Hypoglycaemia in adults without diabetes mellitus is uncommon and requires systematic evaluation. While insulin-mediated causes are most prevalent, non-insulin-mediated mechanisms—particularly inborn errors of metabolism (IEMs)—are diagnostically challenging. Although IEMs are classically paediatric, adult-onset presentations are increasingly recognised, especially during catabolic stress (1,2).
A 59-year-old woman presented with recurrent symptomatic hypoglycaemia (blood glucose ~2.8–3.0 mmol/L) in both fasting and post-prandial states, worsening after a COVID-19 infection in 2024. She had no known history of diabetes mellitus, no insulin or sulfonylurea exposure, and a stable BMI of 20.3 kg/m². Continuous glucose monitoring revealed 40% time in the low range (BGL 3.0–3.8 mmol/L) and 5% time in the very low range (BGL <3.0 mmol/L). A supervised 72-hour fast was terminated at 29 hours due to symptomatic hypoglycaemia (glucose 2.3 mmol/L), with undetectable insulin, proinsulin, and low C-peptide, and elevated beta-hydroxybutyrate (3.0 mmol/L), consistent with preserved ketogenesis. Imaging (MRI pancreas, FDG-PET, DOTATATE-PET) showed no evidence of an insulinoma or neuroendocrine tumour. IGF-2–mediated hypoglycaemia was excluded based on the preserved ketotic response and absence of malignancy.
Metabolic testing between episodes, including acylcarnitine profile, lactate, urate and creatine kinase, was normal. Given her mixed fasting and post-prandial symptoms and the absence of insulin excess, rare metabolic disorders such as fatty acid oxidation defects or partial glycogen storage disorders were considered. She is awaiting review by a tertiary metabolic genetics service for further evaluation.
This case underscores the value of a structured approach to unexplained hypoglycaemia. Suppressed insulin markers and preserved ketogenesis effectively exclude insulin-mediated causes. Adult-onset inborn errors of metabolism, though often subtle, may be unmasked by stressors such as illness or fasting (2). Normal metabolic markers between episodes do not rule out partial defects (2). In such cases, early referral for genetic evaluation is key to diagnosis and management.