Diagnostic Tests for Hyperosmolar Hyperglycemic State (HHS)
The initial laboratory evaluation for suspected HHS must include plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes (with calculated anion gap), serum osmolality, urinalysis, urine ketones by dipstick, arterial blood gases, complete blood count with differential, and electrocardiogram. 1
Essential Laboratory Tests for HHS Diagnosis
Immediate Testing (First Hour)
- Plasma glucose - typically ≥600 mg/dl in HHS
- Serum electrolytes - to calculate anion gap and corrected sodium
- Blood urea nitrogen/creatinine - to assess renal function and dehydration
- Serum osmolality - diagnostic criterion is ≥320 mOsm/kg H₂O
- Arterial blood gases - to differentiate from DKA (pH >7.3, bicarbonate ≥15 mmol/L in HHS)
- Serum ketones - minimal or absent in pure HHS (≤3.0 mmol/L)
- Complete blood count with differential - to identify infection
- Urinalysis and urine ketones - typically shows glycosuria with minimal ketonuria
- Electrocardiogram - to assess for cardiac complications
Calculated Values
- Effective serum osmolality = 2[measured Na⁺ (mEq/L)] + glucose (mg/dl)/18 1
- Corrected sodium - add 1.6 mEq to measured sodium for each 100 mg/dl glucose >100 mg/dl 1
- Anion gap - to differentiate from other metabolic disorders
Additional Testing to Identify Precipitating Factors
- Bacterial cultures (urine, blood, throat) - infection is a common precipitant 1
- Chest X-ray - to identify pneumonia or other pulmonary conditions 1
- HbA1c - useful to determine if this is an acute episode in a previously well-controlled patient or the culmination of an evolutionary process 1
Monitoring During Treatment
- Measure or calculate serum osmolality regularly to monitor response to treatment 2
- Monitor electrolytes, particularly potassium, every 2-4 hours during initial treatment 1
- Track blood glucose levels hourly until stable 1
- Monitor fluid input/output and hemodynamic parameters 1
Diagnostic Criteria for HHS
HHS is diagnosed when the following criteria are met:
- Blood glucose ≥600 mg/dl
- Arterial pH >7.3
- Serum bicarbonate >15 mEq/L
- Minimal ketonuria or ketonemia
- Effective serum osmolality ≥320 mOsm/kg H₂O
- Altered mental status or severe dehydration 1
Common Pitfalls in HHS Diagnosis
- Failure to differentiate from DKA: HHS has minimal ketosis and less acidosis compared to DKA
- Overlooking mixed DKA/HHS: Some patients may present with features of both conditions 3
- Neglecting to correct sodium for hyperglycemia: Falsely low sodium readings can occur with severe hyperglycemia
- Missing precipitating factors: Always search for underlying causes, especially infection
- Underestimating dehydration: Fluid losses in HHS are typically 100-220 ml/kg, much higher than in DKA 3
The diagnostic approach to HHS requires rapid assessment and comprehensive laboratory evaluation to guide appropriate treatment and prevent complications such as cerebral edema, osmotic demyelination syndrome, and death, which occur at higher rates in HHS compared to DKA 2.