Spontaneous hypoglycemia: should we mind the gap? Long-term follow-up of healthy people who met Whipple's triad criteria.

Context: Patients discharged as "healthy" with the symptoms of spontaneous hypoglycemia, commonly known as Whipple's triad, need more attention.

Objective: Characterization and long-term follow-up of symptom development in patients with spontaneous hypoglycemia discharged as "healthy". The objective was to ascertain whether any conditions related to the symptoms were diagnosed during the follow-up period.

Methods: Retrospective analysis of patient data and evaluation of a specific questionnaire on the development of symptoms of spontaneous hypoglycemia. In addition, patient questionnaires were evaluated and primary care physicians were asked about possible diseases not recorded at baseline that occurred during the follow-up period.

Setting: Center for Endocrinology, Diabetology, and Osteology at the University Hospital Marburg, Inpatient Department, Germany.

Patients: All patients who presented to our center for the 72-hour fast between 2005 and 2018 and were discharged without an internal medicine diagnosis were included.

Interventions: Survey by questionnaire, via telephone interview.

Main outcome measures: Patient-reported information on current symptoms compared to original symptoms, diagnosis of insulinoma or diabetes mellitus during follow-up, matched with primary care physician data, and metabolic and biometric data such as body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA IR), insulin sensitivity Matsuda Index (ISI-M), and area under the curve.

Results: A total of 41 datasets were evaluated at baseline and 38 patients were followed for an average of approximately 10 years. In total, 61% of respondents still reported the same symptoms as at baseline. No insulinoma was missed in these patients. Only two of the 38 patients developed diabetes mellitus.

Conclusion: The high percentage of patients who are discharged as "healthy" and still have symptoms after many years is disturbing. It is possible that the symptoms are not due to low blood glucose. We urge caution with use of the term "healthy". We advocate a multidisciplinary therapeutic approach after an organic cause of hypoglycemia has been ruled out. Psychosomatic treatment seems to be useful. In addition, more research should be conducted on this topic.