Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma.

Aurelio Negro,Nicoletta Campanini,Enrico Farnetti,Anna Calvi,Stefano Tedeschi,Ignazio Verzicco,Gallia Graiani,Pietro Coghi,Davide Cunzi,Emanuele Negri,Davide Nicoli,Luigi Gerra,Rosaria Santi,Magda Zanelli,Riccardo Volpi,Barbara Palladini,Aderville Cabassi

doi:10.3389/fendo.2021.652045

Abstract

BackgroundPheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP).Clinical CaseA 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus.ConclusionsA rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.

Highlights

Pheochromocytomas (PHEO) and sympathetic paragangliomas are rare neuroendocrine tumors arising from chromaffin cells in the medulla of the adrenal glands or from neural crest-derived ganglia
Our patient represents a new case of with hypokalemia and achlorhydria (WDHA) syndrome caused by a malignant vasoactive intestinal peptide (VIP)-secreting PHEO with massive dehydration, severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse diarrhea
VIP-secreting PHEO is an extremely rare tumor and from the first description given in 1975 by Lowry et al, only about twenty five cases of PHEO associated with WDHA syndrome have been reported, so far [13,14,15,16,17,18,19,20]

Summary

Background

Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP). Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. Patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus

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ETHICS STATEMENT