Endocrine Emergencies: Diabetic Ketoacidosis and Adrenal Crisis

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Endocrine Emergencies Diabetic Ketoacidosis and
Adrenal Crisis

• Kevin R. Schwartz, MD
• Massachusetts General Hospital
• Department of Pediatrics

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Diabetic Ketoacidosis

• Definition
• 1) Hyperglycemia. blood glucose gt200mg/dL
• 2) Metabolic Acidosis, venous pHlt7.3 and/or
  plasma bicarbonate lt15meq/L
• The above are accompanied by hyperketosis
  (gt5mmol/L ketone bodies) and hyperosmolality.

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Diabetic Ketoacidosis

• Epidemiology
• - Often the initial presentation of children
  with Type I diabetes (38 of cases)
• Risk factors for recurrent DKA are generally
  related to compliance
• -high HbA1C levels
• -female adolescents
• -Children gt13y/o
• -longer duration of DM
• Precipitating Factors
• -missed insulin injections, stress (?
  increased cortisol and glucagon), infection,
  exogenous steroids.

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Diabetic Ketoacidosis

• Pathophysiology
• - decreased insulin secretion ? glucose not
  transported into cells and shift to ketogenic
  state.
• Excess serum glucose creates osmotic gradient to
  draw water out of cells into ECF, glucose
  overwhelms kidneys tubular reabsorption gradient
  and therefore acts as osmotic diuretic causing
  excess urine output.
• Ketone production creates anion gap metabolic
  acidosis.

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Diabetic Ketoacidosis

• Clinical Presentation of DKA and initial
  presentation of Type I DM
• Hyperglycemia Causes polyuria, nocturia,
  polydipsia, fatigue and weight loss with
  hypovolemia.
• Ketoacidosis Causes hyperventilation with deep
  (Kussmaul respirations) reflecting respiratory
  compensation, fruity breath 2/2 exhaled acetone
  may be present.
• Polyphagia may be present, as can abdominal pain
  with vomiting.
• Severe hyperosmolarity may result in
  drowsiness/lethargy or obtundation.
• Physical Examination Note that degree of
  dehydration is difficult to estimate on exam as a
  large proportion of fluid loss in intracellular

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Diabetic Ketoacidosis

• Labs/Studies
• Initial laboratory studies should include
• -serum glucose (gt200mg/dL)
• -electrolytes (Na low, K variable, Bun,
  creatinine(variable), VBG (pHlt7.3), HbA1C and
  urinalysis (ketones, glucose)

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Diabetic Ketoacidosis

• Assesment of Severity

Defining Feature Mild Moderate Severe
Venous pH 7.2-7.3 7.1-7.2 lt7.1
Serum Bicarbonate 10-15 5-10 lt5
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Diabetic Ketoacidosis Treatment

• 1) Fluids
• For moderate to severe DKA, assume
• 10 fluid deficit.
• -Give bolus of 10mL/kg NS over 1 hour, may
  repeat x1 if compromised circulation.
• -Replace remaining fluid deficit over the next
  48 hours (generally run 1.5-2x maintenance rate
  for first 24 hours).
• -Use NS for first 4-6 hours then switch to ½
  NS.

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Diabetic Ketoacidosis Treatment

• 2) Electrolytes
• - Sodium will be low and should rise as
  hyperglycemia is corrected. Run NS x4-6 hours
  then ½ NS.
• - Potassium Irrespective of initially measured
  serum potassium, pt w/ DKA has a total body
  potassium deficit. Therefore add K immediately
  to fluids for hypokalemic pts. Add K at start of
  insulin therapy for normokalemic patients, add K
  once serum K normalizes for hyperkalemic patients

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Diabetic Ketoacidosis Treatment

• Insulin
• -After initial fluid bolus, start continuous
  insulin infusion at 0.05 to 0.1units/kg/hour
• (mix 50 units insulin in 50mL NS to make
  solution). DO NOT give insulin bolus. Do NOT stop
  insulin drip when glucose normalizes but rather
  when acidosis resolves
• Glucose No glucose in initial fluids. Add D5
  once glucose lt300, Add D10 once glucoselt200.
  Glucose should not fall faster than 90mg/dL/hour.
• Monitoring check blood glucose, electrolytes,
  venous pH q1 hour x3-4 hours Then glucose q1
  hour, electrolytes and pH q2 hours.

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Diabetic Ketoacidosis Treatment Summary

• Definition Glucosegt200mg/dL and pHlt7.3 and/or
  bicarblt15.
• - Give 10mL/kg NS bolus over 1 hour(repeat x1 if
  needed)(add KCl if hypokalemic)
• - Then start insulin drip at 0.05-0.01U/kg/hr
• - Start NS at 1.5-2x M (replace 10 deficit over
  48 hours), if hypo or normokalemic add 20mEq/L
  KCL 20mEq/L KPhos.
• Change to ½ NS after 4-6 hours. Add D5 once
  glucoselt300, add D10 once glucoselt200
• Check blood glucose hourly, VBG and lytes hourly
  x4h, then q2h.

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Diabetic Ketoacidosis Cerebral Edema

• Occurs in 1 of DKA w/ mortality of 20-90, most
  common cause of mortality in children w/ DKA
• Major Criteria fluctuating level of
  consciousness, sustained bradycardia, age
  innapropriate incontinence
• Minor Criteria vomiting, headache, lethargy,
  diastolic BPgt90, agelt5y/o
• Diagnostic Criteria abnormal response to pain,
  decorticate/decerebrate posture, CN palsy,
  abnormal respiratory pattern.
• Cerebral edema is more likely if 1 diagnostic
  criteria, 2 major criteria or 1 major and 2 minor
  criteria are present.
• Treatment Treat as soon as cerebral edema
  suspected
• -Mannitol 0.25 1.0g/kg IV over 20 minutes
• -Slow rate of fluid administration

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Adrenal Insufficiency

• Definition impaired synthesis and release of
  adrenocortical hormones.
• -Primary (Addisons dz.) disease intrinsic to
  adrenal cortex
• -Secondary caused by impaired release or effect
  of ACTH from pituitary gland
• -Tertiary impaired release or effect of CRH from
  hypothalamus

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Adrenal Insufficiency
Site of tertiary adrenal insufficiency
Site of secondary adrenal insufficiency
Site of primary adrenal insufficiency
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Adrenal Insufficiency Adrenal Crisis

• Pathophysiology Acute mineralocorticoid and
  glucocorticoid deficiency, seen only in PRIMARY
  Adrenal Insufficiency
• Clinical Presentation hypotension and shock.
  Also may have nausea/vomiting/abdominal pain,
  weakness, lethargy.
• Labs/Studies electrolytes show hyponatremia with
  hyperkalemia.

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Adrenal Insufficiency Adrenal Crisis

• Treatment
• Send baseline electrolytes and glucose, EKG for K
  related changes
• Give 20cc/kg D5NS, NO potassium over 1 hour.
• Manage hyperkalemia as needed(see electrolyte
  lecture).
• Administer
• Hydrocortisone sodium succinate(SoluCortef)
• 25mg for 0-3y/o
• 50mg for 3-12y/o
• 100mg gt12y/o
• Give bolus as above then the same dose at a
  divided over next 24 hours (may divide q4h).

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Adrenal Insufficiency Primary

• Clinical presentation
• Glucocorticoid Deficiency
• fasting hypoglycemia, muscle weakness, morning
  headache. Increased ACTH production leads to
  increased pro-opiomelanocortin ?increased melanin
  ?hyperpigmentation.
• Mineralocorticoid deficiency hypotension,
  dizziness, salt craving, weight loss, electrolyte
  abdnormalities
• Adrenal androgen deficiency decreased axillary
  and pubic hair, decreased libido in females.

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Adrenal Insufficiency Primary

• Causes
• -steroidogenesis disorders (e.g. CAH)
• -adrenal damage (trauma/hemorrhage/infection)
• -Abnormal adrenal development
• -Adrenal unresponsiveness to ACTH

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Adrenal Insufficiency Congenital Adrenal
Hyperplasia

• The most common cause of primary adrenal
  insufficiency in infants. 95 involve defective
  conversion of 17 hydroxyprogesterone to
  110deoxycortisol.

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Adrenal Insufficiency Congenital Adrenal
Presentation

• CYP21A2(21-hydroxylase)deficiency
• Presents in the first few days-weeks of life
• May take two forms
• -Salt-wasting hypotension w/ hypokalemia and
  hypotension, females have ambiguous genitalia
• -Simple Virilizing form without salt wasting.
• Therefore, infants w/ ambiguous genitalia require
  urgent attention and a 17-hydroxyprogesterone
  level should be checked.

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Adrenal Insufficiency Secondary

• Clinical Presentation
• Similar to Primary AI, however,
  mineralocorticoid deficiency usually not observed
  as RAA axis remains intact, hyperpigmentation not
  present.
• Causes congential hypopituitarism, pituitary
  hemorrhage or tumor

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Adrenal Insufficiency Tertiary

• Presentation Same as that for secondary AI.
• Causes Congenital hypothalamic insufficiency,
  infiltrative disorders (e.g. hemochromatosis,
  sarcoid, LCH), anorexia, trauma/hemorrhage

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Adrenal Insufficiency Laboratory Diagnosis

• 1) Measure cortisol and ACTH in the morning(8am,
  normally peak time) while fasting. If cortisol
  is low cortisol insufficiency
• a) if low cortisol, high ACTH give ACTH
  stimulation test(give
• ACTH and recheck serum cortisol in
  60mins), if cortisol fails to
• riseprimary adrenal insufficiency.
• b) if low cortisol, low ACTH give
  insulin-induced hypoglycemia
• test. Measure serial cortisol at
  before and 15, 30, 45 and
• 60mins after giving a 0.05units/kg
  infusion of insulin, do NOT
• allow blood glucose to drop below
  30mg/dL. Hypoglycemia
• should stimulate ACTH and subsequent
  cortisol release, cortisol
• levels should double over baseline. If
  they do not, ACTH
• secretion is impaired.
• c) To differentiate secondary from tertiary
  AI, exogenous CRH may
• be administered, which, in tertiary AI,
  will result in a
• corresponding increase in ACTH levels

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References

• Jeha, G et al. Treatment and Complications of
  Diabetic Ketoacidosis in Children.
  www.uptodate.com 2008
• Jeha, G et al.Clinical Features and Diagnosis of
  Diabetic Ketoacidosis in Children.
  www.uptodate.com 2008
• Jeha, G et al. Cerebral Edema in Children with
  Diabetic Ketoacidosis. www.uptodate.com 2008
• Donohoue, P et al. Causes and Clinical
  Manifestations of Primary Adrenal Insufficiency
  in Children. www.uptodate.com 2008
• Donohoue, P et al. Causes and Clinical
  Manifestations of Secondary (pituitary) and
  tertiary (hypothalamic) adrenal insufficiency in
  children. www.uptodate.com
• Donohoue, P et al. Diagnosis of Adrenal
  Insufficiency in Children. www.uptodate.com 2008
• Merke, D et al. Treatment of Classic Congential
  Adrenal Hyperplasia due to CYP21A2(21-hydroxylase)
  deficiency in Infants and Children.
  www.uptodate.com 2008