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Urologia Journal
Assessment of the diagnostic efficacy of radiological and functional evaluation of primary adrenal mass and its’ surgical outcomes
Urologia Journal 2024, Vol. 91(4) 674-680 @ The Author(s) 2024 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/03915603241259881 journals.sagepub.com/home/urj S Sage
Yash Manharlal Tilala (D, Sabyasachi Panda, Abhilekh Tripathi, Sachin Sharma, Amiya Shankar Paul, Sanjay Choudhuri and Samir Swain
Abstract
Introduction: Objective of this study was to assess the diagnostic efficacy of the most commonly used radiological evaluation in form of contrast enhanced computed tomography of abdomen with adrenal protocol, basic functional evaluation and surgical outcomes of primary adrenal masses.
Material and methods: We have retrospectively analysed the institutional records of 108, patients admitted from August 2017 to September 2023, who had underwent surgical intervention for their adrenal mass after thorough evaluation and stabilization.
Results: Flank pain was the most common symptoms in 44 (40.74%) patients. Non-functional adrenal adenoma was found in 36 (33.33%) patients. Pheochromocytoma was the most the common functional adrenal mass found in 24 (22.22%) patients. CECT abdomen had suggested features of malignancy in 16(14.81%) patients. In final histopathological report 26(24.07%) patients had pheochromocytoma and 12 (11.11%) patients had adrenocortical carcinoma. CECT abdomen had sensitivity of 75%, specificity of 95.6%. Plasma free metanephrines and normetanephrine analysis had shown sensitivity of 90%, specificity of 92.86%, aldosterone to renin ratio had sensitivity of 92%, specificity of 100%. Sensitivity and specificity of the low-dose dexamethasone suppression test and plasma dehydroepiandrosterone was 100% in our study. Eighty patients (74.07%) were operated with laparoscopic adrenalectomy, 20 (18.52%) patients with open adrenalectomy. Eight patients (7.41%) were converted from laparoscopic to open. Laparoscopic approach had significantly lesser mean operating time, lesser blood loss, lesser hospitalization and lesser post-operative complications. Conclusion: Radiological analysis and functional analysis has shown good sensitivity and high specificity. Laparoscopic approach has advantage of lesser operative time, lesser hospitalization and lesser post-operative complications.
Keywords
Laparoscopic adrenalectomy, adrenal mass, radiological evaluation, functional evaluation, sensitivity and specificity
Date received: 30 January 2024; accepted: 20 May 2024
Introduction
The adrenal mass, as an incidentaloma, incidence ranges from 4% to 7%, male:female ratio is 1:1.4 and a peak inci- dence in the 5th-7th decades of life. The management of the adrenal mass depends upon whether the lesion has fea- tures suggestive of malignancy, whether the mass is func- tional, symptomatic and size of the mass. There for all adrenal mass needs through functional and radiological
evaluation through contrast enhanced computed tomogra- phy (CECT) abdomen with adrenal protocol.1
Department of Urology and Renal Transplant, S.C.B. Medical College & Hospital, Cuttack, Odisha, India
Corresponding author:
Sabyasachi Panda, Department of Urology and Renal Transplant, S.C.B. Medical College & Hospital, Cuttack, Odisha 753001, India. Email: yash89071@gmail.com
In present study we have shared our experience of man- agement of primary adrenal mass. We have also assessed the diagnostic efficacy of biochemical, radiological analy- sis and have compared laparoscopic adrenalectomy with open adrenalectomy.
Materials and methods
We have retrospectively, analysed prospectively main- tained departmental record, from August 2017 to September 2023 of total 108 patients who were diagnosed with adrenal mass. The data included a detailed history, physical examination, radiological investigations, func- tional biochemical analysis, surgical records, histopatho- logical examination reports of the specimen and follow-up of 108 patients were analysed in this study. Ethical clear- ance obtained from institutional ethical committee.
All the patients were evaluated with basic biochemical evaluation, to assess functional activity, included morning (8:00 am) serum cortisol after overnight low dose dexa- methasone suppression test (LDDST), plasma free metane- phrines and normetanephrine, morning (8:00-10:00 am) ambulatory plasma aldosterone to renin ratio, plasma adrenocorticotropic hormone (ACTH) and plasma dehy- droepiandrosterone (DHEA).
All the patients had optimum renal function and all were underwent contrast-enhanced computerised tomog- raphy (CECT) of the abdomen with adrenal protocol con- sists of a multiphasic scan including an unenhanced scan followed by early (enhanced scan) venous phase at 60 s and a 15-min delayed enhanced scan. The absolute per- centage washout (APW) and relative percentage washout (RPW) was calculated to differentiate lipid-poor adeno- mas from primary carcinoma and metastases.
Patients with functional adrenal mass as per symptoms received adequate specific treatment and were stabilized before surgery. All the patients were thoroughly under- went preoperative anaesthetic check-up. All cases were operated by the same surgical team. The preferred surgi- cal techniques were the laparoscopic adrenalectomy and the open adrenalectomy was done in large mass and sus- pected malignancy. All resected specimen sent for histo- pathological report in each case. Patients with benign functional adrenal mass were followed-up with detail his- tory, physical examination, biochemical analysis, imaging of chest, abdomen and pelvis at 6-month interval then with imaging for the first years and then annually. Median follow up of 58 (10-62) months was available for 108 patients.
In functionally active mass hormonal evaluation was compared with histopathological report. Radiological evaluation in form of CECT abdomen with adrenal proto- col with features suggestive of malignancy was compared with histopathological report to assess sensitivity, specific- ity, positive predictive value and negative predictive value.
| Variables | Results |
|---|---|
| Mean age + SD (years) | 44.9 ±12.8 |
| Variables | N (% N/108*100) |
| Gender | |
| Female | 80 (74.07%) |
| Male | 28 (25.93%) |
| Male to female ratio (M:F) | 1:2.9 |
| Laterality | |
| Left | 60 (55.55%) |
| Right | 48 (44.45%) |
| Mean size (cm) | 5.6 ±3.1 |
| Clinical presentation | |
| Flank pain | 44 (40.74%) |
| Hypertension with type 2 diabetes mellitus | 20 (18.52%) |
| Resistant hypertension | 16 (14.81%) |
| Hypertension with proximal myopathy | 12 (11.11%) |
| Hirsutism | 8 (7.41%) |
| Hypertension with throbbing headache | 8 (7.41%) |
Statistical analysis
Descriptive statistics were used for demographic and clini- cal data. Continuous variables with a normal distribution were reported as the mean ± standard deviation (SD). Non-normal continuous variables were expressed as the median (interquartile range). Categorical variables were reported as the number (percentage). Sensitivity, specific- ity, positive predictive value and negative predictive value were calculated using standard formula. Student’s t test was used for continuous variable and Chi-square test used for categorical variable. SPSS 29.0 (IBM, Chicago, IL, USA) was used for statistical analysis. p Value <0.05 was considered as statistically significant.
Results
Demographic and clinical characteristics as mentioned in Table 1. Mean age was 44.9 ± 12.8 with range 20-72 years with male to female ratio 1:2.9. Total 60 (55.55%) patient had left adrenal mass. The most common clinical presenta- tion was flank pain in 44 (40.74%) patients, hypertension with type 2 diabetes mellitus in 20 (18.52%) patients; hir- sutism was the cause of presentation in 8 (7.41%) patients. There were 36 (33.33%) patients who had non-functional benign adrenal adenoma (Table 2). Functional evaluation was suggestive of pheochromocytoma in 24 (22.22%) patients, 20 (18.52%) patients with hypercortisolism and hyperaldosteronism. On radiological evaluation with CECT abdomen with adrenal protocol 16 (14.81%) patients had malignant features as well as RPW <40% and APW <60%. In final histopathological report 26 (24.07%)
| Functional evaluation of adrenal mass | N (Number of patients)/108 | % (N/108*100) |
|---|---|---|
| Non-functional | 36 | 33.33 |
| Pheochromocytoma | 24 | 22.22 |
| Hyperaldosteronism | 20 | 18.52 |
| Hypercortisolism | 20 | 18.52 |
| Hyperandrogenism | 8 | 7.41 |
| Radiological characteristics (as per CECT abdomen with adrenal protocol) | ||
| Variable | n (Number of patients)/108 | % (n/108*100) |
| Malignant | 16 | 14.81 |
| Benign | 92 | 85.19 |
| Final histopathological report | ||
| Final report | n (Number of patients)/108 | % (n/108*100) |
| Non-functioning benign adenoma | 36 | 33.33 |
| Pheochromocytoma | 26 | 24.07 |
| Aldosterone secreting adenoma (Conn's syndrome) | 18 | 16.67 |
| Adrenocortical carcinoma with cortisol secretion | 12 | 11.11 |
| Cortisol secreting adenoma | 8 | 7.41 |
| Androgen secreting adenoma | 8 | 7.41 |
| Size of mass and radiological characteristics | ||
| Size of adrenal tumour (cm) | N (Number of patients) (%(N/108*100)) | n (Radiological characteristics of malignancy) (%(n/N* 100)) |
| <4 | 44 (40.74) | 0 (0) |
| 4-6 | 16 (14.81) | 2/16 (12.50) |
| >6 | 50 (46.29) | 14/50 (28) |
patients had pheochromocytoma, 18 (16.67%) patients had aldosterone secreting adenoma, 8 (7.41%) patients had cortisol secreting adenoma and androgen secreting ade- noma, while adrenocortical carcinoma (ACC) with corti- sol secretion was found in 12 (11.11%) patients.
There were 16 (14.81%) patients who had adrenal mass of size between 4 and 6 cm, 44 (40.74%) patients had adre- nal mass of size <4 cm and 50 (46.29%) patients had adre- nal mass of size >6cm. On radiological evaluation 2 out of 16 (12.50%) patients with adrenal mass size between 4 and 6 cm had malignant features whereas 14 out of 50 (28%) patients with adrenal mass size >6 cm had malig- nant features on CECT abdomen with adrenal protocol (Table 2).
The diagnostic efficacy of radiological evaluation, after comparison with final histopathological examination report, sensitivity of 75%, specificity of 95.60%, positive predictive value of 98.10%, negative predictive value of 56.10% and accuracy of 92.60% (Figure 1).
In functional evaluation diagnostic efficacy of plasma free metanephrines and normetanephrine analysis had shown sensitivity of 90%, specificity of 92.86%, positive predictive value of 99%, negative predictive value of 50.78% and accuracy of 90.29%. Diagnostic efficacy of
aldosterone to renin ratio had sensitivity of 92%, specific- ity and positive predictive value of 100%, negative predic- tive value of 52.03% was and accuracy of 93%. Sensitivity and specificity of the LDDST and plasma DHEA was 100% in our study.
Laparoscopic trans-peritoneal approach was the most employed approach in 40 (74.07%) patients. Open approach was employed in 20 (18.52%) patients (Table 3). Largest size of mass operated via laparoscopic approach was 14cm (Figure 2). Largest mass operated via open approach was 16 cm in size. Mean size of the masses man- aged via open approach was 6.3 ± 1.2 cm, whereas mean size of the masses managed via laparoscopic approach was 5.9±3.4cm. Comparison between the sizes of mass was statistically insignificant (Table 4). Eight patients (7.41%) were converted from lap. to open due to mainly intraopera- tive bleeding.
In comparison of Lap. to open approach, Lap. Trans- peritoneal approach had significantly lesser mean operat- ing time, lesser intraoperative blood loss, lesser analgesic (inj. tramadol) requirement and lesser hospitalization and lesser post-operative complications (Table 4).
We have median 58 (10-62) months of follow up avail- able of 108 patients.
92.8%
100%
100%
92%
95.6%
98.1%
99%
100%
90%
92.6%
90.2%
93%
80%
75%
56.1%
50.7%
60%
52.03%
40%
20%
0%
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Accuracy
Radiological Evaluation
Plasma free metanephrine & nor-metanephrine
Plasma aldosterone to renin ratio
Discussion
The prevalence of adrenal mass, as non-functional ade- noma, has increased in past decade due to generous use of abdominal imaging.2 Apart from history and physical examinations, functional and radiological evaluations are the essential aspects in management of adrenal mass.
In present retrospective study the review of 108 patients with adrenal mass the mean age of the patients was 44.9 ± 12.8 (range 20-72 years). In present study 74.07% patients were female and male to female ratio was 1: 2.9. Study by Shanmugam et al.3 had mean age of presentation was 44.6 years (range, 9-61 years) with female preponder- ance of 52.6%. Their finding of age was in concordance of our study. The prevalence of adrenal mass in the patients younger than 30 years is <1%, while in patients with 7th decade it increase up to 7%.4 Non-functional adenomas were the majority of findings with almost 75% incidence in various literatures.5 In present study 33% adrenal masses were non-functional adrenal adenoma and most common clinical presentation was flank pain (40.74%). Khanna et al.6 also reported the most common presentation was flank pain in 61.4% of the patient in their study.
In present study the adrenal masses were found slightly left predominance in 55.55% of the patients. Hao et al.7 also reported 75% of adrenal adenomas were on the left side in their study.
In present study the pheochromocytoma was the most common functional benign mass with prevalence of 22.22%. The prevalence of pheochromocytoma in litera- ture varies between 1.5% and 23%.8 Rafiq et al.9 reported prevalence of pheochromocytoma of 26.2% of the patients which was in resemblance in our study.
The functional evaluation of adrenal mass with over- night low-dose dexamethasone suppression test (LDDST), plasma-free metanephrine and morning aldosterone to renin ratio are generally used as a functional evaluation. These tests have high cost and false positive rate but with great clinical relevance in management of adrenal mass and preoperative planning. In various literatures sensitiv- ity of plasma free metanephrines and normetanephrine ranges from of 73% to 100% and specificity around 90%.10 In our study plasma free metanephrines and norme- tanephrine had shown sensitivity was 90%, specificity was 92.86%. In present study sensitivity and specificity of serum aldosterone to renin ratio was 92% and 100%. Hung et al.11 in their meta-analysis reported sensitivity and spec- ificity, of serum aldosterone to renin ratio, varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Other functional evaluation had very high sensitivity and specificity 100% in our study.
The incidence of ACC is 1.2%-12% in various litera- tures.12 We had ACC in 11.11% of the patients. CECT abdomen with adrenal protocol is the primary, most com- monly used and mainstay of imaging modality in evalua- tion of the adrenal mass, gives the information about features of malignancy like density, enhancement, size, calcification, necrosis, local invasion and spread. Bharwani et al.13 found that adrenal mass with characteristics like larger in size (>6cm), heterogeneously enhancing with areas of central necrosis, haemorrhage and calcifications found in 30% cases of adrenocortical carcinoma. Also, Hamrahian et al. had reported that adrenal masses with APW and RPW values of less than 60% and 40%, respec- tively, has higher chances of malignancy. Washout analy- ses have been found to be accurate in many studies.14 Lee et al.15 in their study have found 71% sensitivity and 98% specificity of CECT abdomen with adrenal protocol. In our results the sensitivity and specificity of CECT abdo- men with adrenal protocol was 75% and 95.65%, respec- tively. Various studies have mentioned a cut-off of 4 cm, beyond which suspicion of malignancy would increase.
| Management approach | N (Number of patients)/108 (%(N/108*100)) |
|---|---|
| Laparoscopic (Trans peritoneal adrenalectomy) approach | 80 (74.07%) |
| Open (retroperitoneal adrenalectomy) approach | 20 (18.52%) |
| Lap. to open conversion | 8 (7.41%) |
| Mean size of adrenal mass managed via laparoscopic approach | 5.9 ±3.4 |
| Mean size of adrenal mass managed via open approach | 6.3 ±1.2 |
(a)
(d)
(b)
(e)
(c)
| Variables | Open (trans peritoneal) approach + Lap. to open conversion (n=28) | Laparoscopic (Trans peritoneal) approach (n=80) | p Value |
|---|---|---|---|
| Mean size of the adrenal masses (cm) | 6.3 ± 1.2 | 5.9 ±3.4 | 0.47 |
| Mean operating time(min.) + SD | 98± 11.83 | 115 ±12.8 | 0.09 |
| Mean intraoperative blood loss (ml) + SD | 112.1 ± 10.6 | 70.1 ±9.7 | 0.04 |
| Mean analgesic requirement (mg) ± SD | 432 ±61.8 | 218±56.41 | 0.01 |
| Mean duration of hospital stay (days) + SD | 4.3 ±2.6 | 3.2 ± 1.9 | 0.02 |
| Post-operative complications | |||
| Shock | 4/28 (14.28%) | 2/80 (2.5%) | 0.03 |
| Sepsis | 2/28 (7.14%) | 0 | 0.01 |
| Wound infection | 8/28 (28.57%) | 4/80 (5%) | 0.01 |
Iñiguez-Ariza et al.16 in there retrospective study of large cohort of 705 patients reported rate of malignancy 31% in adrenal masses with size of >4cm. In present study 12.50% patients had malignancy with adrenal mass size 4-6 cm, 28% in patients with size adrenal mass size >6 cm and no malignancy was found in patients with adrenal mass <4cm. In study by Sturgeon and Kebebew17 have found rate of malignancy in their study as 4%-5% in tumours smaller than 4cm, 10% in tumours larger than 4 cm and 25% in tumours larger than 6 cm.
Recommendations for surgical intervention as per National Institute of Health (NIH) 2002 consensus are in
malignancy, large (>5cm in size), symptomatic and/or functionally active adrenal masses.18 Regarding manage- ment approaches, in a comparison with open approach, the laparoscopic adrenalectomy has advantages over open approach in a way that it gives better visualization of the adrenal, effective haemostasis and liver/spleen easily retractable. In present study we have observed blood loss (p=0.04), analgesic requirement (p=0.01) and duration of hospital stay (p=0.02) were significantly lesser in laparo- scopic group. In our study the mean size of 5.6 ±3.1 cm with range 3-16cm. In our observation larger the size increased operative time and blood loss. Larger tumour
that we have operated with laparoscopic route was 14 cm and via open approach was 16 cm. However mean size of the masses in both the approaches was approximately sim- ilar. Gumbs and Gagner19 have also shown that the hormo- nal disorder had no effect on operative time; however, they noted that blood loss was higher in patients with larger size of the tumour. Intra-operative blood loss was the most common complication we have experienced in open and laparoscopic procedure. It was the most common reason for laparoscopy to open conversion. Postoperative compli- cations rates like wound infection and sepsis were higher in open approach. However, no mortality was reported.
No definite consensus on follow up protocol, for benign functional adrenal mass, has been described after adrenal- ectomy. However, most commonly practised and we have followed-up the patients, after adrenalectomy with rele- vant history, physical examination and biochemical analy- sis to be done at 6 month and annually thereafter for life long, as long term recurrence of pheochromocytoma has been reported in literature. In pheochromocytoma 4/24 (16.67%) patients had hypertension that was controlled with one drug with normal radiological or biochemical analysis. So 83.33% patients were diseased and symptoms free on median follow up of 58 (10-62) months. In litera- ture biochemically and/or radiological cure rate in pheo- chromocytoma ranges from 79% to 92.6%.20 Patients with functional benign masses with hyperaldosteronism, hyper- cortisolism and hyperandrogenism had complete resolu- tion of the symptoms in our study.
In the case of adrenocortical carcinoma to detect the high rate of loco-regional and metastatic recurrence, we have followed-up the patients with a strict radiological and biochemical analysis post operatively at 3 month then imaging of chest, abdomen and pelvis at 3-month interval for the first 3 years and then every 6 month for 5 years. In our study no patient had loco-regional and metastatic recurrence during follow-up. However, with locally advanced adrenocortical carcinoma the outcome is uni- formly poor. We didn’t have any such patients with locally advanced malignancy in our study. Limitations of this study are small sample size and retrospective in nature.
Conclusion
Functional evaluation has also shown excellent sensitivity and specificity. CECT abdomen with adrenal protocol has shown excellent specificity in detection of malignant lesion. In comparison to open approach, laparoscopic approach has significantly lesser complications.
Limitations of this study
The small sample size and retrospective in nature are the limitations of this study. A multicentric experience with large sample size is required to consolidate the outcomes.
Acknowledgements
We thankful to our colleagues and staff of our institution.
Author contributions
Y.M.T .: conception, design, materials, data collection and pro- cessing, writing, analysis and interpretation, literature review. S.P .: materials, data collection and processing, analysis and interpretation, writing. A.T., S.S., A.S.P., S.C., S.S .: design, supervision, analysis and interpretation, writing, critical review.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship and/or publication of this article.
Ethics committee approval
Research protocol approved as per norms by institution ethical committee (I.E.C.) after full review: No: 1152. Date: 08.11.23 Institute name - S.C.B. Medical College and Hospital, Cuttack, Odisha, India.
Informed consent
Written informed consent was obtained from all the patients for their clinical information to be published in this article.
ORCID İD
Yash Manharlal Tilala İD https://orcid.org/0009-0004-6940-
1205
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