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Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers. [ABSTRACT FROM AUTHOR]

Adrenocortical carcinomas (ACC) are rare endocrine malignancies, often with a poor prognosis. Visfatin/NAMPT regulates a variety of signaling pathway components, and its overexpression has been found in carcinogenesis. Our study aimed to assess the clinical usefulness of visfatin/NAMPT serum level in discriminating between ACC and benign adrenocortical tumors. Twenty-two patients with ACC and twenty-six patients with benign adrenocortical tumors were recruited. Fasting blood samples were collected from each patient, and visfatin serum levels were measured with the ELISA Kit. Clinical stage, tumor size, Ki67 proliferation index, hormonal secretion pattern, and follow-up were determined in ACC patients. Patients with ACC had significantly higher visfatin serum concentrations (7.81 ± 2.25 vs. 6.08 ± 1.32 ng/mL, p-value = 0.003). The most advanced clinical stage with metastases was associated with significantly elevated visfatin levels (p-value = 0.022). Based on ROC analysis, visfatin serum concentrations higher than 8.05 ng/mL could discriminate ACC with a sensitivity of 50.0% and specificity of 92.3%. Univariate Cox regression indicated that tumor size was significantly related to shorter survival, and the visfatin level was borderline significant in all patients (HR = 1.013, p-value = 0.002, HR = 1.321, p-value = 0.058). In the Kaplan-Meier method, patients with visfatin serum concentrations higher than 6.3 ng/mL presented significantly lower survival probability (p-value = 0.006). Serum visfatin/NAMPT could be a potential risk predictor for the malignancy of adrenal tumors. However, further studies are needed on this subject. [ABSTRACT FROM AUTHOR]

Introduction. Ghrelin, originally isolated from the endocrine cells of the gastric mucosa, is also expressed in many peripheral tissues, including normal adrenals and adrenocortical tumors. It was shown that ghrelin stimulates proliferation and inhibits apoptosis of adrenocortical cells. In the current study, we compared ghrelin expression at the protein level in various adrenal tumors. We analyzed whether immunoreactive ghrelin could be considered as a potential marker for different types of adrenal tumors. Material and methods. Study was carried out on 200 adrenal specimens arranged on microscope slide in tissue microarray format. We performed standardized immunohistochemical reactions with semiquantitative reaction intensity measurements. Results. At the protein level, the expression of ghrelin was significantly reduced in adrenocortical adenocarcinoma in relation to the control group and pheochromocytoma as well as cancer-adjacent normal adrenal tissue. In contrast, a relatively high ghrelin expression was found in pheochromocytoma compared to all analyzed groups, with the exception of cancer-adjacent normal adrenal tissue. Conclusions. The ghrelin expression profile at the protein level may be associated with the type of adrenal tumor. In this context, our results suggest that adrenal immunoreactive ghrelin may be considered as a sensitive and specific marker for differentiating adrenocortical carcinoma from adrenocortical adenoma and pheochromocytoma. [ABSTRACT FROM AUTHOR]

Summary: Context: Adrenal tumours belong to one of the most prevalent neoplasms. It is a heterogeneous group with different aetiology, clinical manifestation and prognosis. Its histopathologic diagnosis is difficult and identification of differentiation markers for tumorigenesis is extremely valuable for diagnosis. Design: To assess ghrelin expression and the relationship among ghrelin, IGF2 and the clinicopathological characteristics of adrenal tumours. To investigate the influence of ghrelin on ACC cell line proliferation. Materials and methods: Expression of ghrelin and IGF2 in a total of 84 adrenal tissue samples (30 adenoma, 12 hyperplasia, 8 myelolipoma, 20 pheochromocytoma, 7 carcinoma and 7 unchanged adrenal glands) were estimated. Every operated patient from whom samples were obtained underwent clinicopathological analysis. All the parameters were compared among the groups examined and correlations between these were estimated. H295R cell line was incubated with ghrelin to assess its effect on proliferation and migration rate. Results: The highest ghrelin expression was observed in carcinoma samples and the lowest in the control group. Ghrelin expression was 21 times higher in carcinoma (P = .017) and 2.4 times higher in adenoma (P = .029) compared with controls. There were no statistically significant differences between myelolipoma (P = .093) and pheochromocytoma (P = .204) relative to the control. Ghrelin level was significantly higher in carcinoma compared to adenoma (P = .049) samples. A positive correlation between ghrelin and IGF2 expression was observed only in myelolipoma (P = .001). Ghrelin at concentrations of 1 × 10−6 mol/L and 1 × 10−8 mol/L significantly stimulated proliferation and migration rate in the H295R cell line. Conclusion: Ghrelin appears to be an essential factor in driving adrenal tumours development. [ABSTRACT FROM AUTHOR]

Epithelioid angiomyolipoma (EAML) is a rare mesenchymal neoplasmic variant of angiomyolipoma characterized by aggressive growth and unpredictable outcome. Cases of local recurrence and distant metastasis have been described. The histopathological diagnosis may be difficult, as EAML often mimics other neoplasms. This is the case report of a 39-year-old male patient with EAML, which was initially diagnosed as adrenal cortical carcinoma, due to the lack of cooperation between clinicians and pathologists. [ABSTRACT FROM AUTHOR]