Diagnosis and Treatment > Medication
Search for other papers by Avital Nahmias in
Google Scholar
PubMed
Search for other papers by Simona Grozinsky-Glasberg in
Google Scholar
PubMed
Search for other papers by Asher Salmon in
Google Scholar
PubMed
Search for other papers by David J Gross in
Google Scholar
PubMed
Summary
Approximately 35% of the pancreatic neuroendocrine tumors (pNETs) are functional, the most common of which is an insulinoma. Rarely can initially nonfunctioning tumor undergo biological transformation to a hormone-secreting tumor with subsequent changes in the clinical picture. We present here three unique patients with long-standing pNETs who developed life-threatening hyperinsulinemic hypoglycemia along with tumor progression. In two of the patients, everolimus (Afinitor) was administered in an attempt to control both tumor growth and hypoglycemia. In two cases everolimus therapy resulted in the abolishment of hypoglycemia and induced significant tumor regression; however these beneficial responses were transient. These cases highlight the exceptional ability of pNETs to change biological behavior in parallel with disease progression. Our experience concurs with recently published studies demonstrating the utility of everolimus for the control of both hypoglycemia and tumor progression.
Learning points
-
Nonfunctional pNET can gain new features such as insulin secretion with related morbidity.
-
Gain of function in a previously nonfunctional pNET signifies tumor progression and is usually associated with poor prognosis.
-
Everolimus proved to be a viable treatment for hypoglycemia in insulinoma patients and was also proven highly effective in the patients presented here.
-
As disease progresses, the effect of everolimus on hypoglycemia wanes. We report for the first time the development of hypoglycemia during everolimus treatment.
Search for other papers by Kun Zhang in
Google Scholar
PubMed
Search for other papers by Lukas J Lehner in
Google Scholar
PubMed
Search for other papers by Damaris Praeger in
Google Scholar
PubMed
Search for other papers by Gert Baumann in
Google Scholar
PubMed
Search for other papers by Fabian Knebel in
Google Scholar
PubMed
Search for other papers by Marcus Quinkler in
Google Scholar
PubMed
Search for other papers by Torsten K Roepke in
Google Scholar
PubMed
Summary
Neuroendocrine tumours (NETs) represent a broad spectrum of tumours, of which the serotonin-producing carcinoid is the most common and has been shown to cause right ventricular heart failure. However, an association between heart failure and NETs other than carcinoid has not been established so far. In this case report, we describe a 51-year-old patient with a glucagon-producing NET of the pancreas who developed acute heart failure and even cardiogenic shock despite therapy. Heart failure eventually regressed after initialising i.v. treatment with the somatostatin analogue octreotide. Chromogranin A as a tumour marker was shown to be significantly elevated, and it decreased with clinical improvement of the patient. The effects of long-time stimulation of glucagon on the myocardium have not been studied yet; however, sarcoplasmic reticulum calcium leak can be discussed as a possible mechanism for glucagon-induced heart failure.
Learning points
-
Glucagonoma can be a cause for heart failure.
-
i.v. infusion of octreotide can be successfully used to treat glucagonoma-induced acute heart failure.
-
We suggest that cardiac function should be monitored in all NET patients.
Search for other papers by Chiara Baratelli in
Google Scholar
PubMed
Search for other papers by Maria Pia Brizzi in
Google Scholar
PubMed
Search for other papers by Marco Tampellini in
Google Scholar
PubMed
Search for other papers by Giorgio Vittorio Scagliotti in
Google Scholar
PubMed
Search for other papers by Adriano Priola in
Google Scholar
PubMed
Search for other papers by Massimo Terzolo in
Google Scholar
PubMed
Search for other papers by Anna Pia in
Google Scholar
PubMed
Search for other papers by Alfredo Berruti in
Google Scholar
PubMed
Summary
Insulinoma is a rare form of insulin-secreting pancreatic islet cell neuroendocrine (NE) tumor. The medical treatment of the malignant NE disease of the pancreas deeply changed in the last years, thanks to the introduction of new target molecules, as everolimus. Even if the exact mechanism is not actually known, one of the side effects of everolimus, hyperglycemia, has been demonstrated to be useful to contrast the typical hypoglycemia of the insulinoma. We report the case of a patient with a metastatic malignant insulinoma treated with intermittent everolimus, obtaining an important improvement in the quality of life; this suggests the necessity of preclinical studies to analyze the cellular pathways involved in insulin-independent gluconeogenesis.
Learning points
-
Effect of somatostatin analogs is long-lasting in the control of functioning NE tumors.
-
Persistent everolimus control of hypoglycemia despite serum insulin levels and disease progression.
-
Open issue: are disease progression and the increase in serum markers the only valid criteria to reject a treatment?
