COPERNICUS
Characteristics of Adrenal Hemorrhage: A Single Clinic’s Experience
Authors’ Contribution:
A-Study Design
B-Data Collection
C-Statistical Analysis
D-Data Interpretation
E-Manuscript Preparation
F-Literature Search
G-Funds Collection
Siavash Świeczkowski-Feiz1ABCDEFG, Sadegh Toutounchi1ABCDE, Piotr Kaszczewski1CDF, Ewa Krajewska1CDF, Krzysztof Celejewski1CDF, Remigiusz Gelo2CDF, Ryszard Pogorzelski1EG, Zbigniew Gałązka1EG
“Department of General, Endocrine and Vascular Surgery, University Clinical Center of the Medical University of Warsaw, Poland 2nd Clinic of Anesthesiology and Intensive Care, University Clinical Center of the Medical University of Warsaw, Poland
Historia artykułu:
Otrzymano: 04.12.2023 Zaakceptowano: 04.03.2024 Opublikowano: 02.04.2024
ABSTRACT:
Introduction: Adrenal hemorrhage (AH) is a very rare and potentially life-threatening disease which may be secondary to trauma or of non-traumatic etiology.
Aim: The aim of the study was to present the characteristics and management of adrenal hemorrhage and show that adrenal hemorrhage is more common than expected and that the clinical symptoms are not specific.
Materials and methods: This retrospective study involved 199 patients with postoperative diagnosis of adrenal hemorrhage.
Discussion: The factors identified as potential causes of adrenal hemorrhage are adrenocortical carcinoma, pheochromocy- toma, and adrenal adenoma. The study group included 199 patients with postoperative diagnosis of AH. It showed that all pa- tients with postoperative diagnosis had pheochromocytoma (n = 54), adrenal adenoma (n = 68), or adenocarcinoma (n =17). If we look more careful at the results, we can find only 30% of patients (n = 39) with preoperative diagnosis of AH. This group of 39 patients was prepared for expedited surgery. In this group of patients, the preoperative diagnosis of AH was pheochromo- cytoma 28% (n =11), adenocarcinoma (n = 4), and adrenal adenoma (n = 9).
Conclusions: Bleeding into adrenal tumors is still an insufficiently understood topic due to its unpredictability and, as can be seen in our material, of varying severity. Out of 199 patients, only 30% (n = 39) were prepared for surgery with a preoperative diagnosis of AH; most of them had pheochromocytoma. We suggest that is very important to prepare patients for surgery with a preoperative diagnosis of AH using a-adrenoreceptor antagonists. Prolongation of the diagnostic process (time between the imaging examination and the surgery) may result in the disease progressing and adrenal bleeding.
KEYWORDS: adenocarcinoma, adrenal hemorrhage, pheochromocytoma
ABBREVIATIONS
ACC - adrenocortical carcinoma
AH - adrenal hemorrhage
CT - computed tomography ESE - European Society of Endocrinology HU - Hounsfield units MRI - magnetic resonance imaging SD - standard deviation US - ultrasonography
INTRODUCTION
Adrenal hemorrhage (AH) is a very rare and potentially life- -threatening disease which may be secondary to trauma or of non-traumatic etiology. Bilateral AH is an extremely dangerous and potentially lethal condition, which may lead to adrenal tissue destruction and primary adrenal insufficiency [1-3]. According to the literature data, stress (including severe systemic infection, septicemia, or extensive thermal burns), coagulopathy, birth trauma, and adrenal and idiopathic tumors can lead to AH, being non-traumatic causes of this condition. Among adrenal tumors, adrenocortical carcinoma (ACC), metastases to the suprarenal grands, and phaeochromocytomas are the most common causes of AH [2, 4, 5].
Based on autopsy data, it is estimated that 0.14% to 1.1% of deaths, and up to 14% of deaths caused by hemorrhagic shock, are caused
by AH. The incidence of AH is seven times higher in the pediatric population and is followed by higher mortality in this population (i.e., Waterhouse-Friderichsen syndrome, usually involving severe bacterial infection caused by Neisseria Meningitidis, is featured with 55-60% mortality) [2, 6, 7].
The symptoms of AH are varied and non-specific; they depend on the intensity of the bleeding, the size of the hematoma, and the extent of adrenal tissue damage. Such symptoms as left or right flank pain, nausea, vomiting, asthenia, or confusion may be manifestations of other more common conditions, such as retroperitoneal hematoma or nephrolithiasis [2, 5, 8-10].
AH should always be taken into consideration and excluded in pregnant women with unilateral flank or back pains [11].
Contemporary imaging techniques, such as ultrasonography (US), computed tomography (CT), or magnetic resonance imaging (MRI) allow for quick diagnosis of AH [5]. However, it is worth mentioning that there are diseases, such as melanoma metastases to the adrenal glands, that may mimic AH [3].
AIM
The aim of the study was to describe the symptoms of AH and its management, demonstrating at the same time that adrenal hemorrhage is a more common condition than might be expected
that should be taken into consideration in case of the presence of various non-specific symptoms.
MATERIALS AND METHODS
Between the years 2012 and 2022 there were altogether 649 adre- nalectomies in the Department of General, Endocrine and Vascu- lar Surgery: 605 laparoscopic procedures and 44 open surgeries. In 199 cases there was a final diagnosis of AH, and in 39 cases it was confirmed with preoperative imaging examinations.
All patients with AH were initially treated or diagnosed in the En- docrinology Department and subsequently qualified for elective surgery. In 39 patients diagnosed with AH, elective surgery was performed after previous pharmacological preparation, either in the endocrinology department or on an outpatient basis. The mean time between release from the Endocrinology Department to admission to the Surgical Department was 40 days. In 160 pa- tients, AH hemorrhage was diagnosed only on postoperative his- topathological examination. The surgical method was adapted to the size of the tumor and the AH itself was not a determinant of the surgical method (laparoscopic or open).
RESULTS
The study group included 199 patients with a postoperative diagnosis of AH, 127 female (63.8%, mean age 58.83 +12.77 years) and 72 male (36.2%, mean age 57.46 +14.46 years). The data concerning the study group are presented in Tab. I. Analysis of the medical data shows that phaeochromocytoma, ACC, and oral anticoagulants are connected with an increased risk of adrenal hemorrhage.
In the group of patients with postoperative diagnosis of AH, there were two subgroups. The first contains patients who were admitted to the emergency room with acute onset of right flank, left flank, or back pain. The second group consist of patients who - despite positive medical history of adrenal tumor - never got diagnostic of left or right back pain, abdominal pain after diagnosis of adrenal tumor, but the final diagnosis of adrenal hemorrhage was made on postoperative histopathological examination.
In the first group (39 patients: 20 females, aged 57.3 +16.55 years; 19 males, aged 55.15 +17.20 years), the most common diagnoses were phaeochromocytoma (n = 11), adenoma (n = 9), and ACC (n = 4). The mean age of patients with phaeochromocytoma was 50.8 years in women and 57 years in men; for those with adenoma, it was 38.4 years in women and 55.25 years in men; and in those with ACC it was 51.5 years in women and 47 years
in men. In our group, all patients were prepared for early elective surgery, due to the lack of preoperative diagnostics. None of our patients required emergency surgery. In the preoperative period, endocrinological workup for diagnosis of the hormonal activity of the lesion was carried out. The pharmacological preparation included the administration of alpha-blockers. According to the guidelines in Diagnosis and Management of Neuroendocrine Tumors, preoperative alpha-blockers are mandatory in patients with pheochromocytoma or those with normal levels of catecholamines to minimize the intraoperative and perioperative risk by protecting against the release of catecholamines due to anesthesia and surgical manipulation of the tumor. In this group, only 7 out of 39 tumors were diagnosed as hormonally active. However, this information was obtained postoperatively. It is worth emphasizing that with such a method of pharmacological preparation for surgery, there were no AH-related deaths in the perioperative or postoperative periods.
The second group consisted of 160 patients. In this group, the most common diagnoses were adenoma (36.74%, n = 61), phaeochromocytoma (27.71%, n = 46), ACC (7.83%, n = 13), and metastases (7.23%, n = 12). This group, with extensive preoperative diagnostics of adrenal tumors, was prepared for surgery according to the preoperative diagnosis and in line with the endocrine surgery consensus and guidelines. In this group as well, there were no perioperative or postoperative deaths.
In both groups there were no significant differences concerning operation time (Tab. I., II.). The only difference was the preoperative pharmacotherapy. All patients without preoperative diagnosis of the lesion received alpha-blockers in preparation for the surgery. In the 160 patients with preoperative diagnosis, the pharmacological preparation depended on the type of the lesion: alpha-blockers were administered only to patients with confirmed phaeochromocytoma and those with no clear diagnosis of the lesion type, which is in accordance with the guidelines in Diagnosis and Management of Neuroendocrine Tumors.
The data concerning the size and type of the tumors in our study group are presented in Tab. I.
In patients with phaeochromocytoma or ACC, an increased risk of adrenal bleeding was observed in lesions greater than 54 mm and 51 mm, respectively. The phaeochromocytomas measuring >60 mm accounted for 88% of all phaeochromocytomas with preoperative diagnosis of AH, while in the group without preoperative diagnosis, it accounted for 35.7% of all lesions. ACCs >60 mm accounted for 50% of all ACCs complicated with AH in the first group and 58.8% of those in the second group.
In the first group, in whom AH was the first manifestation of the disease, nine patients did not have a preoperative diagnosis. This may suggest that hemorrhage caused the destruction of the adrenal tissue, preventing diagnosis.
The time interval from making the diagnosis of AH to surgical treatment varied. Patients with phaeochromocytoma underwent at least two weeks of pharmacological preparation with doxazosin. Patients with suspicion of malignancy were operated on within one or two weeks of the initial diagnosis. Patients with preoperative diagnosis of AH but no clear diagnosis of the type of the lesion underwent two weeks’ preparation with doxazosin.
| PARAMETER | ADRENAL ADENOMA (n =68) | ADRENAL HEMATOMA (n = 7) | ADRENAL HYPERPLASIA (n=13) | ADRENAL MYELOLIPOMA (n= 4) | ADRENAL PSEUDOCYSTS (n=7) | ACC (n = 17) | METASTASIS (n = 15) | PHEOCHROMOCYTOMA (n =57) | OTHERS (n =10) | TEST | p-VALUE |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Male | 20.6% (n = 14) | 85.7% (n = 6) | 30.8% (n = 4) | 25% (n = 1) | 57.1% (n = 4) | 35.3% (n = 6) | 73.3% (n = 11) | 36.8% (n = 21) | 50% (n = 5) | Fisher | < 0.001 |
| Female | 79.4% (n = 54) | 14.3% (n= 1) | 69.2% (n = 9) | 75% (n = 3) | 42.9% (n = 3) | 64.7% (n=11) | 26.7% (n = 4) | 63.2% (n = 36) | 50% (n = 5) | ||
| n | 68 | 7 | 13 | 4 | 7 | 17 | 15 | 57 | 10 | Kruskal-Wallis | 0.0027 |
| Mean (SD) | 61.34 (10.1) | 45.43 (22.85) | 66.54 (9.13) | 61.75 (10.37) | 62 (26.87) | 51.94 (12.56) | 61.73 (9.82) | 54.84 (12.61) | 58.3 (17.33) | ||
| Median (Q1-Q3) | 63 (57-68) | 42 (26.5-63.5) | 69 (63-72) | 64.5 (59-67.25) | 74 (46-80.5) | 53 (39-60) | 61 (57.5-67.5) | 57 (45-64) | 57 (49.75-64) | ||
| Range | 31-79 | 20-76 | 44-77 | 47-71 | 20-87 | 30-71 | 38-80 | 32-76 | 29-91 | ||
| n | 68 | 7 | 13 | 4 | 7 | 17 | 15 | 56 | 10 | Kruskal-Wallis | < 0.001 |
| Mean (SD) | 47.57 (17.43) | 71.29 (59.29) | 47.69 (17.28) | 77.5 (16.58) | 71.43 (37.61) | 85.24 (40.6) | 80.27 (29.14) | 53.7 (26.04) | 94.2 (67.9) | ||
| Median (Q1-Q3) | 45 (36.5-51.25) | 57 (42.5-68.5) | 50 (30-60) | 80 (73.75-83.75) | 60 (50-87.5) | 80 (55-110) | 75 (60-90) | 52.5 (30-70) | 90 (42.5-116.25) | ||
| Range | 13-95 | 20-200 | 17-75 | 55-95 | 25-140 | 32-180 | 48-160 | 13-120 | 22-240 | ||
| <40 | 27.9% (n= 19) | 14.3% (n=1) | 30.8% (n = 4) | 0% (n = 0) | 14.3% (n=1) | 11.8% (n = 2) | 0% (n = 0) | 37.5% (n = 21) | 20% (n = 2) | Fisher | |
| 40-60 | 54.4% (n = 37) | 42.9% (n = 3) | 53.8% (n =7) | 25% (n= 1) | 42.9% (n = 3) | 29.4% (n=5) | 33.3% (n = 5) | 26.8% (n = 15) | 20% (n = 2) | < 0.001 | |
| 60+ | 17.6% (n= 12) | 42.9% (n = 3) | 15.4% (n = 2) | 75% (n = 3) | 42.9% (n = 3) | 58.8% (n = 10) | 66.7% (n = 10) | 35.7% (n = 20) | 60% (n = 6) | ||
| n | 62 | 6 | 10 | 2 | 7 | 15 | 10 | 49 | 8 | Kruskal-Wallis | 0.0438 |
| Mean (SD) | 8.89 (3.26) | 7.5 (5.68) | 8.7 (3.4) | 9.5 (2.12) | 6.86 (1.68) | 10.87 (4.26) | 10.7 (5.06) | 8.84 (2.66) | 11.12 (3.18) | ||
| Median (Q1-Q3) | 8 (7-10) | 7 (4-7.75) | 8 (7.25-10.5) | 9.5 (8.75-10.25) | 6 (6-7.5) | 9 (8-13) | 9 (8-14) | 8 (7-10) | 11 (8.75-14) | ||
| Range | 4-22 | 2-18 | 4-16 | 8-11 | 5-10 | 6-20 | 5-20 | 4-17 | 7-15 | ||
| n | 61 | 6 | 10 | 2 | 7 | 15 | 10 | 47 | 8 | Kruskal-Wallis | 0.0131 |
| Mean (SD) | 5 (1.53) | 4.17 (3.87) | 4.4 (1.84) | 4.5 (0.71) | 4.57 (0.79) | 6.33 (2.44) | 6.9 (3.14) | 4.83 (1.56) | 6.75 (3.2) | ||
| Median (Q1-Q3) | 5 (4-6) | 3 (2.25-3) | 4 (4-4.75) | 4.5 (4.25-4.75) | 5 (4.5-5) | 6 (5-8) | 7 (4.5-8) | 5 (4-6) | 6 (4.75-8.25) | ||
| Range | 3-9 | 2-12 | 2-9 | 4-5 | 3-5 | 2-11 | 3-13 | 1-9 | 3-13 | ||
| Right | 50% (n = 34) | 50% (n = 3) | 38.5% (n = 5) | 75% (n = 3) | 42.9% (n = 3) | 58.8% (n = 10) | 46.7% (n=7) | 64.3% (n=36) | 40% (n = 4) | Fisher | 0.5996 |
| Left | 50% (n = 34) | 50% (n = 3) | 61.5% (n = 8) | 25% (n = 1) | 57.1% (n = 4) | 41.2% (n =7) | 53.3% (n = 8) | 35.7% (n = 20) | 60% (n = 6) | ||
| Open | 5.9% (n = 4) | 28.6% (n = 2) | 0% (n = 0) | 0% (n = 0) | 28.6% (n = 2) | 58.8% (n = 10) | 40% (n = 6) | 12.3% (n=7) | 60% (n = 6) | Fisher | <0.001 |
| Laparoscopic | 94.1% (n = 64) | 71.4% (n = 5) | 100% (n = 13) | 100% (n = 4) | 71.4% (n = 5) | 41.2% (n =7) | 60% (n = 9) | 87.7% (n = 50) | 40% (n = 4) |
| VARIABLE | PARAMETER | ADRENAL ADENOMA (n =9) | ADRENAL HEMATOMA (n = 5) | ADRENAL PSEUDOCYST (n = 4) | ADRENOCORTICAL CARCINOMA (n = 4) | HYPERPLASIA (n= 3) | METASTASIS (n= 3) | PHEOCHROMOCYTOMA (n=11) | TEST | P-VALUE |
|---|---|---|---|---|---|---|---|---|---|---|
| Sex | Male | 44.4% (n = 4) | 40% (n = 2) | 75% (n = 3) | 50% (n = 2) | 33.3% (n= 1) | 33.3% (n=1) | 54.5% (n = 6) | Fisher | |
| Female | 55.6% (n = 5) | 60% (n = 3) | 25% (n= 1) | 50% (n = 2) | 66.7% (n = 2) | 66.7% (n = 2) | 45.5% (n=5) | 0.9629 | ||
| Age [years] | n | 9 | 5 | 4 | 4 | 3 | 3 | 11 | Kruskal-Wallis | |
| Mean (SD) | 60.33 (12.55) | 54.6 (32.17) | 58.75 (17.82) | 58.75 (16.07) | 47 (24.02) | 56.33 (16.5) | 54.64 (11.51) | |||
| Median (Q1-Q3) | 62 (58-65) | 70 (20-76) | 64 (55.5-67.25) | 60.5 (51.5-67.75) | 55 (37.5-60.5) | 61 (49.5-65.5) | 56 (47-60.5) | 0.9056 | ||
| Range | 31-77 | 20-87 | 33-74 | 38-76 | 20-66 | 38-70 | 38-73 | |||
| Size of tumor with hematoma [mm] | n | 9 | 5 | 4 | 4 | 3 | 3 | 11 | Kruskal-Wallis | |
| Mean (SD) | 47.56 (22.18) | 106 (65.8) | 65 (23.8) | 102 (57.29) | 52.67 (10.21) | 88.67 (54.05) | 68.55 (26.92) | 0.2043 | ||
| Median (Q1-Q3) | 40 (29-59) | 90 (70-140) | 65 (47.5-82.5) | 89 (65-126) | 57 (49-58.5) | 68 (58-109) | 75 (46.5-89.5) | |||
| Range | 22-90 | 30-200 | 40-90 | 50-180 | 41-60 | 48-150 | 22-100 | |||
| Size of tumor with hematoma [mm]- division Hospital stay [days] | <40 | 33.3% (n = 3) | 20% (n=1) | 0% (n = 0) | 0% (n= 0) | 0% (n = 0) | 0% (n = 0) | 9.1% (n=1) | ||
| 40-60 | 44.4% (n = 4) | 0% (n = 0) | 50% (n = 2) | 25% (n=1) | 100% (n = 3) | 33.3% (n=1) | 27.3% (n = 3) | Fisher | 0.2047 | |
| 60+ | 22.2% (n = 2) | 80% (n = 4) | 50% (n = 2) | 75% (n =3) | 0% (n = 0) | 66.7% (n = 2) | 63.6% (n = 7) | |||
| n | 9 | 5 | 4 | 4 | 3 | 3 | 11 | Kruskal-Wallis | 0.469 | |
| Mean (SD) | 9.78 (5.89) | 9 (5.61) | 6 (1.41) | 11 (5.48) | 5 (3.61) | 9.67 (5.03) | 7.27 (2.1) | |||
| Median (Q1-Q3) | 8 (5-12) | 7 (7-10) | 6.5 (5.5-7) | 11 (7.25-14.75) | 4 (3-6.5) | 9 (7-12) | 7 (6-8) | |||
| Range | 4-22 | 3-18 | 4-7 | 5-17 | 2-9 | 5-15 | 4-11 | |||
| Days after surgery | n | 9 | 5 | 4 | 4 | 3 | 3 | 11 | Kruskal-Wallis | |
| Mean (SD) | 5.56 (2.24) | 6 (4.06) | 5 (1.63) | 6.25 (3.3) | 3 (1.73) | 5.67 (2.52) | 4.82 (1.08) | |||
| Median (Q1-Q3) | 5 (4-7) | 5 (3-8) | 5 (4.5-5.5) | 6 (3.75-8.5) | 2 (2-3.5) | 6 (4.5-7) | 5 (4-5) | 0.6836 | ||
| Range | 3-9 | 2-12 | 3-7 | 3-10 | 2-5 | 3-8 | 3-7 | |||
| Operated side | Right | 44.4% (n = 4) | 60% (n = 3) | 25% (n= 1) | 25% (n=1) | 33.3% (n= 1) | 66.7% (n = 2) | 54.5% (n = 6) | ||
| Left | 55.6% (n =5) | 40% (n = 2) | 75% (n = 3) | 75% (n = 3) | 66.7% (n = 2) | 33.3% (n =1) | 45.5% (n=5) | Fisher | 0.8761 | |
| Surgery type | Open | 11.1% (n=1) | 40% (n = 2) | 25% (n= 1) | 25% (n=1) | 33.3% (n= 1) | 33.3% (n=1) | 9.1% (n=1) | Fisher | |
| Laparoscopic | 88.9% (n = 8) | 60% (n = 3) | 75% (n = 3) | 75% (n = 3) | 66.7% (n = 2) | 66.7% (n = 2) | 90.9% (n = 10) | 0.6448 | ||
| Operation time [minutes] | n | 9 | 5 | 4 | 4 | 3 | 3 | 11 | Kruskal-Wallis | |
| Mean (SD) | 122.78 (38.33) | 113 (49.57) | 115 (19.58) | 132.75 (31.42) | 123.33 (52.04) | 155.33 (31.63) | 148.64 (38.41) | 0.4507 | ||
| Median (Q1-Q3) | 140 (95-140) | 120 (75-135) | 117.5 (105-127.5) | 135.5 (113.75-154.5) | 140 (102.5-152.5) | 165 (142.5-173) | 150 (105-177.5) | |||
| Range | 65-185 | 55-180 | 90-135 | 95-165 | 65-165 | 120-181 | 105-210 |
The data concerning the surgical approach in relation to tumor size are presented in Tab. I. Fig. 1. shows the preoperative diagnosis of an adrenal hemorrhage in CT angiography and the same tumor after operation.
The surgeries we performed consisted of 81.4% (n = 162) laparoscopic operations and 18.6% (n = 37) classical operations. Laparoscopic operations were performed in tumors up to 40 mm in 92% (n = 46), in tumors 40-60 mm in 92.4% (n = 73), and in tumors over 60 mm only in 60.9% (n = 42) (Tab. I.). In our study group, there was no perioperative or postoperative mortality related to AH.
DISCUSSION
Characteristics of Adrenal Hemorrhage
AH is a life-threatening condition, especially in infancy. In adults, the clinical course of the disease is not connected with increased mortality, except in cases with hemorrhagic shock. In our study group, none of the patients with AH of non-traumatic etiology required emergency surgery. In two cases, a red-blood-cell transfusion was made due to reasons other than AH.
In the 10-year period, there were 199 histopathological diagnoses of adrenal bleeding in a total of 649 adrenalectomies (30.5%). In 39 patients, which is only 6% of all adrenalectomies, the AH was diagnosed preoperatively. Those patients required pharmacological preparation for surgery. All patients with preoperative diagnosis of adrenal bleeding reported flank or back pains. In 160 patients with histopathological diagnosis of AH, there was no evident correlation between the clinical symptoms and adrenal lesion.
Pathophysiology of Adrenal Hemorrhage
The adrenal gland is supplied in arterial blood by three arteries (the superior, middle, and inferior suprarenal arteries, which are branches of the inferior phrenic artery, the abdominal aorta, and the renal artery, respectively) [1, 2, 5, 12, 13]. The venous blood outflow is provided by a single adrenal vein. The adrenal cortex arterial blood supply is provided by numerous small arteries and it drains into a limited number of venules (this configuration is called a vascular dam). The large number of smooth-muscle cells situated in a longitudinal manner in the venous wall makes the vein susceptible to the influence of catecholamines. The excess of catecholamines causes a significant increase in vascular resistance and higher pressure and blood stasis in the adrenal glands. The decreased perfusion may result in small-arteriole ischemic necrosis, and after restoration of proper blood flow, can lead to AH.
Catecholamines cause platelets to aggregate and blood vessels to spasm. The adrenal vein wall structure facilitates its susceptibility to catecholamines, which may lead to adrenal vein thrombosis and weakening and rupture of the venous wall [12, 13].
In our study group, phaeochromocytoma accounted for 28.6% (n = 57), metastases for 7.5% (n = 15), and ACC for 8.5% (n = 17) of all lesions. The correlation between these types of lesion and AH was the strongest; the AH was likely caused by degenerative lesions in the adrenal glands.
Imaging of Adrenal Hemorrhage
Imaging modalities in the diagnosis of adrenal gland pathologies include US, CT, and MRI. CT is the most commonly used for diagnosing AH. The morphological features of AH, such as the size, intensity, severity, and the presence of calcifications may suggest the etiology of the bleeding [10, 11, 13]. Acute AH has a radiodensity of 50-90 HU. In the vast majority of cases, conservative treatment of AH results in complete resolution within one year. Calcifications appear in the early stages of hemorrhage development, usually after one week [13, 14]. In our study group, the most common causes of AH included ACC (8.5%, n = 17), metastases to the adrenal glands (7.5%, n = 15), phaeochromocytoma (28.6%, n = 57), and adrenal adenoma (34.2%, n = 68). Based on these observations, adrenal tumors with the features of AH should not be treated conservatively. In the overwhelming majority of cases, if the patient state is stable, early elective surgery should be performed, preceded by pharmacological treatment.
Management of a Tumor’s Adrenal Hemorrhage
Bleeding to an adrenal tumor is a rare clinical condition and a non- -invasive cause of adrenal hemorrhage. According to the literature data, it is most commonly observed in ACC, metastases to the adrenal glands, and phaeochromocytomas [3, 11]. Every adrenal lesion should undergo mandatory assessment of the hormonal activity and potential malignancy. In the vast majority of cases, incidentalomas are benign, non-functional adenomas, but 5-8% of lesions are malignant. In our study group, ACC and metastases to the adrenal glands were the most common lesions in patients with AH confirmed in postoperative histopathological examinations.
In every patient without an apparent cause of AH, a thorough analysis of the imaging examinations should be conducted in order to differentiate between traumatic causes of bleeding or potential malignancy. AH may be the first and only symptom of adrenal lesion malignancy.
The overnight low-dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium, and - in hypertensive patients - upright plasma aldosterone/plasma renin activity ratio should be conducted during the diagnostic process [15].
Management of Adrenal Hemorrhage into Pheochromocytomas
Patients with AH secondary to phaeochromocytoma should undergo early elective surgery preceded by pharmacological preparations. In order to achieve control of the symptoms of catecholamines, hypersecretion of a-adrenoreceptor antagonists (doxazosin) is used. When the treatment is accompanied with tachycardia, beta-blockers are administered (bisoprolol, metoprolol, or nebilein) [16-19].
Pharmacological preparation for surgery should be conducted in patients with and without blood pressure fluctuation; it should last at least 14 days. In some cases, blood pressure surge or cardiac arrhythmia appear during the induction of anesthesia, insufflation of the gas into the peritoneal cavity, or manipulation in the vicinity of the adrenal lesion. The lack of proper pharmacological preparation
for surgery may result in hypertensive crisis or cardiac arrhythmia, which may lead to potentially life-threatening complications [17, 19].
In our study group, 7 out of 39 patients (17.94% of the whole study group and 70% of patients with phaeochromocytoma) with preopera- tive diagnosis of AH had elevated levels of methoxy catecholamines. In a study by Rzepka et al., in patients with hemorrhage due to a pheo- chromocytoma, both urinary and plasma catecholamines/metaneph- rines were elevated in 21 out of 24 patients (87.5%).
In phaeochromocytoma, the adrenal tissue destruction secondary to adrenal bleeding may result in normalization of catecholamine secretion and resolution of its symptoms. It is doubtful, however, whether such a condition may be considered a self-healing process. Some phaeochromocytomas may be asymptomatic and the hypersecretion of catecholamines and clinical symptoms may occur after a stressful predisposing factor such as surgery, injury, infection, or pregnancy. About 10% of phaeochromocytomas are malignant lesions. In a small percentage of lesions, which are hormonally non- -active, hormonal activity appears after a stressful factor [20].
Therefore, the decision to undergo surgery must be made individually for every patient. Laparoscopic adrenalectomy currently serves as the method of choice for patients in whom the AH is limited to tumor tissue and the lesion does not exceed 4-6 cm [19]. If the hemorrhage exceeds the tumor capsule, the laparoscopic surgery may be difficult to perform due to the inflammation of surrounding tissues in the retroperitoneal space and the complete excision of the adrenal tumor may be problematic. In such patients, conventional open surgery remains the treatment of choice.
Management of Adrenal Hemorrhage into Adrenocarcinoma
Adrenal hemorrhage may be the first manifestation of an adrenocortical carcinoma. Initial diagnosis of such lesions is based on the assessment of the hormonal activity and any potential malignancy features on CT imaging. It is worth pointing out that about 60% of ACCs are hormonally active [21]. In our study group, bleeding to the ACC was observed in 8.5% of all AH cases (n = 17). It is worth knowing that AH can be the first symptom of ACC [22].
The choice of surgical approach in ACC remains controversial. Some authors claim that a laparoscopic approach should not be used for the treatment of ACC due to the higher risk of rupturing the tumor capsule and the potential local spread of carcinoma or metastases to the peritoneum.
On the contrary, other experts regard the laparoscopic approach as fea- sible even in the treatment of adrenal malignancies, facilitating shorter recovery and shortening the interval between the surgery and adjuvant treatment. Those experts also stress that the less invasive procedure may feature a lower risk of malignant cells spreading in the peritoneal cavity. According to the ESE recommendations for the treatment of ACC, the tumor and surrounding adipose tissue should be completely excised. In our study group, 10 out of 17 ACC patients had conven- tional open surgery and in seven patients laparoscopy was performed.
Metastasis to the Adrenal Gland
Large autopsy studies have shown that the percentage of cancers which metastasize to the adrenal glands is about 42% for lung,
58% for breast, 16% for gastric, 10.3% for esophageal, and 14% for colorectal cancer and 50% for malignant melanomas. Metastases to the adrenal glands have also been reported for renal cell carcinoma, hepatocellular carcinoma, carcinoma of the bladder, lymphoma, seminoma of the testis, and osteogenic sarcoma. In patients who have an adrenal mass and an extra-adrenal malignancy, the frequency of this mass being metastatic ranges from 32% to 73% [18].
In our study group, in 7.5% (n = 15) of patients with AH, there was a hemorrhage to the metastatic lesion located in the adrenal gland. The detailed characteristics of metastatic lesions in our study group are presented in Tab. II.
Controversies in the Preoperative Management of Patients with Adrenal Hemorrhage
According to the guidelines for the management of patients with phaeochromocytomas, both hormonally active and non- -functioning, a minimum 10-day preoperative administration of alpha-blockers is recommended in order to minimize the perioperative risk [23]. A group of German surgeons do not use a-adrenoreceptor antagonists in the preoperative period. In their study, they claim that such pharmacological preparation is not connected with clear benefits to the patients [24]. On the contrary, our experience clearly shows that pharmacotherapy with alpha- -blockers in the preoperative period increases the safety of the surgical procedure and minimizes the risk of complications during the surgery and in the perioperative period.
Operation Time
The average operation time in patients with AH was 120 minutes (90-150 min). The operation time in our study group was slightly shorter than that reported by Duralska et al. (130 min, SD = 42 min, 55-320 min) for patients without adrenal bleeding [22]. The detailed data concerning the operation time in patients with different postoperative diagnosis are shown in Tab. II. and Fig. 1.
Size of tumors with Adrenal Hemorrhage
The adrenal tumors are divided based on their size into three groups: < 4 cm, 4-6 cm, and >6 cm. Adrenal bleeding is observed most commonly in the lesions < 4 cm and >6 cm. Among the tumors measuring >6 cm, AH is most commonly observed in phaeochromocytomas (29%), adenomas (17.4%), ACC (6.4%), and metastases to the adrenal glands (6.4%).
The average size of the tumor with preoperative diagnosis of the AH was 7 cm.
CONCLUSIONS
Adrenal hemorrhage is still an underdiagnosed condition that should always be taken into consideration in the case of non-specific symptoms such as sudden back, flank, or abdominal pain. Prolongation of the diagnostic process (time between the imaging examination and the surgery) may result in the disease progressing and adrenal bleeding. Pheochromocytomas, ACCs, adrenal adenomas, and metastases feature a higher risk of adrenal hemorrhage.
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| Table of content: | https://ppch.pl/issue/16227 Page count: 8 | Tables: 2 | Figures: 1 | References: 24 |
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| Copyright: | Some right reserved: Fundacja Polski Przegląd Chirurgiczny. Published by Index Copernicus Sp. z o. o. | |||
| Competing interests: | The authors declare that they have no competing interests. | |||
| 8 | The content of the journal „Polish Journal of Surgery" is circulated on the basis of the Open Access which means free and limitless access to scientific data. | |||
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| Corresponding author: | Siavash Swieczkowski-Feiz; Department of General, Endocrine and Vascular Surgery, University Clinical Center of the Medical University of Warsaw; Banacha street 1A, 02-091 Warsaw, Poland; E-mail: siavashfeiz@gmail.com | |||
| Cite this article as: | Swieczkowski-Feiz S., Toutounchi S., Kaszczewski P., Krajewska E., Celejewski K., Gelo R., Pogorzelski R., Galazka Z .: Characteristics of Adrenal Hemorrhage: A Single Clinic's Experience; Pol Przegl Chir 2024; 96 (4): 36-43; DOI: 10.5604/01.3001.0054.4570 | |||