Endocrine Abstracts

AKT serine-threonine kinases are critical mediators of both growth and metabolic actions of insulin. AKT2 is believed to exert predominantly metabolic effects, while AKT1 has been more strongly implicated in growth. We have recently reported that the de novo AKT2 p.Glu17Lys mutation produces a sporadic syndrome of severe persistent hypoinsulinaemic hypoglycaemia associated with left-sided hemihypertrophy. Glucose requirements in affected patients are far lower than seen in hyp...

Background: Phosphatidylinositol-3-kinase (PI3K) is a critical mediator of insulin action, and influences cellular growth, survival and metabolism. Recently, somatic gain-of-function mutations in the p110α catalytic subunit of PI3K (PIK3CA) have been found in a spectrum of overgrowth disorders, outlining the possibility of treatment with inhibitors of the PI3K–AKT–mTOR pathway.Methods/Results: A 37-year-old female, presented with life-long...

Introduction: We recently reported cases of segmental overgrowth due to mosaic heterozygous activating mutations in the p110α catalytic subunit of PI3K. The index case presented with life-long, massive overgrowth of both legs with a lean upper body. Mobility was threatened by continued growth. mTORC1 inhibition has been effective at slowing excess growth due to loss of PTEN function, a negative regulator of PI3K. We hypothesised that mTORC1 inhibition would also be effect...