A 59-year-old woman is brought to the emergency department by her husband due to increasing fatigue and drowsiness for the past week. The patient has also been urinating frequently with several episodes of incontinence. Medical history is significant for type 2 diabetes mellitus, primary hypothyroidism, and bipolar disorder. Four weeks ago, the patient was prescribed olanzapine for refractory depression. Temperature is 36.7 C (98.1 F), blood pressure is 110/65 mm Hg, pulse is 100/min, and respirations are 12/min. Physical examination shows dry mucous membranes and decreased skin turgor. The patient is confused and disoriented but moves all extremities on command. There is no nuchal rigidity. The rest of the examination is unremarkable. Which of the following tests is most likely to reveal the underlying cause of this patient's symptoms?
Hyperosmolar hyperglycemic state | |
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Clinical | Subacute or acute onset of:
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This patient has altered mental status (eg, confusion), volume depletion (eg, dry mucous membranes, decreased skin turgor), and polyuria in the setting of type 2 diabetes mellitus; hyperosmolar hyperglycemic state (HHS) is the most likely cause. HHS can be triggered in patients with type 2 diabetes mellitus by use of atypical antipsychotics, such as olanzapine; these drugs can cause hyperglycemia acutely, possibly due to decreased insulin secretion or signaling, or chronically due to weight gain and insulin resistance.
Patients with suspected HHS should have an urgent serum chemistry profile, which shows markedly elevated serum glucose (often >600 mg/dL) and can be used to calculate the anion gap (typically normal, unlike in diabetic ketoacidosis) and serum osmolality (typically >320 mOsm/L). Urinalysis typically demonstrates absent ketones.
(Choice A) Adrenal insufficiency can cause fatigue and dehydration. However, altered mentation is typically a sign of severe disease (eg, adrenal crisis), which would be accompanied by marked hypotension. This patient's blood pressure is within normal limits.
(Choice B) Hypoxia (eg, due to pneumonia, pulmonary embolus) can cause acute alterations in mental status. However, this patient has no symptoms (eg, chest pain, cough, dyspnea) or signs (eg, tachypnea, abnormal lung examination) to suggest an acute respiratory disorder.
(Choices C and D) Severe systemic infection (eg, sepsis, meningitis) can cause altered mentation but is less likely in this patient who lacks expected signs of bacteremia (eg, fever, rigors, hypotension) or meningitis (eg, nuchal rigidity, headache).
(Choice F) Hypothyroid crisis (myxedema coma) can cause altered mentation; however, this patient does not have the expected features of hypothermia, bradycardia, hypoventilation, and hypotension.
(Choice G) Drug toxicity can be associated with confusion and altered mental status, and risk for overdose (eg, potential suicide attempt) is higher in patients with refractory depression. However, this patient's weeklong course of symptoms is not typical for drug overdose, which typically manifests rapidly (eg, minutes to hours). Moreover, expected anticholinergic features of olanzapine overdose (eg, pupillary changes, extrapyramidal adverse effects such as dystonia, urinary retention) are absent.
Educational objective:
Hyperosmolar hyperglycemic state (HHS) is characterized by altered mental status and volume depletion, marked hyperglycemia (>600 mg/dL) and hyperosmolarity, and absence of ketones. Olanzapine, an atypical antipsychotic, is a potential trigger for HHS because it can precipitate hyperglycemia and metabolic derangements.