Patient Presentation
A 41-year-old male was admitted for elective nephrectomy for 3.8 cm renal mass. The patients had a medical history of end-stage renal disease (ESRD) on intermittent hemodialysis (iHD) secondary to lupus nephritis, heart failure with reduced ejection fraction, and chronic pain managed with methadone. Post-surgery, the patient had persistent hypoglycemia with point-of-care (POC) blood glucose levels ranging from 50 to 70 mg/dL, along with symptoms of lightheadedness and dizziness that were improved with food intake.

Medical History and Previous Evaluation
Medical records showed multiple POC blood glucose levels between 40 and 60 mg/dL and a documented value of 62 mg/dL on formal blood draw. The patient was advised to monitor his blood glucose levels, but had no access to a glucometer. He had intermittent episodes of weakness and presyncope during the past year that was alleviated by food. He denied nocturnal hypoglycemia, unintentional weight loss, hyperpigmentation, a history of diabetes or bariatric surgery, and any exposure to insulin or oral hypoglycemics.

 Medication and Substance Use History
The patient had a 20-year history of prednisone use at varying doses (5–60 mg daily), self-discontinued over one year before admission. He denied use of NSAIDs and antibiotics due to his renal disease. He was maintained on a stable methadone dose of 175 mg daily for chronic pain and had no family history suggestive of endocrine tumors.

Clinical Examination and Initial Workup
The patient had normal heart rate, afebrile status, and systolic BP ranging between 90 and 100 mmHg. The patient underwent adrenocorticotropic hormone (ACTH) stimulation test because of concern for secondary adrenal insufficiency after abrupt cessation of long-term glucocorticoid therapy. The test ruled out adrenal insufficiency.

Hypoglycemia Evaluation
A 72-hour fast was initiated during which dextrose was withheld. Five hours into the fast, the patient developed symptomatic hypoglycemia with POC glucose of 46 mg/dL and confirmatory serum glucose of 56 mg/dL. Insulin and c-peptide levels were elevated at 20.2 uU/mL and 8.1 ng/mL, respectively. These results were consistent with endogenous hyperinsulinemic hypoglycemia.

Initial Management and Outpatient Planning
The patient was started on diazoxide 50 mg twice daily and a nightly dose of cornstarch. Methadone was considered a possible contributor to his hypoglycemia; however, the patient opted to continue the medication. With this regimen, he remained euglycemic for over 48 hours without intravenous glucose and was discharged.

Recurrent Hypoglycemia and Multidisciplinary Reevaluation
After two months, the patient returned with abdominal pain, nausea, vomiting, and recurrent hypoglycemia. He had poor oral intake and medication non-adherence due to persistent emesis. A multidisciplinary team designed a structured, 10-day inpatient protocol to transition the patient from methadone to buprenorphine/naloxone, with contingency medications including ketamine, clonidine, and hydroxyzine.

Clinical Course and Outcome
On day six of the protocol, methadone was halved. By day seven, the patient was fully transitioned off methadone and was discharged several days later after maintaining euglycemia for over 48 hours without pharmacologic support.
At follow-up, the patient reported fasting blood glucose readings between 110 and 130 mg/dL with no pre-syncopal symptoms. His chronic pain was controlled with buprenorphine/naloxone.