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JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES
Volume 16, Number 5, 2006
© Mary Ann Liebert, Inc.
Case Report
Robot-Assisted Cortical-Sparing Adrenalectomy in a Patient
with Von Hippel-Lindau Disease and Bilateral
Pheochromocytomas Separated by 9 Years
JAMII ST. JULIEN, MPH, DOUGLAS BALL, MD, and RICHARD SCHULICK, MD
ABSTRACT
Von Hippel-Lindau disease is a heritable syndrome that confers an increased risk of developing various benign and malignant tumors to those with a germline mutation of the tumor suppressor gene.
We present a case of a male patient who initially presented at age 9 with headaches, fevers, and fatigue. He was found to have a left pheochromocytoma which was successfully managed with open
total adrenalectomy. He presented again at age 18 with a second pheochromocytoma in the right
adrenal gland. DNA analysis revealed a de novo Val84Leu mutation in the Von Hippel-Lindau gene,
not seen in either parent. The challenge presented was that of balancing the obvious benefits of cortical-sparing adrenalectomy with the risk of tumor recurrence in spared tissue. Ultimately, management consisted of a robot-assisted laparoscopic partial right adrenalectomy with successful
preservation of adrenocortical function.
INTRODUCTION
V
HIPPEL-LINDAU (VHL) DISEASE is an autosomal
dominant disorder characterized by benign and malignant tumors involving the central nervous system
(CNS), kidneys, pancreas, adrenal glands, paraganglia,
and reproductive adnexal organs (including epididymal
and broad ligament cystadenomas). Inactivating mutations in the VHL gene lead to inappropriate accumulation of the hypoxia-inducible transcription factor (HIF1) and overabundance of a number of hypoxia-induced
proteins involved in tumorigenesis.1 Pheochromocytomas, though rare, represent an important clinical manifestation of this syndrome that must be addressed
promptly.
We describe a patient with VHL who underwent two
metachronous (separated by 9 years) procedures for
ON
adrenal pheochromocytomas involving both adrenal
glands. The case is exceptional because it demonstrates
the multidisciplinary approach necessary for the proper
management of patients with VHL, the unique challenges
presented by multiple adrenal tumors, and a novel approach to minimally invasive cortical-sparing adrenalectomy using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA).
CASE REPORT
A 9-year-old Caucasian male with a history of caféau-lait spots since birth, was referred to Johns Hopkins
Hospital in 1993 for evaluation of a suspected pheochromocytoma. The patient reported four months of nighttime sweats, three weeks of fevers, bifrontal headaches,
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
473
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ST. JULIEN ET AL.
and fatigue. On admission the patient was hypertensive,
tachycardic, and had an elevated 24-hour urine norepinephrine level of 1235 g (normal range, 11–86 g/24
hr). A magnetic resonance imaging (MRI) scan demonstrated a 3-cm left adrenal mass, and an I131 metaiodobenzylguanidine (MIBG) scintigraphy scan confirmed increased activity confined to the left adrenal gland (Figs.
1, 2).
One month later, after being appropriately volume-resuscitated and premedicated with an alpha-blocker, the
patient underwent an exploratory laparotomy and left
adrenalectomy, with an uncomplicated postoperative
course. The adrenalectomy was carried out using a left
transverse incision, mobilizing the splenic flexure of the
colon medially, and elevating the spleen and tail of the
pancreas out of the retroperitoneum. The left adrenal
gland was then resected in total by dividing the left
adrenal vein and other structures attaching it to the kidney, aorta, and retroperitoneum. A 24-hour urine collection one month later revealed a norepinephrine level of
88 g, epinephrine of 18 g (normal range, 0–16 g/24
hr), and dopamine of 546 g (normal range, 100–440
g/24 hr)—all minimally elevated.
The patient did well until 1997, when he again began
to have bitemporal headaches, fatigue, and low-grade
fevers. A 24-hour urine collection for catecholamines revealed an epinephrine level of 9 g, norepinephrine level
of 57 g, and a total metanephrine level of 0.4 mg (normal range, 1.2 mg/24 hr). An abdominal MRI one
month later did not reveal an obvious pheochromocytoma
or paraganglioma. An MIBG scan at this time was also
FIG. 1. Left adrenal pheochromocytoma in 1993. A: T1weighted axial magnetic resonance imaging (MRI) without contrast enhancement demonstrates a 3-cm mass in the left adrenal
gland. B: T2-weighted axial MRI shows the brightness of the
same mass. C: T2-weighted coronal MRI.
FIG. 2. An I131 metaiodobenzylguanidine (MIBG) scintigraphy scan in 1993 demonstrating increased activity in the area
of the left adrenal gland.
ROBOT-ASSISTED ADRENALECTOMY IN VON HIPPEL-LINDAU
475
FIG. 3. Right adrenal pheochromocytoma in 2002. A: A T1weighted axial magnetic resonance imaging (MRI) with contrast demonstrates a 1.7 1.6 2 cm right adrenal mass. B:
A T2-weighted axial MRI shows the brightness of the same
mass. C: A T2-weighted coronal MRI.
negative. In 1998, the patient’s symptoms worsened, but
notably there was no hypertension. A repeat MRI scan
still did not reveal any obvious recurrence, and an In111
pentetreotide scintigraphy (OctreoScan,, Mallinckrodt
Inc., Hazelwood, MO) scan was also negative.
The patient did not have any subcutaneous manifestations of neurofibromatosis (NF), and an ophthalmology
evaluation noted the absence of Lisch nodules. There was
also an absence of retinal angiomas, which are a manifestation of VHL. A DNA analysis demonstrated a conservative alteration in codon 84 (val-84-leu) of the VHL
gene. The VHL Val84Leu mutation has been associated
with a risk of pheochromocytoma, but low risk of renal
cell carcinoma or CNS disease.2 The mother’s and father’s DNA analyses were both negative for mutations in
the VHL gene. The patient was intermittently placed on
phenoxybenzamine and labetalol, with significant improvement of his symptoms. Several subsequent MRIs
failed to reveal any possible foci of pheochromocytoma
or paraganglioma.
In 2002, a routine MRI revealed a 1.7 1.6 2 cm
right adrenal mass (Fig. 3). A 24-hour urine collection
for catecholamines revealed elevated norepinephrine of
160 g and normetanephrine level of 679 g (normal
range, 44–540 g/24 hrs). The epinephrine and
metanephrine levels were too low to detect. The patient
was asymptomatic at this time and off all antihypertensive medications. An MIBG scan showed increased up-
take in the right adrenal gland with no evidence of extra-adrenal disease (Fig. 4). The patient was started on
phenoxybenzamine. At this point a discussion was held
with the family about the risk of recurrent tumors as well
as the risks and benefits of partial versus total adrenalectomy, and it was agreed that the best course of action
would be a partial adrenalectomy, if possible, with the
goal of postponing lifelong steroid replacement therapy
in a young, athletically active individual.
Laparascopic robot-assisted
partial adrenalectomy
Three months later, a laparoscopic robot-assisted partial right adrenalectomy was performed. The patient was
placed in the left lateral decubitus position on a beanbag.
A 12-mm trocar was placed midway between the umbilicus and the right costal margin using the open Hasson technique. The peritoneal cavity was insufflated to
15 mm Hg with carbon dioxide and a limited adhesiolysis was performed in the right upper quadrant. Two 7mm ports were placed along the right costal margin for
the robotic arms, a 10-mm liver retraction port was placed
in the midline epigastrium through which an expanding
fan was placed, and a 10-mm energy port was placed between the camera and the most lateral 7-mm port through
which the LigaSure device could be placed. The fan retractor was used to elevate the liver out of the right sub-
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ST. JULIEN ET AL.
mg hydrocortisone once a day for three days, followed
by 20 mg once a day for three days, and finally switched
to 10 mg once a day. He also started fludrocortisone 0.1
mg once a day. One month postoperatively, after his
morning dose of hydrocortisone was withheld, the patient’s basal cortisol level was 13.5 g/dL (normal range,
6–26 g/dL). However, an adrenocorticotropic hormone
(ACTH) stimulation test (using 1 g ACTH) demonstrated a 30-minute peak cortisol level of 14.4 g/dL
(normal response 18 g/dL). This indicated impaired
adrenocortical reserve, and the patient was therefore
maintained on replacement glucocorticoids and mineralocorticoids with a planned slow taper. The patient was
advised to increase his hydrocortisone to 40 mg in the
morning and 10 mg in the afternoon in case of serious
stress such as fever, and was also given a prescription for
100 mg hydrocortisone injection in case of acute stress
in order to prevent adrenal crisis. Over the course of the
next year the patient was weaned off steroids, temporarily restarting them as needed during times of illness. The
patient is now undergoing annual surveillance with history, physical examination, urine catecholamines, plasma
metanephrines, and bilateral renal ultrasound, as well as
slit-lamp examination every two years.
FIG. 4. An I131 metaiodobenzylguanidine (MIBG) scintigraphy scan in 2002 demonstrating increased activity in the area
of the right adrenal gland.
diaphragmatic space and retroperitoneum. The entire
right lobe of the liver was then mobilized out of the
retroperitoneum and off the diaphragm using the hook
cautery device. At this point the da Vinci surgical system was engaged to perform the rest of the dissection.
The peritoneum covering the vena cava and the adrenal
gland was then dissected. The right adrenal gland was
easily located and the mass clearly seen at the level of
the right adrenal vein as it entered the vena cava. The
vein was encircled, four clips were placed, and the vein
was divided. The retroperitoneal and renal attachments
of the superior-lateral limb were then divided with the
harmonic scalpel and electrocautery device. The adrenal
gland was then transected with the harmonic scalpel just
caudal to the mass, leaving the inferior-medial limb of
the gland intact with its attachments (Fig. 5). The argon
beam was used for hemostasis. The mass was removed
through the energy port in an endobag without incident
and the incisions were closed. The patient tolerated the
procedure well.
DISCUSSION
VHL disease is a heritable multisystem syndrome that
predisposes to the development of tumors involving the
CNS, kidneys, pancreas, adrenal glands, paraganglia, and
reproductive adnexal organs.1 The incidence of VHL is
roughly one in 36,000 live births.3 It is inherited as an
autosomal dominant trait and exhibits greater than 90%
penetrance.3 The most common manifestations are retinal angiomas and CNS hemangioblastomas, as well as
Postoperative course
The patient had an uncomplicated postoperative
course. Immediately postoperatively he was placed on 30
FIG. 5. Robot-assisted partial right adrenalectomy: the
adrenal gland is transected with the harmonic scalpel just caudal to the mass.
ROBOT-ASSISTED ADRENALECTOMY IN VON HIPPEL-LINDAU
renal cell carcinoma.4 The frequency of pheochromocytomas in patients with VHL ranges between 7% and
16%.4,5 Pheochromocytomas (and functional paragangliomas) are particularly concerning because of the rapid
and unanticipated release of catecholamines—sudden
death is a major concern. Patients with VHL and
pheochromocytoma require lifetime biochemical and
clinical follow-up, even following total bilateral adrenalectomy, because of a significant risk of paraganglioma
in this disorder.
The first report of the preservation of adrenocortical
function during surgery for bilateral pheochromocytoma
was in 1982.6 Prior to this, the procedure of choice for
these patients was an open total bilateral adrenalectomy.
However, this led to much more difficult recovery periods, necessitated a lifetime of adrenocortical steroid replacement, and increased the frequency of potentially fatal Addisonian crises.7
Experience has since shown partial adrenalectomy to
be a technically feasible and effective procedure: reports
have documented that 20% of well-perfused adrenal
cortical tissue from a single gland is sufficient to maintain an adequate stress response.8 Partial adrenalectomy
is currently specifically recommended for patients with
a single adrenal gland, bilateral adrenal tumors, or hereditary adrenal tumors. One group recommended it as the
procedure of choice for hereditary pheochromocytomas;9
however, the pros and cons of the procedure should be
carefully considered for each individual patient. The risks
and benefits, as well as alternative treatment approaches,
should be discussed in detail with the patient and the decision reached together.
Partial adrenalectomies can be considered in appropriate
cases and, if successful, do not require corticosteroid supplementation. In this case we used the da Vinci surgical
system because of its superior visualization and increased
dexterity. Since its introduction, early experience has suggested that the safety and efficacy of the da Vinci system
is comparable to that of conventional laparoscopy.10,11 The
system provides the surgeon with enhanced laparoscopic
degrees of motion while also restoring the three-dimensional view lost in conventional laparoscopic surgery.
In our literature search, we found no reports describing the use of the da Vinci surgical system for laparoscopic cortical-sparing adrenalectomy. We have demonstrated that it is a feasible, safe, and effective alternative
to conventional laparoscopy. In our experience, the robotic system allows precise dissection of affected tissue
477
from the adrenal gland, leaving enough functional tissue
intact to maintain adrenocortical sufficiency.
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Address reprint requests to:
Richard Schulick, MD
Department of Surgery
The Johns Hopkins University School of Medicine
1650 Orleans Street
CRB BLDG Room 442
Baltimore, MD 21231
E-mail: [email protected]
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