48uep6bbphidcol2|ID

48uep6bbphidvals|1923

48uep6bbph|2000F98CTab_Articles|Fulltext

Neuroendocrine tumours of the GI tract are very rare tumours accounting for less than 2% of all cancers of GI tract.¹ They are unique because of their varied paraneoplastic presentation apart from their local mechanical effect. This occurs because of the production of various bio-active amines that can cause systemic symptoms.² One of the common symptoms associated with these tumours is diarrhoea and hypokalaemia.³ Here we report a case of chronic diarrhoea and hypokalaemia quadriparesis, which was found to be due to PET-VIPoma on evaluation.

 A 40-year-old man was admitted to the Gastroenterology department with complaints of episodic large volume chronic diarrhoea for the last six months and limb weakness for ten days. He denied abdominal pain, blood in stools, skin rashes, or ulcerations but reported significant weight loss. He was diagnosed with functional diarrhoea when the symptom started six months before the current presentation. At the time, he had a negative workup, including a normal UGI Endoscopy, Colonoscopy, USG abdomen, and routine blood investigations, including LFT, KFT, Thyroid Profile, and HIV & celiac disease serology. He was being managed symptomatically with loperamide as and when required. Physical examinations revealed vitals that were within normal limits apart from tachycardia with pulse rate 112/min, blood pressure 110/80 mmHg, and respiratory rate of 16/min. Systemic examination was within normal limits except for decrease muscle power in all limbs.

Laboratory data were grossly un-remarkable, only report worth mentioning is his persistent hypokalaemia and hyponatremia requiring continuous intravenous replacement.

Abdominal CT revealed a well-circumscribed, homogenous, hypodense enhancing mass lesion of size 43×41 mm in the tail of the pancreas. There was no evidence of liver metastasis or significant lymphadenopathy (Figure 1A).

EUS was done, and it showed a solid hypo-echoic homogenous mass measuring 43×28 mm in the tail of the pancreas (Figure 1B). EUS-FNA was taken that was suggestive of a well-differentiated neuroendocrine tumour. 

Serum chromogranin levels were 910 ng/ml (normal range<108 ng/ml).

Somatostatin receptor scintigraphy (gallium 68-octreotide-DOTA NOC PET-CT) revealed a large lobulated intensely DOTA-NOC avid exophytic mass lesion in the body of the pancreas without any other evidence of tracer uptake in the liver or elsewhere in the body (Figure 1C). Serum levels of VIP were 741 pg/ml (ref. range < 75 pg/ml).

The patient was started on octreotide therapy and responded abruptly, with a significant decrease in bowel movements within a few days of therapy.

He was simultaneously planned for surgical excision of the tumour and underwent distal pancreatectomy with splenectomy. Pancreatic specimen revealed a greyish white nodular mass measuring 4×3.5 cm in the body with a congested spleen. Histopathology revealed a well-differentiated neuroendocrine tumour with tumour-free margins (Figure 2A-D). Post-operatively patient remained symptom-free and was discharged in a stable condition.

Pancreatic endocrine tumours (PETs) are rare pancreatic tumours with an incidence of 0.4/100,000 population and are diagnosed in approximately 1% of patients with pancreatic masses.⁴ PETs are functional when they produce clinical syndrome due to hormone over-secretion. Approximately 40% to 60% of PETs are not associated with the clinical syndrome of hormone secretion and are designated as non-functional PETs.⁵

Diarrhoea is a common symptom associated with these tumours, but diarrhoea occurring as a presenting symptom is very rare. More often, diarrhoea occurs as a part of a constellation of symptoms, as with carcinoid syndrome. Diarrhoea is commonly seen during the clinical course in carcinoid tumours, gastrinoma, glucagonoma, VIPoma and somatostatinoma. Carcinoid tumours and gastrinoma are the commonest of NET and rest of PETs; because of their rarity, they are rarely considered in the diagnostic evaluation of a patient with chronic diarrhoea.

VIPoma syndrome, traditionally called pancreatic cholera, because of the severe diarrheal disease seen in these tumours with life-threatening fluid and electrolyte wasting requiring intensive monitoring and continuous replacement.⁶

The acronym WDHHA (watery diarrhoea, hypokalaemia, hypochlorhydria, acidosis) is often used to describe the clinical consequences of VIP over-secretion.⁷ Occasionally patients may have associated features like hypercalcemia, impaired glucose tolerance, hypomagnesemia, tetany, and distended gall bladder.⁸ All of these features are consistent with the known actions of VIP.

The most prominent symptom in most patients is profuse secretory diarrhoea, with 70% of patients having a stool volume exceeding 3 litres in 24 hours. The stool has a gross appearance of dilute tea and is rich in electrolytes with an average secretion of 300 meq of potassium in 24 hours.

Several physicians saw the present patient in the six months before his presentation, but the hypokalaemia was probably overlooked. Persistent electrolyte derangement requiring continuous replacement was the clue in this case that prompted us to evaluate further.

Abdominal CT was obtained, which showed an enhancing hypodense mass in the body of the pancreas. Fine needle aspiration cytology with immune-histochemical analysis showed cells positive for chromogranin A which clinched the diagnosis of a neuroendocrine tumour of the pancreas.

Except for insulinomas, which are almost always benign, the remaining PETs, including VIPomas, behave similarly and show metastasis to liver or lymph nodes in 50% to 90% cases.⁹ In the presence of metastatic disease, somatostatin analogues remain the mainstay of treatment providing symptomatic relief from consequences of hormonal secretion.¹⁰

However, in this patient, somatostatin receptor scintigraphy revealed somatostatin receptor-positive mass in the body of the pancreas without any tracer uptake in the liver, thus allowing us to go for curative resection.

The patient was operated upon with distal pancreatectomy and splenectomy following which the patient showed symptomatic improvement.

PETs can be associated with Multiple-Endocrine-Neoplasia-Type-1 syndrome (especially gastrinoma and insulinoma) and can have familial aggregation as well.¹¹ So, all patients with PETs should be screened for other endocrinopathies as a part of the clinical syndrome of MEN-1. In this patient, there was no evidence of hypercalcemia at the time of presentation, nor was there any family history of any endocrinopathy.

Although a rarity, the possibility of neuroendocrine tumours of GI tract and pancreas should be considered in patients with chronic un-resolving diarrhoea, especially when other investigations are unrewarding and inconclusive.