Endocrine Abstracts

JOINT2334

Introduction: Chronic exposure to elevated cortisol levels in Cushing’s syndrome (CS) is known to cause insulin resistance and hyperglycemia. While remission of CS often leads to improved glycemic control, some patients continue to experience persistent diabetes. This study aims to evaluate the long-term evolution of diabetes after the resolution of hypercortisolism.

Methods: A total of 22 patients previously diagnosed with CS were followed for an average of five years after achieving remission. Glycemic parameters, including fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), were measured before and after treatment. In addition, insulin resistance (assessed using HOMA-IR) and beta-cell function (measured with HOMA-B) were evaluated. The occurrence of diabetes-related complications were also recorded.

Results: Most patients experienced a significant improvement in glycemic control following remission. On average, HbA1c decreased from 7.8% to 6.3% (P=0.004), and fasting blood glucose showed a similar decline. However, 41% of the patients (9 out of 22) remained diabetic five years after remission, with a mean HbA1c of 7.2% (±1.1%). This group displayed higher baseline cortisol levels (P=0.02) and greater insulin resistance (HOMA-IR: 4.1±0.9 vs. 2.3±0.7, P=0.01) compared to patients who regained normoglycemia. Beta-cell function was also significantly lower in these patients (HOMA-B: 49.5±13.6 vs. 76.8±14.2, P=0.03). Among those with persistent diabetes, 33% developed microvascular complications, including two cases of diabetic neuropathy, one case of nephropathy, and one case of early-stage retinopathy.

Discussion: These findings suggest that although remission of Cushing’s syndrome leads to significant improvements in glucose metabolism, a subset of patients continues to experience long-term metabolic dysfunction. The persistence of diabetes may be due to the prolonged effects of hypercortisolism on insulin sensitivity and pancreatic beta-cell function. Chronic exposure to high cortisol levels may induce irreversible metabolic changes, predisposing some patients to ongoing hyperglycemia despite normalization of cortisol levels.

Conclusion: This study highlights the importance of long-term metabolic follow-up in patients recovering from Cushing’s syndrome. While many patients experience an improvement in glycemic control, a significant proportion remains at risk for persistent diabetes and associated complications. Identifying these patients early and implementing targeted interventions, such as lifestyle modifications and pharmacological treatment, may help mitigate the long-term consequences of hypercortisolism on glucose metabolism. Further research is needed to better understand the underlying mechanisms and to develop optimized management strategies for this patient population.