VIPoma in a 37-year-old man

Abstract

In September, 2011, a 37-year-old man with a past history of pulmonary tuberculosis came to our hospital with persistent watery diarrhoea, weight loss, and hypokalaemia of 2 years’ duration. The diarrhoea did not stop with fasting, and serum potassium had remained at 2∙5 mmol/L despite multiple cycles of intravenous potassium replacement. Physical examination and routine blood investigations were normal, as were both upper and lower gastrointestinal tract endoscopies. An abdominal CT showed a 5∙9 × 3∙4 cm lesion in the pancreatic tail and a solitary hepatic metastasis, confi rmed by MRI (fi gure). However, in view of the patient’s past history of tuberculosis, the medical team waited for mycobacterial culture results before making a diagnosis of probable stage IV pancreatic adeno carcinoma. Meanwhile, an endocrine referral was made to address the hypokalaemia. The patient’s signs and symptoms made the clinical team consider the extremely rare diagnosis of a vasoactive intestinal peptide endocrine tumour— VIPoma, also known as Verner-Morrison syndrome. We requested serum chromogranin A and 24-h urinary 5-hydoxyindoleacetic acid, which were both negative. The news of Steve Jobs’s death from a neuroendocrine tumour, which occurred around this time, prompted the clinical team to reconsider this diagnosis despite initial negative results. Endoscopic ultrasound-guided pancreatic tail biopsy was therefore done next, and immunohistochemistry of the tumour tissue stained positive for cytokeratin AE1/3, synaptophysin, and chromo granin. Blood samples were taken for vasoactive intestinal peptide ELISA assay, before a trial of octreotide was initiated. His diarrhoea resolved within 3 days, accompanied by the resolution of hypokalaemia. The plasma vasoactive intestinal peptide was 175 pmol/L (normal 3 cm in diameter. About 75% occur in the pancreatic tail, and 60–80% are already metastasised at diagnosis. Being slow growing, VIPomas are generally compatible with long survival of 5–10 years. Most adult patients are diagnosed between 30–50 years of age. High volume secretory diarrhoea (>700 mL/day) that persists with fasting is virtually universal. Hypo kalaemia occurs in 70–100% of patients. Investigations include serum vasoactive intestinal peptide, pancreatic polypeptide, and chromogranin A. Functional PET imaging such as 68-Ga DOTA fusion PET/CT scans have sensitivity of about 97%, compared with about 80% in CT scans, and 85% in MRIs. This higher accuracy facilitates much earlier detection of metastases. When used therapeutically, peptide receptor radionuclide therapy was reported in one case report to reduce widespread metastatic disease down to a single liver metastasis at 1-year follow-up. A limitation of peptide receptor radionuclide therapy is the potential lack of somatostatin receptor expression by the tumour. In such cases, sunitinib and everolimus (both in phase III trials) are among the most promising alternatives to traditional hepatic-directed therapies including resection, ablation, hepatic artery embolisation, and liver transplantation. Surgery remains the defi nitive treatment for VIPoma. Octreotide is useful in suppressing VIP secretion, and interferon-alpha and glucocorticoids are sometimes used in refractory cases to improve symptoms of hormonal secretion.