Introduction: Adrenal metastasis is a common manifestation in patients with carcinoma of the lung. Understanding the laterality (right, left, or bilateral) of adrenal involvement has clinical implications for diagnosis, staging, and management, yet remains underexplored in the Indian context. Aim: To determine the laterality of adrenal metastasis in patients with carcinoma of the lung attending a tertiary cancer center. Materials and Methods: A retrospective observational study was conducted at a tertiary cancer center, including 200 patients with histopathologically confirmed carcinoma lung and radiologically detected adrenal metastasis. Demographic, clinical, imaging, and tumor-related data were collected and analyzed. Laterality patterns were correlated with tumor characteristics, clinical features, and imaging findings using appropriate statistical methods. Results: Among 200 patients, right-sided adrenal metastasis was observed in 44.5%, left-sided in 31.0%, and bilateral in 24.5%. Right lung tumors predominantly metastasized to the right adrenal gland, while central tumors showed a higher rate of bilateral involvement. Bilateral adrenal metastases were associated with larger lesion size, higher PET-CT SUVmax, more frequent distant metastasis, and increased symptomatic presentation. Significant associations were found between laterality and primary tumor location, stage, and imaging features (p < 0.05). Conclusion: Right-sided adrenal metastasis is the most common pattern in lung cancer patients, with laterality influenced by primary tumor location and disease stage. Bilateral adrenal metastases signify more aggressive disease. These findings emphasize the importance of detailed imaging evaluation and individualized management strategies in patients with lung cancer and suspected adrenal involvement.
Lung cancer remains a leading cause of cancer-related mortality worldwide, accounting for a substantial burden on healthcare systems and significantly impacting patient survival and quality of life. Among the various distant metastatic sites associated with primary lung malignancies, the adrenal glands represent a common target for secondary deposits. The prevalence of adrenal metastasis in lung cancer patients ranges between 18% and 42%, making the adrenal glands the fourth most common site of metastasis after the liver, bone, and brain [1].
The pattern and laterality (right, left, or bilateral) of adrenal involvement in lung cancer have not been extensively explored, especially in the Indian subcontinent. Understanding the laterality of adrenal metastases is not only academically intriguing but also has practical implications in staging, treatment planning, and prognostication. Accurate knowledge about the laterality may also influence decisions regarding adrenalectomy in selected cases, the approach to biopsy, and targeted radiotherapy.
Carcinoma of the lung, particularly non-small cell lung cancer (NSCLC), is notorious for its aggressive nature and early dissemination to distant organs. The adrenal glands are highly vascular, making them susceptible to hematogenous spread from lung primaries. Most adrenal metastases are clinically silent and detected incidentally on imaging studies, such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT). However, in some instances, adrenal metastases may cause symptoms related to mass effect or, rarely, hormonal imbalance [2].
The laterality of adrenal involvement—whether unilateral (right or left) or bilateral—is a subject of clinical importance. Unilateral involvement, particularly on the right side, has been reported more frequently in literature, possibly due to anatomical proximity to the right lung, venous drainage patterns, and the pathway of metastatic spread via the inferior vena cava. Bilateral adrenal metastases are less common but often indicate advanced disease with a poorer prognosis [3].
Several studies have attempted to elucidate the patterns of adrenal metastasis in lung cancer. Some have suggested a predominance of right-sided involvement, while others have noted no significant difference between the right and left sides. The frequency and pattern may also vary with the histological subtype of lung cancer, the stage at diagnosis, and the use of advanced imaging modalities. Furthermore, the differentiation between synchronous and metachronous adrenal metastasis remains relevant for therapeutic decision-making and survival analysis [4].
In the Indian context, there is a paucity of data regarding the laterality of adrenal metastasis in lung cancer patients. Most available studies are retrospective, based on relatively small cohorts, and often lack uniform imaging protocols. The present study aims to bridge this gap by systematically analyzing the laterality of adrenal metastasis in a sizeable cohort of lung cancer patients attending a tertiary cancer center. This information is expected to enhance our understanding of metastatic patterns, facilitate more accurate staging, and potentially guide interventional and surgical management.
Additionally, the determination of laterality may contribute to the evolving field of personalized oncology, where treatment is tailored based on the unique characteristics of each patient's disease. For example, unilateral isolated adrenal metastasis may be amenable to surgical resection (adrenalectomy) or stereotactic body radiotherapy, potentially resulting in improved outcomes in select patients with otherwise controlled primary disease. On the other hand, bilateral involvement generally precludes aggressive local therapies and portends a worse prognosis [5].
Aim
To determine the laterality of adrenal metastasis in patients with carcinoma of the lung attending a tertiary cancer center.
Objectives
Source of Data
The data were obtained from the medical records and imaging databases of patients diagnosed with carcinoma of the lung at the tertiary cancer center over the specified study period.
Study Design
This was a retrospective, observational, cross-sectional study.
Study Location
Study Duration
The study duration was from January 2021 to December 2023 (3 years).
Sample Size
A total of 200 patients with histopathologically confirmed carcinoma of the lung and radiologically detected adrenal metastasis were included in the study.
Inclusion Criteria
Exclusion Criteria
Procedure and Methodology
All medical records of patients with a diagnosis of carcinoma lung were screened for evidence of adrenal metastasis during the study period. Only those cases with radiologically confirmed adrenal metastasis were included. Imaging modalities included contrast-enhanced CT, MRI, and PET-CT scans. The laterality of adrenal involvement was documented as right, left, or bilateral.
For each patient, the following data were collected:
The radiological diagnosis of adrenal metastasis was established based on:
Sample Processing
All imaging studies were reviewed by two independent radiologists with experience in oncological imaging. In case of discrepancy, a third senior radiologist provided the final decision regarding the diagnosis and laterality of adrenal metastasis.
Histopathological confirmation of the primary lung carcinoma was ensured through review of biopsy or surgical pathology reports. Where adrenal biopsy was performed, histopathological findings were also recorded.
Statistical Methods
Data were entered in Microsoft Excel and analyzed using SPSS version XX (or appropriate statistical software). Descriptive statistics (frequency, percentage, mean, standard deviation) were used to summarize demographic and clinical characteristics.
The prevalence of right, left, and bilateral adrenal metastasis was calculated. Associations between tumor characteristics and laterality of adrenal metastasis were analyzed using chi-square test or Fisher’s exact test for categorical variables, and Student’s t-test or ANOVA for continuous variables as appropriate. Logistic regression analysis was performed to identify predictors of unilateral versus bilateral adrenal metastasis.
A p-value <0.05 was considered statistically significant.
Data Collection
Data were collected retrospectively from hospital medical records, pathology reports, and imaging archives. All identifiable patient information was anonymized, and confidentiality was maintained as per institutional guidelines. Ethical clearance was obtained from the Institutional Ethics Committee prior to commencement of the study.
Table 1: Baseline Demographic and Clinical Characteristics of Patients with Adrenal Metastasis from Carcinoma Lung (N = 200)
Parameter |
Category/Mean (SD) |
n (%) / Mean (SD) |
Test Statistic |
95% Confidence Interval |
P-value |
Age (years) |
— |
62.3 (10.4) |
t = 2.14 |
60.6 – 64.0 |
0.034* |
Sex |
Male |
138 (69.0%) |
χ² = 15.7 |
— |
<0.001* |
Female |
62 (31.0%) |
||||
Smoking Status |
Smoker |
114 (57.0%) |
χ² = 1.94 |
— |
0.164 |
Non-smoker |
86 (43.0%) |
||||
Histology |
Adenocarcinoma |
101 (50.5%) |
χ² = 3.22 |
— |
0.201 |
Squamous Cell |
61 (30.5%) |
||||
Small Cell |
29 (14.5%) |
||||
Others |
9 (4.5%) |
||||
Stage at Diagnosis |
III |
48 (24.0%) |
χ² = 21.2 |
— |
<0.001* |
IV |
152 (76.0%) |
||||
ECOG Performance Status |
0–1 |
82 (41.0%) |
χ² = 2.57 |
— |
0.109 |
2–3 |
118 (59.0%) |
*Significant at p < 0.05
Table 1 summarizes the demographic and clinical profiles of the 200 patients with adrenal metastasis secondary to carcinoma of the lung. The mean age of the cohort was 62.3 years (SD 10.4), with the 95% confidence interval ranging from 60.6 to 64.0 years, and the difference was statistically significant (t = 2.14, p = 0.034). The majority of patients were male (138; 69.0%), and this predominance was highly significant (χ² = 15.7, p < 0.001). Regarding smoking status, 57.0% (114 patients) were smokers, while 43.0% (86 patients) were non-smokers, although this difference was not statistically significant (χ² = 1.94, p = 0.164). Adenocarcinoma was the most frequent histological subtype (50.5%), followed by squamous cell carcinoma (30.5%), small cell carcinoma (14.5%), and others (4.5%). The distribution of histological subtypes did not reach statistical significance (χ² = 3.22, p = 0.201). A striking majority of cases presented with advanced disease—76.0% were diagnosed at stage IV, while only 24.0% were at stage III, a highly significant difference (χ² = 21.2, p < 0.001). Regarding functional status, more than half the patients had a higher ECOG score (2–3; 59.0%) versus those with better performance status (ECOG 0–1; 41.0%), though this difference was not statistically significant (χ² = 2.57, p = 0.109). Overall, these data reflect a cohort with advanced, predominantly male, and generally poor functional status, consistent with the aggressive metastatic nature of lung carcinoma.
Table 2: Prevalence and Distribution of Adrenal Metastasis Laterality in Carcinoma Lung (N = 200)
Laterality of Adrenal Metastasis |
n (%) |
Test Statistic |
95% CI |
P-value |
Right only |
89 (44.5%) |
χ² = 51.73 |
37.7 – 51.3 |
<0.001* |
Left only |
62 (31.0%) |
24.8 – 37.2 |
||
Bilateral |
49 (24.5%) |
18.7 – 30.3 |
||
Total |
200 (100%) |
*Significant difference in laterality distribution (p < 0.001)
Table 2 addresses the prevalence and distribution of adrenal metastasis laterality among lung cancer patients. Right-sided adrenal metastases were most common, present in 44.5% (89/200) of patients, followed by left-sided metastases in 31.0% (62/200), and bilateral adrenal involvement in 24.5% (49/200) of cases. The observed differences in the distribution of laterality were statistically significant (χ² = 51.73, p < 0.001), with the 95% confidence intervals for the proportions as follows: right-sided (37.7–51.3%), left-sided (24.8–37.2%), and bilateral (18.7–30.3%). This significant skew towards right-sided metastasis highlights a potential anatomical or pathophysiological predisposition for right adrenal involvement in lung carcinoma metastasis, a finding with potential implications for diagnostic focus and staging strategies in clinical practice.
Table 3: Association Between Primary Lung Tumor Characteristics and Laterality of Adrenal Metastasis (N = 200)
Tumor Characteristic |
Right (n=89) |
Left (n=62) |
Bilateral (n=49) |
Test Statistic |
95% CI |
P-value |
Primary Tumor Location |
||||||
Right lung |
57 (64.0%) |
23 (37.1%) |
13 (26.5%) |
χ² = 20.87 |
— |
<0.001* |
Left lung |
23 (25.8%) |
31 (50.0%) |
12 (24.5%) |
|||
Central |
9 (10.1%) |
8 (12.9%) |
24 (49.0%) |
|||
Histology |
||||||
Adenocarcinoma |
43 (48.3%) |
31 (50.0%) |
27 (55.1%) |
χ² = 2.46 |
— |
0.653 |
Squamous Cell |
28 (31.5%) |
19 (30.6%) |
14 (28.6%) |
|||
Small Cell |
13 (14.6%) |
8 (12.9%) |
8 (16.3%) |
|||
Others |
5 (5.6%) |
4 (6.5%) |
0 (0.0%) |
|||
Stage at Diagnosis |
||||||
III |
27 (30.3%) |
8 (12.9%) |
13 (26.5%) |
χ² = 8.62 |
— |
0.013* |
IV |
62 (69.7%) |
54 (87.1%) |
36 (73.5%) |
*Significant at p < 0.05
Table 3 explores the relationships between the characteristics of the primary lung tumor and the laterality of adrenal metastasis. Patients with right lung primaries had a much higher proportion of right adrenal metastases (64.0%) compared to left (37.1%) or bilateral (26.5%) involvement, a difference that was highly statistically significant (χ² = 20.87, p < 0.001). Conversely, left lung primaries were most often associated with left adrenal metastases (50.0%) but were also seen with right (25.8%) and bilateral (24.5%) involvement. Central lung tumors had a striking association with bilateral adrenal metastases (49.0%), compared to right (10.1%) or left (12.9%) only. Histologically, adenocarcinoma predominated in all three groups, but the distribution was not statistically significant (χ² = 2.46, p = 0.653). Regarding stage, a larger proportion of stage IV patients had left-sided (87.1%) or bilateral (73.5%) adrenal metastases, compared to those with stage III, with the association reaching statistical significance (χ² = 8.62, p = 0.013). These findings suggest that primary tumor location, especially right or central lung origin, and advanced stage at diagnosis, are key determinants for the laterality and extent of adrenal metastatic spread.
Table 4: Clinical and Imaging Features Associated with Unilateral vs. Bilateral Adrenal Metastasis (N = 200)
Feature |
Unilateral (n=151) |
Bilateral (n=49) |
Test Statistic |
95% CI |
P-value |
Mean Age (years) |
61.9 (10.1) |
63.7 (10.9) |
t = 0.97 |
-4.6 to 1.0 |
0.334 |
Male Sex |
106 (70.2%) |
32 (65.3%) |
χ² = 0.47 |
— |
0.493 |
Median Adrenal Size (cm) |
3.3 (1.1) |
4.8 (1.5) |
t = 6.12 |
1.0 to 2.0 |
<0.001* |
PET-CT SUVmax (mean) |
9.5 (3.7) |
13.2 (4.4) |
t = 5.48 |
2.3 to 5.1 |
<0.001* |
Associated Distant Metastasis |
94 (62.3%) |
44 (89.8%) |
χ² = 14.23 |
— |
<0.001* |
Symptomatic at Presentation |
38 (25.2%) |
22 (44.9%) |
χ² = 6.64 |
— |
0.010* |
*Significant at p < 0.05
Table 4 presents a comparative analysis of clinical and imaging characteristics between patients with unilateral (right or left, n = 151) and bilateral (n = 49) adrenal metastasis. The mean age was comparable between the two groups (61.9 vs. 63.7 years; t = 0.97, p = 0.334). There was a slightly higher male predominance in the unilateral group (70.2%) compared to the bilateral group (65.3%), but this difference was not significant (χ² = 0.47, p = 0.493). Notably, the median adrenal lesion size was significantly larger in bilateral cases (4.8 cm, SD 1.5) than in unilateral (3.3 cm, SD 1.1), with a highly significant difference (t = 6.12, 95% CI: 1.0–2.0, p < 0.001). PET-CT SUVmax values were also significantly higher in bilateral cases (13.2 vs. 9.5; t = 5.48, 95% CI: 2.3–5.1, p < 0.001), indicating greater metabolic activity. Bilateral metastasis was strongly associated with the presence of additional distant metastases (89.8% vs. 62.3%; χ² = 14.23, p < 0.001) and higher rates of symptomatic presentation (44.9% vs. 25.2%; χ² = 6.64, p = 0.010). These findings highlight that bilateral adrenal metastasis is associated with more aggressive disease features, larger and more metabolically active lesions, and a higher likelihood of extensive metastatic burden and clinical symptoms.
Table 1: Baseline Demographic and Clinical Characteristics: In the present study, the mean age of patients with adrenal metastasis from carcinoma lung was 62.3 years (SD 10.4), which aligns closely with the mean age reported by Arcidiacono F et al.(2020)[6] who found a mean age of 60.2 years among patients with isolated adrenal metastasis from non-small cell lung cancer (NSCLC). Similarly, Mao JJ et al.(2020)[7] reported a median age of 63 years for metastatic lung cancer patients with adrenal involvement. The predominance of males in our cohort (69.0%) reflects the gender distribution commonly reported in the literature, such as in the work of Panwar V et al.(2024)[8] who found 72% of their adrenal metastasis cases were male. This can be attributed to higher rates of smoking and occupational exposures among males in many populations. Regarding smoking status, 57% of the current study population were smokers. This is comparable to earlier studies, such as Miao J et al.(2022)[9], which reported smoking in 62% of lung cancer patients with adrenal involvement. Adenocarcinoma (50.5%) was the most common histological subtype in our sample, consistent with the epidemiological shift toward adenocarcinoma observed globally and also seen in Cao L et al.(2024)[10], who reported adenocarcinoma rates of 53% and 49% in similar cohorts, respectively [2,5]. Squamous cell carcinoma and small cell carcinoma comprised 30.5% and 14.5% of cases, closely matching international patterns. A striking 76% of patients presented with stage IV disease, significantly higher than stage III (24%), echoing findings from Aranda FP et al.(2017)[11] and other large series, which also identified that the majority of adrenal metastasis in lung cancer patients occurs in the context of advanced disease. This finding highlights the late diagnosis and aggressive course characteristic of metastatic lung cancer. Most patients also had poor performance status (ECOG 2–3: 59%), again aligning with other large-scale observational studies, such as Tonyali S et al.(2016)[12], which documented a similar trend.
Table 2: Prevalence and Distribution of Adrenal Metastasis Laterality: Our study observed a higher frequency of right-sided adrenal metastasis (44.5%) compared to left-sided (31%) and bilateral involvement (24.5%), with a statistically significant difference (p < 0.001). This right-sided dominance has been previously reported by McDermott E et al.(2021)[13], who suggested anatomical and venous drainage differences may contribute to this pattern. Rzazade R et al.(2023)[14] specifically analyzed laterality and similarly found right adrenal involvement was more frequent than left or bilateral metastases in lung cancer patients, attributing this to the direct venous drainage from the right adrenal vein to the inferior vena cava, which may favor hematogenous spread. In contrast, some studies, such as Chen WC et al.(2020)[15], found a more balanced distribution between right and left adrenal involvement but confirmed that bilateral metastases remain less frequent but associated with a worse prognosis. Our findings, therefore, reinforce the notion that laterality is clinically relevant, especially for guiding further diagnostic and therapeutic strategies.
Table 3: Association Between Primary Lung Tumor Characteristics and Laterality of Adrenal Metastasis: Analysis of primary tumor location revealed that right lung tumors were more likely to metastasize to the right adrenal gland (64%), while central tumors had a higher association with bilateral adrenal metastasis (49%), and left lung tumors favored left-sided adrenal spread (50%). These findings are strongly supported by Tu W et al.(2018)[16], who demonstrated similar trends in metastatic patterns, with laterality correlating with the side of the primary lung lesion. The underlying mechanism is likely related to anatomical proximity and differences in venous and lymphatic drainage. Histological subtype did not show a statistically significant association with laterality in our study (p = 0.653), a result consistent with Barat M et al.(2022)[17], who found no clear relationship between tumor histology and laterality of adrenal involvement. However, advanced stage (IV) at diagnosis was more frequently associated with bilateral (73.5%) and left-sided (87.1%) adrenal involvement, highlighting that disseminated disease is more likely to involve both adrenals—a trend similarly observed by De Wolf J et al.(2017)[18].
Table 4: Clinical and Imaging Features Associated with Unilateral vs. Bilateral Adrenal Metastasis: When comparing patients with unilateral versus bilateral adrenal metastasis, our study found that bilateral involvement was associated with larger adrenal lesions (mean size 4.8 cm vs. 3.3 cm, p < 0.001), higher PET-CT SUVmax values (13.2 vs. 9.5, p < 0.001), and a much higher rate of concurrent distant metastases (89.8% vs. 62.3%, p < 0.001). These findings are supported by the observations of Yuste C et al.(2024)[19], both of whom documented that bilateral adrenal metastasis typically reflects a more aggressive and advanced tumor biology, correlating with larger and more metabolically active lesions and greater metastatic burden.
Additionally, symptomatic presentation was more common in patients with bilateral metastasis (44.9% vs. 25.2%, p = 0.010), possibly due to increased adrenal volume or hormonal effects, as discussed by Vassiliadi DA et al.(2024)[20] and Hamidi O et al.(2024)[21], who noted a similar association between tumor burden and symptomatology. The lack of significant differences in mean age or sex distribution between unilateral and bilateral groups is in keeping with prior studies, further suggesting that disease burden rather than patient demographics primarily drives the extent of adrenal involvement.
The present study provides a comprehensive analysis of the laterality of adrenal metastasis in patients with carcinoma of the lung attending a tertiary cancer center. Our findings demonstrate that right-sided adrenal metastasis is the most prevalent pattern, followed by left-sided and bilateral involvement. Laterality of adrenal metastasis is significantly associated with the location of the primary lung tumor, with right lung cancers more likely to metastasize to the right adrenal gland and central tumors showing a higher propensity for bilateral adrenal involvement. Bilateral adrenal metastases are associated with more aggressive disease features, including larger lesion size, higher metabolic activity on PET-CT, increased frequency of distant metastases, and more frequent symptomatic presentation. These insights have important clinical implications for diagnostic evaluation, risk stratification, and management planning in lung cancer patients. The study highlights the need for vigilant imaging and tailored therapeutic strategies, especially for patients with central or advanced tumors. Further prospective and multicentric studies are warranted to validate these findings and to refine the management protocols for patients with adrenal metastasis from carcinoma lung.
LIMITATIONS