Percutaneous Bilateral Adrenal Radiofrequency Ablation in Severe Adrenocorticotropic Hormone-dependent Cushing Syndrome.

OBJECTIVES: The objectives of the study were to evaluate adrenal radiofrequency ablation (RFA) as a method of treatment in patients with severe adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome, among whom bilateral adrenalectomy is not a suitable option. MATERIAL AND METHODS: Five patients with ACTH-dependent Cushing syndrome underwent RFA of both adrenal glands. Four of them presented with Cushing disease unsuccessfully treated with pituitary surgery and medical therapy, while one patient had ACTH-dependent Cushing syndrome due to pancreatic endocrine tumor with liver metastases. All patients were disqualified from adrenalectomy due to morbid obesity or lack of consent. RESULTS: A technical success was obtained in all cases, with only one re-intervention necessitated by a cooling effect of the inferior vena cava. Despite pre-procedural adrenergic blockade, severe hypertension was noted during the procedure in three cases, this being treated immediately using direct-acting vasodilators. No complications occurred otherwise. In all cases, significant improvement of clinical symptoms was observed, as well as marked decreases in levels of serum cortisol, free urine cortisol, and dehydroepiandrosterone sulfate. CONCLUSION: Bilateral RFA under CT-guidance is technically feasible and clinical improvement can be achieved using the method. In patients disqualified from adrenal surgery, RFA might be considered as an alternative method of ACTH-dependent Cushing syndrome treatment.

A Flow Procedure for Linearization of Genome Sequence Graphs.

Efforts to incorporate human genetic variation into the reference human genome have converged on the idea of a graph representation of genetic variation within a species, a genome sequence graph. A sequence graph represents a set of individual haploid reference genomes as paths in a single graph. When that set of reference genomes is sufficiently diverse, the sequence graph implicitly contains all frequent human genetic variations, including translocations, inversions, deletions, and insertions. In representing a set of genomes as a sequence graph, one encounters certain challenges. One of the most important is the problem of graph linearization, essential both for efficiency of storage and access, and for natural graph visualization and compatibility with other tools. The goal of graph linearization is to order nodes of the graph in such a way that operations such as access, traversal, and visualization are as efficient and effective as possible. A new algorithm for the linearization of sequence graphs, called the flow procedure (FP), is proposed in this article. Comparative experimental evaluation of the FP against other algorithms shows that it outperforms its rivals in the metrics most relevant to sequence graphs.

Prognostic factors in adrenocortical carcinoma: data from a large Polish series.

Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge about the clinical course and treatment of these tumors is limited. Objectives Survival rates in ACC are still low and the percentage of relapse is high. Thus, it is crucial to identify the prognostic factors of overall survival (OS) and recurrence­free survival (RFS). Patients and methods This was a retrospective analysis of 66 patients diagnosed with ACC between 2002 and 2015. Results The median OS was 43.5 months, 78.19 months for stage I + II, 22.95 months for stage III, and 19.54 months for stage IV ACC. Older age, stage IV ACC, margin status R2, and no mitotane treatment were associated with poor OS. Low Ki67 and mitotic indices were related to improved OS in a univariate analysis. The median RFS was 101.1 months. Disease recurrence after potentially curative surgery was reported in 1 patient (25%) with stage I, 12 patients (46%) with stage II, and 9 patients (45%) with stage III ACC. Male sex and no mitotane treatment were associated with a reduced RFS in a multivariate analysis and higher Ki67 and mitotic indices in the univariate analysis. Conclusions Ki67 and mitotic indices should be considered as prognostic factors when planning the adjuvant treatment of ACC. Mitotane treatment may be independently associated with better outcomes regardless of the tumor stage.

Adrenal incidentaloma in adults - management recommendations by the Polish Society of Endocrinology.

INTRODUCTION: A wide use of imaging techniques results in more frequent diagnosis of adrenal incidenataloma. AIM: To analyse the current state of knowledge on adrenal incidentaloma in adults in order to prepare practical management recommendations. METHODS: Following a discussion, the Polish Society of Endocrinology expert working group have analysed the available data and summarised the analysis results in the form of recommendations. IMAGING AND HORMONAL ASSESSMENT: Unenhanced adrenal computed tomography (CT) may be recommended as an initial assessment examination helpful in the differentiation between adenomas and "non-adenomatous" lesions. In the case of density > 10 Hounsfield units, CT with contrast medium washout assessment or MRI are recommended. However, in all patients with adrenal incidentaloma, hormonal assessment is recommended in order to exclude pheochromocytoma and hypercortisolism, notwithstanding the clinical picture or concomitant diseases. In addition, examination to exclude primary hyperaldosteronism is suggested in patients with diagnosed hypertension or hypokalaemia. TREATMENT: Surgical treatment should be recommended in patients with adrenal incidentaloma, where imaging examinations suggest a malignant lesion (oncological indication) or with confirmed hormonal activity (endocrinological indication). The basis of the surgical treatment is laparoscopic adrenalectomy. Patients with suspected pheochromocytoma must be pharmacologically prepared prior to surgery. In patients not qualified for surgery, control examinations (imaging and laboratory tests) should be established individually, taking into consideration such features as the size, image, and growth dynamics of the tumour, clinical symptoms, hormonal tests results, and concomitant diseases.

The NIH BD2K center for big data in translational genomics.

The world's genomics data will never be stored in a single repository - rather, it will be distributed among many sites in many countries. No one site will have enough data to explain genotype to phenotype relationships in rare diseases; therefore, sites must share data. To accomplish this, the genetics community must forge common standards and protocols to make sharing and computing data among many sites a seamless activity. Through the Global Alliance for Genomics and Health, we are pioneering the development of shared application programming interfaces (APIs) to connect the world's genome repositories. In parallel, we are developing an open source software stack (ADAM) that uses these APIs. This combination will create a cohesive genome informatics ecosystem. Using containers, we are facilitating the deployment of this software in a diverse array of environments. Through benchmarking efforts and big data driver projects, we are ensuring ADAM's performance and utility.

Application of parametric ultrasound contrast agent perfusion studies for differentiation of hyperplastic adrenal nodules from adenomas-Initial study.

OBJECTIVES: To evaluate the possibilities of differentiation of non-malignant adrenal masses with the application of the new technique for the evaluation of enhancement after administration of an ultrasound contrast agent: parametric imaging. PATIENTS AND METHODS: 34 non-malignant adrenal masses in 29 patients were evaluated in a dynamic examination after the administration of ultrasound contrast agent with parametric imaging. Patterns on parametric imaging of arrival time were evaluated. The final diagnosis was based on CT, MRI, biochemical studies, follow up and/or histopathology examination. RESULTS: The study included: 12 adenomas, 10 hyperplastic nodules, 7 myelolipomas, 3 pheochromocytomas, hemangioma with hemorrhage and cyst. The pattern of peripheral laminar inflow of Sonovue on parametric images of arrival time of was 100% sensitive for hyperplastic nodules and 83% specific in regard to adenomas. CONCLUSIONS: Parametric contrast enhanced ultrasound may accurately differentiate hyperplastic adrenal nodules from adenomas and could be complementary to CT or MRI. Incorporation of perfusion studies to CT or MRI could possibly enable one-shop complete characterization of adrenal masses. This could deliver additional information in diagnostics of patients with Conn Syndrome and warrants further studies in this cohort of patients.

Adrenal (131)I-6ß-iodomethylnorcholesterol scintigraphy in choosing the side for adrenalectomy in bilateral adrenal tumors with subclinical hypercortisolemia.

PURPOSE: Adrenal scintigraphy with 131I-6ß-iodomethylnorcholesterol is considered by several authors the gold standard for assessing tumors with subclinical hypercortisolemia. However, most of the described series consist mainly of cases with unilateral lesions. The aim of our study was to assess whether scintigraphy is useful in choosing the adrenalectomy side in the case of bilateral adrenal tumors with subclinical hypercortisolemia. METHODS: The study focused on 15 consecutive patients with benign bilateral adrenal tumors and subclinical hypercortisolemia. The scintigraphy with 131I-6ß-iodomethylnorcholesterol was performed. Fourteen patients underwent unilateral adrenalectomy; the gland with predominant uptake on scintigraphy was removed. Cortisol and ACTH concentrations were measured one and six months after surgery. Post-dexamethasone cortisolemia was assessed six months after surgery. To date, the patients have been under postoperative observation for 1-4 years. RESULTS: Four patients showed unilateral uptake of radiotracer, and nine patients showed predominant accumulation of radiotracer in one of the adrenal glands. The smaller tumor was predominant in 2 cases. Percentage of activity on the predominant side correlates positively with the difference between tumors' diameters. Unilateral uptake of radiotracer predicts long-lasting postoperative insufficiency of the second adrenal gland. Excision of predominating tumor led to cessation of hypercortisolemia in all patients. CONCLUSIONS: The corticoadrenal scintigraphy is useful in choosing the side for operation in the case of bilateral adrenal tumors with subclinical hypercortisolemia.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Adrenal-preserving surgery of adrenal tumours.

Currently, laparoscopic adrenalectomy is seen as more than just the preferred method, in fact as a routine procedure, always bearing in mind, however, the developed restraints on its usage. The size of the tumour, recurrent disease, and the existing invasive process all remain factors which determine the indications for operation. The situation is similar in cases of qualifying for sparing (non-radical) operations on adrenal glands. The basic challenge in terms of qualification, choice of technique and the range of operation of adrenal lesions remains: obtaining a reliable preoperative diagnosis, the localisation of lesions including their ectopic location, the evaluation of the imaging phenotype, as well as a proper pre-surgical preparation. Maintaining one third of properly vascularised adrenal mass allows one to avoid a substitutive therapy, with the possible necessity of its application in stressful situations. The first partial adrenalectomy has been conducted on a patient with a bilateral pheochromocytoma, in order to retain the glucocorticoid adrenal functions. The recommendations for its administration remain: hereditary pheochromocytoma of at least 2cm diameter, unilateral adenoma of at least 5cm diameter in Cushing's syndrome without any concomitant lesions in the oposite adrenal gland, and unilateral adenoma in Conn's syndrome. It seems that non-radical resection should always be considered for patients at risk of bilateral adrenalectomy in cases of concomitant lesions in both adrenals.

Echogenicity of benign adrenal focal lesions on imaging with new ultrasound techniques - report with pictorial presentation.

AIM: The aim of the research was to assess the echogenicity of benign adrenal focal lesions using new ultrasound techniques. MATERIAL AND METHOD: 34 benign adrenal masses in 29 patients were analyzed retrospectively. The examinations were conducted using Aplio XG (Toshiba, Japan) ultrasound scanner with a convex probe 1-6 MHz in the B-mode presentation with the combined use of new ultrasound techniques: harmonic imaging and spatial compound sonography. The size of the adrenal tumors, their echogenicity and homogeneity were analyzed. Statistical analysis was conducted using the STATISTICA 10 software. RESULTS: The following adrenal masses were assessed: 12 adenomas, 10 nodular hyperplasias of adrenal cortex, 7 myelolipomas, 3 pheochromocytomas, a hemangioma with hemorrhage and a cyst. The mean diameter of nodular hyperplasia of adrenal cortex was not statistically different from that of adenomas (p = 0.075). The possibility of differentiating between nodular hyperplasia and adenoma using the parameter of hypoechogenicity or homogeneity of the lesion was demonstrated with the sensitivity and specificity of 100% and 41.7%, respectively. The larger the benign adrenal tumor was, the more frequently did it turn out to have a mixed and inhomogenous echogenicity (p < 0.05; ROC areas under the curve: 0.832 and 0.805, respectively). CONCLUSIONS: A variety of echogenicity patterns of benign adrenal focal lesions was demonstrated. The image of an adrenal tumor correlates with its size. The ultrasound examination, apart from its indisputable usefulness in detecting and monitoring adrenal tumors, may also allow for the differentiation between benign lesions. However, for lesions found incidentally an algorithm for the assessment of adrenal incidentalomas is applicable, which includes computed tomography and magnetic resonance imaging.

Bilateral adrenal incidentaloma with subclinical hypercortisolemia: indications for surgery.

INTRODUCTION: According to some authors, a higher incidence of subclinical hypercortisolemia is found among patients with bilateral benign adrenal tumors than in those with unilateral tumors. It is still unknown whether all patients with bilateral adrenal tumors and subclinical hypercortisolemia should undergo surgery, and, if so, which tumor should be removed first. OBJECTIVES: The aim of the study was to investigate whether unilateral adrenalectomy can lead to resolution of hypercortisolemia in patients with bilateral adrenal tumors and to improvement of their clinical status. PATIENTS AND METHODS: The study group consisted of 25 patients with bilateral benign adrenal tumors and subclinical hypercortisolemia. In 24 patients, unilateral adrenalectomy was performed. The adrenal gland was selected for removal on the basis of scintigraphy and/or tumor diameter. Cortisol concentrations were measured before the surgery and at 1 and 6 months after the surgery at 8:00 AM, 10:00 PM, and after dexamethasone suppression. The morning blood levels of adrenocorticotropic hormone, dehydroepiandrosterone, 17­hydroxyprogesterone, glycated hemoglobin, and lipid profile were determined. RESULTS: In all surgical patients, hypercortisolemia resolved after the surgery. However, only in 14 patients (58%), the clinical improvement was evident (improved control of diabetes and hypertension, body mass loss). CONCLUSIONS: Although subclinical hypercortisolemia resolved after surgery in all patients with bilateral adrenal tumors, only patients with poorly controlled diabetes and hypertension and a rapid increase in body mass benefited from the surgery.

Castleman's disease - an unusual indication for laparoscopic adrenalectomy.

Castleman's disease is one of the rare entities which cause lymph node hyperplasia with no characteristic clinical symptoms. Pathomorphological examination usually enables diagnosis, especially in the case of a localized form. Its uncommon location in the retroperitoneal cavity is estimated at 12% in the literature. Asymptomatic nature of the disease and its untypical location in the adrenal field imitated incidentaloma of this gland in the imaging examinations. Surgical treatment, laparoscopic excision of the tumour (lymph node) and right adrenal gland from the lateral, transperitoneal approach allowed final diagnosis and offered effective therapy.

Adrenocortical oncocytoma - a case report.

Adrenocortical oncocytoma is found very rarely. Most such tumours are benign and nonfunctioning. We report the case of a nonfunctioning adrenocortical oncocytoma located in the right adrenal gland in a 35-year-old man. The patient was tested because of arrhythmia. An adrenal mass of 68 × 64 mm was found during ultrasonography, followed by CT examination. Physical examination indicated obesity with BMI of 32.8 kg/m(2). Abnormal laboratory findings based on an oral glucose tolerance test revealed impaired glucose tolerance and elevated cholesterol level. The patient underwent a laparotomy for a pathological mass located in the right adrenal gland. The pathology report confirmed adrenocortical oncocytoma of uncertain malignant potential. The patient is still alive with no metastases, 37 months after the surgery. Adrenocortical oncocytoma, although extremely rare, should be considered in the differential diagnosis of adrenal tumours.

Surgical treatment of adrenal tumours.

INTRODUCTION: Nowadays operations of adrenal glands became the fastest-expanding field of the endocrine surgery. Besides the development of surgical techniques and introduction of laparoscopic method as a routine operating treatment of adrenal lesions, also other factors like a development of the endocrinological and imaging diagnosis together with the knowledge of etiology and understanding of hormonal interactions of the arenal glands have contributed to it. MATERIAL AND METHODS: Based on experience of the Department of General, Vascular and Transplant surgery WUM where between 1997-2009 711 adrenalectomies were carried out (529 laparoscopic and 182 classical) current methods of adrenal operation, qualifications and indications were presented. RESULTS: Laparoscopic adrenalectomy confirming it's safety and benefits has gained the approval of the medical fraternity and became the main method of surgical treatment. CONCLUSIONS: 1. Videoscopic/laparoscopic adrenalectomy became the recommended operation in the treatment of adrenal lesions. 2. Close multidisciplinary cooperation of doctors participating in the treatment of patients with adrenal pathology has made the adrenal gland surgery the most rapidly developing field of the endocrine surgery.

Germinal mutations of RET, SDHB, SDHD, and VHL genes in patients with apparently sporadic pheochromocytomas and paragangliomas.

INTRODUCTION: Pheochromocytomas and paragangliomas are derived from neural crest cells and are localized mainly in adrenal medulla and sympathetic or parasympathetic ganglia. They can be inherited (25%) and be part of multi-endocrine syndromes such as MEN2 syndrome, von Hippel-Lindau syndrome, pheochromocytoma/paraganglioma syndrome, neurofibromatosis type 1, and Sturge-Weber syndrome. Clinical presentation can sometimes be atypical and does not always allow proper diagnosis. In such situations, DNA analysis can be helpful, especially when the pheochromocytoma is the first and only symptom. MATERIAL AND METHODS: We analyzed DNA from 60 patients diagnosed and treated in the Centre of Oncology with a diagnosis of pheochromocytoma or paraganglioma. DNA analysis was carried out for RET (exons 10, 11, 13, and 16), SDHB, SDHD, and VHL genes. Techniques used for the analysis were direct sequence analysis, MSSCP, and RFLP. RESULTS: Germinal mutations were found in 16 patients (26,7%). Most frequent were mutations in RET proto-oncogene, followed by VHL gene, one mutation in SDHB, and one in SDHD genes. A comparison of some of the clinical features of both groups (with and without mutation) showed statistically significant differences. CONCLUSIONS: The results of our study show that genetic predisposition is frequent in chromaffin tissue tumours, which indicates that DNA analysis is necessary in every case, also because of possible atypical clinical presentation. (Pol J Endocrinol 2010; 61 (1): 43-48).

Bilateral, incidentally found adrenal tumours - results of observation of 1790 patients registered at a single endocrinological centre.

INTRODUCTION: During the last 22 years we registered 1790 patients with incidentally found adrenal tumours (AI, adrenal incidentalomas). In 351 of them, bilateral tumours were detected. The aim of our study was to analyze the character of bilateral tumours and summarize the methods of their management. MATERIAL AND METHODS: In the whole group of 1790 patients, there were 1311 women and 479 men, aged 11-87 years. The group of patients with bilateral adrenal tumours included 258 women and 93 men, 25-83 years old. Hormonal investigations and imaging examinations were performed to search for subclinical adrenal hyperfunction and to define the malignant potential of the tumours. RESULTS: Sixty-nine patients were treated by surgery for oncological or endocrinological purposes (mainly pre-Cushing's syndrome). Histological findings included malignant tumours: metastases - 9, adrenal cancer - 7, and lymphomas - 5; and non-malignant tumours: adenomas - 24, nodular hyperplasia - 14, myelolipomas - 4, and pheochromocytomas - 4. Subclinical Cushing's syndrome was relatively more frequent in nodular hyperplasia (40%) than in adenomas (30%). CONCLUSIONS: Indications for surgery were recommended in 20% of patients with bilateral AI, most frequently for adenomas, nodular hyperplasia, and oncological pathologies, with a good prognosis in the non-malignant group. (Pol J Endocrinol 2010; 61 (1): 69-73).

[Surgical treatment of adrenal tumors]. / Leczenie chirurgiczne guzów nadnerczy.

INTRODUCTION: Nowadays operations of adrenal glands became the fastest-expanding field of the endocrine surgery. Besides the development of surgical techniques and introduction of laparoscopic method as a routine operating treatment of adrenal lesions, also other factors like a development of the endocrinological and imaging diagnosis together with the knowledge of etiology and understanding of hormonal interactions of the adrenal glands have contributed to it. MATERIAL AND METHODS: Based on experience of the Department of General, Vascular and Transplant surgery WUM where between 1997-2009 711 adrenalectomies were carried out (529 laparoscopic and 182 classical) current methods of adrenal operation, qualifications and indications were presented. RESULTS: Laparoscopic adrenalectomy confirming it's safety and benefits has gained the approval of the medical fraternity and became the main method of surgical treatment. CONCLUSIONS: 1. Videoscopic/laparoscopic adrenalectomy became the recommended operation in the treatment of adrenal lesions. 2. Close multidisciplinary cooperation of doctors participating in the treatment of patients with adrenal pathology has made the adrenal gland surgery the most rapidly developing field of the endocrine surgery.

1,111 patients with adrenal incidentalomas observed at a single endocrinological center: incidence of chromaffin tumors.

A majority of incidentally found adrenal tumors derive from the adrenal cortex. The aim of our study was evaluation of the incidence of chromaffin tumors in a group of 1,111 patients with adrenal incidentalomas. In this group there were 803 women and 308 men, aged 10-87 years. Clinical examination, imaging studies (ultrasound scans, CT, and MRI if necessary), and hormonal determinations (cortisol, ACTH and androgens in the blood, dexamethasone suppression test, urinary excretion of 17-OHCS, aldosterone and 17-KS, as well as PRA/aldosterone stimulation test and metanephrines in hypertensive patients and those with density in CT over 20 HU) were used. In 380 patients treated by surgery (mainly by laparoscopic approach), histological and immunocytochemical examinations were performed. Clinical examination revealed hypertension in 25% of the patients under study. Chromaffin tumors were detected in 43 patients, 33 women, and 10 men aged 20-75 years: pheochromocytoma in 36 (malignant in 3); chromaffin cells hyperplasia in 2; paraganglioma in 3; ganglioneuroblastoma in 1; ganglioneuroma in 1; and schwannoma in 2. The tumors' diameter ranged between 1.1 and 20.0 cm, density=25 Hounsfield units (HU) or more before contrast medium injection. Hypertension was present in 53% of these patients. The urinary metanephrines excretion was elevated in 31 of 38 patients, in whom the determinations were done. Chromaffin tumors were detected in 4% (pheochromocytomas in 3%) of 1,111 patients with adrenal incidentalomas. Malignancy was present in 9% of 43 patients with chromaffin tumors. High density in CT was a very important diagnostic finding in the incidentally found medullary tumors.

[The effect of retinoic acid on primary cultures of human pheochromocytoma cells]. / Wplyw kwasu retinowego na komórki pheochromocytoma.

INTRODUCTION: Retinoic acid is a regulator of gene expression which, by binding to its nuclear receptor, determines the degree of differentiation in multiple cancer cell types. On the basis of this capability it was introduced, e.g. in the therapy of neuroblastoma. In cells derived from neural crest, such as neuroblastoma cells, retinoic acid initiates differentiation into neurons. This substance acts in a similar way on a rat pheochromocytoma cell line PC12. The aim of our work was to examine the influence of retinoic acid on the phenotype of human pheochromocytoma cells in primary culture. MATERIAL AND METHODS: Observations were made on two primary cultures isolated from human pheochromocytoma. Cells were grown in RPMI1640 medium supplemented with 10% foetal bovine serum. Subsequently, the cultures were treated with 100 mMol retinoic acid for three-days. An evaluation of the phenotype change was performed by estimating the expression levels of F-actin, MAP-2 protein, and chromogranin, with the use of a confocal microscopy. RESULTS: The introduction of retinoic acid into the culture caused an increase in the F-actin level and its redistribution in the form of stress fibers. Simultaneously, the cells changed their shape, generating more processes. No change was detected in the expression level of neuroendocrine markers: MAP-2 and chromogranin. CONCLUSIONS: Retinoic acid appears to have an influence on some phenotype parameters of human pheochromocytoma cells. Further work is needed to determine the molecular mechanisms of this process, and to evaluate thoroughly the benefits of introducing retinoic acid into therapy of pheochromocytoma tumors.