From the Guidelines
Recurrent hypoglycemia in this patient with a normal ACTH stimulation test and multiple comorbidities, including cerebral palsy, seizure disorder, hypertension, hyperlipidemia, and gastroesophageal reflux disease, suggests causes unrelated to adrenal insufficiency, and a comprehensive approach is necessary to identify the underlying cause. The most common causes of recurrent hypoglycemia in such patients include medication effects, particularly insulin or insulin secretagogues like sulfonylureas, which may be inappropriately dosed or accumulated due to renal impairment 1. Other medications such as beta-blockers, ACE inhibitors, and pentamidine can also cause hypoglycemia. Nutritional factors are important considerations, including irregular eating patterns, malnutrition, or inadequate caloric intake, which may be particularly relevant in a nonverbal, wheelchair-bound patient with cerebral palsy who might have feeding difficulties.
Key considerations in managing this patient's condition include:
- Medication review to assess the potential for drug-induced hypoglycemia
- Assessment of nutritional status and feeding patterns to ensure adequate caloric intake
- Evaluation for occult infection or organ dysfunction, particularly hepatic or renal impairment, which can contribute to hypoglycemia
- Investigation into endocrine disorders such as insulinoma, non-islet cell tumors, IGF-producing tumors, or reactive hypoglycemia
- Consideration of critical illness with increased metabolic demands that may deplete glycogen stores
Given the complexity of this patient's condition, a multidisciplinary approach involving healthcare professionals from various specialties is crucial to identify and manage the underlying cause of recurrent hypoglycemia. This approach should prioritize the patient's quality of life, morbidity, and mortality outcomes, and be guided by the most recent and highest-quality evidence available, such as the standards of medical care in diabetes-2022 1.
From the FDA Drug Label
Hypoglycemia: All sulfonylureas including glyburide are capable of producing severe hypoglycemia. Renal or hepatic insufficiency may cause elevated drug levels of glyburide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose lowering drug is used.
The patient's recurrent hypoglycemia could be caused by:
- Renal or hepatic insufficiency
- Elderly, debilitated or malnourished state
- Adrenal or pituitary insufficiency
- Caloric intake deficiency
- Severe or prolonged exercise
- Alcohol ingestion
- Combination therapy with more than one glucose-lowering drug
- Beta-adrenergic blocking drugs 2
From the Research
Causes of Recurrent Hypoglycemia
- Recurrent hypoglycemia can be caused by various factors, including Sheehan's syndrome, a rare condition characterized by hypopituitarism due to postpartum hemorrhage 3.
- Insulin autoimmune syndrome (IAS) is another cause of recurrent hypoglycemia, characterized by the presence of high titers of insulin autoantibodies (IAA) 4.
- Other potential causes of recurrent hypoglycemia include insulinoma, a rare tumor of the pancreas that produces excess insulin 5.
- Certain medications, such as insulin secretagogues, can also increase the risk of hypoglycemia, particularly when used concomitantly with angiotensin-converting enzyme inhibitors (ACEIs) 6.
Diagnosis and Management
- The diagnosis of recurrent hypoglycemia requires a careful workup to exclude other causes of hyperinsulinemic hypoglycemia 5, 4.
- Laboratory tests, such as insulin and proinsulin levels, can help differentiate between intrinsic and extrinsic causes of hypoglycemia 5.
- Management of recurrent hypoglycemia depends on the underlying cause and may include dietary modifications, pharmacological therapies, and supportive measures 4.
- In patients with diabetes, management of recurrent hypoglycemia and hypoglycemia unawareness requires avoidance of hypoglycemic events and optimization of insulin therapy 7.