How can I diagnose Hyperosmolar Hyperglycemic State (HHS) in a patient with a history of diabetes who presents to the office?

Testing for Hyperosmolar Hyperglycemic State (HHS) in the Office

If you suspect HHS in a patient with diabetes presenting to your office, immediately obtain point-of-care glucose and arrange urgent transfer to the emergency department—HHS is a medical emergency requiring hospitalization, not office-based management. 1, 2

Immediate Office Assessment

Point-of-Care Testing

• Measure fingerstick blood glucose immediately—HHS requires glucose ≥600 mg/dL for diagnosis 2, 3
• Check urine ketones by dipstick—HHS shows small or absent ketones (unlike diabetic ketoacidosis) 1, 2
• If available, measure blood pressure and assess mental status, as altered consciousness correlates with hyperosmolarity severity 2, 4

Clinical Red Flags Requiring Emergency Transfer

• Blood glucose ≥600 mg/dL with any degree of dehydration 2, 3
• Altered mental status ranging from confusion to lethargy or coma 2, 4
• Severe dehydration (dry mucous membranes, poor skin turgor, tachycardia, hypotension) 5, 6
• History of polyuria, polydipsia, and weight loss developing over days to weeks 2, 6

Why Office Testing is Insufficient

HHS cannot be fully diagnosed or managed in the office setting because it requires comprehensive laboratory evaluation and intensive monitoring. 1, 2 The complete diagnostic workup mandated by the American Diabetes Association includes:

Required Laboratory Tests (Hospital-Based)

• Plasma glucose (not just fingerstick) 1, 2
• Serum electrolytes with calculated anion gap to distinguish from diabetic ketoacidosis 1, 2
• Calculated effective serum osmolality: 2[measured Na (mEq/L)] + glucose (mg/dL)/18, with threshold ≥320 mOsm/kg H₂O required for HHS diagnosis 2, 6
• Arterial blood gases to confirm pH ≥7.30 (distinguishing from DKA) 2, 3
• Serum bicarbonate (must be ≥15 mEq/L for HHS) 2, 3
• Blood urea nitrogen and creatinine to assess renal function and dehydration severity 1, 2
• Complete blood count with differential 1, 2
• Serum ketones (preferably β-hydroxybutyrate, not just urine ketones) to confirm minimal ketonemia ≤3.0 mmol/L 2, 6
• Electrocardiogram 1, 2
• HbA1c to determine if this represents acute decompensation versus chronic poor control 1, 2

Additional Testing Based on Clinical Suspicion

• Bacterial cultures (blood, urine, throat) if infection suspected—infection is the most common precipitating factor 1, 2
• Chest X-ray if pneumonia suspected 1, 2
• Cardiac enzymes if myocardial infarction suspected as precipitant 2, 3

Diagnostic Criteria Summary

HHS is definitively diagnosed when ALL of the following metabolic criteria are met: 2, 3, 6

• Blood glucose ≥600 mg/dL
• Effective serum osmolality ≥320 mOsm/kg H₂O
• Arterial pH ≥7.30
• Serum bicarbonate ≥15 mEq/L
• Small or absent ketones (ketonemia ≤3.0 mmol/L)
• Altered mental status or severe dehydration (though patients meeting metabolic thresholds warrant HHS management even if fully alert) 2, 7

Critical Pitfall to Avoid

Do not attempt to manage suspected HHS in the office setting. 2, 3 HHS has mortality rates up to 15% and requires:

• Intensive care unit admission for most patients 2, 3
• Continuous intravenous insulin infusion (not subcutaneous sliding scale) 3, 6
• Aggressive fluid resuscitation (15-20 mL/kg/h initially, with total deficits of 100-220 mL/kg) 2, 3, 6
• Frequent laboratory monitoring every 2-4 hours 3, 6
• Careful osmolality correction (not exceeding 3-8 mOsm/kg/h to prevent central pontine myelinolysis) 2, 5, 6

Office Action Plan

When HHS is suspected based on glucose ≥600 mg/dL and clinical presentation: 2, 4

1. Call 911 or arrange immediate emergency department transfer
2. Do not give insulin in the office (fluid resuscitation takes priority and premature insulin may be detrimental) 5, 6
3. Document precipitating factors: recent infections, medications (corticosteroids, thiazides, SGLT2 inhibitors), stroke, or myocardial infarction 1, 2
4. Communicate suspected HHS diagnosis to receiving emergency department

Distinguishing HHS from Other Conditions

HHS differs from diabetic ketoacidosis (DKA) in key ways: 2, 7, 6

• DKA: glucose ≥250 mg/dL, pH <7.3, bicarbonate <15 mEq/L, moderate-to-large ketones
• HHS: glucose ≥600 mg/dL, pH ≥7.3, bicarbonate ≥15 mEq/L, minimal ketones
• HHS develops over days to weeks versus DKA developing over hours to days 2, 5

Other conditions to consider with high anion gap acidosis: 1

• Starvation ketosis (glucose rarely >250 mg/dL, bicarbonate usually ≥18 mEq/L)
• Alcoholic ketoacidosis (variable glucose, can be hypoglycemic)
• Lactic acidosis, salicylate toxicity, methanol/ethylene glycol ingestion, chronic renal failure