Metachronous hormonal syndromes rare but ominous with neuroendocrine tumors

Last Updated: 2015-05-21

By Reuters Staff

NEW YORK (Reuters Health) - Metachronous hormonal syndromes (MHSs) that occur after the diagnosis of pancreatic neuroendocrine tumors (PNETs) are rare, but they often signal progression of PNETs and decrease survival, according to new research.

MHSs have not been well described to date, so Dr. Guillaume Cadiot, from Robert-Debre University Hospital, Reims, France, and colleagues from four French referral centers reported their experience with the clinical and pathological characteristics of patients with sporadic PNETs who developed MHSs.

Their retrospective study included 16 MHSs identified in 15 of 435 patients (3.4%). Biopsy specimens of the PNETs showed well-differentiated tumors in all patients.

The MHSs showed hypersecretion of insulin in five patients, gastrin in two patients, vasoactive intestinal peptide in five patients, and glucagon in four patients. They developed a median 55 months (range 7 to 219 months) after the initial PNET diagnosis.

Retrospective assessment of the original PNET pathology specimens showed positivity for the hormone that would later cause MHSs in eight of 14 cases tested, according to the May 19 Annals of Internal Medicine report.

"Our observations suggest that MHSs represent a turning point in tumor evolution," the authors say. "Indeed, tumor progression was seen in greater than one-half of the patients diagnosed with MHSs in our study, with apparently increased Ki-67 indices in comparison with initial PNET diagnosis."

During a median follow-up of 73 months (range 21 to 223 months), seven patients died (all related to PNET) with a median survival after MHS diagnosis of 28 months (range 3 to 56 months). Four of these seven patients had an insulin-related MHS.

"Although frequently elevated, plasma concentrations of neuroendocrine hormones are not correlated with the development of hormonal syndromes," the researchers noted. "Therefore, serum hormonal levels should not be routinely assessed unless symptoms develop."

"The occurrence of any unexpected or unexplained symptoms potentially due to hormone hypersecretion, such as watery diarrhea, abdominal pain, diabetes mellitus, hypoglycemic malaise, repeated vomiting, or esophagitis, should lead to consideration of assessing serum levels of PNET-associated hormones," the researchers advised. "In addition to those reported here, other MHS related hormones include adrenocorticotrophic hormone and parathyroid hormone-related peptide."

"Future research could assess the relevance of systematic repeated biopsy of PNETs at MHS onset and evaluate their effects on patient management and outcome," they added.

Dr. Cadiot did not respond to a request for comments.

The authors reported no relevant financial relationships for this study.

SOURCE: http://bit.ly/1Si9X74

Ann Intern Med 2015.