SAT-022 - Diabetes Remission Following Surgical Cure of ACTH-Dependent Cushing Syndrome

Introduction
Type 2 diabetes mellitus (T2DM) is a common comorbidity of ACTH-dependent Cushing syndrome (ADCS) mediated by insulin resistance and beta cell impairment that may persist after surgical remission. However, there are few real-world data about predictors and postoperative time to resolution of T2DM.

Design
We retrospectively studied 36 adults with pathology proven ACTH-dependent Ectopic ACTH syndrome (EAS) or Cushing disease (CD, n=25) complicated by T2DM who achieved surgical remission from 1/2008 to 12/2025 and were discharged on hydrocortisone 10 – 12 mg/M2/d. T2DM was defined as HbA1c ≥6.5%, fasting plasma glucose (FPG) ≥125 mg/dl, and/or use of T2DM therapy. Patients (pts) were evaluated at baseline diagnostic visit and during the surgical visit (n=36). Thirty had follow-up at 6, and/or 12 months later. Resolution of T2DM was defined as appropriate discontinuation of medications (meds) with normal FPG and/or HbA1c < 6.5% off all medications. A decrease in medical management was defined as a decrease in number of medications and/or decrease in dosage.

Main Results
At baseline, mean A1c was 7.81.8 (range 6.2 – 13.8), FPG 146.460.4 mg/dL (71-303). Meds included insulin (n=12), metformin with (n=3) or without insulin in 16, and sulfonylureas, DPP-4 or SGLT2 inhibitors, and GLP1 agonists. At surgical discharge, the number of anti-diabetic meds decreased from 1.8+0.9 to 0.9+0.8 (p < 0.0001): 13 pts required none; 5 had no change, 13 decreased dose (n=7), or number of medications (n=4), or both (n=2). Three decreased dose and/ or changed to insulin and one changed oral meds. At 6 mo another 8 patients were off meds (19/29); 5 decreased the number or dose of meds, including one with a daily insulin dose from 340 to 125 units; and 4 had an increase or change in a single oral agent (n=3), or no change. One pt required no meds at 12 mo, and the pt with an initial insulin requirement of 340 units had an A1c of 6.1. Age, sex, race, BMI, disease type (CD vs EAS), duration of CS or of diabetes, A1c at the time of surgery, use of insulin, did not predict remission at 1 year.

Interpretation/Conclusion

All patients with ADCS demonstrated improvement in diabetes following curative surgery by reduction in medication number/dose, insulin requirement, and A1c improvement, with many (36%) showing improvement immediately post-operatively, and again by 6 (66%) and 12 (69%) months. Thus, it is important to closely monitor glucose status following cure of ADCS.

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