A 35-year-old patient was referred to a tertiary referral unit for further investigation of severe watery diarrhea. Infectious agents had already been excluded. Biochemistry revealed a strikingly raised serum calcium concentration of 4.09 mmol/l (NR 2.12.65 mmol/l), chromogranin A was grossly elevated at 293 U/l (NR 218 U/l) and vasoactive intestinal peptide (VIP) was also raised at 130 pg/ml (NR 1060 pg/ml). Computed tomography (CT) of the abdomen demonstrated an eight-centimeter mass in the body of the pancreas which led to the working hypothesis of a VIP producing neuroendocrine tumour as the cause of this patients condition. Molecular genetic testing showed a deletion of 4 base pairs in exon 2 resulting in a termination of the Menin protein at codon 116, leading to a diagnosis of MEN1, with a suspected VIPoma and primary hyperparathyroidism. Screening for other manifestations of MEN1 did not reveal any pituitary abnormalities, however genetic testing of family members revealed that the patients 9 year old son carried the same mutation. As a bridging therapy to surgery somatostatin-analogues were administered which led to a cessation of diarrhea and allowed the patient to undergo a total pancreatectomy. Histology demonstrated VIP-positivity in the known tumour and numerous other neuroendocrine tumours throughout the organ. All tumours were graded as G1, with lymph nodes unaffected. After recovery the patient underwent bilateral neck exploration with subtotal parathyroidectomy. Intraoperatively an incidental lymph node metastasis of papillary thyroid cancer was found in the central neck on frozen section; adequate surgery for the thyroid malignancy was therefore performed in the same session. The patient has been followed up for over 10 years with infrequent biochemical and radiological investigations every two to three years. Screening 7 years post-diagnosis did not reveal any new manifestations of MEN1, however, when he next attended for screening, nine years post-diagnosis, a new incidental 7-centimeter mass arising from the left adrenal was demonstrated on CT. The patient went for surgery and histology confirmed adrenocortical carcinoma. Follow-up scans have not shown any residual or recurrent disease 18 months after surgery. This case demonstrates that patients with MEN1 may not necessarily present with the classical manifestations of the syndrome, occult tumours may be found incidentally on screening and may develop after patients have been disease-free for years. Life-long regular biochemical and radiological screening of MEN-1 patients is therefore necessary to improve morbidity and mortality in this patient group.
16 - 18 Apr 2018
Society for Endocrinology