LBODP066 A Conservative Approach To The Management Of Glucagon Receptor (GCCR) Mutation (Mahvash Syndrome)
Authors: Morgenthau Ari , Amer Lama , Silver Josh , Kim Raymond , Morel Chantal , Ezzat Shereen Z 
Published: November 2022

Background

Mahvash Syndrome a rare autosomal recessive cause of pancreatic neuroendocrine tumors (pNET) results from inactivation of GCCR. Clinically it presents with hyperglucagonemia without glucagonoma syndrome. Since described in 2008 all surviving adult cases have been managed surgically. We describe 2 related cases managed medically.

Case 1

In 2015 a 52 year old female with history of an enlarged pancreas (Aunt of Case 2) presented with incidentally identified hypovascular pancreatic masses while being assessed for back pain. An EBUS-guided FNA of the pancreas demonstrated a pNET with elevated serum glucagon of 100,991 pmol/ml, and Chromogranin A of 183 ng/ml but normal C-peptide, insulin, glucose, and HbA1C. CT chest abdomen pelvis, and octreotide scan had no evidence of metastasis. Due to vague abdominal discomfort, persistently high glucagon levels and pruritis without rash she was started on somatostatin analog therapy. Given her high glucagon without glucagonoma syndrome she was referred to genetics for GCCR sequencing which was notable for homozygous c.187G&gt;A p. Asp63Asn variant (subsequently reclassified as pathogenic). Her case was also reviewed at the multidisciplinary tumor board given her dominant but stable conglomerate 3.2×1.7cm pancreatic lesion (individually measuring 1.6 and 1.4cm). Continued SSA for 7 years showed a slow change in size of the pNET with the dominant lesion at the pancreatic head (1.8cm from 1.6cm in 2015), with no evidence of metastatic spread or clinical changes.

Case 2

a 46 year old man with IBD and Psoriatic Arthritis, presented in 2010 with choledocholithiasis. Imaging identified a bulky pancreas with a 1.2 cm nodule consistent with a neuroendocrine tumor. His investigations included 5HIAA, Gastrin, Prolactin, Chromogranin A, Insulin, Fasting Glucose, and HgbA1C all of which were normal. In 2015 following identification of an Aunt (Case 1) with a GCCR Variant of Uncertain Significance his glucagon level was found to be above the limit of detection for the assay. Given his preferences and lack of symptoms, he was monitored clinically without surgery or medications. His Glucagon levels have remained stably elevated at 12940 pg/ml, and the initial pNET has slowly progressed to 1.3cm with an additional 1.1cm and 0.5cm pNETs identified over a 7 year interval.

Conclusion

These cases describe 2 patients with homozygous c.187G&gt;A GCCR variants, resulting in Mahvash Syndrome. In contrast to previously published cases of the syndrome, and specifically the case report with the same variant, they have been managed non-surgically with regular imaging, and in Case 1 with SSA therapy. While there has been slow growth of the underlying pNET, there has been no clinical changes or evidence of metastatic disease, providing insight into the natural history of Mahvash Syndrome caused by c.187G&gt;A variant, and possibly supporting a less aggressive clinical approach.

Presentation: No date and time listed