LNSLNS

In our article we aimed to provide an overview of the numerous and very different gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). We did not aim to focus exclusively on insulin producing processes and their diagnostic evaluation. However, we will discuss this briefly in what follows.

The European Neuroendocrine Tumor Society (ENETS) guidelines for the diagnostic evaluation of insulinoma stipulate a standardized fasting attempt with preceding glucose loading and recommend measuring insulin and C-peptide. Alternatively to C-peptide, proinsulin may be measured. However, this is not required as an additional test because of the associated costs, which are substantially higher. The calcium stimulation test is done for the purposes of diagnosing the localization, and in patients with unclear hypoglycemia, measuring sulfonylureas is advisable (1).

Sporadic insulinomas have to be differentiated from multifocal insolinomatosis and adult nesidioblastosis, clinically also known as NIPHS (non-insulinoma pancreatic hypoglycemia-syndrome). NIPHS is not, as postulated by Starke et al, the same as pancreatic islet cell hyperplasia, but functional hyperactivity of the beta cells, which can manifest as beta cell hypertrophy. As both conditions have been described in detail only very recently (2, 3), clinical guidelines are lacking.

In our view, the new therapeutics, such as everolimus and sunitinib—for which a prolonged progression-free interval has been shown, and, in the case of sunitinib, prolonged mean overall survival—represent a clear advance compared with the traditional therapeutic modalities, especially for patients who do not respond to these any more. It goes without saying that these rather new therapeutics will need to be evaluated in further studies, especially in comparison to established therapies.

DOI: 10.3238/arztebl.2012.0066b

On behalf of the authors:

Prof. Dr. med. Matthias Schott

Universitätsklinik Düsseldorf

matthias.schott@med.uni-duesseldorf.de

Conflict of interest statement
Professors Schott, Knoefel, and Klöppel have received expenses from Novartis/Ibsen. The other authors declare that no conflict of interest exists.

1.
O'Toole D, Grossman A, Gross D, et al.: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology 2009; 90(2): 194–202. MEDLINE
2.
Raffel A, Krausch MM, Anlauf M, et al.: Diffuse nesidioblastosis as a cause of hyperinsulinemic hypoglycemia in adults: a diagnostic and therapeutic challenge. Surgery 2007; 141(2): 179–84. MEDLINE
3.
Anlauf M, Bauersfeld J, Raffel A, et al.: Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol 2009; 33(3): 339–46. MEDLINE
4.
Schott M, Klöppel G, Raffel A, Saleh A, Knoefel WT, Scherbaum WA: Neuroendocrine neoplasms of the gastrointestinal tract. Dtsch Arztebl Int 2011; 108(18): 305–12. VOLLTEXT
1.O'Toole D, Grossman A, Gross D, et al.: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology 2009; 90(2): 194–202. MEDLINE
2. Raffel A, Krausch MM, Anlauf M, et al.: Diffuse nesidioblastosis as a cause of hyperinsulinemic hypoglycemia in adults: a diagnostic and therapeutic challenge. Surgery 2007; 141(2): 179–84. MEDLINE
3.Anlauf M, Bauersfeld J, Raffel A, et al.: Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol 2009; 33(3): 339–46. MEDLINE
4.Schott M, Klöppel G, Raffel A, Saleh A, Knoefel WT, Scherbaum WA: Neuroendocrine neoplasms of the gastrointestinal tract. Dtsch Arztebl Int 2011; 108(18): 305–12. VOLLTEXT