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ENDOCRINE EMERGENCIES Dr.Sami qashqary FRCPC Qatar EM board review course Dr. Zohair Al aseri MD FRCP,EM & CCM The National Diabetes Data Group (NDDG) defines four major types of diabetes mellitus: type 1 diabetes mellitus type 2 diabetes mellitus gestational diabetes Impaired glucose tolerance (IGT) and its analogue, impaired fasting glucose (IFG). The CNS cannot: 1. Synthesize glucose 2. Store more than a few minutes supply 3. Concentrate glucose from the circulation Glucose is the predominant metabolic fuel used by the central nervous system (CNS). Brief hypoglycemia can cause profound brain dysfunction Prolonged severe hypoglycemia may cause cellular death Glucose is derived from three sources: 1. Intestinal absorption: from the diet 2. Glycogenolysis: the breakdown of glycogen 3. Gluconeogenesis: the formation of glucose from precursors, including lactate, pyruvate, amino acids, and glycerol Sulfonylurea oral hypoglycemic agents work, in part by stimulating the release of insulin from the pancreas. Insulin receptors on the beta cells of the pancreas sense elevated blood glucose & trigger insulin release into the blood Under normal circumstances, insulin is rapidly degraded through the liver and kidney. The half-life of insulin is 3 to 10 minutes in the circulation. Insulin is the major Anabolic hormone pertinent to the diabetic disorder Glucagon plays the role of the major catabolic hormone in disordered glucose homeostasis. The liver is essentially the sole source of endogenous glucose production. Renal gluconeogenesis contribute substantially to the systemic glucose pool only during prolonged starvation. Insulin inhibits hepatic gluconeogenesis and glycogenolysis Glucoregulatory hormones 1. Insulin: include: Insulin is the main glucose-lowering hormone. Insulin suppresses endogenous glucose production and stimulates glucose use 2. Glucagon: The body perceives a “fasting state” and releases glucagon, attempting to provide the glucose necessary for brain function 3. Epinephrine: Stimulates hepatic glucose production and limits glucose use Acts directly to increase hepatic glycogenolysis and gluconeogenesis 4. Cortisol 5. Growth hormone Type 1 diabetes: Type 1 diabetes results from a chronic autoimmune process that usually exists in a preclinical state for years. The classical manifestations of type 1 hyperglycemia & ketosis occur late in the course of the disease, an overt sign of beta cell destruction. Type 2 Diabetes Mellitus: May remain asymptomatic for long periods Show low, normal, or elevated levels of insulin because of insulin resistance The diagnosis of type 2 is often made because of an elevated blood glucose found on routine laboratory examination Decompensation of disease usually leads to hyperosmolar nonketotic coma rather than ketosis. Gestational Diabetes: Abnormal oral glucose tolerance test (OGTT) that occurs during pregnancy Reverts to normal during the postpartum period or remains abnormal. Impaired Glucose Tolerance: Impaired glucose tolerance (IGT) and its analogue, impaired fasting glucose (IFG). This group is composed of persons whose plasma glucose levels are between normal and diabetic and who are at increased risk for the development of diabetes and cardiovascular disease Maturity-onset diabetes: They have an autosomal dominant inheritance of their disease Are usually not obese Have a relatively mild course of disease. DIAGNOSTIC STRATEGIES: Serum Glucose: Any random plasma glucose level greater than 200 mg/dL A fasting plasma glucose concentration greater than 140 mg/dL or a 2-hour postload OGTT is sufficient to establish the diagnosis of diabetes Glycosylated Hemoglobin HbA1: Provides insight into the quality of glycemic control over time Given the long half-life of red blood cells, the percentage of HbA1c is an index of glucose concentration of the preceding 6 to 8 weeks Normal values nearly 4% to 6% of total hemoglobin Urine dipsticks: Both falsely high and falsely low urine glucose readings can also occur. Urine Ketones: Urine ketone dipsticks use the nitroprusside reaction good test for acetoacetate but does not measure β-hydroxybutyrate. Usual acetoacetate / β-hydroxybutyrate ratio in DKA is 1:2.8 it may be as high as 1:30 in which case the urine dipstick does not reflect the true level of ketosis. Dipstick blood glucose: Hematocrit < 30% cause false high readings Hematocrit > 55% cause false low readings Hypoglycemia Symptoms consist with diagnosis. < 50-60mg/dL. Resolve following glucose adminstration. The most dangerous acute complication Severe hypoglycemia is usually associated with a blood sugar level below 40 to 50 mg/dL Due to: DM Sepsis Liver disease Alcohol intoxication Starvation Certain toxic ingestion. Brain uses 150 g/d of glucose. Hypoglycemia: Glucose decrease by insulin. Glucose increased by glucagon , catecolamines ,growth hormone , glucocorticoides. Insulin: Is the major metabolic regulatory factor. 1st defense against hypoglycemia is decrease insulin secretion. Insulin inhibit glycogenolysis ,gluconneogenesis ,lipolysis , proteolysis. Most tissues use FFA except brain and cellular blood elements. Hypoglycemia: Diabetic patients using insulin are vulnerable to hypoglycemia because of insulin excess & failure of the counterregulatory system Hypoglycemia may be caused by: 1. Missing a meal 2. increasing energy output 3. increasing insulin dosage Single hypoglycemic episode can reduce neurohumoral counterregulatory responses to subsequent episodes Factors associated with recurrent hypoglycemic attacks include: 1. Overaggressive or intensified insulin therapy Longer history of diabetes Autonomic neuropathy Decreased epinephrine secretion or sensitivity 2. 3. 4. Precipitants of Hypoglycemia in DM Patients: Addison's disease Antimalarials Decrease in usual food intake Ethanol Factitious hypoglycemia Hepatic impairment Increase in usual exercise Insulin Malnutrition Old age Oral hypoglycemics Pentamidine Propranolol Recent change of dose or type of insulin or oral hypoglycemic Salicylates Sepsis Hypoglycemia Unawareness: Development of low serum sugar without the physiologic ability to react is a dangerous complication of type 1 diabetes Increase risks in : Extremes of age. Comorbidity. Medications ( B – blockers) Autonomic neuropathy. Somogyi phenomenon: Common problem associated with iatrogenic hypoglycemia in the type 1 diabetic patient. Excessive insulin dosage, which results in an unrecognized hypoglycemic episode that usually occurs in the early morning while the patient is sleeping. The counterregulatory hormone response produces rebound hyperglycemia, evident when the patient awakens. Often, both the patient and the physician interpret this hyperglycemia as an indication to increase the insulin dosage which exacerbates the problem Clinical features: Symptomatic hypoglycemia occurs in most adults at a blood glucose level of 40 to 50 mg/dL. Signs and symptoms of hypoglycemia are caused by excessive secretion of epinephrine and CNS dysfunction and include: Sweating Nervousness Tremor Tachycardia Hunger Neurologic symptoms ranging from bizarre behavior and confusion to seizures & coma DDX of hypoglycemia: STROKE. TIA. SEIZURE. TRAUMATIC HEAD INJURY. BRAIN TUMOR. NARCOLEPSY. MS. PSYCHOSIS. SYMPATHOMIMETIC DRUG INGESTION. HYSTERIA. Hypoglycemia: Glucose values in whole blood 15% less than that of serum or plasma. Venous blood has 10% lower glucose concentration than capillary or arterial blood. Management: ABC In alert patients with mild symptoms, consumption of sugarcontaining food or beverage (drinks) orally is often adequate 1 to 3 ampules of 50% dextrose in water (D50W) Augmentation of the blood glucose ampule of D50W may range from less than 40 to more than 350 mg/dL All patients with severe hypoglycemic reactions require aspiration and seizure precautions D50W should not be used in infants or young children because venous sclerosis can lead to rebound hypoglycemia. In a child younger than 8 years it is advisable to use 25% (D25W) or even 10% dextrose (D10W). The dose is 0.5 to 1 g/kg body weight or, using D25W, 2 to 4 mL/kg 25-75 g glucose as D50W (1-3 ampules) IV Children: 0.5-1 g/kg glucose as D25W IV (2-4 mL/kg) Neonates: 0.5-1 g/kg glucose (1-2 mL/kg) as D10W Treatment: The condition of alcoholics ,the elderly, and others with depleted glycogen stores will generally not improve with glucagon. Fructose & lactose should not used to correct hypoglycemia (not cross BBB “blood brain barrier”). Octreotide inhibits the release of insulin and used in sulfonylurea-induced hypoglycemia. Octreotide used after initial glucose therapy. Steriod use in resistant to aggressive glucose replacement or associated with the signs of adrenal insufficiency. If unable to obtain IV access: 1-2 mg glucagon IM or SC , may repeat q20min Children: 0.025-0.1 mg/kg SC or IM; may repeat q20min The onset of action is 10 to 20 minutes Peak response occurs in 30 to 60 minutes. It may be repeated as needed. Glucagon is ineffective in causes of hypoglycemia in which glycogen is absent, notably alcohol-induced hypoglycemia. Nondiabetic Hypoglycemia: Postprandial hypoglycemia: The most common cause of is alimentary hyperinsulinism Such as gastrectomy, gastrojejunostomy, pyloroplasty, or vagotomy. Fasting hypoglycemia: is caused when there is an imbalance between glucose production and use. The causes of inadequate glucose production include: Hormone deficiencies Enzyme defects Substrate deficiencies Severe liver disease Drugs (salicylates , propranolol) Causes of overuse of glucose include: The presence of an insulinoma Exogenous insulin, sulfonylureas Drugs Endotoxic shock Extrapancreatic tumors A variety of enzyme deficiencies 1. 2. 3. 4. 5. Diabetic ketoacidosis (DKA) Insulin deficiency & Glucagon excess Can occurs in both types of DM. Approximately 25% of all episodes of DKA occur in patients whose diabetes was previously undiagnosed Mortality is high in the elderly due to underlying renal disease or coexisting infections. The primary ketone bodies are BHB “beta-hydroxybutyrate” & AcAc “acetoacetate” in DKA. The hyperosmolarity produced by hyperglycemia and dehydration is the most important determinant of the patient's mental status Glucose in the renal tubules draws water, sodium, potassium, magnesium, calcium, phosphorus, and other ions from the circulation into the urine. This osmotic diuresis combined with poor intake and vomiting produces the profound dehydration and electrolyte imbalance associated with DKA Insulin deficiency results in: 1. Activation of a hormone-sensitive lipase that increases circulating (FFA) levels and converted in the liver to acetoacetate & β-hydroxybutyrate 2. There is decrease in the peripheral tissue's use of ketones as fuel. The combination of increased ketone production with decreased ketone use leads to ketoacidosis Ketoalkalosis: vomiting for several days and in some with severe dehydration and hyperventilation. The finding of alkalemia, however, should prompt the consideration of alcoholic ketoacidosis DKA in pregnancy : MFSG level is low, relative insulin deficiency. Increase in FFA “free fatty acid” Increased levels of counterregulatory hormones . Chronic respiratory alkalosis (low Hco3). Increased vomiting and infections. Clinical features: Elevated temperature: is rarely caused by DKA itself and suggests the presence of sepsis. Abdominal pain: In children: Usually idiopathic Probably caused by gastric distention or stretching of the liver capsule Resolves as the metabolic abnormalities are corrected. In adults: More often signifies true abdominal disease. Typical Laboratory Values in Diabetic Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar Nonketotic Coma (HHNC) DKA HHNC Glucose (mg/dl) >350 >700 Sodium (mEq) low 130s 140s Potassium (mEq) ∼4.5–6.0 ∼5 Bicarbonate (mEq) <10 >15 BUN (mg/dL) 25–50 >50 Serum ketones Present Absent Investigations: Euglycemic DKA (blood glucose <300 mg/dL) in 18% of patients Venous pH is not significantly different from arterial pH in patients with DKA Urine test only can detect AcAc (aceto-acetate) Ketones need to be checked in urine initially. The high anion-gap the only clue to presence of metabolic acidosis. 1.6 mEq should be added to the reported Na for every 100mg of glucose over 100mg/dL. WBC increased due to stress & hemoconcentration, but absolute bands more10,000 predict infection Sodium level is normal or low. Potassium, magnesium, and phosphorus deficits are usually marked. As a result of acidosis and dehydration, however, the initial reported values for these electrolytes may be high. Dehydration produces hemoconcentration, contributes to normal or high initial serum potassium, magnesium, and phosphorus readings in DKA, even with profound total deficits Acidosis and the hyperosmolarity: Shift potassium, magnesium, and phosphorus from the intracellular to the extracellular space. Hypokalemia may further inhibit insulin release The serum sodium value: is often misleading in DKA. When hyperglycemia is marked, water flows from the cells into the vessels to decrease the osmolar gradient, thereby creating dilutional hyponatremia. Lipids also dilute the blood, thereby further lowering the value of sodium. Newer autoanalyzers remove triglycerides before assay, thus eliminating this artifact. the true value of sodium may be approximated by adding 1.6 mEq/L to the sodium value on the laboratory report for every 100 mg/dL glucose over the normal Leukocytosis more closely reflects ketosis than the presence of infection. Only the elevation of band neutrophils has been demonstrated to indicate the presence of infection with a sensitivity of 100% and a specificity of 80%. Serum amylase: The diagnosis of pancreatitis is confounded by the usually elevated urine and serum amylase levels in DKA. Typically, this is salivary amylase, but most laboratories are not equipped to make this distinction. A serum lipase determination helps to distinguish pancreatitis from elevated salivary amylase levels. Metabolic acidosis with anion gap is secondary to: 1. Elevated plasma levels of acetoacetate and β-hydroxybutyrate 2. Lactate 3. FFAs 4. Phosphates 5. Volume depletion A well-hydrated patient with DKA may have a pure hyperchloremic acidosis & no anion gap ( due to IFV resuscitation) DKA : Blood glucose more 250mg/DL. Hco3 less 15mEq/L. PH less 7.3 with moderate ketonemia. Resolving hyperglycemia is not the end-point. Add D5 if glucose level is 250-300mg/dL. Mointre CVP in elderly and cardiac disease. Insulin dose is = 0.1u/kg/hr. Half-life is 4-5 min Discard 1st 25mL of insulin solution. DKA : No IM or SC insulin. Infection is the primary reason for failure to respond. Hypokalemia the most life-threatening. Each 0.1 in PH, inversely 0.5 mEq/Dl “decrease in” in k. No IV phosphate in ED. No Hco3 routine treatment. Hco3 : No Hco3 routine treatment. SEs of NaHCO3 (bicarbonate) therapy: Na overload Acidosis (Paradoxical CNS acidosis) & Worsening intracellular acidosis. Hypokalemia. Hypertonicity Impaired O2 curve to left. Delayed recovery from alkalosis. Elevation of lactate. Cerebral edema. Mortality in DKA: Increased osmolarity ,BUN , BS “blood sugar” Decreased Hco3 less than 10mEq/L. Infection and AMI. Old age. Severe hypotension. Prolong and severe coma. Underlying renal and CVS disease Cerebral edema: Young age & new-onset DM are only risk factors. Any change in neurologic function in early treatment give mannitol prior to CT. Vascular thrombosis can occur (CNS). Mnagement of DKA: ABC Once the patient is intubated hyperventilated to prevent worsening acidosis. Rehydrate: 1-2 L normal saline IV over 1-3 hours Children: 20 mL/kg normal saline over first hour Follow with 0.45% normal saline Shock requires aggressive fluid resuscitation with 0.9% saline solution rather than pressors. Search for other possible causes of shock Supplement insulin: NOOOOOOOOOO Bolus Maintenance: 0.1 U/kg/hr regular insulin IV Change IV solution to D5W 0.45% normal saline when glucose ≤300 mg/dL Correct electrolyte abnormalities: Sodium: Correct with administration of normal saline and 0.45% normal saline. Potassium: Ensure adequate renal function. Add 20-40 mEq KCl to each liter of fluid. Phosphorus: Usually unnecessary to replenish No clinical benefit from the routine administration of in DKA has been shown Magnesium: Correct with 1-2 g MgSO4 (in first 2 L if magnesium is low). Deficiency may exacerbate vomiting and mental changes, promote hypokalemia and hypocalcemia, or induce fatal cardiac dysrhythmia. it is reasonable to include 0.35 mEq/kg of magnesium in the fluids of the first 3 to 4 hours, with further replacement dependent on blood levels and the clinical picture. Search and correct underlying precipitant. Monitor progress and keep meticulous flow sheets: Vital signs Fluid intake urine output Serum glucose K+, Cl-, HCO3+, CO2, pH Amount of insulin administered Admit to hospital or intensive care unit. Consider outpatient therapy in children with reliable caretaker and Initial pH > 7.35 Initial HCO3- ≥ 20 mEq/L Can tolerate PO fluids Resolution of symptoms after treatment in emergency department No underlying precipitant requiring hospitalization Insulin in DKA: DKA cannot be reversed without insulin low-dosage insulin therapy has proved as effective as highdosage therapy High dosages of insulin have potentially harmful effects including a greater incidence of iatrogenic hypoglycemia & hypokalemia Important: Because the half-life of regular insulin is 3 to 10 minutes IV insulin should be administered by constant infusion rather than by repeated bolus Reduction of glucose levels in children should be gradual Children are more likely than adults to develop cerebral edema in response to a rapid lowering of plasma osmolarity. Resistance occurs rarely in diabetic patients and requires an increase in dosage to obtain a satisfactory response especially in obese Fluid resuscitation in DKA: The severely dehydrated patient is likely to have a fluid deficit of 3 to 5 L. No uniformly accepted formula Acidosis also decreases after fluid infusion alone: Diminishing the formation of lactate. Increased renal perfusion promotes renal H+ loss Improved action of insulin in the betterhydrated patient inhibits ketogenesis. Potassium in DKA: Should be administered while the laboratory value is in the upper half of the normal range. Renal function should be monitored. In patients with low serum potassium at presentation, hypokalemia may become life threatening when insulin therapy is administered. IV potassium should be aggressively administered in concentrations of 20 to 40 mEq/L as required. Despite initial potassium levels that are normal to high, a total potassium deficit of several hundred milliequivalents results from potassium and hydrogen shifts ( True K is by subtracting 0.6 mEq/L from the laboratory potassium value for every 0.1 decrease in pH noted in the ABG analysis ) Morbidity: largely iatrogenic: (1) (5) Hypokalemia from inadequate potassium replacement Hypoglycemia from inadequate glucose monitoring and failure to replenish glucose in IV solutions when serum glucose drops below 250 to 300 mg/dL Alkalosis from overaggressive bicarbonate replacement Congestive heart failure from overaggressive hydration Cerebral edema probably caused by too rapid osmolal shifts. The primary causes of death infection (especially (2) (3) (4) pneumonia) , arterial thromboses , shock. The decrease in mortality demonstrates that appropriate therapy can make a difference. Poor prognostic signs include: Hypotension Azotemia Coma Underlying illness Cerebral edema: Should be suspected when the patient remains comatose or lapses into coma after the reversal of acidosis. It generally occurs 6 to 10 hours after the initiation of therapy. There are no warning signs, and the mortality is currently 90%. Associated with: Low PCO2 High BUN concentration Use of bicarbonate. Non-Ketotic Hyperosmolar Coma (NKHC) HYPERGLYCEMIC HYPEROSMOLAR NONKETOTIC COMA (HHNC) Hyperglycemic hyperosmolar syndrome (HHS) This disorder represents an extreme of a disease process that includes DKA at one end and NKHC at the other end. Occurs in patients with mild or occult diabetes Usually middle aged to elderly Marked hyperglycemia, hyperosmolarity and dehydration, and decreased mental functioning that may progress to frank coma. Ketosis and acidosis are generally minimal or absent. Focal neurologic signs are common. DKA and NKHC may occur together The reason for the absence of ketoacidosis in HHNC is unknown ( FFA levels are lower than in DKA, thus limiting substrates needed to form ketones) The reason for the absence of ketoacidosis in HHNC is unknown (theories): FFA levels are lower than in DKA thus limiting substrates needed to form ketones Presence of insulin secretion inhibits lipolysis Hyerosmolarity state Counter-regularity hormones NKHC May occur in patients who are not diabetic: Burns Parenteral hyperalimentation Peritoneal dialysis Hemodialysis 20% of patients have no known history of type 2 diabetes. The most common associated diseases are CRF, gramnegative pneumonia, GI bleeding, and gram-negative sepsis. Of these patients 85% have underlying renal or cardiac impairment as a predisposing factor. Arterial and venous thromboses often complicate the picture. Pathogenesis: Mechanism similar to DKA, but more severe hyperglycemia (> 1000 mg/dl) and hyperosmolality (>350 mOsm/kg) develop resulting in more profound fluid and electrolyte loss in the ABSENCE of ketogenesis. The occurrence of nonketosis is not well understood. Because of the absence of acidosis, NKHC is more indolent in development of symptoms and concomitant with an older population, results in a higher mortality rate (40-60%) versus DKA (5-15%). The urine is extremely hypotonic: urine sodium concentration between 50 and 70 mEq/L, compared with 140 mEq/L in extracellular fluid. This hypotonic diuresis produces profound dehydration, leading to hyperglycemia, hypernatremia & associated hypertonicity Non-Ketotic Hyperosmolar Coma (NKHC) Precipitating Causes: 1. Similar to DKA 2. Medications: diuresis, phenytoin, diazoxide, steroids, mannitol, cimetadine, immunosuppressive agents etc. Recognition: A. Onset of NKHC more insidious B. Primary neurologic dysfunction (confusion, seizure, coma) C. Marked dehydration (or profound shock) Clinical features: Extreme dehydration Hyperosmolarity CNS findings predominate On average, the HHNC patient has 9 L in the 70-kg patient. The depression of the sensorium correlates directly with the degree and rate of development of hyperosmolarity. Some patients have normal mental status. Seizures are usually associated with neurologic findings, especially epilepsia partialis continua (continuous focal seizures) and intermittent focal motor seizures. Stroke and hemiplegia are also common. Non-Ketotic Hyperosmolar Coma (NKHC) Laboratory: A. Hyperglycemia (>800 mg/dl) B. No ketones C. Hyperosmolar (>380 mOsm/kg) greater osmolality = greater obtundation D. Hypokalemic E. Sodium variable F. Azotemia G. Metabolic acidosis (lactic or uremic) Glucose greater than 600 mg/dL Serum osmolarity greater than 350 mOsm/L. The BUN concentration is invariably elevated May have a metabolic acidosis secondary to some combination of lactic acidosis, starvation ketosis & retention of inorganic acids attributable to renal hypoperfusion Initial serum sodium readings are inaccurate because of hyperglycemia Non-Ketotic Hyperosmolar Coma (NKHC) Treatment Fluids: Correct hypovolemia. Typically patient has lost 20-25% of their total body water. 1. unstable = normal saline 2. stable = ½ NS or NS with close monitoring of fluids status 3. attempt to replace ½ fluid deficit in the first 12 hours Restore adequate urine output (50 ml/hour) Same as in DKA Overly rapid correction of serum osmolarity may predispose to the development of cerebral edema in children Non-Ketotic Hyperosmolar Coma (NKHC) Insulin: hyperglycemia less resistant than DKA 10 units regular IV (or IM) and follow IV infusion regular insulin 5-10 units/hour OR 10 units regular IM or SQ every 3 to 4 hours with frequent glucose monitoring Dextrose: add 5% dextrose to IV solution when blood sugar approaches 300 mg/dl Potassium: once adequate urine output has been established (1 ml/kg/hour), then add 10-40 mEq/hour with frequent monitoring of [K+]. For rapid rates of IV administration, cardiac monitoring in mandatory. Phosphate: as needed Non-Ketotic Hyperosmolar Coma (NKHC) Treat precipitating causes Monitor intake and output Consider CVP or SG “Swan-Ganz” catheter Evaluate for other causes of coma Phenytoin (Dilantin) is contraindicated for the seizures of HHNC because it is often ineffective and may impair endogenous insulin release. Phenytoin-induced HHNC even occurs in nondiabetic patients All patients with HHNC must be hospitalized Low-dosage subcutaneous heparin may be indicated to lessen the risk of thrombosis, which is increased by: Hypohydration Volume depletion Hyperviscosity Hypotension Hypo or Inactivity Sulfonylureas: increase insulin secretion by binding to specific beta cell receptors works best in patients with early onset of type 2 diabetes and fasting glucose less than 300 mg/dL. Contraindicated in patients with known allergy to sulfa agents. Daonil (Glibenclamide ): for non-obese 5 mg po od or bid Diamicron (Gliclazide): non-obese 40 – 80 mg Biguanide: Works by decreasing hepatic glucose output leading to decreased insulin resistance and lower blood glucose. Does not cause hypoglycemia Contraindicated in patients with renal insufficiency and metabolic acidosis. Should be withheld for 48 hours before or after administration of iodinated contrast media because of the risk of acidosis. Must be used with caution in patients with hypoxemia, liver compromise & alcohol abuse. These patients are at increased risk for developing lactic acidosis which has a 50% mortality rate. Glucophage (metformin): for obese 500 mg po NEW-ONSET HYPERGLYCEMIA: Glucose greater than 200 mg/dL but are not ketotic. These patients with normal electrolytes may be treated with IV hydration alone or with insulin, often reducing the glucose to 150 mg/dL. In reliable patients whose initial glucose is greater than 400 mg/dL An HbA1c value should be obtained Start with sulfonylureas is appropriate: glyburide (2.5 to 5 mg once daily) or glipizide (5 mg once daily) In obese patients or those in whom sulfonylureas are contraindicated metformin may be an alternative. Follow-up should be stressed and warning signs of hypoglycemia discussed. Alcoholic Ketoacidosis (AKA) Probably more common than DKA Often unrecognized Seen in both acute and chronic ETOH abuse Associated with marked decrease in PO intake Alcoholic Ketoacidosis (AKA): Pathogenesis: Precise mechanism unknown Probably due to decreased ability of liver to handle free fatty acids “FFA” with resultant ketogenesis Unclear why profound acidosis occurs Precipitating cause: Heavy ETOH consumption Decreased caloric intake Volume loss from vomiting Alcoholic Ketoacidosis (AKA): Recognition: History of recent heavy ETOH consumption Abdominal pain and vomiting Kussmaul respiration No specific findings Laboratory: Metabolic acidosis Increased anion gap (may also have metabolic alkalosis component because of vomiting) Glucose is variable (< 300 mg/dl) Serum ETOH is low or undetected Treatment of AKA: Thiamine: 100 mg IV (PO) IV D50 or D5W as needed 1. Glucagon 1 mg IM if no IV access 2. oral dextrose preparations Fluids: D5NS or D5 ½ NS Bicarbonate: Judicious use for severe acidosis or [HCO3] < 7 mEq/L Insulin not indicated Potassium: once urine output established, replace as needed. Total deficit not as severe as in DKA. Magnesium: as needed Phosphorus: as needed Alcoholic Ketoacidosis (AKA): Other considerations: Watch for alcohol withdrawal symptoms Work up other causes of abdominal pain, dehydration and acidosis (DD): 1. pancreatitis 2. Sepsis 3. Trauma 4. GI blood loss 5. hepatic encephalopathy etc Endocrine Emergencies: 1. 2. 3. Hyperthyroidism Hypothyroidism Adrenal insufficiency Symptom complexes are subtle and may be difficult to recognize Potentially lethal if untreated No confirmatory laboratory studies are immediately available. Initiate treatment on the basis of clinical judgment alone. Acute Adrenal Insufficiency Variable clinical presentation Usually an insidious disorder with acute decompensation Production of glucocorticoids, primarily cortisol inadequate to meet the metabolic requirements of the body is the hallmark of the condition. The most common cause of adrenal insufficiency is (HPA) axis suppression More than 50% of patients with septic shock may have adrenal supression. The mortality usually secondary to either hypotension or hypoglycemia. Pathophysiology of Acute Adrenal Insufficiency: Adrenal gland consists of: 1. cortex (glucocorticoids, mineralocorticoids, androgenic hormones) 2. medulla (catecolamine, epinophrine, noreepinephrine) which is under neural control. Adrenal cortical function is via ACTH from the hypothalamus which is in turn is under anterior pituitary control via corticotropin releasing factor (CRF). Clinically, isolated failure of medullary function has not been reported. Most manifestations of acute adrenal failure are due to diminished glucocortoids “cortisol” (maintenance of blood glucose and ICF and ECF voumes) and mineralocorticoid “aldosterone” (promotes sodium reabsorption and potassium excretion). Underlying insufficiency may be: 1. primary (Addison’s Disease) 2. secondary: Hypothalamic failure Pituitary failure iatrogenic steroid suppression In primary adrenal insufficiency (Addison's disease): The adrenal gland itself cannot produce cortisol, aldosterone, or both. Absence of glucocorticoids produces a compensatory elevation of adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH) Lack of aldosterone leads to a reflex increase in renin production. In secondary adrenal failure: The locus of failure is the hypothalamic-pituitary axis. Secondary adrenal failure is usually characterized by depressed ACTH secretion and blunted cortisol production but aldosterone levels remain appropriate because of stimulation by both the renin-angiotensin axis and hyperkalemia. A special case, often called functional adrenal insufficiency Iatrogenic depression of ACTH secretion. Acute Adrenal Insufficiency: Precipitation Causes: Idiopathic Infiltrative or infectious (TB, fungal, sarcoid, amyloid, neoplastic) Hemorrhagic “adrenal hemorrhage”: if acute “adrenal apoplexy” consider septicemia secondary to meningococcus, staph, H. flu., pneumococcus [Waterhour – Friderichsen Syndrome]) Rare condition more than 90% of the gland must be destroyed Adrenal hemorrhage associated with sepsis (acute fulminating meningococcemia, or Waterhouse-Friderichsen syndrome) may lead to adrenal failure that may contribute to shock and death Acute discontinuation of maintenance steroids Chronic steroids with adrenal suppression and acute stress (sepsis, trauma, MI, etc.) Hypothalamic or pituitary failure secondary to mass lesion or infection Acute Adrenal Insufficiency: Recognition: If chronic insufficiency: Anorexia Weakness GI upset: Nausea & vomiting: are present in 56% to 87% of cases Weight loss Salt craving mucocutaneous hyperpigmentation: The mechanism is compensatory ACTH and melanocyte-stimulating hormone secretion. No hyperpigmentation is seen in secondary adrenal insufficiency. If acute insufficiency: Hypotension: responds well to glucocorticoid replacement with IV hydration Circulatory collapse Abdominal pain Delirium, seizure, coma If on chronic exogenous steroid replacement: Evidence of Cushing’s syndrome Anorexia Weakness lethargy Acute Adrenal Insufficiency: Laboratory: Hypoglycemia: respondto IV administration of D5W Hyponatremia: is present in 88% Hyperkalemia: is present in 64% (Hyperkalemia in adrenal insufficiency is produced by acidosis, aldosterone deficiency, and depressed glomerular filtration rate) Hypotension Decreased cortisol Azotemia & elevated hematocrit levels both referable to hypovolemia. Anemia Mild metabolic acidosis (with gap) secondary to hypoperfusion Hypercalcemia in 6% to 33%. In some patients the condition is suggested by a history of chronic adrenal failure or glucocorticoid therapy. Several mechanisms produce hypotension: 1. 2. 3. 4. Cortisol deficiency Depressing myocardial contractility Responsiveness to catecholamines is also reduced. If aldosterone deficiency coexists, sodium wasting can lead to hypovolemia. Volume deficits are greater in primary than in secondary adrenal insufficiency. Adrenal insufficiency should be considered in patients with hypotension of uncertain etiology. As many as 19% of vasopressor-dependent hypotensive patients may be suffering from adrenal dysfunction. The goals in treating adrenal insufficiency are: (1) Glucocorticoid replacement (2) correction of: Electrolyte Metabolic Hypovolemia (3) treatment of the precipitating factors Treatment of Acute Adrenal Insufficiency: Treatment: Fluids: D5 NS rapidly 500 cc/hour for 24 hours (average fluid deficit 20% total body water) Dextrose: D50 IV Glucocorticoids: hydrocortisone 100-300 mg IV Q 6 hours (has both glucocorticoid and mineralcorticoid activity) Mineralcorticoids: usually not necessary initially. As hydrocortisone is tapered over the next few days. Fludrocortisone (Florinef) 0.050.1 mg PO Q day. Potassium: if elevated (6.5 to 7.0 mEq/L) and ECG changes suggestive of hyperkalemia or [K+] greater than 8 mEq/L, administer Bicarbonate 50cc D50 and 10 units Regular insulin IV. Following fluids and steroids, potassium may fall dramatically and may need replacement. Vasopressors may be needed. Admit to ICU for further close management. Glucocorticoid Replacement: If the diagnosis of adrenal failure is unconfirmed, dexamethasone phosphate 4 mg IV every 6 to 8 hours Replacement with hydrocortisone could confound interpretation of serum cortisol determinations. If the patient is known to have adrenal failure 100 mg of hydrocortisone hemisuccinate IV every 6 to 8 hours should be used If IV access cannot be maintained, cortisone acetate 100 mg intramuscularly every 6 to 8 hours Supportive care: 100 mg of hydrocortisone has the salt-retaining effect of 0.1 mg of Florinef. If dexamethasone is used Florinef should be added to prevent salt loss. 20% volume depleted, correction of hypovolemia should be aggressive. Up to a total of 3 L may be required over the first 8 hours. D5W is usually added to treat accompanying hypoglycemia. Electrolyte abnormalities are usually corrected with saline rehydration. Special attention must be given to the potassium level. hyperkalemia should be treated Acute Adrenal Insufficiency: If patient is NOT critically ill, initial diagnostic testing can be combined with therapy: Fluids Dextrose administration, electrolyte correction Obtain baseline serum cortisol level Dexamethasone 4 mg IV (will not interfere with cortisol assay) for initial replacement. Synthetic ACTH: Cosyntropin (Cortosyn) 0.25 mg IV Redraw serum cortisol level after one hour If cortisol levels increase to 15-18 mg/dl, etiology of insufficiency is of hypothalamic or pituitary origin If cortisol does not increase etiology is due to primary adrenal insufficiency HYPERTHYROIDISM Thyroid storm & thyrotoxic crisis life-threatening manifestations of thyroid hyperactivity, including: High fever Cardiovascular, neurologic & gastrointestinal dysfunction True thyroid storm is rare. The transition from simple thyrotoxicosis to thyroid storm may be abrupt Thyroid Storm Thyroid storm is a life-threatening, clinical syndrome characterized by exaggerated signs and symptoms of hyperthyroidism, including fever and altered mentation. It occurs most commonly in patients with Graves' disease and is often precipitated by a concurrent illness or injury. Exceedingly difficult diagnosis in the Emergency Department (ED) Over 40% of cases occur in previously undiagnosed patients High mortality (60-90%) if untreated (cardiovascular collapse, hepatic failure, renal failure) Thyroid Storm: Pathogenesis: Incompletely understood Poorly controlled preexisting goiter (most commonly is Grave’s disease) Excess sympathetic (adrenergic) activity Increase hormonal release or response by end organs Most cases of thyroid storm are secondary to toxic diffuse goiter (Graves' disease) Factitious hyperthyroidism results from an exogenous source thyroiditis, either Hashimoto's or subacute, rarely causes thyroid storm and is usually but not always mild Precipitating factors: Infection DKA Stress (trauma, CVA, PE, MI, pregnancy etc.) General anesthesia Drug and medication induced (Iodine) No precipitating causes found in 25-50% of cases Amiodarone: An iodine-rich Has complex effects on thyroid physiology. Asymptomatic changes in thyroid hormone levels are common. Clinically relevant thyrotoxicosis has been reported in 1% to 24% Recognition of thyroid Storm: Cardinal manifestations: Temperature over 102 F (is often present) Tachycardia out of proportion to fever Other signs: CNS dysfunction (agitation ,nervousness , tremors, weakness, frank obtundation) Cardiovascular decompensation (tachycardia ,SOB, chest pain, palpitation, A-fib, A-flutter). AF reverts in 20% to 50% of cases after antithyroid therapy Ocular signs (lid lag, exophthalmos, difficulty with convergence) Stigmata of prior Grave’s disease Possible goiter Weight loss is common and may be dramatic Heat intolerance is common and reflects the underlying hypermetabolic state. Differentiation between thyroid storm and uncomplicated thyrotoxicosis (weight loss, weaskness, heat intolerance, nervousness, diarrhea) may not be well defined at times. Practically speaking if one is not certain, treatment for thyroid storm should be initiated. Agitation, anxiety & restlessness. Wide mood swings are typical. Fear and even frank paranoia occur. seizures and even coma. Thyrotoxic periodic paralysis When jaundice occurs as a primary hepatic sign it is primarily unconjugated, mild & probably from the unmasking of occult liver disease (Gilbert's disease). Treatment of the thyrotoxicosis is sufficient to resolve jaundice Activated Hyperthyroidism: Occurs in younger patients & its signs and symptoms, typically with multiple organ involvement, probably reflect the end-organ responsiveness to thyroid hormone in this group. Apathetic hyperthyroidism: Occurs in elders in whom end-organ responsiveness is attenuated Rare form of thyroid storm Hypermetabolic manifestations may not be as pronounced and may be more slowed, lethargic and apathetic in appearance Comparison of Activated & Apathetic Thyrotoxicosis Parameter Activated Apathetic Age 4th decade 7th decade Duration of symptoms 8 mo 26 mo Weight loss 10 lb 40 lb Thyroid weight 70 g 45 g Eye findings Frequent Rare Congestive heart failure Common Common Atrial fibrillation One third Three fourths Depression/apathy Uncommon Common Thyroid Storm: Laboratory (usually not helpful): thyroid levels are not necessarily acutely elevated: TFTs: Increase FT4 and FT3 (triiodothyronine) Decreased TSH Hyperglycemia: is present in 30% to 55% of patients. Possible explanations for hyperglycemia include insulin resistance, decreased insulin secretion, increased glycogenolysis & rapid intestinal absorption of glucose LFTs: Increased bilirubin, SGOT, LDH CBC: A normocytic, normochromic anemia is common, as is leukocytosis. Electrolytes: hypernatremia or hyponatremia Depressed cholesterol levels are often noted. The TSH level: Is an excellent screening tool Hyperthyroidism is virtually excluded if TSH is in the normal range. The only exception would be the exceedingly rare clinical entity of secondary hyperthyroidism, which is due to a TSH-producing anterior pituitary adenoma Serum TSH may be reduced as a result of chronic medical illnesses such as liver disease or renal failure. In addition, various drugs such as glucocorticoids may cause a reduction in TSH The most useful tests are FT4 & FT3. A low TSH with an elevated FT4 confirms thyrotoxicosis. low TSH combined with a normal FT4 and an elevated FT3 is also diagnostic (T3 thyrotoxicosis). Thyroid storm Management: Five goals: (1) Inhibit hormone synthesis (2) Block hormone release (3) Prevent peripheral conversion of T4 to T3 (4) Block the peripheral effects of thyroid hormone (5) Provide general support: Hyperpyrexia should be treated aggressively with acetaminophen. Aspirin should not be used because it displaces thyroid hormone from thyroglobulin Ice packs and hypothermia blankets may also be used. Thyroid Storm management: Recognition (most difficult part of treatment) Supportive measurements: Decrease De Nova Synthesis: Lugol’s (SSKI): 10 qtts PO Q 8 hours or Sodium iodine: 10-20 gm PO or slow IV drip Q 6 hours (potassium iodide 3-5 drops PO/NG q8h) or Lithium carbonate (iodine allergy): 300 mg PO Q 6 hours Decrease catecholamine effects: Methimazole (tapazole): 40 mg PO initially followed by 25 mg PO Q 6 hours Or PTU: 900-1200 mg/day PO / NG in 4 – 6 divided doses Decrease release of hormone: Airway management, O2 IV fluid replacement Cooling (antipyretics [not ASA]) Treat heart failure with digitalis and diuretics Identify and treat precipitating factors Rehydrate Propranolol (beta-blockade): 160-480 mg/day PO in 4 divided doses or Propranolol 1- 2 mg IV Q 4-6 hours (Propranolol 1-2 mg IV q15 min prn) Corticosteroids Dexamethasone 2 mg PO/NG q6h (Prevent peripheral conversion of T4 to T3) or hydrocortisone 100 mg iv q 8 h Reserpine (2.5-5.0mg IM Q 4 hours) Quanethidine (30-40 mg PO Q 6 hours) Plasmapherasis/ thyroid ablation Treat underlying precipitating causes Admit to ICU Inhibition of Hormone Synthesis: Thioamides including propylthiouracil (PTU) & methimazole inhibit thyroidal peroxidase thereby preventing hormone synthesis. PTU is generally preferred over methimazole because it has the additional minor effect of inhibiting peripheral conversion of T4 to T3 PTU is given in an initial dose of 600 to 1000 mg by mouth (PO) or by nasogastric (NG) tube, followed by 200 to 250 mg every 4 to 6 hours. Further organification of iodine is blocked within 1 hour of PTU administration, but the drug should be continued for several weeks while the hyperthyroidism is brought under control. In the rare patient who has contraindications to PTU or methimazole, such as a prior severe reaction, direct removal of thyroid hormone has been described. Plasmapheresis, charcoal plasma perfusion, and peritoneal dialysis may be considered Blockage of Hormone Release: Both iodine & lithium can inhibit thyroid hormone release. Lithium is not generally used because it can be difficult to titrate the dose & toxic effects are common. Thioamides should be given at least 1 hour before iodine therapy to prevent organification of the iodine. Lugol's iodine solution: 30 drops per day in 3 or 4 divided doses, is administered PO or by NG tube potassium iodide (saturated solution of KI): 5 drops every 6 hours PO or by NG tube, is also acceptable Iodine is contraindicated in patients with a history of iodine anaphylaxis. In these patients lithium carbonate should be given in a dose of 300 mg every 6 hours. Lithium levels should be monitored and kept below 1 mEq/L. In addition, iodine should not be given to patients with iodine overload– induced hyperthyroidism such as those with amiodarone-induced thyrotoxicosis. These patients should be treated with potassium perchlorate, which blocks thyroid uptake of iodine. The recommended dose is 0.5 g of potassium perchlorate per day Prevention of Peripheral Hormone Conversion: The peripheral conversion of T4 to T3 PTU, propranolol, or dexamethasone. Dexamethasone however, is effective through this mechanism and should be given as 2 mg intravenously (IV) every 6 hours If hydrocortisone is given, dexamethasone is probably unnecessary Peripheral Adrenergic Blockade: Propranolol: Can reduce dysrhythmias, hyperpyrexia, tremor, palpitations, restlessness, anxiety, and perhaps myopathy is effective IV in slow 1- to 2-mg boluses, which may be repeated every 10 to 15 minutes until the desired effect is achieved. Effective oral propranolol therapy usually begins at 20 to 120 mg per dose or 160 to 320 mg/day in divided doses High-output CHF and heart failure associated with tachydysrhythmias may respond to β-blocker therapy. In rare cases, β-blockers have been associated with worsening of CHF, usually in patients with preexisting, nonthyroid cardiac disease. In severe asthmatics reserpine 2.5 mg every 4 hours may be considered in lieu of β-blockade The complicated patient with both a tachydysrhythmia and CHF might be managed with a judicious combination of β-blockade and digitalis. HYPOTHYROIDISM: Most cases of hypothyroidism become manifest during the winter months. The two major causes of primary hypothyroidism are: 1. Autoimmune destruction 2. iatrogenic failure after surgical The significant life threats that accompany profound hypothyroidism are: Respiratory insufficiency, hypotension & coma. These elements are more characteristic of myxedema coma in its dramatic extreme than of simple hypothyroidism Myxedema Coma Myxedema coma is coma that results from either hypothyroidism or one of the causes or complications of hypothyroidism Rare syndrome Acute complication of chronic hypothyroidism 80% mortality rate if untreated 30% mortality rate even if well treated Myxedema Coma: Pathogenesis: thyroid failure secondary to improperly treated, neglected or undiagnosed hypothyroidism. Primary: Idiopathic Autoimmune thyroiditis (of which Hashimoto’s is most common) Post-ablation hypothyroidism Iodine deficiency Drugs Secondary: Pituitary or hypothalamic failure Tumor or infiltrative disease (sarcoid) Myxedema Coma: Precipitating factors: Infection (usually pulmonary) Noncompliance Stress (trauma, cold exposure, CVA, CHF etc.) Drugs (opiates, barbiturates “phenobarbital” , phenothiazines , anesthetics, benzodiazepines, lithium ) Recognition: (marked decreased metabolism) Cardinal manifestations: Hypothermia Bradycardia Altered sensorium with signs of myxedema Other signs: Hypotension Hypoventilation Myxedema Coma: Physical findings: Hypothermia, hypotensive, bradycardia Classical findings of myxedema (rounded facies, hypokinesia, weakness, pretibial edema) Lethargic Stigmata of prior Grave’s disease Palpable goiter or surgical scar Croaky harsh voice Dry, course skin delayed deep tendon reflexes (DTR) Myxedema Coma: Laboratory (usually not helpful): Decreased T4 and T3 Increased TSH (decreased TSH if secondary to pituitary or hypothalamic lesion) Cortisol Anemia: A mild normocytic, normochromic anemia Hyponatremia: ? (SIADH) & thyroid replacement therapy reverses the abnormality. Acidosis (mixed): Respiratory acidosis secondary to hypoventilation. Hypoglycemia: The presence of hypoglycemia should suggest hypothalamic-pituitary involvement because it is more characteristic of secondary than primary hypothyroidism. Hyperkalemia Hypercalcemia Diagnostic strategies: TFTs: The serum TSH assay most sensitive depressed FT4 Early in the course of hypothyroidism, a physiologic compensatory elevation in TSH levels may maintain normal FT4. Therefore, a high TSH level may be the only laboratory abnormality in hypothyroidism. T4 levels may be spuriously depressed or elevated in hypothyroidism because of alterations in thyroxine-binding globulin (TBG) levels T3 may be normal in patients with overt hypothyroidism. a low T3 level is not necessarily an indication of thyroid disease. Sick euthyroid state: These patients are physiologically euthyroid but have low T3 levels In secondary or tertiary hypothyroidism: both the FT4 and TSH levels are low A chest x-ray study may reveal an enlarged cardiac silhouette Pleural effusions may also be present. Pericardial effusions demonstrated by echocardiography may be present in 30% of patients. ECG evidence of a pericardial effusion (lowvoltage, diffuse ST-T changes) is present in only 50% of patients with an effusion in as many as 20% without an effusion Causes and Complications in Myxedema Coma and Hypothyroidism: Pulmonary complications: Depression in respiratory drives both hypoxic and hypercapnic. Hypoxia is correctable with hormone replacement, but hypercapnia is only partially correctable. CO2 narcosis (hypercapnic narcosis) is a cause of altered sensorium Upper airway obstruction from glottic edema, vocal cord edema, and glossomegaly. Pleural effusions are demonstrable in one third of cases. Hypothermia: in 80% of patients with myxedema (a normal temperature should suggest an underlying infection) Hypotension: The blood pressure may be elevated, normal, or low. 50% initially exhibit clinical shock, with systolic pressure less than 100 mm Hg Sinus bradycardia is the most common dysrhythmia seen in myxedema. Hypoglycemia Hyponatremia Sepsis Drugs: sedatives, hypnotics, anesthetics, tranquilizers Drug-induced coma (Metabolism of tranquilizers, sedatives, and anesthetics is reduced in hypothyroidism) The effects of these agents are thus potentiated and prolonged. Adrenal insufficiency capillaries are “leaky.” Transudation produces pleural and pericardial effusions. accumulate slowly, are unlikely to produce tamponade, and resolve with thyroid replacement therapy in 6 months to 1 year. Ascites is present in less than 4% of hypothyroid patients. Ascitic fluid has a high protein content. Pseudomyotonic, or “hung up” deep tendon reflexes are observed in 58% to 92% of patients Paresthesias are present in 80% Cerebellar symptoms were recognized in the original descriptions of myxedema Myxedema Coma: Emergency treatment: Recognition Supportive measurements (? Airway, ? Ventilatory support) Monitoring (ICU) Slow external re-warming Avoid fluid overloading (consider CVP or S-G “Swan-Ganz”) Correct hyponatremia: Hyponatremia is usually mild and responds to water restriction. Indications for hypertonic saline (sodium level < 110 to 115 mEq/L, mental status changes, seizures) are the same as in other medical conditions. Hypercalcemia is rarely significant L-thyroxine: 250-500 ug slow IV, then 50-100 ug IV per day Consider T3: 25 ug PO Q 12 hours Treat underlying causes: CHF and infection, especially pulmonary infection, are the two most common stresses. Four areas should be addressed in treating myxedema: (1) immediate thyroid replacement therapy: Thyroid replacement, in the form of T4 is the cornerstone of treatment for hypothyroidism. (2) identification and treatment of precipitating factors (3) Reversal of metabolic abnormalities (4) General supportive care Thyroid hormone replacement: The efficacy of thyroid hormone replacement therapy appears to be dose related Levothyroxine (T4) is generally preferred to T3 because it has a more gradual onset of action A dose of 500 μg of T4, administered PO or IV on day 1, is followed by 100 μg/day. Patients should receive cardiac monitoring and periodic ECGs. If signs of ischemia or dysrhythmias are observed, the dose of T4 may be reduced by 25% and continued. Bradycardia generally improves in 24 to 48 hours. Supportive care: Blood pressure, ventilatory support when necessary Avoidance of sedatives, narcotics & anesthetics when possible. A fluid challenge should be the first line of therapy; however, pressors are often necessary if hypotensive The approach to hypothermia is less aggressive. There are few data on active core rewarming of extremely low temperatures in conjunction with thyroid therapy of patients with hypothyroidism and hyperthermia. Stress dosages of corticosteroids: such as 300 mg of hydrocortisone IV followed by 100 mg IV every 6 to 8 hours, are routinely given to patients in myxedema coma because of panhypopituitarism or a coexisting condition with primary adrenal failure. Untreated, myxedema coma is lethal. With aggressive treatment, mortality rates of 0% to approximately 50% have been reported. Pheochromocytoma Age: most commonly occur in adults aged 20-40 years Mortality/Morbidity: if unrecognized, result in serious morbidity or in mortality such as: Obtundation Shock Disseminated intravascular coagulopathy Seizures Rhabdomyolysis Acute renal failure Death. Pathophysiology: Increased catecholamine results in hypertension, which may be episodic, as classically described, or sustained. Causes: Precipitants of a hypertensive crisis: Anesthesia induction Opiates Dopamine antagonists Cold medications Radiographic contrast media Drugs that inhibit catecholamine reuptake, such as tricyclic antidepressants and cocaine Childbirth Clinical features: 4 characteristics together are strongly suggestive of a pheochromocytoma: 1. Headaches 2. Palpitations 3. Diaphoresis 4. Severe hypertension (Not uncommonly, patients are entirely normotensive between episodes) Clinical Symptoms: Headache Diaphoresis Palpitations Tremor Nausea Weakness Anxiety, sense of doom Epigastric pain Flank pain Constipation Weight loss Clinical signs: Hypertension (paroxysmal in 50% of cases) Postural hypotension: This results from volume contraction. Hypertensive retinopathy Weight loss Pallor Fever Tremor Neurofibromas Café au lait spots Tachyarrhythmias Pulmonary edema Cardiomyopathy Ileus Diagnostic workup: Diagnosed when a combination of clinical signs and symptoms and elevated catecholamine levels are present Plasma metanephrine testing has the highest sensitivity (96%) for detecting a pheochromocytoma, but it has a lower specificity (85%) Obtain a serum intact parathyroid hormone level and a simultaneous serum calcium level to rule out primary hyperparathyroidism CT scanning and MRI have higher sensitivity MRI is more specific Laboratory features: Hyperglycemia Hypercalcemia Erythrocytosis Management: Medical Care: Surgical resection of the tumor is the treatment of choice Labetalol is a noncardioselective betaadrenergic blocker and selective alphaadrenergic blocker that has been shown to be effective in controlling hypertension associated with pheochromocytoma. It has also been associated with paradoxic episodes of hypertension thought to be secondary to incomplete alpha blockade. Phentolamine: Nonselective alpha-adrenergic blocking agent. Drug action is transient and alpha-adrenergic blockade incomplete. Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on alphareceptors. 5-15 mg IV Contraindications: Documented hypersensitivity Coronary or cerebral arteriosclerosis Renal impairment Myocardial infarction or a history of a myocardial infarction