MON-489 The role of hypoxia-induced cortisol reduction in nondiabetic hypoglycemia

Abstract Disclosure: O. Samburskaya: None. S. Kalinchenko: None. L. Vorslov: None. T. Sviderskaya: None. V. Chepykova: None. Annotation: Hypoglycemia caused by the presence of prolonged hypoxia is associated with reduced steroidogenesis, resulting in decreased synthesis of cortisol- a key counter-regulatory hormone essential for maintaining glucose homeostasis, and supporting the body’s response to stress. Materials and methods: The study included 10 non-diabetic patients aged 25 to 40 years (average age 31.8±7.66 years; 9 female, 1 male) who exhibited signs of hypoglycemia, manifested mainly in the evening. Steroid hormone levels were assessed using a steroid analysis in saliva via mass spectrometry. Blood glucose levels were determined using the FreeStyle Libre continuous glucose monitoring system. Hypoxia was determined by serum ferritin levels. The results: Ferritin levels in all 10 patients below 45 ng/ml, ranging from 25 to 42 ng/ml (average: 34±8.67 ng/ml). All 10 patients showed signs of hypoglycemic episodes after 19:00, including tremor, tachycardia, cold sweats, and intense hunger. Salivary steroid analysis showed cortisol and cortisone levels below their respective reference ranges (700-2,200 pg/mL and 27,400-39,200 pg/mL). Continuous glucose monitoring showed glucose levels falling below 3.0 mmol/L during symptomatic episodes. Patients were treated with weekly intravenous iron infusions for one month. After one month of treatment, all patients showed normalization of glucose levels on the FreeStyle Libre system and resolution of hypoglycemic symptoms. Discussion: Steroidogenesis, specifically synthesis of glucocorticoids, relies on cytochrome enzymes which contain iron-dependent heme groups for proper function. In iron deficiency, activity of these enzymes is impaired, disrupting glucocorticoid production in the adrenal gland. Cortisol, a critical hormone in stress regulation and counter-regulation of insulin, becomes depleted in response to daily stressors. This depletion, particularly during the second peak of cortisol synthesis in the evening, results in insufficient counter-regulatory effects and relative insulin activity, which contributes to this development of hypoglycemic episodes. Iron repletion restores cytochrome function, enabling steroidogenesis and glucocorticoid synthesis, which in turn counterbalances insulin and restores normal blood glucose levels. Conclusion: Correction of iron deficiency resolves hypoxia-induced disruptions in steroidogenesis, which restores adrenal hormone synthesis and increases levels of cortisol and cortisone. This recovery reestablishes stress-regulation and counter-regulatory effects, stabilizing blood glucose levels and preventing hypoglycemic events. Presentation: Monday, July 14, 2025