Vipoma: Effective Treatment with Octreotide in the Oldest Old

To the Editor: We describe an older woman with a rare cause of secretory diarrhea. Diagnosis of VIPoma—the oldest ever described patient—with hepatic metastases was made and palliative treatment with the somatostatin analog octreotide started. The diagnostic approach is delineated and emphasis given to successful palliative octreotide therapy. An 86-year-old woman was admitted to the geriatric department because of weight loss, dehydration, and, as the main complaint in the previous few weeks, profuse, tea-like diarrhea. She did not present flushing or epigastric pains. Tongue cancer treated by radiotherapy, deep-vein thrombosis 4 years earlier, and severe carotid stenosis dominated her previous medical history. Laboratory tests showed hypokalemia at 2.5 mmol/l (normal range (NR): 3.1–4.4 mmol/l), hypercalcemia at 2.65 mmol/l (NR: 2.25–2.52 mmol/l), and hypophosphatemia at 0.47 mmol/l (NR: 0.8–1.4 mmol/l), but no anion gap. Initial evaluation of stools included leukocyte count, bacterial cultures, and fecal fat, which were all normal. Daily stool volume was more than 1,000 ml and diarrhea was secretory, without an osmotic gap. Laxative abuse was ruled out. A colonoscopy including biopsies was normal with no signs of inflammation. Finally, the potential diagnosis of a hormone-producing tumor was raised. Increased hormone levels were found for vasoactive intestinal polypeptide (VIP) and other gastrointestinal peptides. The respective values were as follows: VIP 188 pmol/l (normal <25 pmol/l), chromogranine-B-sequence 340 pmol/l (normal <80 pmol/l), peptide histidine methionine-27 240 pmol/l (normal <30 pmol/l), pancreatic polypeptide 188 pmol/l (normal < 100 pmol/l). In addition, plasma concentrations for gastrin, neurotensin, and parathormone were within normal limits. A carcinoid was excluded by normal plasma substance P, neurokinine A levels, and a normal urinary 5-hydroxyindolacetic acid output. Normal and pentagastrin-stimulated calcitonin levels also ruled out a medullary carcinoma of the thyroid. Abdominal computed tomography did not show the primary suspected (pancreatic) tumor, but a hypervascular lesion in the second liver segment, interpreted as hepatic metastasis (Figure 1a), confirmed by Indium-111-octreotide scintigraphy (Figure 1b). (a) A hyperdense mass in the left liver lobe. (b) A strong uptake of 111-Indium-labeled octreotide, a marker for endocrine tumors. The patient refused further investigations, such as an endosonography. After fluid and electrolyte replacement, subcutaneous octreotide (Sandostatine ®), a long-acting somatostatin analog, was initiated at 50 μg bid for 1 month, followed by monthly administration of 10 mg intramuscular long-acting-release (Sandostatine LAR®). Rapid improvement of diarrhea was noted, but the patient relapsed after 8 months, probably due to tachyphylaxis. After a short therapeutic-free window, octreotide at increasing doses up to 500 μg tid was reintroduced. The patient returned home and died 18 months later from pneumonia. VIPoma is a rare neuroendocrine tumor with less than one case per million per year.1 VIPoma usually occurs at around 50 years of age. Its occurrence has not been documented in the oldest old. Since its first description in 1958, so-called pancreatic cholera has been reported in several series in adults.2 The biological hallmark is the increase in plasma VIP levels, paralleled by chromogranin as a good marker for endocrine pancreatic tumors.3 It must be distinguished from other neuroendocrine tumors that can cause diarrhea, such as carcinoid, gastrinoma, and medullary carcinoma of the thyroid and the pancreatic polypeptide (PPoma).4 Although the gastrointestinal symptomatology is very impressive, the small tumor size may escape detection in about one-quarter of cases.5 Ultrasonography, computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and portal venous sampling have all been proposed in the diagnostic approach to detect a VIPoma. Indium-111-octreotide scintigraphy is a newer diagnostic procedure to detect (liver) metastases of neuroendocrine tumors.3 Using this methodology, we could clearly visualize the metastasis within the left liver lobe. Approximately 60% of VIPomas have metastasized at time of diagnosis, so palliative treatment is frequent. Long-term survival of patients with metastatic endocrine tumors is unpredictable and survival as long as 10 years under octreotide treatment has been described.6 Palliative treatment with octreotide is a well-established treatment for secretory diarrhea.7 It is the treatment of choice for unresectable metastatic VIPoma.8 The initial dose should be 100 μg to 150 μg tid, increased progressively to the maximal dose of 500 μg tid. Beneficial effects are usually evident within 12 hours.8 Other treatments for VIPoma include surgery, chemotherapy, chemoembolization, antitumor antibodies, and interferon.6, 9, 10 Such approaches are often impossible in the old because of comorbidities. In conclusion, this case illustrates that the patient's life expectancies contribute to treatment decision strategies such as octreotide in secretory diarrhea, due to few side effects. It enabled the treatment of this patient on an outpatient basis. In addition to providing an appreciable increase in the quality of life, such “high-end” therapeutic approaches may even prove to be cost-effective.