The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2–8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2–0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient’s follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.

Cushing’s disease is a rare severe neuroendocrine disorder caused by chronic overproduction of adrenocorticotropic hormone by a pituitary tumor. Supraphysiological concentrations of cortisol in endogenous hypercortisolism have an immunosuppressive and anti-inflammatory effect similar to therapy with systemic glucocorticosteroids. This may reduce the activity of the patient’s concomitant autoimmune inflammatory diseases. On the other hand, a decrease in cortisol levels during treatment for Cushing’s disease may be associated with a reactivation of the immune system that pose a risk of onset or recurrence of an autoimmune disorder. We present our own clinical case demonstrating the development of sarcoidosis after surgical treatment of Cushing’s disease.

Background: Сomputed tomography (CT) is considered as the gold standard for imaging the adrenal tumors. Tumor size and native density in unenhanced CT images are widely used to predict tumor malignancy, however, their diagnostic accuracy and the added value of clinical and anamnestic data remain uncertain. Objective: To identify clinical markers that possibly could differentiate pheochromocytoma (PCC), adrenocortical cancer (ACC), and hormonally non-functioning adrenal adenoma (NAA) in patients with adrenal masses of non-benign appearance on unenhanced CT. Methods: This was a single-center observational retrospective selective non-controlled study of 123 patients who underwent adrenalectomy between January 2011 and December 2023. All lesions showed native density ≥ 10 Hounsfield units [HU] or maximum diameter ≥ 4 cm, or both features on pre-operative CT. Histology examination confirmed 63 PCC, 30 ACC and 30 NAA. Clinical presentation, comorbidities, laboratory tests and imaging findings were reviewed. Results: Paroxysmal type of arterial hypertension (AH) was common across all groups; its presence did not aid discrimination. AH grade 3, however, prevailed in the patients with PCC only. Patients with an adrenal mass and AH grade 3 had the high probability of PCC presence (odds ratio, OR: 5.978, 95% confidence interval, CI [2.620–13.640]; p 0.001). AH grade distribution was similar in the ACC and NAA groups. Headache (57.1%), palpitations (48.3%) and a history of peptic ulcer disease (25.4%) were also characteristic of PCC. In contrast, generalized weakness and lumbar pain predominated in ACC (63.3% and 60%, respectively) and NAA (56.7% and 73.3%). Tumors with native density of ≥ 10 HU and size 4 cm (the malignant CT phenotype) were found in 90% (27/30) of ACC, 62% (39/63) of PCC, and 36.7% (11/30) of NAA cases. This CT appearance detected a malignant lesion (PCC or ACC) with 71% sensitivity and 63% specificity, while the chance to find NAA was low (OR: 0.237, 95% CI [0.097–0.555]; р 0.001). Tumors with native density ≥ 10 HU and tumor size of 4 cm were found in similar proportions in PCC (36.5%, 23/63) and NAA (30%, 9/30) groups, indicating a low probability of ACC (OR: 0.212, 95% CI [0.048–0.659]; р = 0.016) and focusing the differential diagnosis on PCC versus NAA. Tumors with native density 10 HU and size ≥ 4 cm were rare in PCC (1/63, 1.6%) and absent in ACC, yet presented in 10/30 (33.3%) NAA cases. This CT phenotype is associated with low risk of malignancy (OR: 0.022, 95% CI [0.001–0.123]; р 0.001), although insensitive (33%), it had a specificity of 98.9% for benign NAA. Conclusion: In adrenal tumors of the malignant CT phenotype, the differential diagnosis should be made between ACC and PCC, while the presence of NAA is highly unlikely. In tumors with native density of 10 HU and tumor size of 4 cm, the differential diagnosis should first consider PCC and NAA, while the chance to identify ACC is low. The adrenal masses with the native density of 10 HU and tumor size of ≥ 4 cm were strongly suggestive of benign NAA, with an exceedingly low risk of cancer.

Background: The differentiation of pheochromocytoma (PCC) from other adrenal lesions, particularly in incidentalomas with non-benign radiological characteristics (size > 4 cm or density > 10 HU), remains a clinical challenge. The study aimed to develop and validate an interpretable machine learning (ML) model for pairwise differentiation of PCC from adrenocortical carcinomas (ACCs) and non-functioning adrenal adenomas (NAAs) and to identify the most important clinical features. Methods: We analyzed a dataset of 50 clinical, laboratory, and radiological parameters from 123 patients with histologically verified adrenal tumors (63 PCC, 30 ACC, 30 NAA). Four classifiers—Logistic Regression (LR), Random Forest (RF), Linear Discriminant Analysis (LDA), and Extreme Gradient Boosting (XGBoost)—were trained for binary classification tasks (PCC vs. ACC, PCC vs. NAA, ACC vs. NAA) using a robust nested stratified cross-validation pipeline to ensure generalizability and avoid overfitting. Results: All four models showed strong predictive performance, with discrimination (AUC) more than 0.8. Our analysis, based on the interpretable LR model, identified the key discriminators differentiated PCC from both ACC and NAA: maximum systolic blood pressure, grade 3 hypertension, headache, palpitation, tachycardia, male sex, and concomitant gastric and duodenal ulcers. In contrast, lower back pain and general weakness were strong signs of lower probability of PCC. The tumor density specifically differentiated PCC from NAA, whereas tumor size was an important marker for distinguishing PCC and ACC. Conclusions: We developed robust ML models capable of accurately differentiating PCC from other adrenal tumors in complex cases. The models provide a clinically actionable tool for pre-surgical decision support. Furthermore, the identification of key discriminative features enhances the clinical understanding of PCC and facilitates its differential diagnosis prior to histological verification.

Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs), collectively known as PPGLs, are rare neuroendocrine tumors that produce catecholamines. The majority of PPGL cases are caused by germline and/or somatic mutations in over 20 different genes. A study of post-surgical PCC patients revealed a high risk of new tumor recurrence in both hereditary and apparently sporadic cases, suggesting that some germline mutations remain undetected. Since transcript levels can indicate gene dysfunction, our study focuses on the transcriptional profiling of PCC-associated genes in post-surgical patients. Methods: RT-PCR was performed on blood samples from patients and a control group. The t-SNE algorithm was applied to the transcriptional data. Sanger sequencing was used to identify mutations in the coding sequences of the VHL, SDHB, RET, and NF1 genes. Results: We obtained transcriptional profiles for 11 genes involved in the Krebs cycle and for 21 genes involved in the hypoxia, PI3K/AKT/mTOR, and RAS/RAF/ERK signaling pathways. We identified a minimal set of 16 genes with stable transcription levels that can be used to differentiate PCC patients from controls. Germline mutations in the VHL, SDHB, RET and NF1 genes, which correlated with an altered transcriptional profile, were detected in three patients. Conclusions: Our pilot data suggest that transcript levels of the genes involved in Krebs cycle, hypoxia, PI3K/AKT/mTOR, and RAS/RAF/ERK signaling pathways indicate their potential suitability as a candidate diagnostic marker. The results from this pilot study form the basis for a larger project to investigate gene transcription in an expanded cohort of patients who have undergone surgery for PCC.