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Background: To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA)., Methods: Consecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists., Results: In total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52-0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01)., Conclusion: Contrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The increasing detection of adrenal tumors and the availability of a more sophisticated biochemical work-up leading to rising numbers of sub-clinical Conn's and Cushing's syndromes coincide with a rising number of adrenalectomies worldwide. The aim of our study was to report a single institution's experience with adrenal surgery., Methods: We report data of 528 adrenalectomies, operated at our institution before and after the onset of minimally invasive endoscopic surgery (1986-1994, 1995-2008). Gender, age, indication, imaging, surgical approach, operating time, histology, tumor size, hospital stay, and complications were analyzed retrospectively., Results: A total of 478 patients underwent adrenal surgery during the time observed. The average number of yearly adrenalectomies increased from 14 to 21 (p = 0.001) after the onset of laparoscopic surgery. Imaging techniques showed a significant shift towards magnetic resonance imaging (p < 0.001) and preoperative assessment of tumor size was significantly correlated to malignancy: 10.8 % (11/102) and 42 % (21/50) of tumors measuring 4-6 cm and ≥6 cm, respectively, were malignant in the final histology report (p < 0.001). Patients operated by minimally invasive endoscopy were significantly younger (mean 49.4 years, p = 0.046), had significantly shorter operating times (mean 118 min, p < 0.001), had shorter hospital stays (mean 7.1 days, p < 0.001), and had less complications (6.9 %, p = 0.004) compared to patients resected through open procedures., Conclusion: Although adrenalectomy rates increased and minimally invasive endoscopic surgery reduced hospital stay and complications at our institution, the yearly number of procedures was still low with often high surgical complexity. We therefore believe that adrenal surgery remains a highly specialized procedure that should preferably be performed at endocrine surgery centers.

The adrenal gland contains a well-organized network of blood vessels, and adrenocortical cells are situated in close proximity to endothelial cells. Recently, several new mechanisms have been characterized that control the release of aldosterone by adrenocortical cells, including the involvement of endothelial-cell-derived factors. Interestingly, a CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), which is necessary for adrenal development, has been linked to aldosterone synthesis. We have therefore examined the effects of endothelial-cell-conditioned medium (ECCM), as produced during the incubation of human umbilical vein endothelial cells for 24 h, on the promoter activity and mRNA and protein expression of CITED2 in adrenocortical cells as represented by the NCI-H295R cell line. We have found a dose-dependent effect of ECCM on CITED2 promoter activity; this peaks at 480%. Activation of the CITED2 promoter occurs in parallel to an increase in CITED2 messenger RNA (as quantified by real-time polymerase chain reaction) and protein. The stimulatory effect of ECCM can be reversed by blocking mitogen-activated protein kinase activity with the MEK1-inhibitor PD98059. We conclude that products secreted by endothelial cells control not only steroidogenesis, but also factors that are important for adrenocortical development, thereby highlighting the role of cellular interactions within adrenocortical development and physiology.

Decrease in connexin (Cx) expression and loss of gap junctional intercellular communication (GJIC) have been associated with aberrant cell growth and enhanced neoplastic phenotype. We studied the expression of Cx26, Cx32, Cx43, and Cx50 in chromaffin cells of 10 normal human adrenal glands, 10 benign, and 13 malignant pheochromocytomas. Immunohistochemistry showed that Cx50 expression seemed to be the predominant form of Cx expressed in human chromaffin cells, whereas Cx43 immunoreactivity was the most prominent form found in the adrenal cortex. However, Western blotting revealed that nonphosphorylated and singly and doubly phosphorylated forms of Cx43 were present within the malignant adrenomedullary cells at the same time. Cx26 and Cx32 were distributed inhomogeneously with no emphasis of expression in the types of tissues studied. Cx50 expression was diminished in malignant pheochromocytomas. We conclude that there is a differential expression of Cx in human adrenals. Immunohistological testing for Cx expression does not however allow differentiation of benign from malignant pheochromocytomas.

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters. [ABSTRACT FROM AUTHOR]

Objective: Fibroblast growth factor receptor (FGFR) 2 regulates the development of the adrenal gland in mice. In addition, FGFR2-mediated signalling has been shown to prevent apoptosis and to enhance proliferation in adrenocortical precursor cells. The activation of the Wingless/Int-1 (WNT)/beta catenin pathway as a key mechanism of adrenocortical tumourigenesis has been linked to FGFR2 signalling in other cell types. Therefore we hypothesised that FGFR2 expression may also play a role in adrenocortical carcinoma (ACC). We conducted a pilot study and analysed protein expression of FGFR2 in 26 ACCs using immunohistochemistry technique. Data on the CTNNB1 mutation status and clinical data were correlated to the expression of FGFR2. Results: We observed a high variability in FGFR2 expression between the different tumour samples. There was a subset of ACC with comparatively high nuclear expression of FGFR2. We did not find a clear association between the CTNNB1 mutational status or clinical features and the FGFR2 expression. We conclude that FGFR signalling plays a role in adrenocortical carcinoma. Our data encourages further investigations of FGFR signalling in ACC, especially since new inhibitors of FGFR signalling are already entering clinical trials for the treatment of other cancer types. [ABSTRACT FROM AUTHOR]