Severe paraneoplastic hypoglycemia secondary to a gastrointestinal stromal tumour masquerading as a stroke

Abstract

SummaryWe 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.Learning pointsNICTH 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.

Severe Non-Islet Cell Hypoglycemia From Ileum-Origin Gastrointestinal Stromal Tumor Producing Insulin-Like Growth Factor-2 in a Patient With Liver Cirrhosis Due to Chronic Hepatitis B

“…It is unlikely that hypothyroid influenced the hypoglycemia in our case because the hypothyroid was latent. Therefore, we next suspected NICTH due to GIST, although GIST related-NICTH is very rare [ 13 - 16 ]. As expected, additional immunohistochemical staining with an anti-IGF-2 antibody of the resected tumor tissues was positive, which strongly suggested GIST related-NICTH.…”

“…It has been reported that steroid therapy is beneficial for the prevention of hypoglycemia by NICTH [ 5 , 13 , 14 , 20 ]. We decided to administer the steroid despite the fact that our patient had chronic hepatitis B, for which steroid could affect the reactivation, because the HBV-PCR had been inhibited to the value below the detection limit likely due to continuous entecavir therapy.…”

Paraneoplastic endocrine syndromes

“…In contrast, the great majority of endocrine PNS produced from non-endocrine neoplasms are found in highly malignant tumours mainly involving the lungs, breasts, prostate, ovaries, skin, colon and certain forms of haematological malignancies; however, tumours arising from virtually any tissue have been implicated, albeit rarely (Lorch et al 2007, Nimalasena et al 2008, Gilmore et al 2009, Nella et al 2014, Dimitriadis et al 2015, Thajudeen et al 2016.…”

“…Tumour autoimmune hypoglycaemia may also occur secondary to insulin receptor auto-antibody production, whereas excessive tumour burden with glucose consumption, massive tumour liver infiltration, and pituitary or adrenal gland destruction by the tumour are the other mechanisms in cases of large and aggressive neoplasias (Iglesias & Diez 2014). Non-islet cell tumour hypoglycaemia (NICTH) presents as recurrent or constant hypoglycaemic episodes and mostly affects elderly patients with advanced tumours (Teale & Wark 2004, Dimitriadis et al 2015. Occasionally, these hypoglycaemic episodes can predate the diagnosis of the underlying tumour (Nayar et al 2006, Kim et al 2016.…”

A Successfully Treated Case of Gastrointestinal Stromal Tumor Causing Severe Anemia and Localized Peritonitis Showing Angina Pectoris Resulting in Watershed Cerebral Infarction

“…Gastrointestinal stromal tumors (GISTs) are defined as stromal tumors of the gastrointestinal tract, with a spindle cell, epithelioid, or occasionally pleomorphic morphology, which are potentially malignant [ 2 ]. The predominant localization for GISTs is the stomach (60%) and small intestine (20–30%).…”