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British Medical Journal (Clinical Research Ed.) logoLink to British Medical Journal (Clinical Research Ed.)
. 1988 May 28;296(6635):1489–1491. doi: 10.1136/bmj.296.6635.1489

Antibody that blocks stimulation of cortisol secretion by adrenocorticotrophic hormone in Addison's disease

Pat Kendall-Taylor, Ann Lambert, Robert Mitchell, William R Robertson
PMCID: PMC2546014  PMID: 2839266

Abstract

To investigate whether Addison's disease may in some cases be due to the blocking of adrenocorticotrophic hormone's action at the adrenal cortex by antibodies IgG isolated from a woman with Addison's disease associated with the autoimmune polyglandular syndrome type I was studied. Its effects on guinea pig adrenal cells in vitro were investigated and compared with those of IgG from three normal subjects and IgG obtained commercially. IgG from the patient inhibited the stimulation of cortisol secretion by adrenocorticotrophic hormone by 77 (SD 2)% and 57 (12)% at concentrations of 0·5 and 0·05 g/l, respectively; IgG prepared five months after she had started treatment with replacement steroids inhibited cortisol secretion by 74 (1)% (0·5 g/l) and 51 (15)% (0·05 g/l). The other IgGs had no inhibitory effects. The IgG from the patient and that obtained commercially did not inhibit the stimulation of cortisol secretion by dibutyryl cyclic adenosine monophosphate or precursors of cortisol. None of the IgGs bound to adrenocorticotrophic hormone.

These results suggest that the IgG from the patient acted against the receptor for adrenocorticotrophic hormone, and its presence may explain the patient's raised concentrations of adrenocorticotrophic hormone, failure to respond to exogenous adrenocorticotrophic hormone, and normal basal cortisol concentrations. Addison's disease may thus in some instances be a receptor antibody disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J. R., Goudie R. B., Gray K., Stuart-Smith D. A. Immunological features of idiopathic Addison's disease: an antibody to cells producing steroid hormones. Clin Exp Immunol. 1968 Feb;3(2):107–117. [PMC free article] [PubMed] [Google Scholar]
  2. Arulanantham K., Dwyer J. M., Genel M. Evidence for defective immunoregulation in the syndrome of familial candidiasis endocrinopathy. N Engl J Med. 1979 Jan 25;300(4):164–168. doi: 10.1056/NEJM197901253000403. [DOI] [PubMed] [Google Scholar]
  3. Blecher M. Receptors, antibodies, and disease. Clin Chem. 1984 Jul;30(7):1137–1156. [PubMed] [Google Scholar]
  4. Chiauzzi V., Cigorraga S., Escobar M. E., Rivarola M. A., Charreau E. H. Inhibition of follicle-stimulating hormone receptor binding by circulating immunoglobulins. J Clin Endocrinol Metab. 1982 Jun;54(6):1221–1228. doi: 10.1210/jcem-54-6-1221. [DOI] [PubMed] [Google Scholar]
  5. ESSELBORN V. M., LANDING B. H., WHITAKER J., WILLIAMS R. R. The syndrome of familial juvenile hypoadrenocorticism, hypoparathyroidism and superficial moniliasis. J Clin Endocrinol Metab. 1956 Oct;16(10):1374–1387. doi: 10.1210/jcem-16-10-1374. [DOI] [PubMed] [Google Scholar]
  6. Lambert A., Frost J., Garner C., Robertson W. R. Cortisol production by dispersed guinea-pig adrenal cells; a specific, sensitive and reproducible response to ACTH....and its fragments. J Steroid Biochem. 1984 Aug;21(2):157–162. doi: 10.1016/0022-4731(84)90377-7. [DOI] [PubMed] [Google Scholar]
  7. Maclaren N. K., Riley W. J. Inherited susceptibility to autoimmune Addison's disease is linked to human leukocyte antigens-DR3 and/or DR4, except when associated with type I autoimmune polyglandular syndrome. J Clin Endocrinol Metab. 1986 Mar;62(3):455–459. doi: 10.1210/jcem-62-3-455. [DOI] [PubMed] [Google Scholar]
  8. Neufeld M., Maclaren N., Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann. 1980 Apr;9(4):154–162. [PubMed] [Google Scholar]
  9. Oliver J. R., Hakendorf P., Zeegers P., Ross W. A proposed simple method for detection and measurement of antibodies to insulin in serum by use of Staphylococcus aureus containing protein A. Clin Chem. 1982 Jan;28(1):121–123. [PubMed] [Google Scholar]
  10. Petri M., Nerup J. Addison's adrenalitis. Studies on diffuse lymphocytic adrenalitis (idiopathic Addison's disease) and focal lymphocytic infiltration in a control material. Acta Pathol Microbiol Scand A. 1971;79(4):381–388. [PubMed] [Google Scholar]
  11. Runcie C. J., Semple C. G., Slater S. D. Addison's disease without pigmentation. Scott Med J. 1986 Apr;31(2):111–112. doi: 10.1177/003693308603100212. [DOI] [PubMed] [Google Scholar]
  12. Steel N. R., Weightman D. R., Taylor J. J., Kendall-Taylor P. Blocking activity to action of thyroid stimulating hormone in serum from patients with primary hypothyroidism. Br Med J (Clin Res Ed) 1984 May 26;288(6430):1559–1562. doi: 10.1136/bmj.288.6430.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Takasu N., Yamada T., Katakura M., Yamauchi K., Shimizu Y., Ishizuki Y. Evidence for thyrotropin (TSH)-blocking activity in goitrous Hashimoto's thyroiditis with assays measuring inhibition of TSH receptor binding and TSH-stimulated thyroid adenosine 3',5'-monophosphate responses/cell growth by immunoglobulins. J Clin Endocrinol Metab. 1987 Feb;64(2):239–245. doi: 10.1210/jcem-64-2-239. [DOI] [PubMed] [Google Scholar]
  14. Teding van Berkhout F., Croughs R. J., Kater L., Schuurman H. J., Gmelig Meyling F. J., Kooyman C. D., van der Gaag R. D., Jolink D., Drexhage H. A. Familial Cushing's syndrome due to nodular adrenocortical dysplasia. A putative receptor-antibody disease? Clin Endocrinol (Oxf) 1986 Mar;24(3):299–310. doi: 10.1111/j.1365-2265.1986.tb03271.x. [DOI] [PubMed] [Google Scholar]
  15. Weightman D. R., Shale D. J., Tomlinson W. R. A rapid radioassay for human IgG produced in lymphocyte in vitro culture systems. J Immunol Methods. 1981;46(3):307–312. doi: 10.1016/0022-1759(81)90315-x. [DOI] [PubMed] [Google Scholar]
  16. de Aizpurua H. J., Ungar B., Toh B. H. Autoantibody to the gastrin receptor in pernicious anemia. N Engl J Med. 1985 Aug 22;313(8):479–483. doi: 10.1056/NEJM198508223130805. [DOI] [PubMed] [Google Scholar]

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