Adrenal Insufficiency after Incomplete Resection of Pituitary Macrocorticotropinoma of Cushing's Disease. Role of High Molecular Weight ACTH.

Abstract

Abstract.A 15-year-old girl with Cushing's disease exhibited adrenal insufficiency following incomplete transsphenoidal resection of a large pituitary corticotropinoma, approximately 35 mm in diameter. Within two weeks following surgery, her plasma ACTH level decreased from 42 to 13 pmol/1, while, her plasma cortisol levels and urinary excretion of free cortisol decreased from 607 nmol/l and 1112 nmol/day to 94 nmol/l and 55 nmol/day, respectively. Immunoreactive ACTH was characterized in plasma using Sephadex G-75 column chromatography and measuring ACTH with immunoradiometric assay (IRMA) and radioimmunoassay (RIA) to determine additional peaks, other than the one demonstrated for 1-39 ACTH.In particular, when measured with RIA, a broad peak including the high molecular weight ACTH was detected as well as 1-39 ACTH.The bioactivity of the high molecular weight ACTH in patient plasma was lower than the reference range of 1-39 ACTH, which is determined by the ability of dispersed rat adrenocortical cells to secrete corticosterone.The large pituitary corticotropinoma found in this patient secreted not only 1-39 ACTH but also high molecular weight proopiomelanocortin (POMC)-derived peptides, which could be detected by measuring with IRMA and RIA for ACTH.Based on the results of biological activity and molecular ratios, no positive evidence could be found to support the hypothesis that the high molecular weight ACTH induced any postoperative adrenal insufficiency in this patient. However, based on this study, the possibility of adrenal insufficiency should be carefully monitored, even when post-operative remnant tumor tissue is clearly present in patients with Cushing's disease, accompanied by macrocorticotropinoma.

Malignant Gastric Carcinoid Causing Ectopic ACTH Syndrome: Discrepancy of Plasma ACTH Levels Measured by Different Immunoradiometric Assays

“…In contrast to high ACTH levels determined by Allegro ® assay kit, those determined by Yuka ® assay kit in the same patient's plasma samples were almost normal. Two-site IRMA kit by Allegro ® employs 125 I-labeled antibody against Nterminal fragment (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and antibody against Cterminal fragment(34-39) of ACTH, while that by Yuka ® employs 125 I-labeled antibody against Nterminal fragment (20)(21)(22)(23) and antibody against Cterminal fragment(35-39) of ACTH, respectively. These data strongly suggest that various circulating forms of ACTH molecule in patient's plasma could be differentially recognized by these two different IRMA kits.…”

“…Concentrations of ACTH and b-endorphin were determined by conventional specific radioimmunoassays (RIA) [9,15,16]. The anti-ACTH antibody used fully recognizes ACTH and ACTH(1-39) and POMC, but not with a-MSH, b-endorphin or corticotropin-like intermediate lobe peptide (CLIP); the sensitivity was 2 pg/ml.…”

Reversible impairment of the processing of proopiomelanocortin into ACTH in pituitary enlargement suspected of lymphocytic hypophysitis

“…ACTH after administration of CRH, it was possible that her plasma ACTH had low bioactivity. Sephadex G75 gel exclusion chromatography was performed to determine the size of her plasma ACTH (kindly performed by Dr. Yutaka Oki, the Second Department of Internal Medicine, Hamamatsu University School of Medicine) [4][5][6]. The blood samples showing the basal and peak values after administration of CRH were used for analysis.…”

Isolated Adrenocorticotropin Deficiency Concomitant with Graves' Disease: A Case Report and Literature Review

“…However, there are reported cases of secondary AI in which bioinactive ACTH, which produce a high measured plasma ACTH value, are present (7)(8)(9). Some of these are high molecular weight peptides, such as pro-ACTH and POMC, which are also referred to as "big ACTH" (10,11).…”