title: Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke.
abstract: We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0') 390 nmol/l, Cort (30') 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period.
  
  
  CONCLUSIONS
  NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.NICTH can masquerade as other pathologies thus causing diagnostic confusion.Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.
authors.affiliation: Warwick Institute for the Study of Endocrinology Diabetes and Metabolism (WISDEM Centre), The Arden NET Centre, University Hospitals of Coventry and Warwickshire, UHCW NHS Trust, ENETS CoE , Coventry , UK ; Division of Experimental Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus , London , UK ; Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick , Coventry , UK.
authors.forename: G K
authors.initials: GK
authors.lastname: Dimitriadis
authors.affiliation: Department of Histopathology , Coventry and Warwickshire, Pathology Service, UHCW NHS Trust , Coventry , UK.
authors.forename: K
authors.initials: K
authors.lastname: Gopalakrishnan
authors.affiliation: Warwick Institute for the Study of Endocrinology Diabetes and Metabolism (WISDEM Centre), The Arden NET Centre, University Hospitals of Coventry and Warwickshire, UHCW NHS Trust, ENETS CoE , Coventry , UK.
authors.forename: R
authors.initials: R
authors.lastname: Rao
authors.affiliation: Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick , Coventry , UK ; Department of Clinical Biochemistry and Histopathology , Coventry and Warwickshire, Pathology Service, UHCW NHS Trust , Coventry , UK.
authors.forename: D K
authors.initials: DK
authors.lastname: Grammatopoulos
authors.affiliation: Warwick Institute for the Study of Endocrinology Diabetes and Metabolism (WISDEM Centre), The Arden NET Centre, University Hospitals of Coventry and Warwickshire, UHCW NHS Trust, ENETS CoE , Coventry , UK ; Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick , Coventry , UK.
authors.forename: H S
authors.initials: HS
authors.lastname: Randeva
authors.affiliation: Warwick Institute for the Study of Endocrinology Diabetes and Metabolism (WISDEM Centre), The Arden NET Centre, University Hospitals of Coventry and Warwickshire, UHCW NHS Trust, ENETS CoE , Coventry , UK.
authors.forename: M O
authors.initials: MO
authors.lastname: Weickert
authors.affiliation: Warwick Institute for the Study of Endocrinology Diabetes and Metabolism (WISDEM Centre), The Arden NET Centre, University Hospitals of Coventry and Warwickshire, UHCW NHS Trust, ENETS CoE , Coventry , UK.
authors.forename: N
authors.initials: N
authors.lastname: Murthy