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ABSTRACT: Cushing disease (CD) is caused by overproduction of adrenocorticotropin by a pituitary adenoma (or, rarely, carcinoma). The diagnosis of CD requires distinguishing it from other hypercortisolemic states with a thorough endocrine workup. CD remains a primarily surgical disease, with remission rates of 70% to 95% following microscopic or endoscopic transsphenoidal surgery.
Neurosurgery clinics of North America 10/2012; 23(4):639-51. · 1.73 Impact Factor
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ABSTRACT: Patients with thyrotropin-secreting pituitary adenomas may present with mass effect, hypopituitarism, and/or hyperthyroidism. The spectrum of pathologic and clinical features of patients whose tumors demonstrate β-thyrotropin immunoreactivity (β-TSH IR) has not been characterized. To characterize the phenotype of patients with pituitary adenomas with positive β-TSH IR, we conducted a retrospective analysis of patient records of all adult patients (n = 1,223) undergoing pituitary surgery in our institution over one decade (1999-2009). The search identified 166 adults with tumors which had β-TSH IR. These patients were individually matched to 166 patients whose tumors revealed no β-TSH IR. Clinical, pathological, imaging and biochemical data were extracted. 332 patients, aged 51.4 ± 15.1 years [150 women (45 %) and 182 men (55 %)], with pituitary adenomas (mean tumor diameter ± SD: 22.7 ± 9.0 mm) were studied. The degree of β-TSH IR was associated with the presence of central hyperthyroidism (p < 0.0001) or goiter (p = 0.0217). Patients whose tumors expressed more extensive β-TSH IR were less likely to develop pituitary apoplexy than those without β-TSH IR (p = 0.0428). In addition, the degree of β-TSH IR correlated with the presence of immunoreactivity for β-FSH (p < 0.0001), β-LH (p < 0.0001), alpha subunit (p < 0.0001), and GH (p = 0.0036). Conclusions: Pituitary adenomas expressing β-TSH IR were more likely to demonstrate immunoreactivity for β-FSH, β-LH, GH or alpha subunit. Patients with such tumors were more likely to exhibit hyperthyroidism and goiter, but less likely to develop pituitary apoplexy than patients without β-TSH IR. These findings suggest that β-TSH IR is associated with specific phenotypic features in patients with pituitary adenomas.
Pituitary 08/2012; · 1.83 Impact Factor
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ABSTRACT: Inferior petrosal sinus sampling (IPSS) is a useful technique for confirming a pituitary source of adrenocorticotropic hormone (ACTH) overproduction in Cushing disease. Uncertainty remains regarding the appropriate course of therapy when an ectopic tumor is predicted by IPSS but none can be found and in circumstances when the procedure cannot be successfully completed owing to technical or anatomic limitations.
To determine an appropriate course of action after nondiagnostic IPSS.
We reviewed 288 IPSS procedures in 283 patients between 1986 and 2010 at our center. An IPS:peripheral ACTH ratio ≥ 2 at baseline or ≥ 3 after corticotrophin-releasing hormone was considered predictive of a pituitary source of ACTH. A procedure was considered nondiagnostic if the procedure was successfully performed and the results predicted an ectopic source but none could be found despite extensive imaging or if the IPS could not be bilaterally cannulated because of technical difficulties or anatomic variants.
The sensitivity, specificity, positive predictive value, and negative predictive value of IPSS for detecting a pituitary source in Cushing disease were 94%, 50%, 98%, and 29%, respectively. We identified 3 categories of nondiagnostic IPSS comprising 44 of the total procedures. These patients underwent exploratory transsphenoidal surgery, and in 42 of these patients (95%), a pituitary source was surgically proven, with a remission rate of 83%.
Transsphenoidal surgery should be considered in cases of ACTH-dependent Cushing disease and noncentralized or technically unsuccessful IPSS without evidence of ectopic tumor.
Neurosurgery 02/2012; 71(1):14-22. · 2.79 Impact Factor
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ABSTRACT: Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient's vision improved.
Case reports in ophthalmology. 01/2012; 3(2):190-6.
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ABSTRACT: DLK1-MEG3 is an imprinted locus consisting of multiple maternally expressed noncoding RNA genes and paternally expressed protein-coding genes. The expression of maternally expressed gene 3 (MEG3) is selectively lost in clinically nonfunctioning adenomas (NFAs) of gonadotroph origin; however, expression status of other genes at this locus in human pituitary adenomas has not previously been reported. Using quantitative real-time RT-PCR, we evaluated expression of 24 genes from the DLK1-MEG3 locus in 44 human pituitary adenomas (25 NFAs, 7 ACTH-secreting, 7 GH-secreting, and 5 PRL-secreting adenomas) and 10 normal pituitaries. The effects on cell proliferation of five miRNAs whose expression was lost in NFAs were investigated by flow cytometry analysis. We found that 18 genes, including 13 miRNAs at the DLK1-MEG3 locus, were significantly down-regulated in human NFAs. In ACTH-secreting and PRL-secreting adenomas, 12 and 7 genes were significantly down-regulated, respectively; no genes were significantly down-regulated in GH-secreting tumors. One of the five miRNAs tested induced cell cycle arrest at the G2/M phase in PDFS cells derived from a human NFA. Our data indicate that the DLK1-MEG3 locus is silenced in NFAs. The growth suppression by miRNAs in PDFS cells is consistent with the hypothesis that the DLK1-MEG3 locus plays a tumor suppressor role in human NFAs.
American Journal Of Pathology 08/2011; 179(4):2120-30. · 4.89 Impact Factor
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ABSTRACT: Cushing disease is caused by a corticotroph tumor of the pituitary gland. Patients with Cushing disease are usually treated with transsphenoidal surgery, as this approach leads to remission in 70-90% of cases and is associated with low morbidity when performed by experienced pituitary gland surgeons. Nonetheless, among patients in postoperative remission, the risk of recurrence of Cushing disease could reach 20-25% at 10 years after surgery. Patients with persistent or recurrent Cushing disease might, therefore, benefit from a second pituitary operation (which leads to remission in 50-70% of cases), radiation therapy to the pituitary gland or bilateral adrenalectomy. Remission after radiation therapy occurs in ∼85% of patients with Cushing disease after a considerable latency period. Interim medical therapy is generally advisable after patients receive radiation therapy because of the long latency period. Bilateral adrenalectomy might be considered in patients who do not improve following transsphenoidal surgery, particularly patients who are very ill and require rapid control of hypercortisolism, or those wishing to avoid the risk of hypopituitarism associated with radiation therapy. Adrenalectomized patients require lifelong adrenal hormone replacement and are at risk of Nelson syndrome. The development of medical therapies with improved efficacy might influence the management of this challenging condition.
Nature Reviews Endocrinology 02/2011; 7(5):279-89. · 9.97 Impact Factor
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ABSTRACT: To assess health care costs associated with Cushing disease and to determine changes in overall and comorbidity-related costs after surgical treatment.
In this retrospective cohort study, patients with Cushing disease were identified from insurance claims databases by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for Cushing syndrome (255.0) and either benign pituitary adenomas (227.3) or hypophysectomy (07.6×) between 2004 and 2008. Each patient with Cushing disease was age- and sex-matched with 4 patients with nonfunctioning pituitary adenomas and 10 population control subjects. Comorbid conditions and annual direct health care costs were assessed within each calendar year. Postoperative changes in health care costs and comorbidity-related costs were compared between patients presumed to be in remission and those with presumed persistent disease.
Of 877 identified patients with Cushing disease, 79% were female and the average age was 43.4 years. Hypertension, diabetes mellitus, and hyperlipidemia were more common among patients with Cushing disease than in patients with nonfunctioning pituitary adenomas or in control patients (P<.01). For every calendar year studied, patients with Cushing disease had significantly higher total health care costs (2008: $26 440 [Cushing disease] vs $13 708 [nonfunctioning pituitary adenomas] vs $5954 [population control], P<.01). Annual outpatient costs decreased significantly for patients in remission after surgery, and there was a trend towards improvement in overall disease-related costs with remission. A significant increase in postoperative health care costs was observed in those patients not in remission.
Patients with Cushing disease had more comorbidities than patients with nonfunctioning pituitary adenomas or control patients and incurred significantly higher annual health care costs; these costs decreased after successful surgery and increased after unsuccessful surgery.
Endocrine Practice 02/2011; 17(5):681-90. · 2.49 Impact Factor
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ABSTRACT: Pituitary adenomas are the most common lesions in the sellar region, but other pathologies need to be considered in the differential diagnosis.
To assess the prevalence of unusual sellar masses in a large series of patients and identify clinicopathological factors that may aid the pre-operative diagnosis.
Retrospective case series.
We analysed the records of 1469 transsphenoidal procedures performed between 1998 and 2009. One hundred sixteen cases (7·9%) were not pituitary adenomas.
Final pathological diagnosis.
One hundred sixteen patients (45 men, 71 women; mean age (±SD): 45 ± 17 years) with nonadenomatous lesions were divided into four major aetiological groups: cystic lesions (CYS) (53%); benign neoplasms (BEN) (22%); malignancies (MAL) (16%) and inflammatory lesions (INF) (9%). Rathke's cysts, the most common lesions, represented 42% of all cases. Twenty-five per cent of malignant lesions were metastases, and some of the MAL (e.g., fibrosarcoma, lung metastasis) had a radiographical appearance suggestive of a pituitary adenoma. The most common presenting symptoms were visual field impairment (51%) and headache (34%). Pre-operative pituitary dysfunction was present in 58% of cases, with hyperprolactinaemia (35%), hypogonadism (23%) and hypocortisolism (23%) found most frequently. Postoperative resolution of headache and visual symptoms occurred in 63% and 65% of patients, respectively. Hyperprolactinaemia resolved in 77% of cases.
A substantial minority of sellar masses are not pituitary adenomas. While they frequently present with the symptoms, hormone abnormalities and radiographical appearance typical of pituitary tumours, the possibility of a nonadenomatous lesion needs to be considered in the differential diagnosis.
Clinical Endocrinology 12/2010; 73(6):798-807. · 3.17 Impact Factor
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ABSTRACT: Clinical manifestations and outcomes of pituitary adenomas in children are not clearly defined. We retrospectively reviewed cases of pituitary adenomas in children 0-18 years treated at MassGeneral Hospital for Children over 15 years. Thirty-five patients were identified. Age at presentation was 7-18 years. Seventeen had prolactinomas, 3 had somatotropinomas, and 15 had Cushing disease. Thirteen prolactinoma patients were female and most commonly presented with oligomenorrhea (10/13) and galactorrhea (7/13). Nine were successfully treated medically. Two somatotropinoma patients presented with visual disturbances; the third was an incidental finding. Two were cured by trans-sphenoidal surgery (TSS). Thirteen Cushing disease patients were initially cured by TSS; six recurred after 3-6 years. Patients with or without recurrence did not differ for age, tumor-size and hormone levels. The high recurrence rate of Cushing disease in our series (46%) compared with adults treated surgically at this institution (7%) emphasizes the need for long-term follow-up.
Journal of pediatric endocrinology & metabolism: JPEM 05/2010; 23(5):427-31. · 0.88 Impact Factor
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ABSTRACT: Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing's disease (CD). Postoperative hypercortisolemia mandates further therapy. Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy. Design and Setting: A retrospective case series was conducted at three tertiary care centers. Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 +/- 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007. Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 +/- 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02). Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.
The Journal of clinical endocrinology and metabolism 02/2010; 95(2):601-10. · 6.50 Impact Factor
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Karen K Miller,
Tamara Wexler,
Pouneh Fazeli,
Lindsay Gunnell,
Gwenda J Graham,
Catherine Beauregard,
Linda Hemphill,
Lisa Nachtigall,
Jay Loeffler, Brooke Swearingen,
Beverly M K Biller,
Anne Klibanski
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ABSTRACT: Context: The effects of GH replacement therapy in patients who develop GH deficiency (GHD) after cure of acromegaly have not been established in a placebo-controlled study. Objective: The objective of the study was to determine whether GH replacement improves body composition, cardiovascular risk markers and quality of life in patients with GHD and prior acromegaly. Design: This was a 6-month, randomized, placebo-controlled study. Setting: The study was conducted at a clinical translational science center. Study Participants: Participants included 30 subjects with prior acromegaly and current GHD. Intervention: Interventions included GH or placebo. Main Outcome Measures: Body composition (dual-energy x-ray absorptiometry and cross-sectional computed tomography at L4), cardiovascular risk markers (high-sensitivity C-reactive protein (hsCRP), total, high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and carotid intimal-medial thickness), and quality of life were measured. Results: The mean GH dose at 6 months was 0.58 +/- 0.26 mg/d. Total fat mass, visceral adipose tissue (-15.3 +/- 18.6 vs. 1.3 +/- 12.5%, P = 0.01), and total abdominal fat decreased, and fat-free mass increased, in the GH vs. placebo group. Mean hsCRP levels decreased, but there was no GH effect on other cardiovascular risk markers. There was no change in glycosylated hemoglobin or homeostasis model assessment insulin resistance index. Quality of life improved with GH. Side effects were minimal. Conclusions: This is the first randomized, placebo-controlled study of the effects of GH replacement therapy on body composition and cardiovascular end points in patients who have developed GH deficiency after treatment for acromegaly, a disease complicated by metabolic and body composition alterations and increased cardiovascular risk. GH replacement decreased visceral adipose tissue, increased fat-free mass, decreased hsCRP, and improved quality of life in patients with GHD after cure of acromegaly, with minimal side effects and without an increase in insulin resistance.
The Journal of clinical endocrinology and metabolism 02/2010; 95(2):567-77. · 6.50 Impact Factor
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ABSTRACT: The ability of combined dexamethasone-corticotropin releasing hormone (Dex-CRH) testing to distinguish pseudo-Cushing's syndrome (PCS) from Cushing's syndrome is controversial. One factor potentially impairing diagnostic efficacy is the concomitant use of commonly prescribed medications that may alter dexamethasone metabolism.
Our objective was to assess the diagnostic accuracy of the Dex-CRH test and evaluate the potential impact of concomitant drugs.
The study was a retrospective one.
Participants included 101 patients [60 Cushing's disease (CD); 41 PCS] who underwent 112 Dex-CRH tests. Patients were divided into two groups, depending on use of medications potentially interfering with dexamethasone metabolism: 58 tests were classified as No Meds (32 CD; 26 PCS) and 54 as Meds (34 CD; 20 PCS). The latter group was further subdivided into patients taking one medication vs. those taking multiple medications.
Diagnostic accuracy of different serum cortisol and ACTH thresholds at baseline and 15 min after CRH injection was assessed.
The specificity of a baseline post-low-dose-dexamethasone-suppressed test cortisol lower than 1.4 microg/dl (38 nmol/liter) was significantly higher in the No Meds vs. the Meds group (P = 0.014). Sensitivity and specificity using a post-CRH cortisol cutoff of 1.4 microg/dl (38 nmol/liter) were 93.1% (95% confidence interval = 88.4-97.8) and 92.3% (95% confidence interval = 87-97.6) in the No Meds group. The specificity of a cortisol lower than 1.4 microg/dl (38 nmol/l) at 15 min after CRH was significantly higher in patients taking only one medication vs. those on multidrug treatment (P < 0.05).
Medications commonly prescribed in hypercortisolemic patients undergoing Dex-CRH testing may contribute to the variable diagnostic accuracy of this test. Prospective studies to address this issue are needed.
The Journal of clinical endocrinology and metabolism 10/2009; 94(12):4851-9. · 6.50 Impact Factor
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Tamara Wexler,
Lindsay Gunnell,
Zehra Omer,
Karen Kuhlthau,
Catherine Beauregard,
Gwenda Graham,
Andrea L Utz,
Beverly Biller,
Lisa Nachtigall,
Jay Loeffler, Brooke Swearingen,
Anne Klibanski,
Karen K Miller
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ABSTRACT: Both GH deficiency (GHD) and GH excess are associated with a decreased quality of life. However, it is unknown whether patients with GHD after treatment for acromegaly have a poorer quality of life than those with normal GH levels after cure of acromegaly.
The aim of the study was to determine whether patients with GHD and prior acromegaly have a poorer quality of life than those with GH sufficiency after cure of acromegaly.
We conducted a cross-sectional study in a General Clinical Research Center.
Forty-five patients with prior acromegaly participated: 26 with GHD and 19 with GH sufficiency.
There were no interventions.
We evaluated quality of life, as measured by 1) the Quality of Life Adult Growth Hormone Deficiency Assessment (QoL-AGHDA); 2) the Short-Form Health Survey (SF-36); and 3) the Symptom Questionnaire.
Mean scores on all subscales of all questionnaires, except for the anger/hostility and anxiety subscales of the Symptom Questionnaire, showed significantly impaired quality of life in the GH-deficient group compared with the GH-sufficient group. Peak GH levels after GHRH-arginine stimulation levels were inversely associated with QoL-AGHDA scale scores (R = -0.53; P = 0.0005) and the Symptom Questionnaire Depression subscale scores (R = -0.35; P = 0.031) and positively associated with most SF-36 subscale scores.
Our data are the first to demonstrate a reduced quality of life in patients who develop GHD after cure of acromegaly compared to those who are GH sufficient. Further studies are warranted to determine whether GH replacement would improve quality of life for patients with GHD after cure from acromegaly.
The Journal of clinical endocrinology and metabolism 05/2009; 94(7):2471-7. · 6.50 Impact Factor
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ABSTRACT: A broad spectrum of neoplasms affects the sellar region. Among these, gliomas are rare, most being tumors of pituicytes such as granular cell tumor and pituicytoma. Only 4 ependymomas of the human sellar region have been reported to date and all have had classic histologic features. Herein, we describe the clinicopathologic features of a sellar, low-grade ependymoma with unusual histology, but classic ultrastructural features, occurring in an elderly patient and thus expanding the spectrum of reported cases. The literature is reviewed and concepts of histogenesis are explored, particularly an origin in "ependymal pituicytes." The concept that sellar ependymoma is pituicyte-derived is explored.
Human pathology 12/2008; 40(3):435-40. · 3.03 Impact Factor
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ABSTRACT: Surgical treatment of acromegaly aims to normalize the levels of growth hormone and insulin-like growth factor I (IGF-I) and to control tumor growth; however, not all patients achieve remission. Treatment of residual tumor or recurrent disease, therefore, requires additional modalities, such as somatostatin analogs or radiosurgery. Losa et al. have evaluated the efficacy and safety of radiosurgery in a cohort of 83 patients with acromegaly who had previously undergone surgical debulking. The authors reported a 5-year biochemical remission rate of 52.6% after treatment. Remission was found to correlate with the baseline growth hormone and IGF-I levels, but not with tumor volume. In this Practice Point commentary, we place the findings of Losa et al. into clinical context, discuss the possible limitations of their approach, and comment on the relevance of radiosurgery to the treatment of acromegaly.
Nature Clinical Practice Endocrinology & Metabolism 10/2008; 4(11):592-3. · 7.55 Impact Factor
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ABSTRACT: MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Although highly expressed in the normal human pituitary, it is unknown which of the normal pituitary cell types and pituitary tumors express MEG3.
Our objectives were 1) to investigate cell-type- and tumor-type-specific expression of MEG3 in the human pituitary and 2) to investigate whether methylation in the intergenic differentially methylated region (IG-DMR) at the DLK1/MEG3 locus is involved in the loss of MEG3 expression in tumors.
RT-PCR, quantitative RT-PCR, Northern blot, and a combination of in situ hybridization and immunofluorescence were used to determine the cell-type- and tumor-type-specific MEG3 expression. Bisulfite treatment and PCR sequencing of genomic DNA were used to measure the CpG methylation status in the normal and tumor tissues. Five normal human pituitaries and 17 clinically nonfunctioning, 11 GH-secreting, seven prolactin-secreting, and six ACTH-secreting pituitary adenomas were used.
All normal human pituitary cell types express MEG3. However, loss of MEG3 expression occurs only in nonfunctioning pituitary adenomas of a gonadotroph origin. All other pituitary tumor phenotypes examined express MEG3. Hypermethylation of the IG-DMR at the DLK1/MEG3 locus is present in nonfunctioning pituitary adenomas.
MEG3 is the first human gene identified expressed in multiple normal human pituitary cell types with loss of expression specifically restricted to clinically nonfunctioning pituitary adenomas. The IG-DMR hypermethylation may be an additional mechanism for MEG3 gene silencing in such tumors.
Journal of Clinical Endocrinology & Metabolism 10/2008; 93(10):4119-25. · 6.50 Impact Factor
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ABSTRACT: The increased morbidity and mortality of acromegaly makes early diagnosis and therapy critical. However, whether the type of medical professional who first diagnoses acromegaly, the major complaint prompting medical attention, or the management paradigms used in the setting of novel medical therapies have changed over time has not been well explored.
Our objective was to identify the medical professional who first suspected acromegaly and the complaint prompting the diagnosis, and if these have changed. Additional goals were to assess the interval from symptom onset to diagnosis of acromegaly and to compare treatment trends over consecutive decades.
This was a case-record retrospective study. Setting: The study was performed in a neuroendocrine clinical center at a tertiary care center.
A total of 100 patients (45 men and 55 women) with acromegaly referred from 1985-2005 was included in the study.
Acral changes (24%) and headaches (20%) were most prevalent presenting symptoms prompting diagnosis. Eighteen percent reported no symptoms of acromegaly at diagnosis. The primary care physician most often initiated the evaluation (44%). Comorbidities were more prevalent in older patients (P = 0.001). The interval between symptom onset and diagnosis decreased, compared with previous reports. Radiation therapy was used less frequently in the decade after 1994 than in the prior (16 vs. 33%; P < 0.05).
The primary care doctor plays the major role in diagnosis of acromegaly. The increased use of brain magnetic resonance imaging may contribute to the many incidentally discovered cases and to the shortened time interval to diagnosis. Presumably due to the availability of new medical therapies, the use of radiation therapy has decreased.
Journal of Clinical Endocrinology & Metabolism 07/2008; 93(6):2035-41. · 6.50 Impact Factor
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ABSTRACT: Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 expression are referred to as indicators of aggressive behavior in the World Health Organization Classification of Endocrine Tumors. The real value of these markers including an appropriate threshold for Ki-67 labeling index correlating with tumor progression is controversial. We identified 24 consecutive pituitary adenomas from patients who required surgery for recurrence within 5 years of their first procedure and 31 consecutive adenomas with no evidence of postsurgical progression within 5 years of first surgery. Case selection was based upon availability of complete clinical information, blocks, and slides for study. Immunohistochemistry for Ki-67 revealed that the tumors without progression had a proliferation index of 0.41% +/- 0.01% (mean +/- SEM) (n = 31) (range, 0.08%-1.2%) and the first biopsy from those tumors which progressed had a mean proliferation index of 1.45% +/- 0.09% (mean +/- SEM) (n = 24) (range, 0.1%-10.6%) (P = .01). With the use of ROC analysis, a threshold level of Ki-67 expression greater than 1.3% predicts progression with a high specificity. The group with progression had a higher proportion of nonfunctioning tumors (P < .005, chi(2)). There was no significant difference between the 2 groups with regard to invasion, suprasellar extension, size, tumor type, postoperative radiotherapy, extent of resection, sex, and age. Ki-67 labeling index was an independent predictor of progression (multivariate analysis, P < .011). p53 was positive in 12.5% of cases with surgical progression and in 9.6% of cases without progression, but the difference was not significant (P = .7; chi(2), 0.11).
Human Pathlogy 06/2008; 39(5):758-66. · 2.88 Impact Factor
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ABSTRACT: Radiation therapy is a potentially curative treatment for corticotroph adenomas refractory to surgery. Protons have an advantage over photons (x-rays) by depositing energy at the target with no exit dose, providing a lower dose to adjacent normal tissues. Until recently, proton stereotactic radiotherapy (PSR) was available at only two U.S. centers; use will increase as proton facilities are under development.
Our objective was to evaluate the efficacy and safety of PSR for persistent Cushing's disease (CD) and Nelson's syndrome (NS).
This was a retrospective review of 38 patients (33 with CD and five with NS) treated between 1992 and 2005.
All patients had transsphenoidal surgery without biochemical cure. Four had previous irradiation with photons. The patients with NS underwent bilateral adrenalectomy 29-228 months (median 40) before PSR.
Single-fraction PSR was delivered at a median dose of 20 Cobalt Gray Equivalents (range 15-20) on 1 treatment day.
Complete response (CR) was defined as sustained (> or =3 months) normalization of urinary free cortisol off medical therapy. CR in NS was based on normalization of plasma corticotropin.
At a median follow-up of 62 months (range 20-136), CR was achieved in five patients (100%) with NS and 17 (52%) patients with CD. Among all patients with CR, median time to CR was 18 months (range 5-49). No secondary tumors were noted on follow-up magnetic resonance imaging scans, and there was no clinical evidence of optic nerve damage, seizure, or brain injury. There were 17 patients (52%) who developed new pituitary deficits.
PSR is effective for patients with persistent corticotroph adenomas with low morbidity after a median follow-up of 62 months; longer follow-up is warranted for late radiation-related sequelae.
Journal of Clinical Endocrinology & Metabolism 02/2008; 93(2):393-9. · 6.50 Impact Factor
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Clinical neurosurgery 02/2008; 55:141-4.
