Keywords
macroadenoma - cavernous carotid aneurysm - pipeline - endoscopic - transphenoidal
- pituitary adenoma - intracranial aneurysm
Introduction
Pituitary adenomas are the third most common intracranial tumors in adults with an
estimated prevalence of approximately 15 to 20% of the population.[1] Although pituitary adenomas are overwhelmingly benign, they can still confer significant
health burden due to visual loss and endocrine dysfunction. Management of pituitary
adenomas remains complex due to the heterogeneity of tumor types with multiple guidelines
and consensus statements currently being available; however, surgical resection remains
the mainstay of treatment for the majority of symptomatic pituitary adenomas.[2]
[3]
[4]
Intracerebral aneurysms show a prevalence of 1:50 for unruptured aneurysms; however,
the presence of coincident pituitary adenomas and cerebral aneurysms is rare.[5] Retrospective studies demonstrate an incidence of intracranial aneurysm in patients
with a pituitary adenoma of 2.3 to 5.4%,[6]
[7] suggesting a purely coincidental relationship.
The combination of a cavernous sinus aneurysm embedded within a pituitary adenoma
is even rarer and the approach for treatment is controversial. In this report, we
detail the management of a patient with a nonfunctioning pituitary macroadenoma and
an embedded cavernous carotid aneurysm. A systematic review of the literature was
performed showing 20 prior reports of pituitary adenomas with associated aneurysms
of the cavernous sinus ([Table 1]). We also discuss the integration of modern endovascular therapy and propose a novel
treatment strategy.
Table 1
Reports of internal carotid artery aneurysms associated with pituitary adenomas
|
Study (year)
|
Aneurysm location
|
Discovery of aneurysm
|
Surgical approach for aneurysm
|
Discovery of adenoma
|
Approach for adenoma
|
|
Hori et al (1982)[15]
|
ICA
|
Incidental
|
TC
|
Acromegaly
|
TC
|
|
Matsuyama and Masuda (1993)[16]
|
ICA
|
Incidental
|
TC
|
Amenorrhea
|
TC
|
|
Salpietro et al (1997)[22]
|
CS ICA
|
Incidental
|
IVR (coil)
|
Vision loss
|
TS
|
|
Imamura et al (1998)[32]
|
CS ICA
|
Fatal epistaxis
|
Fatal epistaxis prior to treatment
|
Incidental
|
Fatal epistaxis prior to treatment
|
|
Ohki et al (1999)[33]
|
ICA
|
Incidental
|
TC
|
Hyperthyroidism
|
TS
|
|
Sade et al (2004)[23]
|
CS ICA
|
Incidental
|
IVR (coil)
|
Acromegaly
|
TS
|
|
Yang et al (2005)[27]
|
CS ICA
|
Incidental
|
TC
|
Hyperprolactinemia
|
TC
|
|
Chuang et al (2006)[28]
|
CS ICA
|
Incidental
|
IVR (coil) + TC
|
Vision loss, apoplexy
|
TC
|
|
Curto et al (2007)[34]
|
CS ICA
|
Incidental
|
IVR (balloon)
|
Acromegaly
|
Medication
|
|
Seda et al (2008)[35]
|
ICA
|
Incidental
|
TC
|
Acromegaly
|
TS
|
|
Soni et al (2008)[36]
|
CS ICA
|
Incidental
|
IVR (balloon)
|
Ophthalmoplegia, hyperprolactinemia, apoplexy
|
Medication
|
|
Wang et al (2009)[24]
|
ICA
|
Incidental
|
IVR (coil)
|
Vision loss, hyperprolactinemia
|
TS
|
|
Yu et al (2011)[25]
|
ICA
|
Incidental
|
IVR (coil)
|
Vision loss, facial paresthesia
|
TS
|
|
Yamada et al (2012)[18]
|
ICA-SHA
|
Incidental
|
IVR (coil)
|
Incidental
|
TS
|
|
Xia et al (2012)[26]
|
ICA-SHA
|
Incidental
|
IVR (coil)
|
Acromegaly
|
TS
|
|
Choi et al (2013)[10]
|
ICA-SHA
|
Incidental
|
IVR (coil)
|
Vision loss
|
TS
|
|
Peng et al (2015)[12]
|
CS ICA
|
Epistaxis, vision loss
|
IVR (balloon)
|
Incidental
|
TS
|
|
Khalsa et al (2016)[37]
|
CS ICA
|
Incidental[a]
|
IVR for deconstruction (coil + microvascular plug + onyx)
|
Hyperprolactinemia
|
Medication
|
|
Khachatryan et al (2018)[38]
|
ICA
|
Incidental
|
IVR (coil)
|
Acromegaly
|
Medication
|
|
Kino et al (2020)[14]
|
ICA-SHA
|
Incidental
|
TC
|
Vision loss
|
TS
|
|
Present study
|
CS ICA
|
Incidental
|
IVR (pipeline)
|
Incidental
|
TS
|
Abbreviations: CS, cavernous sinus; ICA, internal carotid aneurysm; IVR, interventional
radiology; SHA, superior hypophyseal artery; TC, transcranial; TS, transsphenoidal.
a Incidental discovery of aneurysm but progressive growth resulted in vision loss and
eventual hemorrhage.
Literature Review
A systematic literature review was performed on PubMed with search terms “pituitary
adenoma” and “aneurysm.” A total of 494 studies were identified and after review of
study titles and abstracts, the number was narrowed down to 20 articles after removing
duplicates, studies not in English, and nonclinical studies ([Fig. 1]). Patients were included if they demonstrated concomitantly treated pituitary adenomas
and intracerebral aneurysms of the cavernous sinus. The Preferred Reporting Items
for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in drafting
this manuscript.
Fig. 1 PRISMA flowchart describing the methods of literature review in this study. PRISMA,
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Case Report
The patient was an asymptomatic 67-year-old male presenting with a nonfunctional pituitary
macroadenoma (17 mm × 16 mm × 13 mm) and an associated left cavernous carotid artery
aneurysm protruding into the left superior aspect of the tumor discovered incidentally
during evaluation for headaches ([Fig. 2]). The pituitary adenoma showed superior displacement of the normal pituitary gland
and minimal suprasellar extension without abutment of the optic chiasm. Vascular imaging
showed a left cavernous carotid artery aneurysm (3.7 mm × 3.4 mm), complete right
internal carotid artery (ICA) occlusion, and a small anterior communicating artery
(ACOM) aneurysm.
Fig. 2 Preoperative MRI and angiogram views of concomitant pituitary adenoma and internal
carotid artery aneurysm. Preoperative (A) coronal and (B) sagittal T1 contrast enhanced imaging demonstrates a pituitary macroadenoma with
expansion of the sella (arrow). The left sided cavernous segment aneurysm can be noted
as a flow void (arrowhead). (C) Anteroposterior and (D) lateral cerebral angiogram views demonstrate a medial projecting cavernous segment
aneurysm.
The macroadenoma and aneurysm were followed closely with serial imaging for 6 years
until slow progressive growth of the pituitary adenoma demonstrated compression of
the optic chiasm. Ophthalmologic evaluation revealed no visual deficits. After a multidisciplinary
discussion, a recommendation for initial repair of the aneurysm followed by delayed
tumor treatment was made. The patient proceeded initially with attempted coil embolization
which could not be completed due to aneurysm anatomy. Subsequently, a 5 mm × 18 mm
pipeline flex flow diverter was placed. The patient was maintained on dual antiplatelet
therapy and the aneurysm showed complete radiographic occlusion 6 months later ([Fig. 3]). Repeat magnetic resonance (MR) imaging showed progression of the macroadenoma
(21 mm × 19 mm × 22 mm) with increasing optic tract compression. Unfortunately, before
tumor surgery could be performed, the patient suffered a minor cerebrovascular accident
(CVA) which was treated with resumption of dual antiplatelet treatment for an additional
6 months and continued on maintenance aspirin.
Fig. 3 Diagnostic cerebral angiogram demonstrating complete occlusion of a medial internal
carotid artery aneurysm. (A) Anteroposterior and (B) lateral cerebral angiogram views demonstrates a medially projection cavernous segment
(arrow) along with the limits of a Pipeline flow diverter (arrowhead). 6-month follow-up
(C) anteroposterior and (D) lateral cerebral angiogram views demonstrate resolution of the aneurysm (arrow).
For the pituitary adenoma resection, an endoscopic transsphenoidal approach was performed
using the previously described “1.5 approach” that involves a full unilateral sphenoidotomy
and smaller contralateral sphenoidotomy with preservation of bilateral sphenopalatine
artery pedicles to the nasal septum.[8] During surgery, extreme caution was taken in the left lateral region of the sella
where the aneurysm and only patent carotid artery were located. A gross total resection
of the tumor was accomplished. The patient was discharged on postoperative day 1 and
aspirin was reinitiated 3 days postsurgery without complication.
Discussion
The presence of a pituitary macroadenoma with an embedded cavernous sinus aneurysm
is an exceptionally rare phenomenon which requires special considerations.[6]
[9] Currently available guidelines[2]
[3]
[4] do not make specific recommendations on this rare situation. The incorporation of
endovascular treatments in the management of pituitary tumors and aneurysms has had
limited exploration.
We conducted a review of the literature and analyzed all case reports discussing the
phenomenon of a cavernous sinus aneurysm embedded within a pituitary adenoma ([Fig. 1]). A total of 20 studies described pituitary adenomas in direct contact with cavernous
sinus aneurysms ([Table 1]). Regarding aneurysm treatment among the 20 studies, 14 involved endovascular approaches,
5 involved open approaches, and 1 case showed a patient fatality prior to treatment.
For adenoma treatment, 4 involved transcranial approaches, 11 involved endonasal approaches,
4 involved medical management, and 1 patient had a fatality prior to treatment ([Fig. 1]). To our knowledge, our case represents the first case of initial aneurysm treatment
with pipeline flow diversion prior to adenoma treatment. The use of the pipeline aided
the treatment of an aneurysm in an otherwise difficult location to treat. Certainly,
the use of a pipeline stent and need for antiplatelet medication complicate the timing
for adenoma resection; however, as most adenomas are slow growing, the urgency of
tumor treatment is less significant.
Several cases of ruptured intracranial carotid artery aneurysms embedded within adenomas
causing subarachnoid hemorrhage have been reported.[10] Additionally, aneurysms in the posterior circulation have also been described which
may confer increased surgical morbidity during pituitary surgery.[11] Cavernous carotid artery aneurysms located proximal to the distal dural ring present
a decreased risk for rupture-associated morbidity and mortality due to their extradural
origin and are therefore less commonly treated surgically or endovascularly.[5] Rupture of aneurysms extending within pituitary adenomas, however, may present as
pituitary apoplexy with visual, cranial nerve, and endocrine dysfunction.[12] Additionally, cavernous aneurysms located within pituitary adenomas carry risk for
catastrophic rupture during surgical resection of these tumors. While the mortality
rate for aneurysm rupture during pituitary surgery is not known, a 14% mortality rate
after carotid artery injury during transsphenoidal surgery has been reported with
a 24% rate of significant neurological disability.[13] As such, the decision to proceed with surgical intervention for pituitary adenomas
in these rare cases requires either a preoperative or concomitant strategy for treating
the aneurysm.
Fortunately, management strategies for the treatment of cerebral aneurysms have greatly
expanded and improved over the last several decades with the decision to coil, flow-divert,
or clip a cerebral aneurysm partially depending on the angiographic features of the
aneurysm and ability to tolerate single or dual antiplatelet agents to prevent thromboembolic
complications. Several cases of simultaneous open transcranial or combined transcranial
and endoscopic clip ligation management of intracranial aneurysm rupture and pituitary
adenoma resection have been reported in the setting of subarachnoid hemorrhage.[14] Although open surgical treatment of a carotid cavernous aneurysm and pituitary adenoma
has been described previously in the literature,[15]
[16] this method has been replaced by modern endovascular techniques. Endovascular treatments
are generally associated with lower medical comorbidity than open treatment but may
require the use of single or dual antiplatelet agents that would delay the timing
of pituitary adenoma treatment, especially with the use of flow diversion.[17]
Modern approaches for the treatment of pituitary adenomas and carotid aneurysms have
incorporated the use of endovascular treatment to secure aneurysms before tumor surgery.[18] Coil embolization typically does not require the postoperative use of antiplatelet
agents and may be considered the preferred option for securing the aneurysm. Endovascular
coiling, however, is highly dependent on the aneurysm morphology and may result in
incomplete aneurysm obliteration or aneurysm recurrence. Alternatively, for aneurysms
with wide necks or not amenable to direct coiling, stent-assisted coiling or flow-diversion
strategies may be utilized. Flow diverters promote aneurysm occlusion through a process
of endoluminal reconstruction of the parent artery and by redirecting blood flow away
from the aneurysm sac. Review of patients at our institution treated with the pipeline
embolization device demonstrated a complete aneurysm occlusion rate of 86% which was
significantly higher than that achieved with coiling (41%).[19] The thrombogenicity of flow diversion stents, however, requires the use of single-
or dual-antiplatelet therapy to reduce the risks of thromboembolic complications.
Overall, thromboembolic events have been observed in approximately 6% of patients
with higher rates of complications occurring in patients treated with aspirin and
clopidogrel therapy for less than 6 months.[20] Therefore, the use of aneurysm obliteration via flow diversion should occur at least
6 months prior to any planned surgical intervention for the pituitary adenoma and
may be best reserved for asymptomatic patients without optic apparatus compression
or progressively enlarging adenomas where intervention may be safely delayed.
Many cavernous sinus aneurysms do not present with symptoms, though some may result
in cranial nerve palsies due to their proximity in the cavernous sinus. According
to Stiebel-Kalish et al, the most common presenting symptoms are diplopia (65%), pain
(59%), and unilateral headaches (33%).[21] Less commonly, the aneurysms may rupture, causing carotid-cavernous fistulas or
severe epistaxis warranting immediate surgical intervention. In 18 of the 20 cases
included in our systematic review, the cavernous aneurysms were found incidentally
on imaging workup ([Table 1]) and the selection of treatment for these incidental aneurysms will depend on patient
risk factors, aneurysm morphology, and tumor behavior including the urgency with which
the adenoma must be treated.
In general, the preferred treatment for ruptured or unruptured cavernous aneurysm
with a pituitary adenoma would be endovascular coiling. Antiplatelet therapy is generally
not required and this intervention has been shown to provide aneurysm protection with
low morbidity and facilitate transsphenoidal resection of the adenoma.[10]
[18]
[22]
[23]
[24]
[25]
[26] The rare cases of aneurysms are not amenable to coiling for which urgent decompression
of the adenoma is necessary, typically due to macroadenomas with suprasellar extension
and vision loss or pituitary apoplexy, a transcranial approach with simultaneous tumor
resection and clipping of the aneurysm may be indicated.[15]
[16]
[27]
[28] While endoscopic endonasal intracranial clipping of cavernous carotid aneurysm has
been reported and is technically feasible, simultaneous endonasal pituitary adenoma
resection and aneurysm has not been performed to the best of our knowledge.[29] Additionally, a recent review of endonasal aneurysm clipping demonstrated significantly
higher rates of complications compared with open clipping and endovascular management.[30] In our opinion, consideration of endoscopic endonasal clipping of an aneurysm during
pituitary adenoma resection is best reserved for emergency management of inadvertent
intraoperative aneurysmal rupture encountered during the tumor resection. In the event
that an unruptured aneurysm is unexpectedly discovered during pituitary adenoma resection,
due to the potential for catastrophic hemorrhagic complications, we recommend that
subtotal tumor resection to be performed without perturbation of the aneurysm. Subsequent
definitive aneurysm therapy may then be pursued followed by delayed reintervention
for the adenoma if clinically indicated.
As an additional point of consideration, surgical reconstruction of the skull base
defect after adenoma resection by use of a nasoseptal flap may warranted to provide
long-term protection of the aneurysm from inadvertent injury from subsequent interventions,
such as nasogastric tube placement or to provide an additional layer of coverage,
to the aneurysm wall in cases of stereotactic radiosurgery is anticipated.[30]
[31]
Conclusion
This case report and systematic review suggests that concomitant treatment of cerebral
aneurysms and pituitary adenomas requires knowledge of up-to-date surgical and endovascular
options for each pathology, as well as careful consideration of the timing and sequence
of intervention.
