ORIGINAL PAPER
RJME Romanian Journal of Morphology & Embryology http://www.rjme.ro/
Clinicopathological spectrum of adrenal tumors: a retrospective study from a Romanian tertiary referral center
RAMONA TEODORA CĂTANĂ1,2), ADELA CORINA NECHIFOR-BOILĂ1,3), SORINA MOICA4), LAURA CHINEZU1,5), ANGELA BORDA1,6)
1) Department of Histology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Romania
2) Department of Endocrinology, Emergency County Hospital, Târgu Mureș, Romania
3) Department of Pathology, Mureș County Hospital, Târgu Mureș, Romania
4) Faculty of Engineering and Information Technology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Romania
5) Institute of Forensic Medicine, Târgu Mureș, Romania
6) Department of Pathology, Emergency County Hospital, Târgu Mureș, Romania
Abstract
Adrenal tumors represent an uncommon and heterogeneous group of lesions with diverse clinical and histopathological features. Their detection has increased in recent years due to the widespread use of advanced imaging techniques. However, epidemiological data regarding the various types of adrenal tumors in Eastern Europe remain scarce and show considerable variability. In this study, we aimed to analyze the clinicopathological characteristics, distribution, and temporal trends of adrenal tumors diagnosed in a Romanian tertiary referral center between 2001 and 2022. We conducted a retrospective review of 116 adrenalectomy specimens documented in the Pathology Database of our institution. Demographic characteristics, tumor laterality, histological subtypes, and temporal distribution patterns were analyzed. Adrenal adenomas were the most common tumors (31.9%), followed by pheochromocytomas (24.1%), and adrenal cortical carcinomas (11.2%); other lesions (e.g., cysts, myelolipoma, etc.) were rare. The number of adrenal surgeries increased by 36% in the period 2012-2022 compared to 2001- 2011. The prevalence of adrenal adenomas almost doubled in the second study period (38.8% vs. 22.4%, p=0.014). Pheochromocytomas remained constant, revealing a similar prevalence (around 24%) in both time periods. Carcinomas’ prevalence was lower in both intervals (7.4% in 2012-2022 vs. 16.3% in 2001-2011, p=0.405). Our findings highlight temporal changes in the histological spectrum of adrenal tumors, with an increasing trend in cortical adenomas and persistently low rates of adrenocortical carcinoma. These results offer insight into local patterns of adrenal pathology and underscore the need for ongoing clinicopathological monitoring.
Keywords: adrenals, adrenal adenoma, adrenal carcinoma, pheochromocytoma, prevalence trend.
Introduction
Before the development of imaging techniques, adrenal tumors were considered extremely rare. Their diagnosis was established late, only when local compressive symptoms or associated hormonal excess were documented [1]. The accessibility to high-performance diagnostic imaging tools has significantly improved medical diagnosis and patient care but has brought a new challenge in the management of incidentally discovered adrenal tumors.
Before 2000s, studies based on computed tomography (CT) scans have reported a low frequency of adrenal tumors (0.3-3.4%), most probably because of low-resolution imaging technology that often failed to detect small lesions. However, later on, when new high-resolution CT techniques were used, the prevalence of adrenal tumors increased, ranging from 1-5.1% [1]. It is well known that these tumors become more prevalent with age: from 4-7% among people older than 40 years old, to 5-10% in individuals older than 70 years [2-5].
Autopsy studies have shown a general prevalence of 1.7% to 3.6% for adrenal tumors, with higher rates in patients over 50 years old (5-7%) and significantly lower rates in children (0.15-0.36%) [5].
When dealing with an adrenal tumor, two critical concerns arise: the likelihood of malignancy and the evaluation of its hormone secretion activity. Most adrenal tumors are usually small benign nonfunctional adrenocortical adenomas [6], that don’t cause symptoms or require treatment [4]. Adrenocortical hormone-active tumors, on the other hand, are associated with endocrine syndromes resulting from the secretion of cortisol, aldosterone, sex hormones or their precursors.
Endogenous Cushing’s syndrome is a rare entity, its incidence ranging from 0.7 to 2.4 cases/1 000 000 inhabitants/year [7]; it is associated with adrenal tumors that secrete excessive amounts of cortisol, leading to multiple comorbidities [8].
Conn’s syndrome is characterized by excessive aldosterone production, accounting for approximately 20%
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of cases of resistant hypertension [9]; it is related to a wide range of pathologies, including microscopic aldosterone- producing cell nests, micronodules, unilateral hyperplasia and bilateral adenomas [10].
Excessive androgen production due to adrenal cortex tumors is extremely rare, with some studies reporting incidence rates of approximately 0.02 cases/1 000 000 inhabitants/year [11, 12]. These tumors are more likely to be malignant [12].
With regard to adrenal cancer, its diagnosis and, even more, its management are extremely challenging in day practice because of its high potential for aggressive behavior and risk of distant metastasis. Its incidence is estimated at 0.72 cases/1 000 000 inhabitants/year, accounting for 0.2% of all cancer deaths in the United States [13-15]. In some clinical and surgical studies, adrenocortical carcinoma has been found to account for about 8-11% of all adrenal tumors [16, 17]. The 5-year survival is stage dependent, ranging from 63-88% for stages 1 to 0-21% for stage 4 [16].
Pheochromocytomas are neuroendocrine neoplasms of chromaffin tissue originating from the adrenal medulla. The excess secretion of catecholamines that characterizes these tumors can lead to severe symptoms that impact the patient’s quality of life. The incidence of pheochromocytoma in The United States is about 2-8/1000 000 inhabitants/ year [18, 19].
This wide array of adrenal neoplasms, ranging from asymptomatic adenomas to fatal carcinomas, raises challenges due to the diverse clinical presentations, imaging characteristics, histopathological (HP) findings, prognosis, and treatment strategies, and has increasingly become a focus of attention in recent years.
Aim
The aim of our study was to illustrate the demographic and HP features of adrenal tumors diagnosed over a 22- year period (2001-2022) in a university hospital in Romania. Additionally, we aimed to highlight the prevalence, and the temporal trends of these rare tumors diagnosed in our department.
Patients, Materials and Methods
Database
We retrospectively reviewed all adrenal surgery cases registered in the Department of Pathology, Emergency County Hospital, Târgu Mureș, Romania, from January 2001 to December 2022. Emergency County Hospital, Târgu Mureș, which is also a University Hospital, is the largest public healthcare institution in Transylvania, serving as a center for local, regional, and county-level medical care. It provides medical services to the population of Mureș County - with a total of 518 193 inhabitants documented in the year 2022 [20] - as well as to patients from neighboring counties, thanks to its advanced infrastructure and broad range of medical specialties.
The study was approved by the Ethics Committee of the Emergency County Hospital, Târgu Mureș (Decision No. 4467/16.02.2023).
Demographic and pathological data
The study included all patients who underwent open or
laparoscopic adrenalectomy between January 2001 and December 2022. Data regarding patient demographics (age and gender), diagnosis year, and detailed pathological findings (complete histological diagnosis, tumor subtype, etc.) were collected from institutional registries and pathology archives.
The HP diagnosis for adrenal tumors was set according to World Health Organization (WHO) Classification of Tumors of Endocrine Organs, 2nd (2000), 3rd (2004) and 4th (2017) editions, respectively [21-23]. Adrenal tumors originating from the cortical region encompassed both benign (adenomas, cysts, myelolipomas, hemangiomas, and nodular hyperplasia) and malignant (cortical carcinomas) tumors (Figure 1, A-D). Tumors of the adrenal medulla included: pheochomocytomas (Figure 2, A-F), benign ganglioneuromas and malignant ganglioneuroblastomas. The 4th edition of the WHO Classification of Endocrine Tumors (2017) states that all pheochromocytomas are considered to have metastatic potential, thus, they are no longer regarded as benign or malignant and extended follow-up of these patients is recommended. Other rare tumors included adrenal lymphomas and metastasis. We focused our analysis on the most common adrenal tumors: adenomas, pheochromocytomas and cortical carcinomas.
Statistical analysis
Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS ver. 22, Chicago, IL, USA), Microsoft Excel 2021, and Minitab Statistical Software (ver. 20.3, 2021). Descriptive statistics were performed. Data were categorized as either nominal or quantitative variables. Numbers and percentages were used to express nominal variables, and their distributions were compared using the x2 (chi-squared) test. The normal distribution of continuous variables was evaluated using the Kolmogorov-Smirnov test and visual assessment of histograms. Normally distributed continuous variables were presented as mean ± standard deviation (SD). The analysis of variance (ANOVA) test was used to compare several mean values. We analyzed the data in a comparative way by dividing the study period into two equal 11 years’ time- intervals: from January 2001 to December 2011 vs. January 2012 to December 2022. Linear regression models were used to assess temporal trends in adrenal tumor cases. Statistical significance was defined as a p-value less than 0.05, with 95% confidence intervals applied throughout the analysis.
Results
Patients’ demographic characteristics
In total, 116 patients who underwent adrenalectomy were recorded in the Department of Pathology, Emergency County Hospital, Târgu Mureș, from January 2001 to December 2022. The patients’ mean age at diagnosis was 52.78±14.21 years (range 3-78). Women accounted for over half of the study population (n=64, 55.2%). The mean age at diagnosis was 52.35±11.55 years for women (range 14-72) and 53.30±16.98 years for men (range 3-78). With regard to the site of origin, cortical lesions were the most prevalent (n=71, 61.2%), followed by medullar lesions (n=31, 26.7%) and other tumor types, herein including
metastatic tumors (n=14, 12.1%) (Table 1). The ages of patients undergoing adrenalectomies ranged widely from 3 to 78 years. The youngest patients were two infants, aged 3 and 5 years old, both diagnosed with ganglioneuroblastoma.
Another notably young patient was a 10-year-old boy diagnosed with pheochromocytoma. Most of the adrenal tumors in our study occurred in patients found in 6th life decade (50-59 years old).
A
B
C
D
| Pathology type | n (%) | Age [years] mean ± SD | Age [years] range | Women/men ratio | Women age [years] mean ± SD | Men age [years] mean ± SD | Laterality left/right ratio |
|---|---|---|---|---|---|---|---|
| Cortical tumors | 71 (61.2) | 53.43±11.40 | 20-78 | 46/25 | 51.95±10.79 | 56.16±12.19 | 45/26 |
| Adenoma | 37 (31.9) | 53.68±9.40 | 35-78 | 27/10 | 52.33±9.15 | 57.30±9.54 | 24/13 |
| Adrenal cyst | 8 (6.9) | 51.63±13.33 | 26-66 | 8/0 | 51.63±13.33 | – | 6/2 |
| Myelolipoma | 6 (5.2) | 59.50±8.80 | 49-71 | 5/1 | 57.20±7.56 | 71 | 2/4 |
| Hemangioma | 3 (2.6) | 47.33±22.36 | 23-67 | 0/3 | – | 47.33±22.36 | 2/1 |
| Nodular hyperplasia | 4 (3.4) | 54.00±7.35 | 50-65 | 1/3 | 50 | 55.33±8.38 | 2/2 |
| Cortical carcinoma | 13 (11.2) | 52.31±15.12 | 20-74 | 5/8 | 45.60±16.60 | 57.22±12.13 | 9/4 |
| Medullar tumors | 31 (26.7) | 48.51±20.27 | 3-78 | 14/17 | 52.71±15.07 | 45.05±23.62 | 16/15 |
| Pheochromocytoma | 28 (24.1) | 51.11±17.12 | 10-78 | 14/14 | 52.71±15.07 | 49.50±19.38 | 15/13 |
| Ganglioneuroma | 1 (0.9) | 65.00 | – | 0/1 | – | 65 | 0/1 |
| Ganglioneuroblastoma | 2 (1.7) | 4.00±1.41 | 3-5 | 0/2 | – | 4.00±1.00 | 1/1 |
| Others | 14 (12.1) | 58.21±8.32 | 46-74 | 4/10 | 55.75±7.50 | 59.2±8.80 | 6/8 |
| Metastases | 12 (10.4) | 57.33±7.48 | 46-71 | 4/8 | 55.75±7.50 | 59.88±9.04 | 6/6 |
| Lymphoma | 2 (1.7) | 63.50±14.84 | 53-74 | 0/2 | – | 63.50±14.84 | 0/2 |
| Total | 116 (100) | 52.78±14.21 | 3-78 | 64/52 | 52.35±11.55 | 53.30±16.98 | 67/49 |
n: No. of cases; SD: Standard deviation.
A
B
C
D
E
F
Although adrenal tumors generally appeared to be slightly more common in women, with a women/men (W/M) ratio of 64/52, it is worth noting that this ratio varied depending on the specific tumor type. The most significant W/M ratio disparity was observed with regard to the prevalence of cysts (8/0), myelolipomas (5/1) and adenomas (27/10). In case of pheochromocytomas, an equal gender distribution was observed. By contrast, carcinomas occurred more
frequently in men (W/M ratio 5/8) and men were typically older than women (57.22 years vs. 45.60 years) with the same diagnosis (Table 1).
Pathological data
Table 1 summarizes the prevalence of different HP subtypes of adrenal tumors, included in the study. With regard to the site of origin, the most prevalent were cortical
lesions (n=71, 61.2%), followed by medullar lesions (n=31, 26.7%) and other tumor types, herein including metastatic tumors (n=14, 12.1%).
In 49.13% (57) cases, a final diagnosis of malignancy was established, including cortical carcinomas, pheochromo- cytomas, neuroblastomas, lymphomas, and metastatic tumors. The remaining 50.87% (59) cases were classified as benign lesions, comprising adenomas, adrenal cysts, myelolipomas, hemangiomas, nodular hyperplasia, and ganglioneuromas.
Figure 3 illustrates the prevalence of adrenal tumors according to the pathological type in our study population. The three most common adrenal tumor types, accounting for nearly 70% of all the cases in our study were: (i) adenomas (31.9%), (ii) pheochromocytomas (24.1%), and (iii) adrenal cortical carcinomas (11.2%).
Pareto Chart of Pathology Type
120
100
100
80
80
Count
60
Percent
60
40
40
20
20
Pathology type
0
Adenoma
Pheo chro mo cytoma
Cortical carcinoma
Metastases
Adrenal cyst
Myelolipoma
Nodular hyperplasia
Hemangioma
0
Other
Count
37
28
13
12
8
6
4
3
5
Percent Cum %
31.9
24.1
11.2
10.3
6.9
5.2
3.4
2.6
4.3
31.9
56.0
67.2
77.6
84.5
89.7
93.1
95.7
100.0
In our study group, adrenal tumors were more frequently found on the left side (left/right ratio: 64/49). Metastatic tumors were equally distributed either in the left or the right adrenal gland. Half of the metastatic tumor (n=6) cases were adenocarcinomas with different primary origins, while three cases corresponded to pulmonary squamous cell carcinomas. The remaining metastatic tumor (n=3) cases corresponded to one case of undifferentiated carcinoma, one melanoma case, and one clear cell renal carcinoma case.
Time trend prevalence of adrenal tumors in our study population
We further analyzed the time trends of adrenal tumor prevalence in our institution from 2001 to 2022, comparing two 11-year intervals: 2001-2011 and 2012-2022.
Between 2012 and 2022, the number of adrenal surgeries increased by 36.7% (67 cases) compared to the period 2001-2011 (49 cases) (p=0.095) (Figure 4). With regard to adenomas, pheochromocytomas and adrenal cortical carcinomas (the three most common adrenal tumor types),
the most significant change was noticed in case of adenomas, where the prevalence rate doubled during the second study period (2012-2022), with 26 (38.8%) cases compared to 11 (22.4%) cases in the previous period (2001-2011) (p=0.014) (Figure 5).
Chart of Time Period, Pathology Type
70
Pathology Type
Lymphoma
Nodular hyperplasia
60
Myelolipoma
Hemangioma
Ganglioneuroblastoma
Ganglioneuroma
50
Adrenal cyst
Metastases
Cortical carcinoma
Pheochromocytoma
Count
40
Adenoma
30
20
10
Time Period
0
T1
T2
Pheochromocytomas revealed an almost equal frequency across the two study periods (12 cases, 24.4% vs. 16 cases, 23.8%), with no significant changes in the occurrence rate (p=0.450) (Figure 5). As for adrenal carcinomas, there was a slight decrease in the number of cases in the second period (2012-2022) with five (7.4%) cases, compared to eight (16.3%) cases in the first period (2001-2011) (p=0.405) (Figure 5). Two cases of adrenal carcinoma were in a metastatic stage at the time of diagnosis: in the kidney (a 74-year-old man case) and in the ovary (a 20-year-old woman case).
To attain a clearer insight into yearly patterns, linear regression analysis was conducted on the annual case data, as shown in Figure 6 and supported by the related regression summary tables. The regression model for total adrenal tumor cases demonstrated a statistically significant association with year (p=0.041), with an R2 value of 19.25%, indicating a general upward trend in case numbers over time. Similarly, the regression model for adenomas revealed a significant increase across the study period (p=0.011), with 28.06% of the variation in cases explained by the model. In contrast, no significant trend was found for carcinomas (p=0.581), with the model accounting for only 1.55% of the variation. Although the regression for pheochromocytomas showed a slight upward slope, the association with year was not statistically significant (p=0.073), and the variation explained by the model remained modest at 15.2%.
Discussions
The present study aimed to highlight and illustrate clinicopathological characteristics of adrenal tumors diagnosed over a 22-year period (2001-2022) in a university hospital in Romania. Additionally, our objective was to assess the temporal trends in the prevalence of these rare tumors diagnosed in our department.
A
Chart of Observed and Expected Values
Expected
25
20
Value
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5
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.
12
B
Chart of Observed and Expected Values
M
Expected
Observed
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14
Value
10
#
.
4
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12
C
Chart of Observed and Expected Values
9
Expected
2 Observed
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7
.
Value
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«
3
2
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Category
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TI
12
| Time period | 2001-2011 Number (%) | 2012-2022 Number (%) | Chi-Square Value (x2) | P |
|---|---|---|---|---|
| Adenomas (A) | 11 (22.4) | 26 (38.8) | 6.08108 | 0.014 |
| Pheochromocytomas (B) | 12 (24.4) | 16 (23.8) | 0.5714 | 0.450 |
| Carcinomas (C) | 8 (16.3) | 5 (7.4) | 0.692308 | 0.405 |
| Total adrenal tumor cases | 49 | 67 | 2.79310 | 0.095 |
14
Total no cases
No adenomas
No carcinomas
12
No pheochromocytomas
10
Y-Data
8
6
4
2
0
2000
2005
2010
2015
2020
2025
Year
| Time period | Regression equation | R2 | p-value (ANOVA) |
|---|---|---|---|
| Total cases | Total no cases = - 447 + 0.225 Year | 19.25% | 0.041 |
| Adenomas | No adenomas = - 258.4 + 0.1293 Year | 28.06% | 0.011 |
| Carcinomas | No carcinomas = 33.5 - 0.0164 Year | 1.55% | 0.581 |
| Pheochromocytomas | No pheochromocytomas = - 148.7 + 0.0745 Year | 15.2% | 0.073 |
Figure 6 - Annual number of adrenal tumor cases diagnosed between 2001 and 2022, stratified by tumor type: total cases (blue), adenomas (red), carcinomas (green), and pheochromocytomas (purple). A clear upward trend is observed in the total number of cases and adenomas, as indicated by the respective regression lines. In contrast, the frequency of carcinomas remains low and stable, while pheochromocytomas show slight fluctuations without a strong upward or downward trend. The table summarizes the results of linear regression analyses evaluating time trends in the prevalence of adrenal tumors from 2001 to 2022. Statistically significant increasing trends were observed for the total number of cases (p=0.041, R2=19.25%) and for adrenal adenomas (p=0.011, R2=28.06%). No significant temporal changes were found for adrenal carcinomas (p=0.581, R2=1.55%) or pheochromocytomas (p=0.073, R2=15.2%), indicating relatively stable frequencies over the study period for these tumor types. ANOVA: Analysis of variance.
Adrenal tumors are rare entities, accounting for approximately 5% of all tumors in the adult population [1]. Our study, covering a large period of time (22 years) included 116 patients who underwent adrenalectomy and were registered in our institution (Department of Pathology,
Emergency County Hospital, Târgu Mureș) between 2002 and 2022. Our data revealed a 36.7% increase in the prevalence of adrenal tumors in the last 11 years (2012- 2022), compared to the previous period (2001-2011). Although this increase did not reach statistical significance,
the regression models indicated a general upward trend in case numbers over time. This observation aligns with trends reported in the literature, reinforcing the notion that the prevalence of adrenal tumors seems to be gradually increasing. A large study conducted in Minnesota, United States, based on medical records confirming the diagnosis of adrenal tumors, found a tenfold increase in the incidence of these tumors over a 23-year period (1995-2017) [2]. Similarly, a 10-year study in Iran, which analyzed adrenal surgical specimens, reported an increase in the incidence of adrenal tumors from three cases in 2004 to 21 cases in 2014 [3]. The increase in the number of adrenal tumors can be partly attributed to improved diagnostic methods, thanks to the widespread availability of advanced imaging technologies, which allow physicians to diagnose these tumors even when they are clinically silent [4].
Our data showed that the most frequent adrenal pathology was represented by cortical adenomas, which doubled between 2011-2022 compared to 2001-2011 (26 cases vs. 11 cases). These results align with data reported in other studies [2-4].
The second most common tumor in our study was pheochromocytoma (24.1%); its prevalence was similar in the last 11 years (2012-2022), compared to the previous period (2001-2011) (23.8% vs. 24.4%). An extensive systematic review of 12 studies, which included 4060 cases of pheochromocytoma diagnosed between 1949 and 2019, highlighted a significant increase in pheochromocytomas’ incidence over time, from 0.19/100 000/year in studies performed before 2000 to 0.58/100 000/year in the studies after 2010 [5]. By contrast, the study performed Ebbehoj et al. reported a slight decrease in the frequency of pheo- chromocytoma cases in Olmsted County, Minnesota, from 2.2% during the period 1995-2002 to 1.0% in the period 2011-2017 [2]. In Denmark, however, there was a 4.8-fold increase in pheochromocytoma cases from 1977 to 2015. This rise was attributed to a new group of older patients with smaller, incidentally discovered tumors, and atypically presenting with few or no paroxysmal symptoms [6]. The higher proportion of pheochromocytomas observed, compared to large population-based registries, may be attributed to the specific referral patterns and surgical focus of our institution, which primarily manages selected functional or symptomatic adrenal lesions.
Diagnostic methods when dealing with pheochromo- cytoma cases have largely evolved over time, and this aspect must be considered when comparing literature data revealing heterogeneous observations. Before 1986, about half of the patients were diagnosed based on symptoms, investigations of potential secondary hypertension, and a quarter through autopsy findings [5, 6]. The increased detection rate in some studies can be attributed not only to advances in medical imaging, but also to improvements in biochemical testing, metanephrine/normetanephrine measurements being now widely available. The recently improved recognition of high germline mutation rates in pheochromocytoma patients, coupled with genetic testing and surveillance of family members at risk, might explain the increased frequency of pheochromocytoma in some studies.
Regarding adrenal carcinomas, our study revealed low prevalence for these tumors in both study periods (only
7.4% during 2012-2022 and 16.3% during 2001-2011, respectively). Literature data on the epidemiology of adrenal carcinomas is however limited and often controversial. A comprehensive study in the United States reported an overall age-adjusted incidence of adrenal carcinomas of 1.02/1 000 000 inhabitants/year, that did not change significantly between 1973 and 2014 [15]. Conversely, a study from Netherlands covering the period from 1993 to 2010 observed a decreasing overall incidence rate of adrenal carcinoma, from 1.3/1 000 000 persons/year in 1993 to 1.0/1 000 000 persons/year in 2010 [24]. Meanwhile, in Denmark, the incidence rate between 2003 and 2019 was reported at 1.4/1 000 000 inhabitants/year. Notably, the incidence rate ratio significantly increased in women by 1.06 per year, while no such trend was observed in men [25].
Differences in the reported prevalence of adrenal tumors across various studies can be attributed to multiple methodological and contextual factors. Firstly, the time periods covered by these studies vary considerably, influencing the extent to which populations had access to advanced imaging methods such as CT and magnetic resonance imaging (MRI), which have become more widely used in recent years. Secondly, geographic differences in healthcare systems, screening programs, and diagnostic protocols can significantly affect early detection rates. Socioeconomic factors, including education level and access to medical services, may also contribute to underdiagnoses in certain regions. Additionally, the presence of founder mutations in specific populations may lead to a higher incidence of adrenal tumors within particular genetic groups. These variables must be carefully considered when comparing findings from different epidemiological studies.
Regarding demographic data, our study shows that adrenal tumors are more common in adults, in the 6th decade of life. In the study performed by Ebbehoj et al. (1995-2017), the patients’ mean age when diagnosed with adrenal tumors was 62 years [2]. By contrast, in a study performed in Iran, the patients were significantly younger, with a mean age of 37.7 years. These results can be attributed to the higher proportion of neuroblastoma cases included in their study [3].
The pheochromocytoma patients included in our study had a mean age at diagnosis of 51.11 years, which aligns with the mean ages reported in other studies, where values range from 43 to 56.2 years [3, 26]. Interestingly, Berends et al. observed a gradual increase in the age of patients diagnosed with pheochromocytoma, with the average age rising from 45 years in 1995 to 55 years by 2015 [27].
In our study, we did not identify any cases of adrenal carcinoma in the pediatric population, and women were much younger (45 years) than men with this pathology (57 years). This finding aligns with literature reports that place the average age of carcinoma diagnosis between 46 and 56 years old [13, 15, 24].
The youngest patients in the study were two pediatric cases (age 3 and 5, respectively), both diagnosed with neuroblastoma. Neuroblastoma accounts for approximately 10% of all pediatric cancers and typically affects children within the first five years of life [28].
In line to literature data, most of patients with adrenal lesions in our study were women (55.2%) [3, 13, 15, 24,
26, 29]. By contrast, adrenal carcinomas occurred more frequently in men in our study (W/M ratio 5:8). The risk factors influencing the gender distribution of adrenal carcinoma are not well-established. Heavy smoking in men, and the use of contraceptives in women, particularly before the age of 25, have been suggested as potential risk factors [13, 30].
Consistent with other research, adrenal lesions were predominantly found on the left side (n=67 vs. n= 49) [2,31].
The adrenal gland is a frequent site of metastases in various number of malignant tumors. In patients with no documented oncological history, the prevalence of adrenal metastases is 0-21% while in oncological patients, the prevalence is referred to be higher, of 32-72% [32]. Cancer of the breast, lung, malignant melanoma and ovary are the most common primary cancers that metastasize to the adrenal glands [32]. Our data showed a 10.2% proportion of metastasis among all adrenal tumors, similar to previously reported series [33, 34]. Apart from two cases: one case of renal carcinoma and another one of squamous pulmonary carcinoma, for the other remaining cases the primary tumor was unknown at the time of surgery.
Study limitations
Our study is subject to several limitations that must be acknowledged. First, it includes only patients who have met the criteria for surgical intervention of an adrenal lesion, as indicated by imaging findings suggestive of malignancy or clinical symptoms, irrespective of the lesion’s functional status. These might have introduced a certain degree of selection bias by excluding asymptomatic individuals or those managed conservatively. The high proportion of pheochromocytomas may reflect institutional surgical selection bias. Nevertheless, our study has covered an extensive period (2001-2022) and included all patients who underwent adrenal surgery (either open or laparoscopic adrenalectomy) in Emergency County Clinical Hospital, Târgu Mureș, considered as the largest public healthcare institution in Transylvania, Romania. The relatively small sample size and the retrospective nature are other limitations of our study that could narrow down the extent to which the findings can be applied broadly. Despite these limitations, the study provides meaningful insights. To the best of our knowledge, this is the first comprehensive analysis of adrenal tumors within a Romanian population, where data on this rare condition remain limited.
Conclusions
Although adrenal tumors are rare in routine pathological practice, our study revealed an increasing trend prevalence of these tumors at our institution over the 22-year study period. These results are largely attributed to the increased detection and diagnosis of adrenal cortical adenomas, whose prevalence almost doubled between 2011-2022 vs. 2001- 2011. The widespread use of advanced imaging technologies in recent years could have significantly contributed to the detection of these tumors, even when they are asymptomatic. Adrenal cortical adenomas were followed in prevalence by pheochromocytomas, cortical carcinomas and adrenal metastasis, whereas other tumors were rare. Pheochromo- cytomas’ occurrence remained constant over the last 22 years, while cortical carcinoma continues to be a rare condition.
Conflict of interests
The authors declare no conflict of interests in relation to this study.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Emergency County Hospital, Târgu Mureș, Romania (Approval No. 4467/16.02.2023).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study. The patients have been informed regarding their possible images used for publication in the manuscript.
Acknowledgments
This research was funded by the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Romania, Research Grant No. 164/10/ 10.01.2023.
References
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Corresponding author
Adela Nechifor-Boila, Associate Professor, MD, PHD, Department of Histology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, 38 Gheorghe Marinescu Street, 540142 Târgu Mureş, Romania; Phone +40265-215 551 (int. 151), e-mail: adela.nechifor-boila@umfst.ro
Received: June 20, 2025
Accepted: July 17, 2025