • Coma
    
• Cardiovascular:
  
  • Dyspnea
    
  • Chest pain
    
  • Cardiorespiratory collapse and death
    
• Other:
  
  • Nausea/vomiting
    
• Oral exposure: Can be caustic, 50 mg has caused death.
  
• Inhalational exposure:
  
  • 50 ppm causes anxiety, palpitations, dyspnea, headache.
    
  • 100–135 ppm <1 hr is lethal.
    

• History of exposure:
  
  • Smoke inhalation
    
  • Industrial exposure
    
  • Intentional suicide
    
  • Intentional homicide
    
• Clinical clues (frequently absent):
  
  • Peculiar odor of bitter almonds
    
  • Bright red (arterialization) retinal vessels
    
  • Abrupt onset and/or deteriorating toxic effects
    
  • Lactic acidosis
    
  • High venous O
    ₂
    saturation (secondary to blocked cellular O
    ₂
    consumption); arterialization of venous blood gases
    

• CBC
  
• Electrolytes, BUN, creatinine, glucose:
  
  • Anion gap acidosis
    
• Liver profile
  
• Creatine phosphokinase (CPK)
  
• Carboxyhemoglobin (CO) level
  
• Methemoglobin (MH) level
  
• CN level:
  
  • Send out lab that is not usually available in a clinically relevant time period.
    
  • Levels >0.5–1 mg/L: Toxic
    
  • Levels 2.5–3 mg/L: Fatal
    
• Blood gas determinations:
  
  • Elevated mixed venous O
    ₂
    : MvO
    ₂
    (normal about 35–40)
    
  • Elevated mixed venous O
    ₂
    saturation (co-oximeter): SmvO
    ₂
    (normal about 75%)
    
  • Decreased arteriovenous O
    ₂
    difference: AVO
    ₂
    D (normal about 3–4.8 mL/dL)
    
• Elevated lactate level >8 mmol/L:
  
  • An elevated lactate is a surrogate marker for the presence of CN with the appropriate history and physical exam.
    

CXR

• Carbon monoxide
  
• Hydrogen sulfide
  
• Methemoglobinemia
  
• Sulfhemoglobinemia
  
• Inert gases “asphyxiants”
  
• Other causes of high anion gap metabolic acidosis
  

TREATMENT