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\begin{document}

\title{Intrapartum adrenalectomy for pheochromocytoma presenting in pregnancy:
A case report}



\author[1]{Paul Naseef}%
\affil[1]{Ain Shams University Faculty of Medicine}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Pheochromocytoma occurs in 1 in every 50,000 hypertensive pregnant lady.
Antenatal diagnosis is critical to reduce maternal and perinatal
mortality rates. Here, we describe a patient diagnosed with
pheochromocytoma at 35 weeks with an atypical presentation of right
flank pain and seizures, her preoperative optimization and intra-partum
surgical management.%
\end{abstract}%



\sloppy


\textbf{Intrapartum adrenalectomy for pheochromocytoma presenting in
pregnancy: A case report}

Paul Naseef, MD

Obstetrics and Gynecology Department, Ain Shams University, Cairo, Egypt

\textbf{Correspondence}

Paul Naseef, ORCID: 0000-0003-4279-5844

Obstetrics and Gynecology Department, Ain Shams University, Cairo, Egypt

Email: paulabeh@hotmail.com

\textbf{Funding information}

None

\textbf{ABSTRACT}

Pheochromocytoma occurs in 1 in every 50,000 hypertensive pregnant lady.
Antenatal diagnosis is critical to reduce maternal and perinatal
mortality rates. Here, we describe a patient diagnosed with
pheochromocytoma at 35 weeks with an atypical presentation of right
flank pain and seizures, her preoperative optimization and intra-partum
surgical management.

\textbf{KEYWORDS}

Pheochromocytoma, adrenal mass, hypertension

\textbf{INTRODUCTION}

Pheochromocytoma is a catecholamine-secreting tumour that arises from
the medullary portion of the adrenal gland or the sympathetic ganglia's
chromaffin cells. It is one of the causes of secondary hypertension that
affects 0.2 to 0.4\% of people and can cause a severe or fatal
hypertensive crisis. During pregnancy, it affects about 1 in 50,000 of
women. A timely diagnosis and adequate care of this condition can reduce
maternal and fetal mortality and morbidity from over 50\% to less than
5\% and 15\%, respectively \textsuperscript{\textbf{1}} .

When significant hypertension arises before 20 weeks of pregnancy and
blood pressure (BP) is labile with episodic headaches, palpitations, or
sweating, pheochromocytoma should be one of the top differential
diagnoses \textsuperscript{\textbf{2}} .

However, pheochromocytoma may not show any signs or symptoms during
pregnancy, and is far less common than other causes of hypertension in
pregnant women. Specific symptoms including paroxysmal sweating,
palpitation, and blood pressure crises are also likely to be less
prevalent in pregnant women than in non-pregnant women. According to a
review of the literature, 90 \% of pregnant women experience
pheochromocytoma symptoms just before
delivery\textsuperscript{\textbf{3}} .

The diagnosis is usually established by detecting high levels of
catecholamines and their metabolites in plasma and urine. Where the
fetus must be protected, ultrasonography and magnetic resonance imaging
(MRI) are the most suitable modalities of tumour localization during
pregnancy. Pheochromocytoma is treated medically with alpha-adrenergic
blockade to regulate hypertension and beta-adrenergic blocker to treat
tachycardia and cardiac dysrhythmias. The only way to cure
pheochromocytoma is to remove the tumour
surgically\textsuperscript{\textbf{4}} .

\textbf{CASE REPORT}

At 35 weeks and two days gestation, a 28-year-old previously healthy
pregnant lady (gravida 2, para 1) presented to the obstetrical triage of
our tertiary care centre with one-week onset of severe hypertension
(\textgreater{}160/110 mmHg). She reported having previous episodes of
moderately high BP dating back to 25 weeks gestation that required no
treatment. She saw her primary care provider, 1 week before, complaining
of headache and right flank pain. Her BP was found to be 165/110 mmHg. A
series of investigations, including a CBC, electrolytes, BUN,
creatinine, liver enzymes and a random urine protein creatinine ratio
which all came back within normal range. A presumed diagnosis of
pregnancy-induced hypertension was made and she was prescribed Labetalol
200 mg BID. An obstetrical ultrasound and umbilical artery (UA) Doppler
were done and showed no signs of fetal growth restriction (FGR). Her
follow-up plan was twice daily BP measurement, twice weekly antenatal
visits and planned delivery at 38 weeks.

However, her BP was still labile on the given dose of Labetalol and her
right flank pain persisted, so an abdominal ultrasound was done to rule
out renal pathology. Surprisingly, the ultrasound showed a heterogeneous
right suprarenal solid mass measuring 6 x 4.5 cm as shown
in\textbf{figure (1).} The patient was referred by her physician to our
hospital. Her BP upon presentation was fluctuating between 200/120 mmHg
above and 110/80 mmHg below. CBC, coagulation profile, liver profile,
electrolytes, urea, and creatinine were all normal. Urinary proteins
were 165 mg/24 hours, all of which made the diagnosis of preeclampsia
unlikely. Pheochromocytoma was suspected given the labile nature of the
patient's blood pressure (BP) and the suprarenal mass discovered in
ultrasound. 24-hour urine collection was sent for metanephrine and
vanillylmandelic Acid (VMA) to confirm the diagnosis which came back
markedly elevated being 703 \selectlanguage{greek}μ\selectlanguage{english}mol/day and 82 \selectlanguage{greek}μ\selectlanguage{english}mol/day respectively. This
was followed by an abdominal MRI, revealing a 5.5 x 4 cm right adrenal
mass, a normal left adrenal gland, and no extra-adrenal tumours were
discovered.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure (1):} Abdominal ultrasound showing a right suprarenal
mass

The patient was admitted to the obstetrical intensive care unit (ICU)
for close monitoring of her blood pressure. The decision was to deliver
the patient via Caesarean section in the attendance of general surgery
team for concurrent adrenalectomy, after optimization of her BP with
alpha-adrenergic blockade using Phenoxybenzamine 30 mg TID and
subsequent beta-blockade with Metoprolol 50 mg BID for 14 and 10 days
respectively. Patient's past medical history and family history were
negative for features suggestive of multiple endocrine neoplasia (MEN)
syndromes.

On the night of the scheduled surgery, the patient developed a
generalized tonic clonic (GTC) seizure that was aborted by 2 mg of
Lorazepam. There were no post-ictal neurological lateralizing signs and
urgent CT brain was done to rule out intracranial hemorrhage and was
negative. MRI stroke protocol was also done and revealed no signs
suggestive of ischemic stroke. Possible metabolic causes of seizures
were also excluded. Exceptionally,~as reported in a few cases in the
literature, seizures were found to be a rare presenting symptom of
pheochromocytoma. Thus, this episode may have directly been related to
the patient's condition.

After optimization of the patient's condition, Caesarean section via
midline skin incision with intrapartum adrenalectomy was performed under
general anesthesia (GA). A \#20 gauge radial arterial line, PAC, and
5-lead ECG were used for intra-operative monitoring. Prior to being
induced, Remifentanil (0.1 mcg/kg/min) with Nitroprusside (0.5
mcg/kg/min) were commenced for baseline BP control. Intermittent BP
fluctuations were also controlled by boluses of Labetalol 10 mg IV
(total 40 mg) (systolic BP 175 mmHg lowered to 115 mmHg pre-induction).
The patient was wedged in a position where her uterus was displaced to
the left. A 5-mg defasciculating dose of Rocuronium was given, and after
three minutes of pre-oxygenation, a rapid sequence induction with 100 mg
Lidocaine, 280 mg thiopental, and 120 mg succinylcholine was conducted
under cricoid pressure.

After delivery of the baby, closure of the uterus and ensuring
haemostasis, general surgery team scrubbed in and performed right
adrenalectomy via an open transabdominal approach upon which there was a
dramatic decline in patient's BP to 95/60 mmHg necessitating the
discontinuation of Nitroprusside infusion. The patient was transferred
back to the ICU for postoperative care. The excised right adrenal gland
was sent for histopathological examination and the results came back
consistent with the diagnosis of benign pheochromocytoma. The patient
had a smooth postoperative course with normalization of her BP. She was
discharged home 6 days following the surgery.

\textbf{DISCUSSION}

Pheochromocytoma is a rare cause of hypertension during pregnancy
occurring only in 1 in 50,000 cases and may be clinically challenging to
differentiate from preeclampsia because hypertension and headache occur
with both disorders. It is a catecholamine-producing tumor arising from
chromaffin cells of medullary region of adrenal gland or sympathetic
ganglia. Symptoms specific to pheochromocytoma include paroxysms of
generalized sweating, palpitations, tremor, pallor, shortness of breath,
generalized weakness, and panic attack-type symptoms. Some women with
pheochromocytoma have an elevated blood glucose level (impaired fasting
glucose, apparent type 2 diabetes mellitus). Our patient had an atypical
presentation which was right flank pain. She also developed seizures
which is one of the uncommon presentations of pheochromocytoma. Overall,
antenatal diagnosis of the condition is crucial because intrapartum
maternal and fetal mortality are high without appropriate
treatment\textsuperscript{\textbf{5}} .

While the diagnosis of preeclampsia may overlap with pheochromocytoma
presenting in pregnancy, the distinguishing feature is that preeclampsia
usually develops after 20 weeks gestation and is associated either with
proteinuria or evidence of end-organ damage whereas pheochromocytoma may
present at any time throughout the entire pregnancy and is rarely
associated with proteinuria \textsuperscript{\textbf{6}} . In this case,
the patient presented late in pregnancy, around 35 weeks gestation, her
24-hour urine collection was negative for proteinuria and her
investigations did not show any evidence of end-organ damage.

A review of literature has shown that 10\% of pheochromocytomas are
bilateral, 10\% of them are extra-adrenal in origin and 10\% are
malignant. They may be part of multiple endocrine neoplasia (MEN type
IIa) syndrome and, if it is the case, the patient should be screened for
medullary cell carcinoma of the thyroid and parathyroid adenomas by
measuring serum calcitonin and parathyroid hormone (PTH) levels
respectively \textsuperscript{\textbf{7}} . Our patient's tumor was
unilateral (right side), adrenal in origin and benign in nature, as per
postoperative histopathological examination. MEN syndrome was ruled by
taking the patient's past medical and family histories.

The diagnosis of pheochromocytoma is made by the detection of elevated
24-hour urinary levels of catecholamines (norepinephrine, metanephrines
and vanillylmandelic acid) and/or raised plasma catecholamines.
Non-specific assays may give false-positive results if the patient is on
alpha-methyldopa or labetalol and screening should ideally be performed
before antihypertensive therapy is started. Once the diagnosis has been
confirmed, CT, ultrasound and MRI offer the best methods for localizing
the tumor, although the latter two are preferable in pregnancy. However,
MIBG (131I-meta-iodobenzylguanidine) scan to localize norepinephrine
uptake is contraindicated in pregnancy \textsuperscript{\textbf{8}} .

When pheochromocytoma presents in pregnancy, there is a greatly
increased maternal and fetal mortality rate, especially if, as in up to
50\% of cases, the diagnosis is not made antenatally, as potentially
fatal hypertensive crises may be precipitated by labor, vaginal or
abdominal delivery, general anesthesia or opiates. Hypertensive episodes
may occur in pregnancy even when patient is in supine position owing to
the pressure caused by the gravid uterus on the tumor. The main causes
of maternal mortality are arrhythmias, cerebrovascular accidents or
pulmonary edema. Its rate may reach up to 17\% in undiagnosed cases
while it is only about 4\% in diagnosed cases. On the other hand, the
perinatal mortality rate is about 26\% in undiagnosed cases and 11\% in
diagnosed cases \textsuperscript{\textbf{9}} .

The only curative option for pheochromocytoma is surgical removal of the
tumor, either open or laparoscopic. The optimal timing for that depends
on the gestational age at which the diagnosis is made. There is an
increasing vogue to delay tumour resection until the puerperium. If
pharmacological blockade, ideally with \selectlanguage{greek}α-\selectlanguage{english}blockade with phenoxybenzamine,
prazosin or doxazosin to control hypertension followed by \selectlanguage{greek}β-\selectlanguage{english}blockade, if
required, to control tachycardia, has been achieved prior to 23 weeks'
gestation, then resection may be performed in pregnancy especially if
the tumor is small. If the pregnancy is more than 24 weeks' gestation,
then surgery becomes more hazardous and should be delayed until fetal
maturity, when caesarean section with concurrent or delayed tumour
removal is undertaken \textsuperscript{\textbf{10}} .

Expert anaesthetic care is necessary in dealing with these cases and
both perinatal and maternal mortality rates have improved significantly
since the advent of \selectlanguage{greek}α-\selectlanguage{english}blockade, which should be given for at least 3
days prior to the surgery. IV Phenoxybenzamine must be available for
caesarean section. In an emergency if IV \selectlanguage{greek}α-\selectlanguage{english}blockade is not available,
then IV labetalol is the appropriate
alternative\textsuperscript{\textbf{11}} .

\textbf{CONCLUSION}

Despite the fact that pheochromocytoma is uncommon cause of
hypertension, particularly in pregnancy, our case emphasized the
importance of early diagnosis and prompt medical optimization of this
condition prior to surgery. Satisfactory maternal and fetal outcomes can
be achieved with the help of expert anesthesia and pediatric teams. Our
case also showed that pheochromocytoma can present atypically with flank
pain and seizures.

\textbf{AUTHOR CONTRIBUTION}

The author was involved in data collection, interpretation, drafting the
article, revision of the manuscript, and the final approval of the
version to be published.

\textbf{ACKNOWLEDGEMENTS}

None.

\textbf{CONFLICT OF INTEREST}

The author declares no conflict of interest.

\textbf{ETHICAL APPROVAL}

This case report was approved by the Research Ethics Committee (REC) of
Faculty of Medicine, Ain Shams University.

\textbf{CONSENT}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
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\item
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\end{enumerate}\selectlanguage{english}
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