Can Cushing's Syndrome Cause Blood Sugar Fluctuations?
Yes, Cushing's syndrome directly causes significant blood sugar fluctuations and abnormalities, with glucose metabolism disturbances occurring in up to 80% of patients, primarily manifesting as elevated postprandial (after-meal) glucose levels that may be missed by fasting glucose measurements alone. 1, 2
Mechanism of Blood Sugar Dysregulation
Excess cortisol in Cushing's syndrome disrupts glucose metabolism through multiple pathways:
- Increased hepatic gluconeogenesis produces more glucose from non-carbohydrate sources 3, 4
- Peripheral insulin resistance impairs glucose uptake in muscle and adipose tissue, reducing the body's ability to clear glucose from the bloodstream 3, 4
- Impaired insulin secretion from the pancreas fails to compensate adequately for the increased insulin resistance 4
- Increased lipolysis releases free fatty acids that further worsen insulin resistance 3
Characteristic Pattern of Glucose Abnormalities
The blood sugar fluctuations in Cushing's syndrome follow a distinctive pattern that differs from typical diabetes:
- Postprandial glucose elevation is disproportionate to fasting glucose levels, meaning blood sugar spikes dramatically after meals while fasting levels may appear deceptively normal 5
- Fasting plasma glucose can be paradoxically lower than expected relative to HbA1c levels (the FPG/HbA1c ratio is significantly reduced in Cushing's patients) 5
- Up to 50% of Cushing's patients develop frank diabetes mellitus, though many others have impaired glucose tolerance without meeting full diabetes criteria 6
Critical Diagnostic Pitfall
Do not rely on fasting glucose alone to assess glucose metabolism in suspected Cushing's syndrome. 5
- An oral glucose tolerance test (OGTT) should be performed in all Cushing's patients, as fasting glycemia may be normal even when significant postprandial hyperglycemia exists 6, 5
- The 2-hour post-glucose load plasma glucose is significantly elevated in non-diabetic Cushing's patients compared to controls, despite similar fasting glucose levels 5
Clinical Implications
The glucose abnormalities in Cushing's syndrome contribute substantially to cardiovascular morbidity and mortality:
- Glucose abnormalities exceed 80% prevalence in Cushing's syndrome cohorts, mimicking severe metabolic syndrome 1, 2
- These metabolic derangements persist as a source of significant morbidity and mortality even after successful treatment of the underlying Cushing's syndrome 4
- The combination of hyperglycemia with other Cushing's features (hypertension, central obesity, dyslipidemia) creates a particularly high cardiovascular risk profile 3
Exogenous Glucocorticoid Consideration
Exogenous corticosteroid administration produces identical glucose metabolism effects:
- The FDA recognizes that corticosteroids cause "decreased carbohydrate tolerance" and "manifestations of latent diabetes mellitus" 7
- Patients on chronic glucocorticoid therapy have "increased requirements for insulin or oral hypoglycemic agents" 7
- This represents the most common cause of Cushing's syndrome overall and should always be excluded first 8