Diagnosis and Treatment > Medication > Glucose

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G K Dimitriadis 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

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K Gopalakrishnan Department of Histopathology, Coventry and Warwickshire, Pathology Service, UHCW NHS Trust, Coventry, UK

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R Rao 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

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D K Grammatopoulos 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

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H S Randeva 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

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M O Weickert 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

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N Murthy 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

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Summary

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.

Learning points

  • 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.

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Chiara Baratelli Dipartimento di Oncologia, Oncologia Medica

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Maria Pia Brizzi Dipartimento di Oncologia, Oncologia Medica

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Marco Tampellini Dipartimento di Oncologia, Oncologia Medica

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Giorgio Vittorio Scagliotti Dipartimento di Oncologia, Oncologia Medica

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Adriano Priola SCDU Radiologia

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Massimo Terzolo Dipartimento di Scienze Cliniche e Biologiche, Medicina Interna, Università di Torino, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Italy

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Anna Pia Dipartimento di Scienze Cliniche e Biologiche, Medicina Interna, Università di Torino, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Italy

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Alfredo Berruti Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica Università di Brescia, Oncologia Medica, Azienda Ospedaliera Spedali Civili, Brescia, Italy

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Summary

Insulinoma is a rare form of insulin-secreting pancreatic islet cell neuroendocrine (NE) tumor. The medical treatment of the malignant NE disease of the pancreas deeply changed in the last years, thanks to the introduction of new target molecules, as everolimus. Even if the exact mechanism is not actually known, one of the side effects of everolimus, hyperglycemia, has been demonstrated to be useful to contrast the typical hypoglycemia of the insulinoma. We report the case of a patient with a metastatic malignant insulinoma treated with intermittent everolimus, obtaining an important improvement in the quality of life; this suggests the necessity of preclinical studies to analyze the cellular pathways involved in insulin-independent gluconeogenesis.

Learning points

  • Effect of somatostatin analogs is long-lasting in the control of functioning NE tumors.

  • Persistent everolimus control of hypoglycemia despite serum insulin levels and disease progression.

  • Open issue: are disease progression and the increase in serum markers the only valid criteria to reject a treatment?

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Kamel Mohammedi Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Charbel Abi Khalil Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Sophie Olivier Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Imane Benabad Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Ronan Roussel Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Michel Marre Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, 46 rue Henri Huchard, 75877 Paris Cedex 18, France

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Summary

Hypoglycemia is a common medical emergency. It is the most frequent complication induced by anti-diabetic treatment. However, it can be observed in other conditions unrelated to diabetes such as insulinoma, autoimmune disorders, and neoplasia. Herein, we report the case of a rare cause of severe and recurrent hypoglycemia in a 77-year-old woman with a malignant solitary fibrous tumor (MSFT). A 77-year-old woman was admitted to the emergency department for loss of consciousness induced by severe hypoglycemia. Her standard laboratory findings were unremarkable. HbA1c, albumin, renal, liver, thyroid, and adrenal function tests were normal. Cerebral CT scan was also normal. At the time of confirmed hypoglycemia, the serum level of insulin and C-peptide was low. On the basis of the past medical history and the absence of other comment etiologies, a paraneoplastic cause was suspected. Thus, the diagnosis of a non-islet cell tumor-induced hypoglycemia (NICTH) was established by the presence of incompletely processed precursors of IGF2 (big IGF2) in plasma electrophoresis. However, the IGF1 level was low. Therapy with corticosteroids improved hypoglycemia and clinical symptoms. NICTH is a rare cause of hypoglycemia. It should be considered in patients with mesenchymal or malignant epithelial tumors suffering from recurrent episodes of hypoglycemia. The diagnosis will be established in the case of low serum insulin concentrations and elevated levels of big IGF2. Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels.

Learning points

  • NICTH is a very rare condition that should be considered in patients known to have mesenchymal or malignant epithelial tumors and suffering from recurrent episodes of hypoglycemia.

  • The diagnosis of an NICTH is established on the basis of the hypoinsulinemic hypoglycemia, the MSFT history, and the presence of paraneoplastic secretion of IGF1 or an immature form of IGF2.

  • Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels in NICTH.

Open access