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Brooke Swearingen

Publications and source records attributed to Brooke Swearingen.

6 recordsLinked to original sources
PubMed2006

The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.

CONTEXT: There is no tumor-directed medical therapy available for Cushing's disease. OBJECTIVE: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. DESIGN/METHODS: Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. RESULTS: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001). CONCLUSION: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.

ACTH-Secreting Pituitary Adenoma↗
PubMed2005

Pituitary surgery and postoperative management in Cushing's disease.

Transsphenoidal pituitary surgery is the therapy for most Cushing's disease patients. This article describes the surgical technique, efficacy, perioperative management, and complications associated with this procedure. Numerous biochemical tests of cortisol status have been studied for the evaluation of the postoperative patient. Factors that predict postoperative remission and future relapse of Cushing's disease are addressed. Secondary interventions for persistent or recurrent disease include repeat transsphenoidal resection, pituitary radiation, medical therapy, and bilateral adrenalectomy

Humans↗
PubMed2004

Diagnostic errors after inferior petrosal sinus sampling.

Although inferior petrosal sinus sampling (IPSS) is useful in the evaluation of Cushing's syndrome, false negative cases have been described, and many patients presumed to have ectopic tumors based upon negative IPSS remain without a final diagnosis. These patients are often managed as if they have as yet undiscovered ectopic tumors. To test this assumption, we conducted a retrospective review of our results to determine the ultimate diagnoses after IPSS. Between 1986 and 2002, 179 patients underwent 185 IPSS procedures as part of their evaluation for Cushing's syndrome. Confirmed diagnoses were available for 149 patients (83%): 139 patients had pituitary adenomas (94%), eight had bronchial carcinoids (5%), and two had adrenal tumors (1%). Threshold criteria for a pituitary source were defined as an inferior petrosal sinus to peripheral (IPS:P) basal ratio of 2:1 or greater without CRH or an IPS:P ratio of 3:1 or greater after CRH stimulation. There were nine patients in whom the IPS:P ratio failed to meet threshold criteria after successful sampling, but were nonetheless found to have pituitary tumors after transsphenoidal exploration (false negatives). Eight of these had received CRH and had a significant rise (>35%) in peripheral ACTH levels after CRH treatment, even though the IPS:P ratio did not reach the threshold. There were two patients in whom the IPS:P ratio reached threshold criteria, and ectopic tumors were demonstrated as the source of ACTH overproduction (false positives). The sensitivity after CRH stimulation was 90% (95% confidence interval, 80.8-95.5%) with a specificity of 67% (95% confidence interval, 11.4-94.5%). The positive and negative predictive values were 99 and 20%, respectively. Our data show that patients with an IPS:P ratio suggestive of a nonpituitary source of ACTH overproduction may still have Cushing's disease. Analyzing the CRH-stimulated peripheral ACTH levels in addition to the standard IPS:P ratios may provide improved diagnostic accuracy. Transsphenoidal exploration should be considered in all cases of unsuccessful sampling and in those cases for which no ectopic source can be identified after further body imaging, even if the IPSS is negative, and especially if peripheral ACTH levels rise significantly with CRH stimulation.

Adolescent↗
PubMed2003

Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume.

Larger surgical caseload is associated with better patient outcome for many complex procedures. We examined the volume-outcome relationship for transsphenoidal pituitary tumor surgery using the Nationwide Inpatient Sample, 1996-2000. Multivariate regression adjusted for patient demographics, acuity measures, medical comorbidities, and endocrine status. A total of 5497 operations were performed at 538 hospitals by 825 surgeons. Outcome measured at hospital discharge was: death (0.6%), discharge to long-term care (0.9%), to short-term rehabilitation (2.1%), or directly home (96.2%). Outcomes were better after surgery at higher-volume hospitals (OR 0.74 for 5-fold-larger caseload, P = 0.007) or by higher-volume surgeons (OR 0.62, P = 0.02). A total of 5.4% of patients were not discharged directly home from lowest-volume-quartile hospitals, compared with 2.6% at highest-volume-quartile hospitals. In-hospital mortality was lower with higher-volume hospitals (P = 0.03) and surgeons (P = 0.09). Mortality rates were 0.9% at lowest-caseload-quartile hospitals and 0.4% at highest-volume-quartile hospitals. Postoperative complications (26.5% of admissions) were less frequent with higher-volume hospitals (P = 0.03) or surgeons (P = 0.005). Length of stay was shorter with high-volume hospitals (P = 0.02) and surgeons (P < 0.001). Hospital charges were lower for high-volume hospitals, but not significantly. This analysis suggests that higher-volume hospitals and surgeons provide superior short-term outcomes after transsphenoidal pituitary tumor surgery with shorter lengths of stay and a trend toward lower charges.

Adolescent↗
PubMed2002

Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis.

The underlying molecular pathogenic mechanisms remain unknown in the majority of human pituitary tumors. GADD45 gamma is a member of a growth arrest and DNA damage-inducible gene family that functions in the negative regulation of cell growth. We have found that the mRNA expression of the GADD45 gamma gene is significantly different between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas using cDNA-representational difference analysis. Although GADD45 gamma mRNA was found in normal human pituitary tissue, it was detectable in only 1 of 18 clinically nonfunctioning pituitary tumors by RT-PCR. Furthermore, this gene was not expressed in the majority of GH- or PRL-secreting pituitary tumors (6 of 8 and 7 of 10, respectively). In colony formation assays, transfection of human GADD45 gamma cDNA into the human pituitary tumor-derived cell line, PDFS, results in a dramatic decrease in cell growth by 88%. GADD45 gamma also reduces colony formation in other pituitary tumor-derived cell lines, AtT20 and GH4, by approximately 60% and 50%, respectively, confirming its function in controlling cell proliferation in the pituitary. These data indicate that GADD45 gamma is a powerful growth suppressor controlling pituitary cell proliferation, and GADD45 gamma represents the first identified gene whose expression is lost in the majority of human pituitary tumors.

Adenoma↗