A 68-year-old woman with a past medical history significant for stable
hypertension and hyperlipidemia managed easily with drug therapy presented with
several weeks of worsening headaches and diplopia.
Physical exam revealed a non-obese woman with anisocoria with the right
pupil dilated and slightly less reactive to light than the left pupil. She also
had a complete right eye ptosis and inability of her right eye to look
laterally. These findings were consistent with oculomotor (CN III) and abducens
(CN VI) nerve palsies. The remainder of her cranial nerve (CN) exam was normal.
Stephanie L. Lee
The combination of CN III and VI palsies raised the concern of a
pituitary adenoma with right cavernous sinus invasion. She had no findings of
acromegaly or Cushingâ€™s syndrome; specifically, no central obesity or
purple striae. Formal visual field exam was intact. An MRI of the sella with
gadolinium revealed a 2-cm x 1.3-cm x 1.5-cm heterogeneously enhancing mass in
the sella with lateral extension into the right cavernous sinus. The pituitary
stalk was displaced to the left. The lesion encased and mildly narrowed the
right internal carotid artery (figure 1). Her optic chiasm was unaffected.
She was immediately treated with oral steroids, which resulted in
improvement of her CN III palsy with resolution of her right eye ptosis and
anisocoria, but she was still unable to abduct her right eye on lateral gaze
(right CN VI palsy; figure 2). Endocrinology evaluation while hospitalized
showed a thyroid-stimulating hormone 1.21 mU/mL, total T4 7.9
mcg/dL, T3 uptake 39.2%, prolactin 8.2 ng/mL, follicle-stimulating
hormone 4.5 mIU/mL, luteinizing hormone 0.3 mIU/mL, growth hormone 0.6 ng/mL,
insulin-like growth factor I 127 ng/mL, adrenocorticotropic hormone 87 pg/mL,
and random cortisol 18 mcg/dL. These results revealed a nonfunctioning
pituitary macroadenoma with a slight increase in serum adrenocorticotropic
hormone, but a urinary-free cortisol collected after discharge from the
hospital was normal at 26 mcg for 24 hours.
One month later, she underwent an uneventful transsphenoidal pituitary
adenoma debulking. Immunohistochemistry of the tumor was positive for
synaptophysin and adrenocorticotropic hormone with rare prolactin staining
cells. The patient responded well postoperatively and was discharged 72 hours
after her procedure with a persistent right CN VI palsy. She will continue to
have close follow-up with neurology, neurosurgery and endocrinology. Residual
tumor remains within the right cavernous sinus because it is not accessible by
transsphenoidal surgery. If growth is documented, the patient will be evaluated
for external beam radiation therapy.
Figure 1. Pituitary MRI
scan. T1 noncontract MRI of sagittal (panel A) and coronal (panel B) views of a
2-cm x 1.3-cm x 1.5-cm pituitary mass (yellow arrow) with lateral extension
into the right cavernous sinus. The mass encases the right internal carotid
artery with minimal narrowing of both arms of the carotid siphon (panel B). The
optic chiasm (red arrow) is separated from the mass by cerebral spinal fluid.
Spenoid sinus (SS). Carotid artery (CA).
Photos courtesy of: Stephanie L. Lee,
2. Ophthalmoplegia from right cranial nerve VI palsy. The patient cannot
laterally abduct her right eye on right-ward gaze because of a cranial nerve VI
palsy, resulting in dysfunction of the right lateral rectus muscle.
Figure 3. Diagram of the pituitary,
cavernous sinus and surrounding structures.
Pituitary adenomas account for 10% to 15% of all intracranial neoplasms
and are normally a tumor of the adult population. Most pituitary adenomas are
less than 1 cm and defined as microadenomas. The prevalence of pituitary
macroadenomas with a diameter greater than 1 cm is estimated to be
approximately 0.2%. The bulk of pituitary macroadenomas (about 80%) are
nonfunctioning tumors. These tumors are clinically silent and present when they
produce symptoms because of mass effect. Nonsecreting pituitary macroadenomas
can present with a diverse array of symptoms that can be predicted based on the
direction of growth.
Ocular CN palsy is a rare complication of pituitary adenomas and
occurred in 59 of 1,000 patients in one large series of pituitary macroadenomas
with lateral extension into the cavernous sinus. The pituitary gland is
separated from the cavernous sinus by dura. The cavernous sinus receives blood
from the middle cerebral vein, the sphenoparietal sinus and the superior
ophthalmic vein and is drained by the superior and inferior petrosal sinuses.
The internal carotid artery (carotid siphon) and CN VI pass through the sinus
while CN III, IV, V1 and V2 are located within the
lateral dural wall of the cavernous sinus (figure 3).
The oculomotor nerve (CN III) contacts nerve fibers that innervate the
levator palpebrae superioris and most of the extraocular muscles that control
eye movement, including the superior rectus, medial rectus, inferior rectus and
inferior oblique muscles but not the superior oblique and lateral rectus
muscles. The nerve also carries parasympathetic fibers to the ciliaris and
sphincter pupillae muscles that control pupillary constriction to light. Injury
of CN III results in drooping of the upper eyelid (ptosis), inability to
constrict the pupil to light and ophthalmoplegia.
The order of injury of the CNs in the cavernous sinus by lateral
extension of macropituitary adenoma is CN III, CN VI, CN IV and then CN V.
Observational studies have revealed that CN III palsy from a pituitary adenoma
presents initially with mydriasis, followed by limitation of gaze and, lastly,
ptosis. After surgical resection of the adenoma, patients tend to improve in
the reverse order in which the symptoms developed. Recovery of CN III palsy can
be slow because the oculomotor nerve is easily injured by stretching or
Isolated abducens nerve palsy
Although much less frequent, isolated abducens nerve palsy (CN VI),
which controls the lateral rectus muscle, has been reported. Occasionally, such
as in our patient, CN III and CN VI palsy are involved. The abducens nerve
traverses the cavernous sinuses and runs alongside the internal carotid artery
(figure 3). The nerve then enters the orbit through the superior orbital
fissure and innervates the lateral rectus muscle of the eye. The abducens nerve
is vulnerable to injury because of its close proximity to the internal carotid
artery and the sella turcica.
It is very rare to have an isolated trochlear nerve (CN IV) palsy and
dysfunction of the superior oblique muscle from pituitary tumors. Because of
its proximity to the other CNs, usually there are other concurrent CN deficits.
Similarly, CN V palsy is unusual, as the ophthalmic branch of the trigeminal
nerve (CN V1) navigates through the superior orbital fissure and
carries sensory information to the upper portion of the face, eyelid and
cornea. When CN V1 palsy from a pituitary tumor is present, it
implies more extension invasion of the tumor into the lateral dural wall of the
cavernous sinus (figure 3) that is not in the same level as the pituitary
When caused by a pituitary adenoma, management of ocular CN palsy is
removal of the tumor. Many pituitary tumors with cavernous sinus invasion and
CN palsies are associated with apoplexy and can be initially treated with
high-dose glucocorticoids. Transsphenoidal resection is currently the widely
accepted surgical approach. Recovery from CN function is directly correlated to
the earlier timing of tumor resection. The average recovery time for isolated
CN III palsy or combined CN III and CN VI palsy ranges widely from 36 days
after trans-sphenoidal surgery to as long a one year. Thus, prompt evaluation,
diagnosis and management of the pituitary tumors are advised to avoid permanent
Karen Choong, MD, is a Fellow in Endocrinology, and Stephanie L. Lee,
MD, PhD, is Associate Professor of Medicine and Associate Chief, both in the
Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center.
For more information:
- Dekkers OM. J Clin Endocrinol Metab.
- Kim SH. J Clin Neurosci. 2007;14:1158-1162.
- Vance ML. Endocr Pract. 2008;14:757-763.