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Pituitary Disorders
continued to document the safety and utility of these minimally invasive 60% were effectively treated with a lumbar drain alone and 40% required
approaches to pituitary tumors. Sanai and colleagues
17
reported results additional surgery. This report gives additional information on the incidence
using the direct, endonasal approach (using the operating microscope) in and expected outcomes from this relatively common complication of
64 patients with challenging pituitary tumors. These included large pituitary surgery. Central diabetes insipidus (DI) is another complication of
macroadenomas (>3cm diameter), tumors with cavernous sinus pituitary surgery that requires prompt diagnosis and treatment. Sigounas
invasion, and craniopharyngiomas. They reported complete removal in and colleagues
22
studied DI in 119 patients who underwent endoscopic
49% and near-gross total removal in 9%. Of those patients who presented removal of pituitary-region tumors. They found that permanent DI occurred
with visual deficits, 81% showed improvement post-operatively. Zhang in 2.7% of cases and transient DI occurred in 13.6%. Risk factors for DI
and colleagues
18
reported results using the purely endoscopic, endonasal included a pathology of Rathke’s cleft cyst, intra-operative CSF leak, and
approach in 78 patients with invasive pituitary adenomas (including 11 prior non-endoscopic surgery.
microadenomas). They achieved complete removal in 79.5% of patients
and improvement in visual symptoms in 96.4% of cases. Dehdashti and Human Tissue Studies
colleagues
19
reported their outcomes in 200 consecutive patients with Many investigators have sought to predict tumor behavior based on
removal of pituitary adenomas using the purely endoscopic, endonasal labeling characteristics of the tumor specimen from surgery. The Ki-67
technique. They reported gross total resection in 91% of cases overall. labeling index (LI) has been useful in predicting tumor growth and
This improved to 96–98% if tumors that invaded the cavernous sinus recurrence rates in a number of tumors, but results in pituitary
were excluded. Visual improvement occurred in 89% of patients. These adenomas have not been consistent throughout the literature. Gejman
reports lend additional support to the use of the minimally invasive and colleagues
23
studied Ki-67 LI in 24 patients who required surgery for
approach to pituitary tumors in the majority of cases. recurrence within five years of the original surgery and compared them
with 31 adenomas that did not progress. They found that a Ki-67 LI above
Several recent papers addressed issues of peri-operative management for 1.3% predicted recurrence within five years of surgery. Fusco and
patients with pituitary adenomas. Many patients with adenomas will have colleagues
24
studied Ki-67 LI in 68 patients with acromegaly. They found
impaired pituitary function pre-operatively and a small percentage will that the LI was higher in tumors with cavernous sinus invasion, lower in
develop impairment secondary to surgical manipulation. Therefore, patients who were cured of their tumor after surgery, and lower in
peri-operative administration of corticosteroids is common practice at patients who responded to medical therapy (somatostatin analogs)
most surgical centers. However, the dosages and duration of this therapy compared with those who did not respond.
vary and there is little hard data to address these issues. Kristoff and
colleagues
20
prospectively studied three groups of patients for 12 weeks Additional studies have focused on growth hormone (GH)-secreting
after surgery: adenoma patients with impaired pituitary function, adenoma tumors and their response to medical therapy. Plockinger and
patients with intact pituitary function, and patients undergoing lumbar colleagues
25
studied the expression of somatostatin receptor subtypes
laminectomy. They treated patients with impaired pre-operative pituitary in 34 patients with acromegaly; 20 of these patients had medical
function with a regimen of intravenous (IV) and oral hydrocortisone that therapy with octreotide (a somatostatin analog that acts primarily at
started with 100mg on the day of surgery and tapered off over six to 10 the sst2A receptor) prior to surgery. All patients who responded (>50%
days after surgery. They followed 24-hour urinary free cortisol levels for reduction in GH secretion) to octreotide expressed sst2A receptors
two weeks in all three groups. They found that cortisol levels increased while none of the non-responders expressed it. In addition, sst1 and
much higher and for much longer in pituitary tumor patients than in sst5 were expressed in 85 and 70% of all tumors, respectively. This
laminectomy patients. They found no difference in cortisol levels between raises the possibility that somatostatin analogs that target the sst1 and
the adenoma patients with hydrocortisone replacement and those with sst5 receptors may be effective in a larger proportion of acromegaly
intact pituitary function. This suggests that the replacement regimen used patients. In addition, Fougner and colleagues
26
showed that low levels
at the University of Bonn (similar to that used by many centers worldwide) of the protein non-phosphorylated Raf kinase inhibitory protein in GH-
is probably sufficient, although they suggested increasing replacement on secreting tumors correlated with a poor response to octreotide. They
the day of surgery from 100mg to 150mg/day based on a non-significant suggest that this may be due to effects on the mitogen-activated
difference between the two groups. protein kinase kinase (MEK)–extracellular regulated kinase (ERK)
signaling pathway that are complementary to the effects of the sst2
Leakage of cerebrospinal fluid (CSF) is the most common complication of receptor. Vazquez-Martinez and colleagues
27
also found that
surgery for pituitary tumors. In most cases is can be managed with packing expression of Rab18, a protein involved in regulation of intracellular
of the surgical site and temporary CSF diversion using a lumbar drain. membrane transport and secretory activity in neuroendocrine cells, is
However, CSF fistulae can, rarely, lead to more serious problems such as inversely correlated with GH levels and GH secretion in tumor cells
life-threatening meningitis and hydrocephalus. Han and colleagues
21
from patients with acromegaly.
reviewed a large series of 529 patients after removal of pituitary
macroadenomas. They found an intra-operative leak rate of 14.2% and a Endocrine-active Pituitary Tumors
post-operative rate of 4.4%. Almost 20% of the post-operative CSF leaks Endocrine-active pituitary tumors pose significant additional challenges
presented with meningitis. Repeat surgery, tenacity (consistency) of the to healthcare providers above the consideration of tumor growth and
tumor, and an indistinct tumor margin were associated with an increased mass effect, with Cushing’s disease representing the most urgent
risk for intra-operative CSF leak. Intra-operative leaks were managed medical issues and most difficult problems in diagnosis and treatment.
effectively in 83% of patients with initial treatment. Of post-operative leaks, In 2007, a panel of worldwide experts met in Budapest, Hungary to
102 US ENDOCRINOLOGY
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