Clinical Spectrum of Adrenal Cushing’s Syndrome and the Caution for Interpretation of Adrenocorticotrophic Hormone: A Single-Center Experience

Abstract

To describe the differences in presentation, biochemistry, and radiological evaluation of various etiologies of adrenal Cushing’s syndrome (CS) from a single center. To emphasize caution for interpretation of plasma adrenocorticotropic hormone (ACTH), as a spuriously unsuppressed ACTH level by immunometric assay may lead to therapeutic misadventures in adrenal CS. Design: Retrospective, single-center, observational study. Methods: Fifty-eight adrenal CS patients [Adrenocortical carcinoma (ACC), n=30; Adenoma (ACA), n=15; Primary pigmented nodular adrenocortical disease (PPNAD), n=10; ACTH independent macronodular adrenal hyperplasia (AIMAH), n=3) evaluated at a tertiary care center in western India between January 2006 to March 2020 were included. Data on demography, clinical evaluation, biochemistry, imaging, management, histopathology, and outcome were recorded in a standard format and analyzed. Results: Cortisol secreting ACC presented at 38(1–50) years with abdominal mass in 26/30 (86.7%) and 16/30 (53.3%) had metastases at presentation. ACA with autonomous cortisol excess presented at 25(4.9–40) years with discriminating features of CS in 14/15 (93.3%), sex steroid production in 2/15, unenhanced HU <10 in only one, and relative washout >40% in 8/11 (72.7%). One ACA and eight ACC patients had plasma ACTH (by Siemens Immulite assay) > 20 pg/ml, despite hypercortisolemic state. Conclusions: Cortisol-secreting ACC and ACA most often present with mass effects and florid CS, respectively. Baseline HU has low sensitivity to differentiate cortisol-secreting ACA from ACC. Plasma ACTH measured by Seimens Immulite is often unsuppressed, especially in ACC patients, which can be addressed by measuring ACTH by more accurate assays.

Low DHEAS Level: A Surrogate Marker of Adrenal Cushing Syndrome with Grey Zone ACTH Levels

“…[ 1 ] IMMULITE-1000 platform, primarily used in this study, is also known to have a positive bias when compared to ROCHE cobas E411 platform. [ 3 , 4 ] Thus, ACTH levels of 10–20 pg/ml may actually be diagnostic of adrenal CS in the IMMULITE platform unlike the ROCHE platform or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. [ 3 , 4 ] Notably, only one patient with ACTH-dependent CS had ACTH in 10–30 pg/ml range, whereas one patient with adrenal adenoma had ACTH in the 20–30 pg/mL range.…”

“…[ 3 , 4 ] Thus, ACTH levels of 10–20 pg/ml may actually be diagnostic of adrenal CS in the IMMULITE platform unlike the ROCHE platform or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. [ 3 , 4 ] Notably, only one patient with ACTH-dependent CS had ACTH in 10–30 pg/ml range, whereas one patient with adrenal adenoma had ACTH in the 20–30 pg/mL range. Hence, increasing the ACTH cut-off to 30 pg/mL could reliably distinguish adrenal adenomas from ACTH-dependent CS except one case in each in present cohort.…”