ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2020) 69 OC6 | DOI: 10.1530/endoabs.69.OC6

MGES: Monoclonal Gammopathy of Endocrine Significance?

Gowri Ratnayake1, David Church2, Robert Semple2, James Cavenagh1 & William Drake1


1St Bartholomew's Hospital, London, UK; 2Cambridge University Hospitals, Cambridge, UK


A 65 year-old male was evaluated at another hospital for frequent episodes of fainting preceded by sweating, palpitations fatigue and hunger over several years. There was no personal or family history of diabetes mellitus. Hypoglycaemia was confirmed on a supervised fast and, guided by some equivocal uptake on a dotatate scan, he underwent a distal pancreatectomy, but the symptoms persisted. He was referred to our centre. He reported relentless weight gain and a need to eat porridge immediately prior to bed, together with nocturnal calories in order to prevent symptoms. In addition a monoclonal paraproteinaemia (IgG kappa, 21 g/l) was noted, without target organ involvement (normal serum calcium, no lytic bone lesions, normal renal function). He developed symptomatic hypoglycaemia after 10 h of a supervised fast: venous blood glucose 2.0 mmol/l; insulin and C-peptide concentrations >1000 IU/l and 6512 pmol/l respectively. During a prolonged oGTT, early hyperglycaemia (12.5 mmol/l at 60 min) was followed by a nadir value of 2.9 mmol/l which was detected at 300 min, in association with marked hyperinsulinaemia (52 850 pmol/l). These features strongly suggested the presence of insulin-binding antibodies and further testing indicated that these were of low affinity and high capacity. The insulin antibody is IgG specific and further detailed testing is underway to determine if the anti-insulin antibodies are monoclonal. The vast majority of patients with clinical symptoms related to anti-insulin antibodies have been treated with insulin or are receiving drugs known to be associated with their formation. Our patient’s case is intriguing; according to conventional practice, he does not merit plasma cell directed therapy, but the demonstration of monoclonality of the anti-insulin antibodies would be considered a clinical indication to offer therapy with bortezemib for a ‘monoclonal gammopathy of endocrine significance’.

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