Why would someone with Cushing's syndrome need glucagon and insulin tablets?

Management of Hypoglycemia in Cushing's Syndrome

Patients with Cushing's syndrome need glucagon and insulin tablets primarily to manage the risk of hypoglycemia that can occur during treatment of their diabetes mellitus, which is a common complication of chronic glucocorticoid excess.

Diabetes in Cushing's Syndrome

• Cushing's syndrome is characterized by chronic exposure to excessive glucocorticoids, which leads to insulin resistance and often diabetes mellitus 1, 2
• The high and prolonged circulating levels of glucocorticoids in Cushing's syndrome cause pleiotropic effects on peripheral tissues governing glucose homeostasis 2
• Patients with Cushing's syndrome have approximately 100% higher basal glucagon levels and 170% greater glucagon response to stimulation compared to normal controls 3
• The hyperglucagonemia contributes to the gluconeogenic and diabetogenic effects of glucocorticoids 3

Insulin Therapy in Cushing's Syndrome

• Insulin therapy is frequently needed in the acute setting of Cushing's syndrome due to the severity of insulin resistance 1
• Despite using adrenal steroidogenesis blockade medications (like metyrapone, ketoconazole) to lower cortisol levels, diabetes-specific therapy is often necessary 1
• Insulin regimens should ideally include insulin analogs rather than human insulins to minimize hypoglycemia risk 4
• Self-monitoring of blood glucose (SMBG) is essential for adjusting insulin therapy based on prevailing blood glucose levels 5

Hypoglycemia Risk and Management

• Patients on insulin therapy (even basal-only regimens) should be prescribed glucagon to treat severe hypoglycemia 4
• Hypoglycemia can occur during insulin treatment, especially when cortisol levels are being actively managed 1
• Family members and close associates should be trained in glucagon administration to prevent unnecessarily prolonged episodes of severe hypoglycemia 4
• Newer glucagon formulations (nasal glucagon, single-dose auto-injector glucagon, dasiglucagon pens) are easier to use than traditional glucagon kits 4

Treating Hypoglycemic Episodes

• For mild hypoglycemia (blood glucose <70 mg/dL or <3.9 mmol/L), patients should consume 15g of carbohydrate in the form of glucose tablets or gels 4
• High-fat foods should be avoided when treating hypoglycemia as they may slow glucose absorption 4
• If hypoglycemia is not resolved within 15 minutes, the 15g carbohydrate treatment should be repeated 4
• For severe hypoglycemia (characterized by altered mental or physical function requiring external assistance), glucagon administration is necessary 4

Monitoring Considerations

• Continuous glucose monitoring (CGM) systems that alert patients of downward glucose trends can help prevent hypoglycemia 4
• CGM data helps identify glycemic patterns and guide adjustment of insulin and other therapies 4
• Patients without access to CGM should use structured SMBG regimens, especially when using medications that can induce hypoglycemia 4
• Monitoring for potential side effects of glucagon is important, including hypokalemia which may require electrolyte monitoring, particularly in patients with cardiovascular disease 6

Long-term Management

• Definitive treatment of Cushing's syndrome (e.g., pituitary surgery) often reduces the severity of diabetes or allows for complete resolution 1, 7
• Despite resolution of Cushing's syndrome, patients may continue to exhibit insulin resistance requiring ongoing attention 1
• Other cardiovascular risk factors associated with prior Cushing's syndrome also require long-term monitoring and management 1
• Early diagnosis and treatment of Cushing's syndrome is warranted to minimize complications related to glucose metabolism 8