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Brain Trauma Neuro-oncology
the surgical site and temporary CSF diversion using a lumbar drain. However, Endocrine-active Pituitary Tumors
CSF fistulae can, rarely, lead to more serious problems such as life-threatening Endocrine-active pituitary tumors pose significant additional challenges to
meningitis and hydrocephalus. Han and colleagues
21
reviewed a large series of healthcare providers above the consideration of tumor growth and mass
529 patients after removal of pituitary macroadenomas. They found an intra- effect, with Cushing’s disease representing the most urgent medical issues
operative leak rate of 14.2% and a post-operative rate of 4.4%. Almost 20% and most difficult problems in diagnosis and treatment. In 2007, a panel of
of the post-operative CSF leaks presented with meningitis. Repeat surgery, worldwide experts met in Budapest, Hungary to review the literature and
tenacity (consistency) of the tumor, and an indistinct tumor margin were provide a current consensus statement on the diagnosis and management of
associated with an increased risk for intra-operative CSF leak. Intra-operative adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome.
28
leaks were managed effectively in 83% of patients with initial treatment. Of
post-operative leaks, 60% were effectively treated with a lumbar drain alone Their recommendations support many practices in effect in major endocrine
and 40% required additional surgery. This report gives additional information surgery centers. Direct, surgical removal of the ACTH-producing tumor is the
on the incidence and expected outcomes from this relatively common preferred initial mode of therapy and carries the highest chances of cure.
complication of pituitary surgery. They recommend early post-operative cortisol levels (<2ng/dl is desired) to
help predict the chances of long-term remission after pituitary surgery.
Central diabetes insipidus (DI) is another complication of pituitary surgery that Management options for recurrent tumors include repeat direct surgery on
requires prompt diagnosis and treatment. Sigounas and colleagues
22
studied the tumor, hypophysectomy, radiation therapy, and adrenalectomy. Patients
DI in 119 patients who underwent endoscopic removal of pituitary-region must be treated for secondary adrenal insufficiency after curative pituitary
tumors. They found that permanent DI occurred in 2.7% of cases and surgery in most cases. Successful management of these complex tumors
transient DI occurred in 13.6%. Risk factors for DI included a pathology of demands an individualized, multidisciplinary approach led by the
Rathke’s cleft cyst, intra-operative CSF leak, and prior non-endoscopic surgery. endocrinologist and surgeon involved.
Human Tissue Studies Hoffman and colleagues
29
reported on a large series of 426 primary
Many investigators have sought to predict tumor behavior based on labeling surgeries for Cushing’s disease performed by a single surgeon from 1971
characteristics of the tumor specimen from surgery. The Ki-67 labeling index to 2004. The median follow-up on the patients was 66 months. After
(LI) has been useful in predicting tumor growth and recurrence rates in a surgery alone, the authors found an early remission rate of 68.5%. After
number of tumors, but results in pituitary adenomas have not been consistent repeat surgeries were included, the long-term remission rate was 62.4%
throughout the literature. Gejman and colleagues
23
studied Ki-67 LI in 24 for surgical therapy alone. Patients with microadenomas fared better
patients who required surgery for recurrence within five years of the original than those with macroadenomas and cases where adenomas were found
surgery and compared them with 31 adenomas that did not progress. They did better than those where no adenoma was identified. These data
found that a Ki-67 LI above 1.3% predicted recurrence within five years of highlight the utility of surgery in the hands of an experienced pituitary
surgery. Fusco and colleagues
24
studied Ki-67 LI in 68 patients with surgeon but also the need for additional forms of therapy in cases that
acromegaly. They found that the LI was higher in tumors with cavernous sinus cannot be cured by surgery alone.
invasion, lower in patients who were cured of their tumor after surgery, and
lower in patients who responded to medical therapy (somatostatin analogs) Among pituitary adenomas, those that produce thyroid-stimulating
compared with those who did not respond. hormone (TSH) are the least common, representing <2% in most series.
Clarke et al.
30
reported on 21 patients with known TSH-immunoreactive
Additional studies have focused on growth hormone (GH)-secreting tumors adenomas that were treated between 1987 and 2003. Endocrine-active
and their response to medical therapy. Plockinger and colleagues
25
studied tumors, based on serum TSH levels, were present in 14 of the 21
the expression of somatostatin receptor subtypes in 34 patients with patients. Ten presented with clinical hyperthyroidism and seven of these
acromegaly; 20 of these patients had medical therapy with octreotide (a patients had undergone ablative procedures of the thyroid prior to
somatostatin analog that acts primarily at the sst2A receptor) prior to diagnosis of the pituitary adenoma. Macroadenomas accounted for 85%
surgery. All patients who responded (>50% reduction in GH secretion) to of these tumors. Tumor remission rate after initial surgery was 50%.
octreotide expressed sst2A receptors while none of the non-responders Immunohistochemical staining for a second pituitary hormone was
expressed it. In addition, sst1 and sst5 were expressed in 85 and 70% of all relatively common, although the second hormone was clinically active in
tumors, respectively. This raises the possibility that somatostatin analogs that only one patient with acromegaly. This report highlights the rarity of
target the sst1 and sst5 receptors may be effective in a larger proportion of these tumors and a relative delay to diagnosis (based on tumor size)
acromegaly patients. In addition, Fougner and colleagues
26
showed that low compared with other endocrine-active tumors.
levels of the protein non-phosphorylated Raf kinase inhibitory protein in
GH-secreting tumors correlated with a poor response to octreotide. They Summary
suggest that this may be due to effects on the mitogen-activated protein Surgical treatment for pituitary tumors continues to evolve based on
kinase kinase (MEK)–extracellular regulated kinase (ERK) signaling pathway improved diagnostic techniques, refinements in surgical technique and
that are complementary to the effects of the sst2 receptor. Vazquez-Martinez technologies, better understanding of tumor behavior, better
and colleagues
27
also found that expression of Rab18, a protein involved in documentation of treatment outcomes, and improved guidelines for peri-
regulation of intracellular membrane transport and secretory activity in operative management and long-term follow-up. All of these developments
neuroendocrine cells, is inversely correlated with GH levels and GH secretion move physicians further toward their ultimate goal of permanent cure with
in tumor cells from patients with acromegaly. minimal side effects in all patients. ■
38 US NEUROLOGY
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