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Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid.
Clin Endocrinol (Oxf) 2014; 81(2):204-9CE

Abstract

OBJECTIVE

Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl-containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients.

RESEARCH DESIGN AND METHODS

Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized.

RESULTS

Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day). HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA-DRB1*04:06 allele was present in one patient.

CONCLUSIONS

This is the first report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.

Authors+Show Affiliations

Endocrinologia, Garibaldi-Nesima Medical Center and University of Catania, Catania, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24111525

Citation

Gullo, Damiano, et al. "Insulin Autoimmune Syndrome (Hirata Disease) in European Caucasians Taking Α-lipoic Acid." Clinical Endocrinology, vol. 81, no. 2, 2014, pp. 204-9.
Gullo D, Evans JL, Sortino G, et al. Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid. Clin Endocrinol (Oxf). 2014;81(2):204-9.
Gullo, D., Evans, J. L., Sortino, G., Goldfine, I. D., & Vigneri, R. (2014). Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid. Clinical Endocrinology, 81(2), pp. 204-9. doi:10.1111/cen.12334.
Gullo D, et al. Insulin Autoimmune Syndrome (Hirata Disease) in European Caucasians Taking Α-lipoic Acid. Clin Endocrinol (Oxf). 2014;81(2):204-9. PubMed PMID: 24111525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid. AU - Gullo,Damiano, AU - Evans,Joseph L, AU - Sortino,Grazia, AU - Goldfine,Ira D, AU - Vigneri,Riccardo, Y1 - 2013/10/23/ PY - 2013/07/09/received PY - 2013/07/31/revised PY - 2013/09/12/revised PY - 2013/09/12/accepted PY - 2013/10/12/entrez PY - 2013/10/12/pubmed PY - 2015/3/31/medline SP - 204 EP - 9 JF - Clinical endocrinology JO - Clin. Endocrinol. (Oxf) VL - 81 IS - 2 N2 - OBJECTIVE: Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl-containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients. RESEARCH DESIGN AND METHODS: Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized. RESULTS: Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day). HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA-DRB1*04:06 allele was present in one patient. CONCLUSIONS: This is the first report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS. SN - 1365-2265 UR - https://www.unboundmedicine.com/medline/citation/24111525/full_citation L2 - https://doi.org/10.1111/cen.12334 DB - PRIME DP - Unbound Medicine ER -