A Rare Case of Adrenocorticotropic Hormone (ACTH)-independent Macroadrenal Hyperplasia Showing Ectopic Production of ACTH

Abstract

A 57-year-old Japanese man presented with drug-resistant hypertension without Cushingoid features. Endocrinological tests revealed autonomous secretion of cortisol with suppressed plasma adrenocorticotropic hormone (ACTH). Imaging examinations showed multiple macronodules in the bilateral adrenal gland. These findings were consistent with subclinical Cushing's syndrome caused by ACTH-independent macronodular adrenal hyperplasia (AIMAH). Left adrenalectomy was performed and the resected adrenal lesion was consistent with the pathological diagnosis of AIMAH. Furthermore, in resected tissue, we demonstrated intraadrenal production of ACTH by immunohistochemical analysis and RIA. This is a very rare case of AIMAH showing ectopic production of ACTH, which may be associated with autonomous cortisol secretion.

Primary bilateral macronodular adrenal hyperplasia

“…Ectopic ACTH production was previously reported in steroidogenic cells in a few cases of BMAH [39,40]. A recent extensive study summarized here reveals that the paracrine production of ACTH was much more prevalent and under more complex regulation than previously recognized amplifying the effect of the aberrant receptors' ligands.…”

Intra‐adrenal corticotropin in bilateral macronodular adrenal hyperplasia: Report of two Japanese cases

“…However, Iwata et al . previously reported a case of bilateral macronodular adrenal hyperplasia showing ectopic production of corticotropin . After that, an analysis of 30 cases of bilateral macronodular adrenal hyperplasia with subclinical or overt Cushing's syndrome was carried out .…”

“…However, Iwata et al previously reported a case of bilateral macronodular adrenal hyperplasia showing ectopic production of corticotropin. 3 After that, an analysis of 30 cases of bilateral macronodular adrenal hyperplasia with subclinical or overt Cushing's syndrome was carried out. 1 The adrenal tumors in our current two Japanese cases of bilateral macronodular adrenal hyperplasia showed that corticotropin is produced by a subpopulation of steroidogenic cells in the hyperplastic adrenals.…”

Genetics of primary macronodular adrenal hyperplasia

“…This implies that ectopic production of ACTH might induce adrenocortical hyperplasia and cortisol secretion (Pereira et al 2001, Lefebvre et al 2003, Mazzuco et al 2007, Iwata et al 2012.…”