Introduction
Adenoma and adenocarcinoma are the most common primary adrenal gland tumors, followed by pheochromocytoma.1–4 Vascular invasion is commonly seen with adrenal malignancy such as pheochromocytomas.2,3,5–8 Adrenalectomy is often recommended for treatment for most adrenal tumors; in cases with caval invasion, additional procedures including cavotomy with tumor thrombus removal and primary closure of the caudal vena cava are needed.2,3 More severe cases have been reported in which tumor thrombus extends into the hepatic caudal vena cava or right atrium.5,9 Good long-term outcomes with survival times > 500 days are reported in cases surviving the perioperative period following adrenalectomy for invasive adrenal neoplasia.2
A prior retrospective study10 assessed dogs diagnosed with adrenal tumors < 3 cm without vascular invasion and identified a short-term survival rate and 1-year disease-specific survival of 92.2% and 83.3%, respectively. While the previously mentioned study supports that adrenalectomy in dogs for small tumors without vascular invasion can be performed with low risk for short-term mortality, the survival of dogs with adrenal tumors when adrenalectomy cannot be performed due to extensive vascular or soft tissue invasion has not been determined. Additionally, the survival of dogs with adrenal tumors has not been determined when owners elect not to proceed with surgery due to concern for a high risk of complications or mortality. The purpose of this study was to report the outcomes in a cohort of dogs diagnosed with adrenal tumors with vascular or soft tissue invasion that did not pursue adrenalectomy.
Methods
Case selection criteria
The electronic medical records of The Ohio State University Veterinary Medical Center were searched to identify dogs that were diagnosed with an adrenal tumor between January 1, 2012, and December 31, 2022. Records were reviewed by a single investigator (GSF). Dogs were included in this study that had undergone abdominal imaging (abdominal ultrasound [AUS] or CT) that diagnosed adrenal gland neoplasia with suspected vascular or soft tissue invasion and had not undergone adrenalectomy. Dogs were excluded from the study if adrenalectomy was recommended but declined by owners for reasons unrelated to intraoperative complications or mortality risk (ie, financial reasons). Follow-up was ascertained by 1 investigator (GSF) with the referring veterinarian if there was no documented examination at The Ohio State University Veterinary Medical Center. Owner follow-up via email or telephone contact was attempted if the data were not available from the referring veterinary clinic. Dogs still alive or that died before the follow-up with the investigator (GSF) were included in the study.
Medical records review
Following case identification, data were collected from the medical records. Data collected from the medical records included signalment and examination findings at the time of initial presentation. Abdominal imaging (AUS or CT) reports from an American College of Veterinary Radiologists board-certified radiologist were retrospectively reviewed to identify vascular or soft tissue adrenal gland tumor invasion. The type of treatment pursued, concurrent neoplasia, reason for death or euthanasia, date of death, and date of last follow-up if still alive were collected.
Statistical analysis
Descriptive statistics were calculated to summarize dog signalment information. Continuous data were tested for normality using the Shapiro-Wilk test. Normally distributed data were reported as mean ± SD (SD), and nonnormally distributed data were reported as median and IQR. Survival time was calculated as the number of days from initial diagnosis to the date of death or euthanasia. Kaplan-Meier survival analysis was performed for calculating the median survival times, and 95% CI and log-rank tests were used to assess for some prognostic factors. If the cause of death could not be determined, death was considered due to disease. Dogs still alive at follow-up were censored in the survival analysis. Factors with a P value of < .05 were considered significant. All statistical analyses were performed using commercial statistical software (SAS, version 9.4; SAS Institute Inc).
Results
Dogs
A total of 402 dogs were initially identified following electronic medical record search. Of these, 370 dogs were excluded from retrospective analysis. Reasons for exclusion included the following: adrenalectomy was performed (n = 246), diagnosis of noninvasive adrenal neoplasia (71), diagnosis of nonadrenal neoplasia (23), missing medical records (22), diagnosis of extra-adrenal neoplasia (2), no follow-up after initial appointment (5), and incomplete medical records (1).
Signalment, history, clinical findings, and diagnostic imaging
A total of 32 dogs met the inclusion criteria, including 15 (46.9%) neutered females, 2 (6.2%) intact males, and 15 (46.9%) neutered males. Mean ± SD age of all dogs was 10.5 ± 2.8 years. The most common breeds represented were Golden Retriever (n = 4) and mixed-breed dog (12).
A history of concurrent neoplasia including acanthomatous ameloblastoma (n = 1), anal sac adenocarcinoma (1), chemodectoma (1), hepatocellular carcinoma (1), splenic hemangiosarcoma (1), and tarsal histiocytic sarcoma (1) was reported in 6 (18.8%) dogs.
Twenty-three (71.9%) dogs underwent either thoracic CT or radiographs at their initial presentation. Four (17.4%) of these dogs were diagnosed with pulmonary metastasis. All 32 dogs underwent either AUS or CT. Two (6.3%) dogs underwent fine-needle aspiration and cytology of their adrenal mass. These 2 dogs were definitively diagnosed with a primary adrenal carcinoma.
Adrenal tumor characteristics seen in the 32 dogs are presented in Table 1. Of the 23 dogs that had CT imaging performed, the median tumor diameter reported was 5.5 cm (range, 1.1 to 15 cm). Based on imaging findings, the majority (28 dogs [87.5%]) of dogs had vascular invasion alone and, of those dogs, 24 (85.7%) had tumor invasion into the caudal vena cava. Vascular structure invasion was reported in the caudal vena cava alone (n = 13), caudal vena cava and left phrenicoabdominal vein (5), caudal vena cava and right phrenicoabdominal vein (4), left phrenicoabdominal vein alone (2), right phrenicoabdominal vein alone (2), and caudal vena cava and left renal vein (2). Both vascular and soft tissue invasion was reported in 3 (9.4%) dogs, and the reported structures were the caudal vena cava and liver (n = 2) and the caudal vena cava, left phrenicoabdominal vein, left renal vein, and left kidney (1). Soft tissue invasion was reported in 1 (3.1%) dog and involved the left kidney. Metastatic disease was confirmed with imaging and/or cytology in 8 (25%) dogs and suspected in 2 dogs at initial presentation. Locations of metastatic spread were confirmed in the liver (n = 5), pulmonary parenchyma (4), spleen (3), peritoneum (3), left kidney (2), and pancreas (1). Thromboemboli (pulmonary, splenic, and aortic) were found in 3 (9.4%) dogs following advanced imaging. None of these dogs exhibited clinical signs of their thromboemboli.
Tumor demographics including tumor location, type of invasion (soft tissue vs vascular vs both), and structures involved of 32 dogs presenting with invasive adrenal neoplasia that did not undergo adrenalectomy.
| Demographic | No. of dogs |
|---|---|
| Tumor location | |
| Left | 12 |
| Right | 19 |
| Bilateral | 1 |
| Structure invasion | |
| Soft tissue | 1 |
| Vascular | 28 |
| Both | 3 |
| Structures involved | |
| Caudal vena cava | 31 |
| Kidney (left) | 2 |
| Liver | 2 |
| Phrenicoabdominal vein (left) | 8 |
| Phrenicoabdominal vein (right) | 6 |
| Renal vein (left) | 3 |
Treatments
Invasion was considered too severe and nonsurgical in the majority (22 [68.8%]) of dogs. Surgery was offered to the owners of 10 (31.3%) dogs but was not pursued due to perceived risk of sudden death (n = 5), risk of hemorrhage (4), or concurrent diagnosis of disseminated intravascular coagulation (1).
For 2 dogs, nonsurgical treatment was pursued for their adrenal neoplasia. For 1 dog, not offered surgery, stereotactic body radiation therapy (5 daily consecutive sessions of 6 Gy each) was pursued, with a survival time of 194 days. This dog was ultimately euthanized following diagnosis of severe thromboembolism. The other dog’s owner declined surgery due to the concern for risk of significant hemorrhage and secondary hypotension. This dog had toceranib phosphate administered PO (Palladia; 2.5 mg/kg, PO, on Mondays, Wednesdays, and Fridays) until its time of death, with a survival time of 837 days. This dog was ultimately euthanized due to owner-perceived poor quality of life unrelated to the adrenal neoplasia.
Survival
Of the 32 dogs with reported follow-up, 30 (93.8%) died or were euthanized during the follow-up period. The median follow-up time was 49 days (range, 0 to 1,910 days). The median survival time for the group was 50 days (95% CI, 4 to 194; Figure 1). The reason for death or euthanasia included the following: active hemoabdomen (n = 8), owner-perceived poor quality of life (7), clinician-determined poor prognosis (5), thromboembolism (3), concurrent congestive heart failure (1), concurrent diabetic ketoacidosis (1), and secondary pancreatitis (1). Natural death, without postmortem necropsy, was reported in 4 dogs.
Kaplan-Meier curve of survival time of 32 dogs presenting with invasive adrenal neoplasia that did not undergo adrenalectomy. Overall median survival time was 50 days.
Citation: Journal of the American Veterinary Medical Association 262, 7; 10.2460/javma.23.12.0689
Two (6.2%) dogs were still alive at the time of follow-up. Following diagnosis, the owners of both dogs chose to proceed with prophylactic therapy, which included daily administration of clopidogrel (3 mg/kg, PO, q 24 h). Both dogs were doing well per verbal follow-up with the owner. The time from diagnosis to last follow-up was 950 and 238 days in the 2 dogs. Age, adrenal gland laterality (left vs right), invasion type (vascular vs soft tissue), the presence of metastasis at diagnosis, the presence of concurrent neoplasia, and the presence of a chronic tumor thrombus were not associated with survival (P = .23, P = .35, P = .81, P = .06, P = .95, and P = .85, respectively).
Discussion
This study was the first to report the survival time in dogs diagnosed with adrenal tumors with vascular or soft tissue invasion that did not undergo adrenalectomy. Prior studies have focused on outcomes following adrenalectomy, and these have reported survival times > 500 days for dogs with adrenal tumors that pursue either unilateral or bilateral adrenalectomy (range, 509 to 1,445 days).2,4,10–13 Comparably, a prior study14 identified that dogs with non–cortisol-secreting adrenal masses that do not undergo adrenalectomy have similar median survival times of about 17.5 months. The current study found a low median survival time of 50 days for dogs with either vascular or soft tissue–invasive adrenal neoplasia that do not undergo surgery. This finding supports the idea that either extensive invasive adrenal tumors or the reported or owner-perceived significant risks associated with adrenalectomy significantly resulted in short survival in this group of dogs. Unfortunately, this finding is biased toward owners who elected to not treat their dogs’ adrenal tumor and therefore may have been more likely to euthanize early. Inherent bias with this finding exists because the decision to euthanize is variable and at the discretion of owners.
In people, adrenalectomy for adrenal gland neoplasia is indicated when the tumor is functional, the adrenal mass has a diameter > 4 to 6 cm, or there is vascular invasion.14 No such consensus statement exists in veterinary medicine, but adrenalectomy is often recommended for similar indications including a functional adrenal tumor, tumors of larger size, and when invasion of surrounding structures has occurred indicating adrenal malignancy is likely. Vascular invasion commonly starts in the phrenicoabdominal vein with subsequent tumor thrombus extension into the caudal vena cava.9 In this study, the caudal vena cava was the most invaded vascular structure reported. Traditionally, invasion of the vena cava is managed with cavotomy, tumor thrombus removal, and primary closure of the vena cava.2,3 When invasion of the adrenal tumor is considered too extensive and therefore inoperable by board-certified surgeons, adrenalectomy is not recommended. If surgical removal of the mass is possible despite invasion, many factors may influence owners’ decisions to not pursue surgery following discussion of potential surgical complications. The most common major complication leading to death in dogs undergoing adrenalectomy is hemorrhage.10 In this study, 10 owners chose not to proceed with surgery. The most common reason for this was risk of sudden death secondary to fatal hemorrhage. Prior to this study, clinicians were unable to provide a median survival time for dogs that did not undergo adrenalectomy, either due to the extent of vascular or soft tissue invasion or owner choice following surgical risk discussion. In this study, a median survival time of 50 days was found for dogs with invasive adrenal gland neoplasia that do not pursue adrenalectomy. This is markedly shorter than that of dogs with noninvasive adrenal masses either pursuing or declining adrenalectomy.2,10,14 In this study, 3 dogs were diagnosed with thromboemboli following advanced imaging, and thromboemboli were the cause of death for those 3 dogs. The authors suspect that more extensive invasion puts dogs at a greater risk for bleeding intraoperatively and thromboembolic complications.
Most importantly, several tumor factors have previously been identified to be associated with a shorter survival time in dogs with adrenal gland neoplasia. In addition to thoracic metastasis of adrenal neoplasia being uncommon, the presence of metastasis does not impact survival of dogs that do not undergo adrenalectomy.14 In the present study, there was no association with survival and the presence of metastasis at presentation in this cohort of dogs. Unsurprisingly, extensive invasion of the caudal vena cava, especially beyond the hepatic hilus, has been previously identified as a poor prognostic indicator.5 With more extensive invasion of an adrenal tumor, a linear increase in technical challenge and life-threatening risk is expected with surgery for its removal. More importantly, extensive invasion has been identified as the most important factor associated with survival of the perioperative period in dogs undergoing adrenalectomy for adrenal neoplasia.15 Prior literature has reported that soft tissue invasion is a poor prognostic indicator.13 In our study, there was no survival difference in dogs that had vascular invasion compared to those with soft tissue invasion. A larger cohort of dogs with only soft tissue invasion is needed to fully evaluate this question.
Aside from differences in disease management between dogs, there were other limitations within the current study, most of which were inherent to the retrospective nature. Only 32 dogs were identified for analysis. A study with a larger cohort of dogs would result in increased statistical power, which could help identify significance of patient or tumor factors on survival time. Because the dogs in this study did not undergo surgical removal of the mass, histopathology or cytological analysis was not available in all dogs; therefore, the effect of tumor type (pheochromocytoma vs other) on survival could not be analyzed.
In conclusion, dogs diagnosed with invasive adrenal neoplasia for which owners did not pursue adrenalectomy have short survival times with a median of 50 days.
Acknowledgments
None reported.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
References
- 1.↑
Lurye JC, Behrend EN. Endocrine tumors. Vet Clin North Am Small Anim Pract. 2001;31(5):1083-1110, ix-x. doi:10.1016/S0195-5616(01)50014-5
- 2.↑
Mayhew PD, Boston SE, Zwingenberger AL, et al. Perioperative morbidity and mortality in dogs with invasive adrenal neoplasms treated by adrenalectomy and cavotomy. Vet Surg. 2019;48(5):742-750. doi:10.1111/vsu.13221
- 3.↑
Mayhew PD, Culp WTN, Balsa IM, Zwingenberger AL. Phrenicoabdominal venotomy for tumor thrombectomy in dogs with adrenal neoplasia and suspected vena caval invasion. Vet Surg. 2018;47(2):227-235. doi:10.1111/vsu.12728
- 4.↑
Piegols HJ, Abrams BE, Lapsley JM, et al. Risk factors influencing death prior to discharge in 302 dogs undergoing unilateral adrenalectomy for treatment of primary adrenal gland tumours. Vet Comp Oncol. 2023;21(4):673-684. doi:10.1111/vco.12931
- 5.↑
Barrera JS, Bernard F, Ehrhart EJ, Withrow SJ, Monnet E. Evaluation of risk factors for outcome associated with adrenal gland tumors with or without invasion of the caudal vena cava and treated via adrenalectomy in dogs: 86 cases (1993-2009). J Am Vet Med Assoc. 2013;242(12):1715-1721. doi:10.2460/javma.242.12.1715
- 6.
Bouayad H, Feeney DA, Caywood DD, Hayden DW. Pheochromocytoma in dogs: 13 cases (1980-1985). J Am Vet Med Assoc. 1987;191(12):1610-1615.
- 7.
Kyles AE, Feldman EC, De Cock HEV, et al. Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001). J Am Vet Med Assoc. 2003;223(5):654-662. doi:10.2460/javma.2003.223.654
- 8.↑
Anderson CR, Birchard SJ, Powers BE, Belandria GA, Kuntz CA, Withrow SJ. Surgical treatment of adrenocortical tumors: 21 cases (1990-1996). J Am Anim Hosp Assoc. 2001;37(1):93-97. doi:10.5326/15473317-37-1-93
- 9.↑
Adin CA, Nelson RW. Adrenal glands. In: Veterinary Surgery: Small Animal. Vol 2. 2nd ed. Elsevier; 2018:2281-2290.
- 10.↑
Cavalcanti JVJ, Skinner OT, Mayhew PD, Colee JC, Boston SE. Outcome in dogs undergoing adrenalectomy for small adrenal gland tumours without vascular invasion. Vet Comp Oncol. 2020;18(4):599-606. doi:10.1111/vco.12587
- 11.
Oblak ML, Bacon NJ, Covey JL. Perioperative management and outcome of bilateral adrenalectomy in 9 dogs. Vet Surg. 2016;45(6):790-797. doi:10.1111/vsu.12514
- 12.
Schwartz P, Kovak JR, Koprowski A, Ludwig LL, Monette S, Bergman PJ. Evaluation of prognostic factors in the surgical treatment of adrenal gland tumors in dogs: 41 cases (1999-2005). J Am Vet Med Assoc. 2008;232(1):77-84. doi:10.2460/javma.232.1.77
- 13.↑
Massari F, Nicoli S, Romanelli G, Buracco P, Zini E. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc. 2011;239(2):216-221. doi:10.2460/javma.239.2.216
- 14.↑
Arenas C, Pérez-Alenza D, Melián C. Clinical features, outcome and prognostic factors in dogs diagnosed with non-cortisol-secreting adrenal tumours without adrenalectomy: 20 cases (1994-2009). Vet Rec. 2013;173(20):501. doi:10.1136/vr.101691
- 15.↑
Knight RC, Lamb CR, Brockman DJ, Lipscomb VJ. Variations in surgical technique for adrenalectomy with caudal vena cava venotomy in 19 dogs. Vet Surg. 2019;48(5):751-759. doi:10.1111/vsu.13168
