Non-Islet Cell Tumour Hypoglycemia

López-Gallardo, Gema; Oulad Ahmed, Bothayna; Soto Moreno, Alfonso

doi:10.1016/j.medcle.2023.05.024

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We describe a patient with NICTH caused by RCC and we conducted a literature search in PUBMED from 2018 to 2023 including the following terms (non-islet cell tumour induced hypoglycaemia) AND (IGF2 induced hypoglycaemia). A 56-year-old male with history of locally advanced RCC and under treatment with pembrolizumab and axitinib was admitted to the emergency department for a low level of consciousness and a blood sugar level of 24mg/dl (1.33mmol/L). Routine clinical laboratories were all within normal limits. The serum level of growth hormone (GH) was normal. Serum cortisol secretion and adrenocorticotropic hormone were normal. Despite marked hypoglycemia (30mg/dl), the serum insulin level was less than 0.2μIU/mL (normal range: 2.6–24.9) and the C-peptide level was 0.33ng/mL (normal range: 1.1–4.0nmol/L) and beta-hydroxybutyrate 51μmol/L (20.00–270.00). Antibodies against insulin and against insulin receptor were negative. The serum IGF-II level was 668ng/mL (normal range: 350–1000ng/mL), and the IGF-I level was less than 31ng/ml (15–225), IGF-II: IGF-I ratio was 21 (reference range<10), confirming a diagnosis of non-islet cell hypoglycemia.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> Computed tomographic (CT) scan revealed progression in the volume of the right renal-hepatic mass, liver metastasis, pulmonary and right bronchopulmonary adenopathies and progression of bone metastasis and peritoneal implants. It was initiated an intravenous destroxe infusion and 30mg of prednisone per day. Despite these measures, the nocturnal hypoglycemia persisted and was recommended 30g of cornstarch at night. A flash glucose monitor was implanted to set alarms and prevent hypoglycemia. Since the patient was receiving immunotherapy as treatment, a differential diagnosis between insulin autoimmune and IGF II-mediated hypoglycemia was necessary.In IGF II-mediated hypoglycaemia, the diagnosis is supported by the detection of low serum concentrations of insulin, proinsulin and C-peptide with normal or elevated serum IGFII and negative anti-insulin antibodies. In contrast, the insulin, proinsulin, C-peptide and anti-insulin antibodies will be high in autoimmune insulin-mediated hypoglycaemia.Tumours producing hypoglycemia are classified into insulin-producing tumours and the much less-common non-islet cell tumours. NICTH is a rare syndrome with nearly 290 cases reported in the English language medical literature in the past quarter century. Hypoglycemia can be the initial symptom, in other cases, it might develop when distance metastasis has occurred, as in our case. Pro-IGF-II precursors (known as big IFG-II) are associated with NICTH and formed due to abnormal processing of the precursor in tumours with aberrant IGF-II gene transcription and gene expression.Although many reported cases of NICTH detail high IGF-II levels, low and normal IGF-II levels are also reported. In our case, despite the patient had IGF II levels within normal limits, a suppressed IGF-I levels and a IGF-II/IGFI ratio>10 suggested NICTH.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>Tumours of mesenchymal or hepatic origin are most commonly described with NICTH, although it is now recognized that a wide variety of tumour types can result in production of big IGF-II. To our knowledge, RCCs causing NICTH have only been reported in few cases.<a class="elsevierStyleCrossRefs" href="#bib0040">3–5</a>In patients in whom surgery is possible, removal of the tumour can cure hypoglycemia. However, surgery was not possible in this patient due to advanced metastatic disease. In this case, in addition to prednisone and dextrose perfusion, glucose sensor implantation was a useful tool to prevent severe hypoglycemia.Ethical considerationsVerbal informed consent.FundingNo.Conflict of interestNo." "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.W. de Groot" 1 => "B. Rikhof" 2 => "J. van Doorn" 3 => "H.J. Bilo" 4 => "M.A. Alleman" 5 => "A.H. Honkoop" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1677/ERC-07-0161" "Revista" => array:6 [ "tituloSerie" => "Endocr Relat Cancer" "fecha" => "2007" "volumen" => "14" "paginaInicial" => "979" "paginaFinal" => "993" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18045950" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Dynkevich" 1 => "K.I. Rother" 2 => "I. Whitford" 3 => "S. Qureshi" 4 => "S. Galiveeti" 5 => "A.L. Szulc" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/er.2012-1033" "Revista" => array:6 [ "tituloSerie" => "Endocr Rev" "fecha" => "2013" "volumen" => "34" "paginaInicial" => "798" "paginaFinal" => "826" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23671155" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal cell carcinoma with non-islet cell tumor hypoglycemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.S. Fernando" 1 => "S.J. Hawkyard" 2 => "P. Poon" 3 => "M. Musa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1442-2042.2006.01452.x" "Revista" => array:5 [ "tituloSerie" => "Int J Urol Off J Jpn Urol Assoc" "fecha" => "2006" "volumen" => "13" "paginaInicial" => "985" "paginaFinal" => "986" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypoglycaemia caused by secretion of insulin-like growth factor 2 in a primary renal cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Berman" 1 => "S. Harland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/clon.2001.9291" "Revista" => array:5 [ "tituloSerie" => "Clin Oncol R Coll Radiol G B" "fecha" => "2001" "volumen" => "13" "paginaInicial" => "367" "paginaFinal" => "369" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypoglycemia caused by recurrent renal cell carcinoma as result of production of high molecular weight insulin-like growth factor 2" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Kimura" 1 => "K. Mitsuzuka" 2 => "S. Yamada" 3 => "Y. Kaiho" 4 => "M. Watanabe" 5 => "Y. Ikeda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2013.49.5374" "Revista" => array:5 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2016" "volumen" => "34" "paginaInicial" => "e120" "paginaFinal" => "e122" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016100000008/v1_202310190859/S2387020623004138/v1_202310190859/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016100000008/v1_202310190859/S2387020623004138/v1_202310190859/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623004138?idApp=UINPBA00004N"]

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Vol. 161. Issue 8.

Pages 364-365 (October 2023)

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