Transcript cortisone and pregnancy

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:
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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:
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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
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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.
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Insulin suppresses endogenous glucose production and
stimulates glucose use
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2. Glucagon:
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The body perceives a “fasting state” and releases glucagon,
attempting to provide the glucose necessary for brain function
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3. Epinephrine:
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Stimulates hepatic glucose production and limits glucose use
Acts directly to increase hepatic glycogenolysis and
gluconeogenesis
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4. Cortisol
5. Growth hormone
Type 1 diabetes:
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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:
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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:
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Abnormal oral glucose tolerance test
(OGTT) that occurs during pregnancy
Reverts to normal during the postpartum
period or remains abnormal.
Impaired Glucose Tolerance:
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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:
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They have an autosomal dominant
inheritance of their disease
Are usually not obese
Have a relatively mild course of disease.
DIAGNOSTIC STRATEGIES:
Serum Glucose:
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Any random plasma glucose level greater than 200 mg/dL
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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:
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Provides insight into the quality of glycemic control over time
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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
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Normal values nearly 4% to 6% of total hemoglobin
Urine dipsticks:
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Both falsely high and falsely low urine glucose readings can also occur.
Urine Ketones:
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Urine ketone dipsticks use the nitroprusside reaction good test for acetoacetate
but does not measure β-hydroxybutyrate.
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Usual acetoacetate / β-hydroxybutyrate ratio in DKA is 1:2.8
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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:
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Hematocrit < 30% cause false high readings
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Hematocrit > 55% cause false low readings
Hypoglycemia
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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
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Due to:
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DM
Sepsis
Liver disease
Alcohol intoxication
Starvation
Certain toxic ingestion.
Brain uses 150 g/d of glucose.
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Hypoglycemia:
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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:
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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
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Single hypoglycemic episode can reduce neurohumoral
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counterregulatory responses to subsequent episodes
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Factors associated with recurrent hypoglycemic
attacks include:
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Overaggressive or intensified insulin therapy
Longer history of diabetes
Autonomic neuropathy
Decreased epinephrine secretion or sensitivity
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4.
Precipitants of Hypoglycemia in DM Patients:
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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:
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Development of low serum sugar without the
physiologic ability to react
is a dangerous complication of type 1
diabetes
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Increase risks in :
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Extremes of age.
Comorbidity.
Medications ( B – blockers)
Autonomic neuropathy.
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Somogyi phenomenon:
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Common problem associated with iatrogenic
hypoglycemia in the type 1 diabetic patient.
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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
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Clinical features:
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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:
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STROKE.
TIA.
SEIZURE.
TRAUMATIC HEAD INJURY.
BRAIN TUMOR.
NARCOLEPSY.
MS.
PSYCHOSIS.
SYMPATHOMIMETIC DRUG INGESTION.
HYSTERIA.
Hypoglycemia:
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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:
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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:
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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:
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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:
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Postprandial hypoglycemia:
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The most common cause of is alimentary hyperinsulinism
Such as gastrectomy, gastrojejunostomy, pyloroplasty, or vagotomy.
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Fasting hypoglycemia:
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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
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Diabetic ketoacidosis (DKA)
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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
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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 :
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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:
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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:
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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:
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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
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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.
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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 :
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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 :
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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 :
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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:
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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:
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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:
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ABC
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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
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Correct electrolyte abnormalities:
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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.
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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:
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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:
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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:
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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.
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The primary causes of death infection (especially
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(3)
(4)
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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:
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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)
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This disorder represents an extreme of a disease process
that includes DKA at one end and NKHC at the other end.
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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)
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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:
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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.
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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:
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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)
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Precipitating Causes:
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
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.
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HYPOTHYROIDISM:
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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
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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:
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Idiopathic
Autoimmune thyroiditis (of which Hashimoto’s is most
common)
Post-ablation hypothyroidism
Iodine deficiency
Drugs
Secondary:

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Pituitary or hypothalamic failure
Tumor or infiltrative disease (sarcoid)
Myxedema Coma:

Precipitating factors:
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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:
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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):
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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
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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
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suggest an underlying infection)

Hypotension: The blood pressure may be elevated, normal, or low.

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50% initially exhibit clinical shock, with systolic pressure less than 100 mm Hg
Sinus bradycardia is the most common dysrhythmia seen in myxedema.

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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
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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

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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:
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(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:

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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:
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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
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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:
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Anesthesia induction
Opiates
Dopamine antagonists
Cold medications
Radiographic contrast media
Drugs that inhibit catecholamine reuptake, such
as tricyclic antidepressants and cocaine
Childbirth
Clinical features:
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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:

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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:
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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
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