The role of adrenal venous sampling (AVS) in primary bilateral macronodular adrenocortical hyperplasia (PBMAH): a study of 16 patients

Abstract

Objective Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of ACTH-independent Cushing’s syndrome. Current guidelines recommend bilateral adrenalectomy for PBMAH, but several studies showed clinical effectiveness of unilateral adrenalectomy despite bilateral disease in selected patients. Our aim was to evaluate the gain of information which can be obtained through adrenal venous sampling (AVS) based cortisol lateralization ratios for guidance of unilateral adrenalectomy. Design We performed a retrospective analysis of 16 patients with PBMAH and clinical overt cortisol secretion in three centers Methods Selectivity of adrenal vein sampling during AVS was defined as a gradient of cortisol or a reference adrenal hormone ≥2.0 between adrenal and peripheral vein. Lateralization was assumed if the dominant to non-dominant ratio of cortisol to reference hormone was ≥4.0. Results AVS was technically successful in all patients based on absolute cortisol levels and in 13 of 16 patients (81%) based on reference hormone levels. Lateralization was documented in 8 of 16 patients. In patients with lateralization, in 5 of 8 cases this occurred toward morphologically larger adrenals, while in 3 patients lateralization was present in bilaterally identical adrenals. The combined volume of adrenals correlated positively with urinary free cortisol, suggesting that adrenal size is the dominant determinant of cortisol secretion. Conclusions In this study the gain of information through AVS for unilateral adrenalectomy was limited in patients with PBMAH and marked adrenal asymmetry.

Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia

“…AVS was performed to identify a hormonally dominant side of cortisol production to guide unilateral adrenalectomy. Most of these patients (patients 1 to 12, patient 17 and patient 18) were already part of our study on the clinical role of AVS in PBMAH ( 14 ). As described also in that publication, patients underwent biochemical screening for Cushing’s syndrome by the three recommended screening tests: 1-mg dexamethasone suppression test (LDDST), late-night salivary cortisol (LNSLC) and 24h urinary free cortisol (UFC), all performed using immunoassay.…”

“…Germline ARMC5 (armadillo repeat containing 5) sequencing was performed in 15 patients. Inactivating mutations of ARMC5 , a putative tumor-suppressor gene, are associated with a more severe hypercortisolism, bigger adrenals with a higher number of nodules ( 15 ).The assays for the screening tests, baseline ACTH and ARMC5 status were described in the online Supplementary Material ( 14 ).…”

“…The decision to perform AVS for patients with bilateral adrenal masses was made independently by the treating endocrinologist before 2012 or by a multidisciplinary endocrine board since 2012. Our group described in detail the exact procedure previously ( 14 ). AVS was conducted without ACTH stimulation and peripheral blood samples were collected simultaneously with each of the selective blood samples.…”

“…Recommendation for unilateral or bilateral adrenalectomy was not based on the results of LC-MS/MS presented in this study. The decision of the interdisciplinary tumour board was guided instead by the severity of CS (clinically and biochemically), the results of radiologic studies, plus AVS results measured with immunoassay as described in our previous study ( 14 ).…”

Adrenal venous sampling for lateralization of cortisol hypersecretion in patients with bilateral adrenal masses

“…A recent study reviewed 16 patients with PBMAH: 11 with CS and 5 with incidental detection of adrenal masses. 23 In their study, they concluded that the use of AVS in the context of CS due to PBMAH with marked asymmetry of the adrenal glands is limited. Unlike our study, lateralization toward the smaller adrenal gland was not seen in any of these patients.…”