The Evolving Clinical Course of Patients with Insulin Receptor Autoantibodies: Spontaneous Remission or Receptor Proliferation with Hypoglycemia
JEFFREY S. FLIER,
ROBERT S. BAR,
MICHELE MUGGEO,
C. RONALD KAHN,
JESSE ROTH and
PHILLIP GORDEN
Diabetes Branch, National Institutes of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health Bethesda, Maryland 20014
Address requests for reprints to: Jeffrey S. Flier, Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts.
Three patients with insulin resistance caused by autoantibodiesto the insulin receptor were investigated serially over a 3-yrperiod. Major changes in carbohydrate metabolism, insulin receptorstatus, and titer of antireceptor antibodies were observed ineach case.
In one patient, normalization of glucose tolerance, insulinsensitivity, and receptor binding were associated with a spontaneousfall in the titer of antireceptor antibody. A second, more severelyaffected patient had two entirely distinct phases to her illness.The first, or hyperglycemic phase, was characterized by insulinresistance, negligible insulin binding to receptors on circulatingmonocytes, and high titers of circulating antireceptor antibodies.The second phase was characterized by refractory hypoglycemia,in association with proliferation of membrane insulin receptors;these occurred despite persistence of high titers of antireceptorantibody. An unusual hepatic lesion, diffuse adenomatosis, wasobserved during this phase. A third patient showed featuresof both of the other patients, with spontaneous fall in antibodytiter as well as a later phase of receptor proliferation.
These studies demonstrate that patients with antibodies to insulinreceptors may have a fluctuating clinical course. There maybe spontaneous changes in antibody titers as well as independentchanges in receptor concentration. Hypoglycemia and hepaticproliferation are newly recognized clinical sequelae in patientswith this syndrome.
Received February 21, 1978.
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