Relapsing and remitting severe hypoglycemia due to a monoclonal anti-insulin antibody heralding a case of multiple myeloma.
BACKGROUND
We report a novel case of insulin autoimmune syndrome (IAS) presenting with hypoglycemia due to production of a monoclonal anti-insulin antibody in a patient subsequently found to have multiple myeloma (MM).


OBJECTIVE
The aim of the study was to describe the 5-yr clinical course of a patient with IAS and MM and to characterize the origin and function of the pathogenic antibody.


METHODS
We conducted a longitudinal case history with laboratory investigations to characterize the anti-insulin antibody subtype, specificity, affinity, and origin.


RESULTS
The patient presented with IAS, which worsened during treatment of hepatitis C. The patient was then discovered to have a monoclonal gammopathy that progressed to MM. Treatment of the MM induced remission of the neoplasia and IAS, which then followed a synchronized course of progression and response to therapy. An anti-insulin IgG(3)-λ that bound specifically but with low affinity to the insulin B chain (amino acids 9-30) and that was distinct from the primary MM IgG(3)-κ clone was recovered from the patient and cloned. The antibody bound insulin and showed mutations of normal affinity maturation.


CONCLUSIONS
We describe a case of MM heralded by IAS, where full characterization of the pathogenic antibody revealed that the monoclonal anti-insulin antibody had originated from a self-reactive clone.
Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
F
F
Waldron-Lynch
S E
SE
Inzucchi
L
L
Menard
N
N
Tai
P
P
Preston-Hurlburt
P
P
Hui
J
J
McClaskey
W A
WA
Hagopian
E
E
Meffre
P W
PW
Marks
L
L
Wen
K C
KC
Herold
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood; D003937:Diagnosis, Differential; D006801:Humans; D007003:Hypoglycemia / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007330:Insulin Antibodies / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000276:immunology; D012008:Recurrence; D012075:Remission, Spontaneous; D012720:Severity of Illness Index; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007330:Insulin Antibodies