Reactive hypoglycemia caused by an insulinoma, pre-diabetic metabolic state, fluctuations in diabetic metabolic situation and antidiabetic medication is commonly known. We report on the case of an unusual multi-factorial occurrence of a woman with recurrent hypoglycemia, which cannot be explained adequately by a single commonly known cause. We refer to a cachectic non-diabetic 52-year-old German woman, admitted to our clinic for clarification of an insulinoma. The possibility of an insulinoma could be excluded as well as co-morbidities linked to non-diabetic hypoglycemia like sepsis, alcohol dependence liver disease, cancer or self-harm with hypoglycaemic agents. However, our diagnostics revealed a corticotrophic insufficiency as a result of longtime cortisol medication. Still, further causes have additionally to be considered, including dysfunctional elimination of glucose, renal and hepatic gluconeogenesis and glucose regulation on dialysis. These reasons are assumed as the pathological factors. Although insulinoma is a possible cause of hypoglycemia, it is not the only pathogenesis. Here, various alternatives factors are defined, examined and in part treated specifically. As therapy, besides nutritional counselling, the patient received cortisol. After a 20 month follow-up symptoms of symptomatic hypoglycemia were absent.