Journal of Clinical Endocrinology & Metabolism, Vol 70, 1391-1397, Copyright © 1990 by Endocrine Society

ARTICLES

Isolated adrenocorticotropin deficiency associated with an autoantibody to a corticotroph antigen that is not adrenocorticotropin or other proopiomelanocortin-derived peptides

NP Sauter, R Toni, CD McLaughlin, EM Dyess, J Kritzman and RM Lechan
Department of Medicine, New England Medical Center Hospital, Boston, Massachusetts 02111.

A 44-yr-old man with hypocortisolism was shown to have an undetectable basal plasma ACTH level and absent or subnormal ACTH and beta- lipotropin responses to provocative testing with insulin, vasopressin, and CRH. Endocrine function after glucocorticoid replacement was otherwise normal, thus establishing the diagnosis of isolated ACTH deficiency. This patient's serum was tested immunohistochemically for the presence of an antipituitary antibody by indirect immunofluorescence of rat pituitary tissue. Positive immunostaining was observed in stellate-shaped cells in the anterior and intermediate lobes. Immunopositive cells were shown by immunoelectron microscopy to have ultrastructural characteristics of corticotrophs. Immunoreactivity was concentrated in secretory granules 120-170 nm in diameter. In a double immunolabeling procedure, staining by the patient's serum was shown to colocalize with rabbit antiserum to ACTH, but not with antisera to PRL, GH, beta TSH, or beta LH. Immunoabsorption of the patient's serum with ACTH-(1-24), ACTH-(1-39), gamma MSH, corticotropin- like intermediate lobe peptide, beta-endorphin, or beta-lipotropin failed to diminish immunolabeling in the pituitary. We conclude that the antipituitary antibody in this patient's serum shows immunohistochemical specificity for a rat corticotroph antigen located in secretory granules that is neither ACTH nor any of the proopiomelanocortin (POMC)-derived peptides tested. The autoantigen could be a cell-specific granular factor involved in the posttranslational processing of POMC or secretion of ACTH. We postulate that an autoimmune process may account for this patient's disease, and that his antipituitary antibody could play a pathogenic role by either inhibiting a POMC-processing enzyme or initiating an antibody-dependent cell-mediated cytotoxicity reaction, resulting in the selective destruction of corticotrophs.

This article has been cited by other articles:

				A. De Bellis, M. Salerno, M. Conte, C. Coronella, G. Tirelli, M. Battaglia, V. Esposito, G. Ruocco, G. Bellastella, A. Bizzarro, et al. Antipituitary Antibodies Recognizing Growth Hormone (GH)-Producing Cells in Children with Idiopathic GH Deficiency and in Children with Idiopathic Short Stature J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2484 - 2489. [Abstract] [Full Text] [PDF]

				P. Caturegli, C. Newschaffer, A. Olivi, M. G. Pomper, P. C. Burger, and N. R. Rose Autoimmune Hypophysitis Endocr. Rev., August 1, 2005; 26(5): 599 - 614. [Abstract] [Full Text] [PDF]

				A. De Bellis, A. Bizzarro, M. Conte, S. Perrino, C. Coronella, S. Solimeno, A. M. Sinisi, L. A. Stile, G. Pisano, and A. Bellastella Antipituitary Antibodies in Adults with Apparently Idiopathic Growth Hormone Deficiency and in Adults with Autoimmune Endocrine Diseases J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 650 - 654. [Abstract] [Full Text] [PDF]

				An unusual case of diarrhoea and weight loss Postgrad. Med. J., June 1, 2001; 77(908): 412h - 412. [Full Text]

				I. S. Farooqi, M. K. Jones, M. Evans, S. O’Rahilly, and J. R. Hodges Triple H Syndrome: A Novel Autoimmune Endocrinopathy Characterized by Dysfunction of the Hippocampus, Hair Follicle, and Hypothalamic-Pituitary-Adrenal Axis J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2644 - 2648. [Full Text]

				P. A. Crock Cytosolic Autoantigens in Lymphocytic Hypophysitis J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 609 - 618. [Abstract] [Full Text]