Correspondence

Screening Patients with Insulin-Dependent Diabetes Mellitus for Adrenal Insufficiency

N Engl J Med 1997; 337:202July 17, 1997

Article

To the Editor:

The occurrence of multiple organ-specific autoimmune disorders in the same patient has been well recognized.1 Because of improved assays for adrenal autoantibodies, we recently instituted routine testing of patients with insulin-dependent diabetes mellitus (IDDM) for antibodies against 21-hydroxylase, using the radioassay described by Falorni and coworkers.2

In 11 of 629 patients with IDDM (age, 11 to 40 years) but none of 239 normal subjects, serum samples were positive for 21-hydroxylase antibodies. Among the 11 patients with positive tests, 2 brothers were found to have adrenal insufficiency and 1 patient was antibody-positive at the time of the initial evaluation and diagnosis of adrenal insufficiency. Five patients with positive tests for antibodies against 21-hydroxylase had normal adrenal function, and the remaining three have not been tested.

The two brothers with adrenal insufficiency had remarkable clinical histories. The younger brother missed a year of school at the age of 10 because of severe fatigue, and from a review of photographs had hyperpigmentation by the age of 11, with adrenal insufficiency diagnosed at the age of 17, after 21-hydroxylase antibodies were detected. The older brother was hospitalized at the age of 22 with severe hypotension and the acute respiratory distress syndrome after a pneumococcal vaccination. He survived with pressor therapy and at discharge had a diagnosis of ``shock syndrome, most likely toxigenic,'' although bacterial cultures were negative; adrenal insufficiency was diagnosed one year later, after 21-hydroxylase antibodies were detected.

We currently screen patients with IDDM for thyroid dysfunction (with serum thyrotropin determinations), adrenal dysfunction (with tests for 21-hydroxylase antibodies); and celiac disease3 (with tests for antiendomysial antibodies). In approximately 5 percent of patients with IDDM hypothyroidism or hyperthyroidism develops, and approximately the same proportion have antiendomysial antibodies; for example, of 168 patients we studied, 10 (6 percent) tested positive for antiendomysial antibodies. More than 60 percent of patients with IDDM who have these antibodies have celiac disease at biopsy. We recommend the routine screening of patients with IDDM for associated autoimmune disorders, including adrenal insufficiency.

Karl W. Brewer, B.E.D.
University of Colorado Health Sciences Center, Denver, CO 80262

Vincent S. Parziale, M.D.
Thomas-Davis Medical Centers, Scottsdale, AZ 85258

George S. Eisenbarth, M.D., Ph.D.
University of Colorado Health Sciences Center, Denver, CO 80262

3 References

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   Eisenbarth GS, Jackson RA. The immunoendocrinopathy syndromes. In: Wilson JD, Foster DW, eds. Williams textbook of endocrinology. 8th ed. Philadelphia: W.B. Saunders, 1992:1555-66.
   

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   Falorni A, Nikoshkov A, Laureti S, et al. High diagnostic accuracy for idiopathic Addison's disease with a sensitive radiobinding assay for autoantibodies against recombinant human 21-hydroxylase. J Clin Endocrinol Metab 1995;80:2752-2755
   CrossRef | Web of Science | Medline

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   Ferreira M, Davies SL, Butler M, Scott D, Clark M, Kumar P. Endomysial antibody: is it the best screening test for coeliac disease? Gut 1992;33:1633-1637
   CrossRef | Web of Science | Medline

Citing Articles (10)

Citing Articles

1. 1

   Alberto Falorni, Shu Chen, Renato Zanchetta, Liping Yu, Claudio Tiberti, Maria Luisa Bacosi, Jadwiga Furmaniak, Vittorio Bini, Francesco Dotta, George S. Eisenbarth, Bernard Rees Smith, Corrado Betterle. (2011) Measuring adrenal autoantibody response: Interlaboratory concordance in the first international serum exchange for the determination of 21-hydroxylase autoantibodies. Clinical Immunology 140:3, 291-299
   CrossRef

2. 2

   Jenn-Tzong Chang, Ying-Yao Chen, Pao-Chin Chiu. (2010) 21-hydroxylase Autoantibody-negative Addison's Disease in a 5-year-old Boy with Adrenal Crisis and Type 1 Diabetes Mellitus. Journal of Pediatric Endocrinology and Metabolism 23:11, 1201-1205
   CrossRef

3. 3

   MICHAEL J. HALLER, WILLIAM E. WINTER, DESMOND A. SCHATZ. 2008. Autoimmune Polyglandular Syndromes. , 770-787.
   CrossRef

4. 4

   James B. Thomas, Nikolai Petrovsky, Geoffrey R. Ambler. (2004) Addison's disease presenting in four adolescents with type 1 diabetes. Pediatric Diabetes 5:4, 207-211
   CrossRef

5. 5

   R. Nigam, E. Bhatia, D. Miao, L. Yu, A. Brozzetti, G. S. Eisenbarth, A. Falorni. (2003) Prevalence of adrenal antibodies in Addison's disease among north Indian Caucasians. Clinical Endocrinology 59:5, 593-598
   CrossRef

6. 6

   Y.S. Park, C.B. Sanjeevi, D. Robles, L. Yu, M. Rewers, P.A. Gottlieb, P. Fain, G.S. Eisenbarth. (2002) Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease. Tissue Antigens 60:2, 155-163
   CrossRef

7. 7

   David T Robles, Pamela R Fain, Peter A Gottlieb, George S Eisenbarth. (2002) The genetics of autoimmune polyendocrine syndrome type II. Endocrinology & Metabolism Clinics of North America 31:2, 353-368
   CrossRef

8. 8

   Alberto Falorni, Stefano Laureti, Fausto Santeusanio. (2002) Autoantibodies in autoimmune polyendocrine syndrome type II. Endocrinology & Metabolism Clinics of North America 31:2, 369-389
   CrossRef

9. 9

   ALBERTO FALORNI, FILIPPO CALCINARO. (2002) Autoantibody Profile and Epitope Mapping in Latent Autoimmune Diabetes in Adults. Annals of the New York Academy of Sciences 958:1, 99-106
   CrossRef

10. 10

    Giovanni Gambelunghe, Francesca Forini, Stefano Laureti, Giuseppe Murdolo, Gianluca Toraldo, Fausto Santeusanio, Paolo Brunetti, Carani B. Sanjeevi, Alberto Falorni. (2000) Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies. Clinical Endocrinology 52:5, 565-573
    CrossRef