: Hyperinsulinaemic hypoglycaemia (HH) has traditionally been classified according to clinical response to diazoxide, with milder diazoxide responsive (DRHH) and severe unresponsive cases. Loss-of-function mutations in ATP-sensitive potassium (KATP) channel genes (ABCC8 and KCNJ11), are the commonest cause for HH. In severe HH, genetic analysis and pancreatic imaging assist in differentiating diffuse from focal forms of HH, as the latter may be cured by lesionectomy. However, these investigations have not been routinely undertaken in DRHH.
Aim: To assess the role of genetic testing and pancreatic imaging in DRHH.
Methods: We conducted a retrospective review of 54 DRHH patients treated at our centre between April 2006 and September 2009. With ethical and parental consent, genotyping was performed and 18[F]-DOPA PET-CT imaging undertaken in those with a genotype suggestive of focal HH.
Results: Fifty-two patients were genotyped and 18 (35%) had a genetic abnormality ((ABCC8 (n=13), KCNJ11 (n=2), GLUD1 (n=1), GCK (n=1) and one unbalanced translocation between chromosomes 9 and 13)). Nine patients with no mutations (n=5) or paternal heterozygous KATP mutations (n=4) underwent 18Fluoro [F]-DOPA PET-CT, identifying three focal lesions (two tracer-positive, one tracer-negative). Three patients underwent curative surgical lesionectomy. Histology confirmed non-malignant insulinomas in two patients, one with a paternal ABCC8 mutation and one who was subsequently found to have an MEN1 mutation. Thirteen patients (25%) had spontaneous resolution of disease, of whom three were mutation positive.
Conclusions: Approximately a third of DRHH patients had a genetic abnormality associated with their disease. Of 6% had a focal lesion amenable to surgical cure and a quarter had late resolution of disease, including mutation positive patients. These findings indicate that mutation screening should be performed in all DRHH patients and 18[F]-DOPA PET-CT imaging undertaken in those with a genotype consistent with a focal lesion, as DRHH does it preclude the possibility of a surgical cure.