Summary
A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 µU/ml (normal range <20 µU/ml) were detected which rose to peak levels of 2,460 µU/ml (normal range <300 µU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation).125I-insulin added to the patient's serum was not bound to dextrancoated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 µU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit.
We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.
Similar content being viewed by others
Abbreviations
- HPLC:
-
high pressure liquid chromatography
- IAIS:
-
insulin autoimmune syndrome
- RIA:
-
radioimmunoassay
- STH:
-
growth hormone
- TSH:
-
thyroid-stimulating hormone
References
Arky RA (1982) Antibodies and disorders of glucose metabolism. N Engl J Med 307:1445–1447
Banting FG, Franks WR, Gairns S (1935) Anti-insulin activity of serum of insulin treated patients. Am J Psychiatry 95:562–66
Benson EA, Ho P, Wang Ch, Wu PC, Fredhund PN, Yueng RTT (1984) Insulin autoimmunity as a cause of hypoglycemia. Arch Intern Med 144:2351–54
Blackshear PJ, Rotner HE, Krianciunas KAM, Kahn CR (1983) Reactive hypoglycemia and insulin autoantibodies in drug-induced lupus erythematosus. Ann Intern Med 99:182–4
Folling J, Norman N (1972) Hyperglycemia, hypoglycemic attacks, and production of anti-insulin antibodies without previous known immunization. Diabetes 21:814–26
Fushima H, Tsuhuda S, Hanafusa T, Matsuyuki Y, Nishihawa M, Ishihara S, Kaneo K (1980) A case of insulin autoimmune syndrome associated with small insulinomas and rheumatoid arthritis. Endocrinol Japan 27:679–687
Goldman J, Baldwin D, Rubenstein AH, Klinik DD, Blachard WC, Fisher LK, Roc TF, Schnewe JF (1979) Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia. J Clin Invest 63:1050–1059
Hirata Y, Ishizu H, Ouchi N (1970) Insulin autoimmunity in a case of spontaneous hypoglycemia. J Jap Diab Soc 13:312–20
Hirata Y, Tominaga M, Ho J, Nuguchi A (1974) Spontaneous hypoglycemia with insulin autoimmunity in Graves' disease. Ann Intern Med 81:214–218
Hirata Y, Tasaka Y, Odagini R, Takei M, Kenbo T, Horino M (1977) A new type of hypoglycemia with spontaneous insulin antibodies. Diabetes 26:401
Hirata Y (1983) Methimazole and insulin autoimmune syndrome with hypoglycemia. Lancet 2:1037–8
Kuzuya T, Matsuda A, Saito T, Yoshida S (1978) Problems on the specificity of iodinated insulin binding by sera of patients with autoimmune thyroid disorders. Endocrinol Japan 25(6):597–606
Ohneda A, Tominaga M, Ito JI, Noguchi A (1974) Hypoglycemia due to apparent autoantibodies to insulin. Diabetes 23:41–50
Rovira A, Valverde I, Escorihuela E, Lopez-Linares (1982) Autoimmunity to insulin in a child with hypoglycemia. Acta Paediatr Scand 71:343–345
Seino S, Fu ZZ, Marks W, Seino Y, Imura H, Vinik A (1986) Characterization of circulating insulin in insulin autoimmune syndrome. J Clin Endocrinol 62:64–69
Tahayama S. Hirata Y (1983) Incidence of insulin autoimmune hypoglycemia in Japan during the three year period from 1979 to 1981. Diabetes 32 [Suppl]:150A
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Trenn, G., Eysselein, V., Mellinghoff, H.U. et al. Clinical and biochemical aspects of the insulin autoimmune syndrome (IAIS). Klin Wochenschr 64, 929–934 (1986). https://doi.org/10.1007/BF01728618
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01728618