Clinical and Hormonal Aspects of the Watery Diarrhea-Hypokalemia-Achlorhydria (WDHA) Syndrome due to Vasoactive Intestinal Polypeptide (VIP)-producing Tumor

Yamaguchi, Ken; Abe, Kaoru; Adachi, Isamu; Tanaka, Masahiro; Ueda, Mitsuharu; Oka, Yuji; Miyakawa, Sumiko; Kameya, Toru; Yanaihara, Noboru

doi:10.1507/endocrj1954.27.supplement_79

Cited by 11 publications

(5 citation statements)

References 7 publications

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“…Calcitonin expression on immunohistochemistry was found in 11% of cases in a large study screening 229 pNETs ( 20 ). It is unclear how often calcitonin-secreting pNETs occur in the setting of MEN1, although previous cases have been reported ( 21 , 22 , 23 , 24 ), including a case with both GHRH and calcitonin secretion, similar to our case.…”

Section: Discussionsupporting

confidence: 45%

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

Nadhamuni

Iacovazzo

Evanson

et al. 2021

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare. Learning points It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1). Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis. Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.

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Section: Discussionsupporting

confidence: 45%

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

Nadhamuni

Iacovazzo

Evanson

et al. 2021

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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“…Third, WDHA patients with type 1 multiple endocrine neoplasia (MEN) have several tumours in the pancreas, indicating that patients with MEN should be treated differently in terms of detecting tumour site and surgical therapy. Many tumours have the capacity to create VIP, and when VIP is produced in significant numbers, plasma VIP levels rise, resulting in the WDHA syndrome [3].…”

Section: Literature Review and Discussionmentioning

confidence: 99%

“…In the study of the molecular pathogenesis of WDHA syndrome and other pancreatic endocrine cancers, significant progress has been achieved. Several genes have been linked to their relevance in studies, including the following: [1,3]. cancer, ganglioneuroblastoma, pheochromocytoma, hepatoma, and adrenal tumours, have been described.…”

Section: Geneticsmentioning

confidence: 99%

“…VIP is a 28-amino-acid straight-chain polypeptide with a wide range of biological activities, and its overproduction by pancreatic endocrine tumours or ganglioneuroblastomas is known to cause profuse watery diarrhoea, the so-called waterydiarrhea-hypokalemia-achlorhydria (WDHA) syndrome [3]. VIP also suppresses stomach acid production, stimulates hepatic glycogenolysis and hyperglycemia, and dilates systemic blood vessels in the periphery.…”

Section: Introductionmentioning

confidence: 99%

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Etiology, Assessment and Management of WDHA (Watery Diarrhea, Hypokalemia, and Achlorhydria) and VIPoma

Hussein

Shaqaqiq

Aldhuaina

et al. 2021

JPRI

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The syndrome of watery diarrhoea, hypokalemia, and achlorhydria (WDHA syndrome) is an uncommon disorder marked by severe, watery diarrhoea caused by non–beta pancreatic islet cell oversecretion of vasoactive intestinal peptide (VIP). The onset of the disease is gradual, and diagnosis is often months or years later. Long-term dehydration, electrolyte and acid-base abnormalities, and chronic renal failure are all linked to morbidity. Pancreatic endocrine tumours are extremely rare, with less than 10 incidences per million people. VIPomas are uncommon tumours that affect between 0.05 and 2.0 percent of people. The most prevalent symptom is diarrhoea, which affects at least 89 percent of patients. VIPoma is treated with a combination of medicine and surgery The goal of first medical treatment is to reduce symptoms and restore fluids and electrolytes as quickly as possible

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“…The typical features of patients with vasoactive intestinal polypeptide-producing tumors include large-volume diarrhea, hypokalemia and hypercalcemia 56 . Plasma vasoactive intestinal polypeptide levels are usually markedly elevated in these patients.…”

Section: Non-parathyroid-related Diseasesmentioning

confidence: 99%

Laboratory approaches for the diagnosis and assessment of hypercalcemia

Meng

Wagar

2014

Critical Reviews in Clinical Laboratory Sciences

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Calcium, the fifth most common element in the body, plays major physiological functions. Measurement of blood calcium is one of the most commonly ordered laboratory tests in assessments of calcium homeostasis and disease diagnosis. Hypercalcemia is an increased level of calcium in the blood. This disorder is most commonly caused by primary hyperparathyroidism and malignancy. However, other less common causes of elevated calcium levels need to be considered when making a differential diagnosis. This review is intended to provide readers with a better understanding of calcium homeostasis and the causes and pathophysiology of hypercalcemia. Most importantly, this review describes useful approaches for laboratory scientists and clinicians to appropriately diagnose and assess hypercalcemia.

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Clinical and Hormonal Aspects of the Watery Diarrhea-Hypokalemia-Achlorhydria (WDHA) Syndrome due to Vasoactive Intestinal Polypeptide (VIP)-producing Tumor

Cited by 11 publications

References 7 publications

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1

Etiology, Assessment and Management of WDHA (Watery Diarrhea, Hypokalemia, and Achlorhydria) and VIPoma

Laboratory approaches for the diagnosis and assessment of hypercalcemia

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