Endocrine Abstracts

Introduction: The MEN1 is inherited as autosomal dominant trait. In MEN 1 families a deletional mechanism of the regulatory gene appears to be the base of the syndrome.

Case 1: 40-year-old lady presented with a two-day history of headaches, blurred vision and funny turns, culminating in loss of consciousness and a generalised tonic-clonic seizure. Her GCS was 3; she was intubated, ventilated and referred to ICU. U+Es normal, Calcium high, phosphate low, and PTH was high. Lumbar puncture and CT brain were within normal limits. Isotope subtraction scan demonstrated a tumour in the lower pole of the thyroid. Her condition improved however she suffered recurrent hypoglycaemic episodes. Insulin and C-peptide were inappropriately. TFTs and cortisol were within normal. The diagnosis of MEN 1 with parathyroid adenoma and insulinoma was reached. MRI abdomen and coeliac angiography were normal.

Portal vein sampling demonstrated the predominant source of insulin to be from the head of the pancreas. Diazoxide failed to control her hypoglycaemic attacks and she underwent total pancreatectomy. Hypercalcaemia was treated with parathyroidectomy. Histology confirmed B-cell hyperplasia in the pancrease and ademonata in all 4 parathyroid glands.

Genetic analysis identified a heterozygous missense mutation in codon 220 in exon 4 of the MEN1 gene, a previously unidentified mutation in MEN1 gene.

Case 2: Family screening uncovered primary hyperparathyroidism in her daughter. Genetic analysis confirmed that she is also heterozygous for the same mutation in MEN1 gene. MRI of neck showed a possible adenoma.

Discussion: Genetic analysis of both grandparents showed no mutations in MEN1 gene. Mutation in codon 220 in exon 4 of MEN1 gene (chromosome 11) has not been described before and it is presence only in the affected members of the family indicates that it is linked to MEN1.