An aggressive phenotype in MEN 1: requirement for more frequent monitoring?
Simpson KA, Tan T, Hatfield ECI, Meeran K, Todd JF.
Department of Endocrinology, Hammersmith and Charing Cross Hospitals, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS
Mr SC is an 18-year old gentleman with MEN 1 with a heterozygous germline mutation at the p.W341X locus of the MEN 1 gene. He was originally referred, aged 16, when he was noted to have mild hyperparathyroidism and raised chromogranin levels (90pmol/L (NR <60)). His other gut and pituitary hormones were normal. Abdominal CT scan revealed a 3cm lymph node between the pancreas and lesser curve of the stomach, which showed increased activity on an octreotide scan. Additional lesions were noted in the pancreatic neck and head, measuring 15mm and 18mm respectively, and a submucosal lesion in the lesser curve of the stomach. Following an endoscopic ultrasound, a coeliac lymph node biopsy revealed a low-grade neuroendocrine tumour. Within 6 months, Mr SC developed symptoms consistent with hypoglycaemia confirmed on a 72h fast. Angiography with calcium stimulation and venous sampling revealed blushes in the tail/body and head of the pancreas after injection of the splenic (SA) and dorsopancreatic (DPA) arteries respectively with a diagnostic rise in insulin (SA: baseline 4.8 to peak 48 mU/L and DPA: baseline 6.4 to 243 mU/L) confirming that both pancreatic lesions were functional. The patient underwent a laparoscopic enucleation of both pancreatic lesions, in addition to a gastric lesion wedge resection and gastric lymph node removal. On histology, both pancreatic lesions were consistent with insulinomas and the gastric wedge resection and adjacent lymph node confirmed a primary gastric neuroendocrine tumour. His hypoglycaemic symptoms have completely resolved following surgery. His father (the index case) presented at age 38 years, in 2005, with recurrent hyperparathyroidism when the diagnosis of MEN 1 was confirmed after genetic testing. Within a year of diagnosis, in addition to a completion parathyroidectectomy, he had undergone hypophysectomy for both aggressive Cushing’s disease and microprolactinoma, and also has multiple pancreatic lesions including a functional gastrinoma indicating a fairly aggressive phenotype. He now has evidence of recurrent Cushing’s disease and also symptoms of hypoglycaemia awaiting investigation. Although, there are no clear genotype/phenotype correlations in MEN 1, this case highlights that more aggressive screening may be appropriate in young patients with MEN 1 whose first-degree relatives have multiple and aggressive endocrine tumours.