MON-923 MENIN Gene Mutation: Unity Amidst Diversity

Nadeem M Rais, Anshul Kumar, Swetha Jain, Vinod Scaria, Savinitha Prakash, Sandeep Kumar Mathur, Apoorva Joshi
2020 Journal of the Endocrine Society  
Introduction The MEN 1 syndrome is an enigmatic disorder, manifesting a wide spectrum of disorders, in members of a family, harbouring the same gene mutation. We present one such family, with a MENIN gene mutation with marked diversity in the clinical presentation Clinical cases 1992: RB (Age: 13) presented with accelerated puberty, galactorrhoea and a lactotroph adenoma. Treated with Bromocriptine, followed by hypophysectomy and radiotherapy. He was on hormone replacement for hypopituitarism.
more » ... r hypopituitarism. 1996: He gained 21 kg of weight and had recurrent episodes of convulsions with unconsciousness.He had hypoglycaemia (13mg/dl; N >70), with hyperinsulinemia (58uIU/ml; N<25). MRI abdomen showed a mass (3.4 x 3.0 cm) over the tail of the pancreas for which a distal pancreatectomy was done (HPE: Neuroendocrine tumour). 2013: He had pain in the lower limbs with hypercalcemia (11.4mg%; N: 8.5-10.5) and hyperparathyroidism (329 pg/ml; N: 10-61) (MIBG Scan: parathyroid adenomas treated by bilateral inferior parathyroidectomy). 2016: He had hypoglycaemia with hyperinsulinemia with multifocal pancreatic NETs. These were enucleated at surgery. 2017: He developed Zollinger Ellison syndrome with raised basal gastrin levels (Gastrin: >200ng/ml; N<180) and multiple duodenal ulcers (Treatment: Pantoprazole). He simultaneously had recurrent hyperparathyroidism and underwent a total parathyroidectomy with allograft. The allograft initially showed evidence of hyperparathyroidism followed by hypoparathyroidism. His father VB (Age: 56) was seen by us in 1996 for skin lesions and a malignant thymic carcinoid, to which he succumbed to, shortly after the surgery. His aunt, SB (Age: 18), has a lactotroph adenoma with severe insulin resistance characterised by obesity, acanthosis nigricans and hyperandrogenism. 2009: His paternal uncle PB (Age: 54) had a pituitary macroadenoma. He underwent a hypophysectomy and was lost to follow up. 2018: PB had massive haemoptysis. A bronchoscopy showed nodules in the right lung which on biopsy revealed a NET. The whole body scan showed a hilar and mediastinal mass along with metastatic disease to the adrenals, liver, spine, skull and rectum. The histopathology examination revealed a malignant carcinoid Clinical lesson Whole exome sequencing of the two of the affected members showed mutations of the MENIN gene at exon 2 c.G2492T:p.G831V; g. chr10. This common mutation in the family was associated with a wide spectrum of diverse clinical manifestations which include the classic disease, malignant carcinoids of the lung and acromegaloid variant of Type A insulin resistance with hyperandrogenism. These observations suggest the unity amidst diversity in the enigmatic syndrome that encompasses MEN1.
doi:10.1210/jendso/bvaa046.1711 fatcat:diiwjq4sh5eqnbgb6pvydbwwpq