Management of non-islet-cell tumor hypoglycemia: a clinical review

J Clin Endocrinol Metab. 2014 Mar;99(3):713-22. doi: 10.1210/jc.2013-3382. Epub 2013 Dec 11.


Context: Non-islet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome in which a tumor secretes high molecular weight IGF-II, causing hypoglycemia. Complete tumor resection is curative but is often delayed or unfeasible. There is no clear "standard of care" for managing these patients.

Evidence acquisition: PubMed searches were conducted for: "non-islet-cell tumor hypoglycemia," "NICTH," "Doege-Potter," "Doege-Potter syndrome," "high molecular weight IGF-II," and "big IGF-II." Relevant articles were reviewed in detail. We limited our review to English-language articles, focusing on 1988-2013 (corresponding with the elucidation of the pathophysiology of NICTH).

Evidence synthesis: The available literature exists as case reports or small case series, with a void of higher-order treatment studies. Thus, an evidence-based approach to data synthesis was difficult. Nevertheless, the available literature is presented objectively with an attempt to describe clinically useful trends and findings in the management of NICTH.

Conclusions: Appropriate identification of NICTH and prompt and complete tumor resection represents ideal management. However, when prompt resection is not feasible, iv glucose or dextrose often does not suffice to prevent hypoglycemia. In such cases, we suggest consideration of local antitumor therapies for disease control and trial of glucocorticoids alone or in combination with GH. Continuous glucagon infusion can be successful if the patient has a positive response to a glucagon stimulation test, and parenteral nutrition may allow higher glucose delivery, but both are limited by the need for continuous iv infusion. Diazoxide and octreotide have no role in NICTH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Hypoglycemia / diagnosis
  • Hypoglycemia / epidemiology
  • Hypoglycemia / etiology*
  • Hypoglycemia / therapy*
  • Islets of Langerhans / pathology
  • Pancreatic Neoplasms / complications*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / therapy*
  • Paraneoplastic Syndromes / diagnosis
  • Paraneoplastic Syndromes / epidemiology
  • Paraneoplastic Syndromes / therapy*