Cent. Eur. J. Med. • 9(5) • 2014 • 663-666
DOI: 10.2478/s11536-013-0308-9
Central European Journal of Medicine
Regressive changes in phaeochromocytomas
and paroxysmal hypertension
Research Article
Ryszard Pogorzelski , Sadegh Toutounchi , Patryk Fiszer , Ewa Krajewska ,
Barbara Górnicka1, Łukasz Zapała*2, Małgorzata M. Szostek1,
Wawrzyniec Jakuczun1, Robert Tworus1, Tomasz Wołoszko1, Maciej Skórski1
1
1
1
1
1 Clinic of General and Thoracic Surgery, Medical University of Warsaw.,
02-096 Warsaw, Poland
2 Department of Urology, Multidisciplinary Hospital Warsaw-Miedzylesie,
04-749 Warsaw, Poland
Received 21 May 2013; Accepted 31 October 2013
Abstract: Introduction. Pheochromocytomas may cause life-threatening episodes of arterial hypertension and surgical treatment is obligatory
following proper general medical preparation. Material and methods. There were 63 patients in years 2006-2011 operated in the
department due to pheochromocytoma. The group comprised 38 women and 25 men of the age range 16 - 80, mean 44,7. All the
specimen were analyzed in pathological examination. The regressive changes that were found were subsequently compared with
the clinical course of the pheochromocytoma both in the preoperative period and at the time of the surgery. Results. There were 44
laparoscopic adrenalectomies performed, out of which 5 resulted in conversions to open surgery, while 19 patients were operated
primarily via open access. The indications for the open procedures: extraadrenal tumors, fibrotic-infiltrative lesions suggestive
of malignancy, vast intratumoral extravasation, and respiratory failure. In all the postoperative specimens pheochromocytomas
were found. In 29 cases intratumoral haemorrhages were observed, in 17 - tumoral necrosis at different stages, and in 3 cases
posthaemorrhagic cystis. In 6 cases the lesions were accompanied by major fibrosis and hyalinization. Conclusions. There is
a statistically significant relationship between regressive changes observed within phaeochromocytomas and a reduction of
paroxysmal hypertension at the time of adrenalectomy (p=0,012).
Keywords: Pheochromocytoma • Paroxysmal hypertension • Regressive changes in pheochromocytoma
© Versita Sp. z o.o
1. Introduction
Pheochromocytoma is a disease in which surgical
treatment is obligatory, and in the perioperative period
intense vigilance of the whole treating medical team
along with a great experience in the management is
necessary. It is a result of the overproduction of catecholamines, uncontrolled release of which may end up
in a life-threatening rise of arterial blood pressure. The
incidence of pheochromocytoma is estimated to be from
2 to 8 cases annually per million habitants [1]. It is the
cause of secondary hypertension in 0,1% to 0,6% of patients, being the top reason of paroxysmal hypertension
cases [2,3]. However, there are mildly symptomatic or
asymptomatic pheochromocytomas reported, and their
incidence is thought to be from 5% to over 30%. It is a
dangerous condition, which in a situation stressful for
the host may cause life-threatening rises of blood pressure [4,5]. There seems to be a connection between
the diameter of a tumor and overproduction of pressive
amines responsible for the major symptoms of the pheochromocytoma. Additionally, it is confirmed by the fact
that acute coronary syndromes (Takotsubo) usually accompany moderate or minor pheochromocytomas [6,7].
During retrospective analysis of own clinical material regarding patients treated due to pheochromocytomas we
concluded that the overproduction of pressive amines
* E-mail: [email protected]
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Regressive changes in phaeochromocytomas
is connected with pathological changes occurring within
the tumor. The most common lesions were blood effusions, necrosis, posthaemorrhagic cysts, fibrosis and
hyalinization.
2. Material and methods
There were 63 patients operated in our department in
years 2006-2011 due to pheochromocytoma. The study
group comprised 38 (60,3%) women and 25 (39,7%)
men of the age range 16–80, mean age 44,7. After standard diagnostic process together with pharmacological
preparation all the patients were operated on. Laparoscopic transperitoneal adrenalectomy was performed in
44 (69,8%) cases, out of which in 5 patients conversions
to open access were necessary. Conversions were
caused in all the cases by intraoperative haemorrhage
which was impossible to control laparoscopically. The
remaining 19 patients (30,2%) were primarily qualified
for open adrenalectomy. The main indications to open
adrenalectomy were diseases of the respiratory system
and anesthetist’s concerns regarding long-term hypertension in the abdominal cavity with possible influence
on effective ventilation during the surgery. In some
cases, these were fibrous lesions visualized in diagnostic
imaging located in the proximity of the tumor suggestive
of malignancy, intratumoral hemorrhages suggesting
retroperitoneal dehiscence and extraadrenal tumors.
Retrospective analysis was performed concerning the
association of regressive changes reported by pathologists based on the findings in specimens taken from
the incised tumors, and severity of clinical symptoms
connected with the overproduction of catecholamines
in preoperative period and at the time of the surgery.
The results obtained were statistically analyzed using
Fisher’s exact test (statistic package 19.0 2010).
3. Results
Data obtained from the patients’ interviews during preoperative care confirmed existence of arterial hypertension
in 50 (79,4%) patients. That group of patients prior to
diagnosis of phaeochromocytoma had been treated for
3 years due to arterial hypertension. The remaining 13
patients (20,6%), who were not treated due to elevated
blood pressure, according to what they reported, did not
have elevated blood pressure at the moment of occasional blood pressure taking. In the direct preoperative
period unstable blood pressure with a tendency towards
rises over 160/90 mm Hg was observed in that group of
patients in 7 (11,1%) cases, irrespective of the engaged
treatment with alpha and beta blockers. Regardless of
previous blood pressure measurements and methods
of preparation, in 34 (54%) patients during the surgery
both via open and laparoscopic access rises in blood
pressure over 180/90 mm Hg were noted. The rises of
the blood pressure were observed until clamping of the
adrenal vein was performed. After its cutting normalization of the blood pressure was usually seen, while in 5
(7,9%) patients long-term hypotension refractory to the
treatment developed. The highest values of the blood
pressure noted in a few patients were 340/150 mm Hg.
All the specimen coming from the incised tumors were
sent for pathological examination. Pathologists reported
tumor diameters to be between 2,2–10 cm, mean 4,3
cm. However, measurements of tumor diameters performed intraoperatively were approximately 30% greater
in comparison with tumors of the adrenal medulla alone.
Among most important pathological lesions determined
by pathologists in the analyzed specimens apart from
the tissue of phaeochromocytoma one observed blood
effusions, necrosis, posthaemorrhagic cysts and advanced fibrosis and hyalinization. Frequency of these in
the studied group was presented in Table 1.
As a result of these processes in 3 patients (4,8%)
complete unilateral destruction of the adrenal gland occurred, while in one case bilateral one and subsequent
adrenal insufficiency was developed with the necessity
to start substitution therapy.
Starting with the premise that regressive changes
within the tumor burden mentioned above cause in a
substantial matter a decrease in its mass, we decided
to follow their influence on catecholamine release and
blood pressure values. As it is very hard to follow these
changes in preoperative period due to its paroxysmal
character, we therefore compared blood pressure values
obtained from constant invasive blood pressure (IBP)
taking during the surgery with the lesions observed in
the tumor in pathological examination postoperatively.
During IBP taking at the surgery rises over 180/90 mm
Hg were noted in 36 (57,1%) cases. In the remaining 27 (42,9%) ones, no rises in blood pressure were
observed. In Table 2 blood pressure values during the
operation together with regressive changes determined
postoperatively in specimen were presented.
As it may be concluded form the findings in Table
2, in the majority of patients no rises in blood pressure
during the surgery together with the regressive changes
occurred. It is clearly visible in cases in which previously
described regressive changes coexisted e.g. haemorrhage and necrosis and haemorrhage and fibrosis plus
hyalinization. It should be emphasized that all these
patients belonged to the group with hypertension diagnosed and treated preoperatively. It seems that the
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R Pogorzelski et al
Table 1. Frequency of major abnormalities found in postoperative
specimen apart from the phaeochromocytoma. *Advanced
fibrosis accompanied in all cases intratumoral haemorhages, and as a consequence numbers in brackets were not
included in the sum in summary.
Abnormality
No of patients
%
Intratumoral haemorrhage
29
46,0
Necrosis
17
26,9
Fibrosis*
(6)*
(9,5)*
Posthaemorrhagic cysts
3
4,7
Summary :
49
77,6
Table 2.
Blood pressure values during the operation together
with regressive changes determined postoperatively in
specimen
Regressive
changes
Intratumoral
haemorrhage
Haemorrhage
and necrosis
Haemorrhage
and fibrosis
Necrosis
Cysts
Overall
P=0,012
Normal
blood
pressure
Hypertension
Overall
N
8
14
22
%
36,4%
63,6%
44,9%
N
8
2
10
%
80,0%
20,0%
20,4%
N
6
0
6
%
100,0%
,0%
12,2%
N
3
5
8
%
37,5%
62,5%
16,3%
N
2
1
3
%
66,7%
33,3%
6,1%
N
27
22
49
%
55,1%
44,9%
100,0%
observed destructive changes that lead to a decrease
in tumor mass may diminish the secretion of pressive
amines and as a result decrease blood pressure values.
4. Conclusions
There is a statistically significant relationship between
regressive changes observed within phaeochromocytoma and reduction of paroxysmal hypertension at the
time of adrenalectomy (p=0,012).
5. Discussion
In some patients with phaeochromocytoma one may
determine based on patients’ interview that apart from
typical symptoms to that pathology there are also other
symptoms present: abdominal pain, pain in lumbar
region, chest pain, nausea, vomiting and epigastric
fullness. These symptoms may accompany intratumoral
haemorrhage due to necrosis of the interstitial tissue.
The most probable reason of the necrosis within phaeochromocytoma is ischemia as a result of tumor vessel
contractions after a release of catecholamine into the
blood flow. When the process of necrosis comprises
some of the tumor area, there is also damage of the
small vessels, which results in blood effusions [8]. Some
authors reported other possible reasons which lead to
blood effusions, such as: minor traumas of the lumbar
region or chronic steroid therapy [9,10]. Consequences
of the intratumoral haemorrhages are connected both
with its diameter and dynamics. In extreme situations
due to massive bleeding a rupture of the organ capsule
and haemorrhage into retroperitoneal space, peritoneal
cavity or pleural cavity and mediastinum may occur leading to a haemorrhagic shock. In these circumstances,
the necessary immediate surgery is connected with a
great risk of overproduction of pressive amines and
instability of circulatory system. The risk is even greater
in individuals, in whom previous diagnosis of phaechromocytoma was not established [11,12].
In the studied group there were no haemorrhages
into the body cavities or retroperitoneal space. Authors, however, observed such cases during previous
clinical experience, i.e. 3 cases of haemorrhages from
phaeochromocytomas into retroperitoneal cavity, the
controlling of which needed surgery. Operations in
such cases are extremely difficult due to problems with
accomplishing complete hemostasis. The other major
problem is hemodynamic instability of patients with no
known previous medical history of pheochromocytoma,
which is associated with increased mortality [2].
However, the majority of haemorrhages is limited to
the tumor itself and evolution of the hematomas may be
various. One of possible result is a formation of posthaemorrhagic psuedocyst, while another is fibrosis and
hyalinization, repeatedly spreading outside the adrenals
into surrounding tissues, which makes the surgery even
more difficult [13]. Despite the occurrence of advanced
posthaemorrhagic regressive changes, which were
frequently very intense in the studied group, in all the
cases phaechromocytoma was proved in pathological
examination. In the presented material necrosis of different stages was noted in 17 patients, while intratumoral
haemorrhages without coexistent necrosis in 29 patients. It may be a proof of another mechanism of forming the blood effusions in phaeochromocytomas. In the
majority of cases these are no effusions that occurred
at the time of surgery because they were visualized in
preoperative diagnostic imaging (CT or MRI). Moreover,
high number of surgeries performed via primary open
access is associated with that fact and it reaches 30% of
cases in the studied group, even though in case of other
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Regressive changes in phaeochromocytomas
diseases it is not as common. Other authors performed
the surgery through the open access more frequently in
the surgeries of paheochromocytomas, as well. Otto et
al. operated on 18,5% of patients with that pathology in
that way [3].
Conflict of interest statement
Authors state no conflict of interest.
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