eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hyperosmolar Hyperglycemic State: Differential Diagnoses & Workup

Author: Paulina B Sergot, MD, Staff Physician, Department of Emergency Medicine, New York University/Bellevue Hospital Center
Coauthor(s): Lewis S Nelson, MD, FACEP, FACMT, FAACT, Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Attending Physician, Department of Emergency Medicine, Bellevue Hospital Center, New York University Medical Center and New York Harbor Healthcare System
Contributor Information and Disclosures

Updated: Oct 28, 2009

Differential Diagnoses

Other Problems to Be Considered

Any cause of altered mental status:²
Central nervous system infection
Hypoglycemia
Hyponatremia
Severe dehydration
Uremia
Hyperammonemia
Drug overdose
Sepsis

Workup

Laboratory Studies

• Serum electrolytes including sodium, potassium, chloride, bicarbonate, calcium, magnesium, and phosphate
  • Hyponatremia or hypernatremia may be present. In the setting of hyperglycemia, pseudo-hyponatremia is common due to the osmotic effect of glucose drawing water into the vascular space. The measured serum sodium concentration can be corrected upward 1.6 mEq/L for every 100 mg/dL increase in serum glucose level to give an estimate of what the serum sodium level would be in the absence of hyperglycemia and its associated osmotic effect.
  • Hypokalemia or hyperkalemia may be present. Serum potassium concentration may be elevated due to an extracellular shift caused by insulin deficiency. However, total body potassium is likely low regardless of its serum value; a low measured serum potassium concentration suggests profound total body losses, and patients should be placed on cardiac monitoring. Serum magnesium levels are also a poor indicator of true total body magnesium. In the presence of hypokalemia, concomitant hypomagnesemia should be presumed and treated.
  • The calculated anion gap is usually less than 12 mmol/L. However, an elevated anion gap metabolic acidosis may be present because of dehydration but usually is less profound than that observed in diabetic ketoacidosis (DKA).
  • Some patients who have primarily a hyperosmolar hyperglycemic state may have a component of DKA; therefore, a small amount of ketoacidosis may contribute to the anion gap acidosis.
• Renal function, (BUN and creatinine concentrations)
  • BUN and creatinine concentrations are likely to be elevated initially due to dehydration.
  • When possible, they should be compared to previous values, as many patients with diabetes have baseline renal insufficiency.
• Serum glucose level usually is elevated dramatically, often to greater than 800 mg/dL.
• Serum osmolarity and/or osmolality are usually greater than 320 mOsm/L
  • Osmolality can be measured directly by freezing point depression or osmometry.
  • Predicted osmolarity is calculated using the following formula: Osm = (2 X Na) + (BUN/2.8) + (glucose/18)
  • The Osmol gap is the difference between the measured osmolality and the calculated osmolarity (at low solute concentrations they are nearly equivalent measures).
  • Although the measured osmolality is very high in patients with HHS, the osmol gap should be unimpressive since the calculated osmolarity includes the elevated serum glucose concentration.
  • If the calculated value is significantly lower than the measured value, and the osmol gap is very large, consider toxic alcohol ingestion.
• Serum ketones can be normal to small in pure HHS, but mild-to-moderate ketosis can be present when the disease has features of both HHS and DKA ("overlap cases").
• Creatine phosphokinase (CPK) with isoenzymes should be measured routinely because both MI and rhabdomyolysis can trigger HHS, and both can be secondary complications of HHS.
• Blood cultures should be obtained to search for bacteremia.
• Arterial blood gas analysis (ABG)
  • ABG is obtained to measure serum pH.
  • A venous blood gas (VBG) may be substituted in patients with normal oxygen saturation on room air. Venous blood gases provide comparable information, are easier to draw, and are less painful to the patient. The pH measured by a VBG is 0.03 pH units less than the pH on an ABG.⁶
  • In most cases of HHS, the blood pH is greater than 7.30.
• Urinalysis can reveal elevated specific gravity (evidence of dehydration), glucosuria, small ketonuria, and evidence of urinary tract infection (UTI).
• Urine cultures are useful because UTIs may be underdetected by urinalysis alone, particularly in patients with diabetes mellitus.
• Cerebrospinal fluid (CSF) cell count, glucose, protein, and culture are indicated in patients with an acute alteration of consciousness and clinical features suggestive of possible CNS infection. Patients who are immunocompromised may require additional studies of the CSF such as polymerase chain reaction (PCR) for herpes simplex virus (HSV) and cryptococcal antigen.
• Send cultures as clinically indicated.
• Although not useful in the acute phase of therapy, hemoglobin A1C (glycosylated hemoglobin) may be obtained as an indicator of the patient's glucose control over the previous several weeks.

Imaging Studies

• A chest radiograph is useful to screen for pneumonia. Abdominal radiographs are indicated if the patient has abdominal pain or is vomiting.
• CT scan of the head
  • CT scan is indicated in many patients with focal or global neurologic changes.
  • It may be useful for patients who show no clinical improvement after several hours of treatment, even in the absence of clinical signs of intracranial pathology.

Procedures

• Venous access
  • Large-bore intravenous (IV) or central venous access is used, especially in cases in which hemorrhage is a precipitant and blood products are likely to be required or when inotropic agents may be necessary.
  • Central venous pressure (CVP) may be helpful in monitoring intravascular volumes.
• Urethral catheterization is useful to obtain a clean urine specimen. This is especially important if the urine dipstick shows signs of infection.
• An indwelling Foley catheter indicates urine output and response to fluid therapy.
• An arterial line provides access for repeated blood draws, particularly in patients who are intubated or require admission to the ICU.
• When meningitis or subarachnoid hemorrhage is suspected, lumbar puncture (LP) is indicated. If meningitis is suspected clinically, do not withhold antibiotics while waiting for the LP to be completed.

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