Metachronous hormonal syndromes in patients with pancreatic neuroendocrine tumors: a case-series study.

Abstract

BACKGROUND:

Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion-related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described.

OBJECTIVE:

To describe MHSs in patients with sporadic PNETs.

DESIGN:

Retrospective, multicenter study.

SETTING:

4 French referral centers.

PATIENTS:

Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014.

MEASUREMENTS:

Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling.

RESULTS:

Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs.

LIMITATION:

Retrospective data collection and heterogeneity of pathologic specimen size and origin.

CONCLUSION:

Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates.

PRIMARY FUNDING SOURCE:

None.

• Authors: Louis de Mestier, Olivia Hentic, Jérôme Cros, Thomas Walter, Guillaume Roquin, Hedia Brixi, Catherine Lombard-Bohas, Pascal Hammel, Marie-Danièle Diebold, Anne Couvelard, Philippe Ruszniewski, Guillaume Cadiot
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 162 Issue 10 Pg. 682-9 (May 19 2015) ISSN: 1539-3704 [Electronic] United States
• PMID: 25984844 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Biomarkers, Tumor
• Gastrins
• Hormones
• Insulin
• Ki-67 Antigen
• Vasoactive Intestinal Peptide
• Glucagon

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Disease Progression
• Female
• Gastrins (metabolism)
• Glucagon (metabolism)
• Hormones (metabolism)
• Humans
• Insulin (metabolism)
• Insulin Secretion
• Ki-67 Antigen (analysis)
• Male
• Middle Aged
• Pancreatic Neoplasms (metabolism, pathology)
• Retrospective Studies
• Syndrome
• Vasoactive Intestinal Peptide (metabolism)