A sixty-four year old man presented for investigation of mild hypercalcaemia (2.68 mmol/L) incidentally discovered during preoperative workup for elective removal of a testicular cyst. He had no family history of renal stones. His younger brother had undergone a parathyroidectomy at the age of 60. His father died in a road traffic accident aged 54. His mother was 84 and had no history of endocrine disease. Urine calcium:creatinine excretion ratio was 0.0207, excluding familial hypocalciuric hypercalcaemia. Bone densitometry revealed osteopaenia of the non-dominant radius. Ultrasound identified a single left superior parathyroid adenoma, concordant with an area of increased uptake and delayed washout on sestaMIBI. Gut hormone profile showed elevations of chromogranin B (233 pmol/L (0150 pmol/L)) and pancreatic polypeptide (575 pmol/L (0300)). Further discussion revealed that his brothers hypercalcaemia had only resolved following the resection of multiple parathyroid glands. Imaging of the pancreas with MRI, Endoscopic Ultrasound and gallium DOTATATE confirmed the presence of multiple lesions with features characteristic of neuroendocrine tumours. MRI of the pituitary was unremarkable. Genetic analysis identified a novel pathogenic MEN1 missense variant, (p.Ile360Phe) (c.1078A>T) which lies in helix 16 of menin, a structurally important region of the protein which forms part of the wall of the JunD binding pocket. JunD, in the absence of menin, switches from a growth suppressor to a growth promoter. Almost all cases of MEN-1 present with hyperparathyroidism before the age of 50, with most cases occurring between 20 and 40 years. Sporadic hyperparathyroidism typically presents in patients over 60 years old. MEN-1 typically causes multiple gland disease, while over 80% of patients with sporadic hyperparathyroidism localise to a single gland. This case demonstrates that older age at presentation and localisation to a single gland does not exclude the diagnosis of MEN-1.
19 Nov 2018 - 21 Nov 2018