Adrenocorticotropic Hormone-secreting Adenoma Research Articles

The Application of Pneumatic Arm in Neuroendoscopic Transsphenoidal Pituitary Adenoma Resection.

To summarize the application experience of the pneumatic arm in transnasal sphenoidal pituitary adenoma resection under neuroendoscope. A retrospective analysis was conducted on the clinical data of 52 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery with pneumatic arm fixation in the Neurosurgery Department of the First Affiliated Hospital of Anhui Medical University from July 2021 to March 2024. Among them, there were 5 cases of pituitary microadenoma, 35 cases of macroadenoma, and 12 cases of giant adenoma. Head CT and a full set of hormones were re-examined within 24 hours after surgery to evaluate the surgical effect. Follow-up was conducted by the outpatient department after surgery to assess the clinical symptoms, hormone level, and imaging of all patients. Among 52 patients, gross total resection was achieved in 48 cases (92.3%), subtotal resection in 3 cases (5.8%), and partial resection in 1 case (1.9%). Preoperatively, 43 patients had diminished vision, with 40 showing improvement postoperatively, 1 worsening, and 2 having no significant improvement. Thirty-eight patients had headaches preoperatively, and all showed varying degrees of improvement postoperatively. Routine hormone examination within 24 hours after surgery showed that all 20 prolactinoma patients had restored normal hormone levels, 10 of 12 growth hormone-secreting adenoma patients normalized, and 4 of 6 cases of adrenocorticotropic hormone-secreting adenoma immediately relieved after surgery. Postoperative complications included intracranial hematoma in 1 case, cerebrospinal fluid leakage in 2 cases, transient diabetes insipidus in 6 cases, intracranial infection in 1 case, and no death cases. The median follow-up time of 52 patients was 18.6 months (range: 1-32 mo). During the follow-up period, the initial clinical symptoms of all patients improved to varying degrees, and they were able to work and live normally. At the last follow-up, 1 patient had recurrent tumor and 1 patient had progression. Transnasal sphenoidal resection of pituitary adenoma using a pneumatic arm-fixed neuroendoscope allows the operator to perform the surgery with both hands, resulting in satisfactory overall tumor resection and fewer surgical complications. This technique has good clinical value for promotion.

Pituitary Adenoma Prevalence and Characteristics of Omani Patients: A Single Center Experience.

To estimate the incidence of pituitary adenomas (PA) in adult Omani patients and describe its epidemiological, clinical, and radiological characteristics. In this longitudinal, descriptive study, we reviewed the records of all PA patients from January 2015 to January 2020 who presented at the endocrinology facilities at Sultan Qaboos University Hospital, Muscat. The participants comprised of 112 Omani patients with PA. The incidence of PA among all adult patients at Sultan Qaboos University Hospital (inpatient and outpatient) over five years (2015-2020) was 0.23%. The cohort had a mean age of 41.0±15.0 years. Of the 112 patients included in this study, 79 (70.5%) were women. Nearly half (51; 45.5%) of adenomas were prolactinomas while 46 (41.1%) were non-functioning adenomas, and seven (6.3%) were growth hormone-secreting adenomas while six (5.4%) were adrenocorticotropic hormone secreting adenomas. Headache was present in 67 (59.8%) patients, followed by visual field defects (40; 35.7%), galactorrhea (26; 23.2%), and fatigue (19; 17.0%). The majority of women (45/79; 57.0%) presented with menstrual cycle abnormalities. Radiological appearances were nearly equally distributed between micro- and macroadenomas. Most cases (58/112; 52.0%) of PA were treated medically by cabergoline, octreotide, and replacement therapies such as hydrocortisone and thyroxin, 38 (33.9%) were treated surgically (mainly by trans-sphenoidal pituitary resection), and the remaining 10 (8.9%) cases were subjected to radiotherapy. Medical treatment combined with surgery was employed for 15 (13.4%) patients. In our investigation, PA was primarily prevalent among Omani female patients, and the most common subtype of pituitary tumors was prolactinomas. The most common presentation symptom was headaches; most female patients had menstrual irregularities. Medical treatment was the primary approach for the applicable types of PAs, while surgery and radiotherapy were found to be secondary and tertiary treatment options, respectively.

Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors

Background18Fluorine-Fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of 18F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve 18F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing’s disease (CD).MethodsWe included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET.ResultsTwenty-two patients were included (age at diagnosis: 37 [13–56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006*), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010*; gray matter, 6.25 vs. 7.95, P = 0.010*).ConclusionDEX suppression did not improve 18F-FDG PET/CT localization in patients with CD.

Multivariable Diagnostic Prediction Model to Detect Hormone Secretion Profile From T2W MRI Radiomics with Artificial Neural Networks in Pituitary Adenomas.

Objective:This study aims to develop neural networks to detect hormone secretion profiles in the pituitary adenomas based on T2 weighted magnetic resonance imaging (MRI) radiomics.Methods:This retrospective model-development study included a cohort of patients with pituitary adenomas (n=130) from January 2015 to January 2020 in one tertiary center. The mean age was 46.49±13.69 years, and 76/130 (58.46%) were women. Three observers segmented lesions on coronal T2 weighted MRI, and an interrater agreement was evaluated using the Dice coefficient. Predictors were determined as radiomics features (n=851). Feature selection was based on intraclass correlation coefficient, coefficient variance, variance inflation factor, and LASSO regression analysis. Outcomes were identified as 7 hormone secretion profiles [nonfunctioning pituitary adenoma, growth hormone-secreting adenomas, prolactinomas, adrenocorticotropic hormone-secreting adenomas, pluri-hormonal secreting adenomas (PHA), follicle-stimulating hormone and luteinizing hormone-secreting adenomas, and thyroid-stimulating hormone adenomas]. A multivariable diagnostic prediction model was developed with artificial neural networks (ANN) for 7 outcomes. ANN performance was presented as an area under the receiver operating characteristic curve (AUC) and accepted as successful if the AUC was >0.85 and p-value was <0.01.Results:The performance of the ANN distinguishing prolactinomas from other adenomas was validated (AUC=0.95, p<0.001, sensitivity: 91%, and specificity: 98%). The model distinguishing PHA had the lowest AUC (AUC=0.74 and p<0.001). The AUC values for the other five ANN were >0.85 and p values were <0.001.Conclusions:This study was successful in training neural networks that could differentiate the hormone secretion profile of pituitary adenomas.

Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery in a single center

Pituitary Adenomas (PA) are a group of benign tumors with diverse biological behavior including different hormonal secretion, cavernous sinus invasion and considerable rates of relapse. The aim of the study was to evaluate the benefits of the Endoscopic Endonasal Transsphenoidal (EET) approach for managing hormonal producing Pituitary Adenomas (PA) in terms of achieving clinical remission in comparison to the Microscopic Endonasal Transsphenoidal (MET) approach. During the period 2014 to 2017 a series of 128 patients with PA were operated on via MET (n=62) and EET (n=66) approach. Endocrinological, neuro-ophthalmic and MRI examinations were assessed preoperatively and postoperatively at 3rd and 12th month. Thirty-two patients were diagnosed with growth-hormone secreting adenomas (GH), 25 with Adrenocorticotropic Hormone secreting adenomas (ACTH), 17 with Prolactin-secreting adenomas (Prl) and 54 with non-secreting pituitary adenomas. The endoscopic group had higher levels of remission in comparison to the microscopic group (81.8% vs. 70.9%), however no significant difference was observed (?=0.128). PA with invasiveness to the cavernous sinus from the endoscopic group had significantly better remission rates opposed to the microscopic group (p<0.05). Macroadenomas not exceeding 40 mm in diameter had higher remission rates in the endoscopic group (p<0.05). Examination of postoperatiove complications showed similar incidence of postoperative diabetes insipidus and CSF leak (p>0.05). The use of endoscopic endonasal transphenoidal approach provides better remission rates in invasive PA compared to the conventional microsurgical approach. A long-term follow-up is still needed for further evaluation of our results.

Cerebrospinal fluid rhinorrhoea following transsphenoidal surgery for pituitary adenoma: experience in a Chinese centre.

SUMMARYThe aim of this study was to elucidate the risk factors for cerebrospinal fluid (CSF) rhinorrhoea following transsphenoidal surgery and discuss its prevention and treatments. We retrospectively reviewed 474 consecutive cases of pituitary adenoma treated with 485 transsphenoidal surgical procedures from January 2008 to December 2011 in our department. We analysed the incidence of intra- and post-operative CSF leakage and outcomes of various repair strategies. Intra-operative CSF leakage was encountered in 85 cases (17.9%), and post-operative CSF rhinorrhoea in 13 cases (2.7%). Seven of the 13 patients with post-operative CSF rhinorrhoea did not experience intra-operative CSF leakage; three of these patients had adrenocorticotropic hormone-secreting adenomas. Of the remaining 6 patients with both intra- and post-operative CSF leakage, 2 were treated for giant invasive prolactinomas, and 2 had previously undergone transsphenoidal surgery. In eight patients, the leak was resolved by lumbar puncture, lumbar external drainage, resting in a semi-reclining position, or other conservative treatment. Two CSF leaks were repaired with gelatine foam and fibrin glue using a transsphenoidal approach, and two with autologous fat graft and sellar floor reconstruction using a transnasal endoscopic approach. After undergoing two transnasal endoscopic repairs, one patient with post-operative CSF rhinorrhoea was successfully treated by further lumbar subarachnoid drainage. In conclusion, procedures using gelatine foam, fibrin glue and autologous fat graft are common and effective techniques for the management of CSF rhinorrhoea after transsphenoidal surgery. When a CSF leak is detected during transsphenoidal surgery, thorough sellar reconstruction and long-term follow-up are necessary.

Parasellar Extension Grades and Surgical Extent in Endoscopic Endonasal Transsphenoidal Surgery for Pituitary Adenomas : A Single Surgeon's Consecutive Series with the Aspects of Reliability and Clinical Validity.

ObjectiveThe inter-rater reliability of the modified Knosp's classification was measured before the analysis. The clinical validity of the parasellar extension grading system was evaluated by investigating the extents of resection and complication rates among the grades in the endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenomas.MethodsFrom November 2008 to August 2015, of the 286 patients who underwent EETS by the senior author, 208 were pituitary adenoma cases (146 non-functioning pituitary adenomas, 10 adrenocorticotropic hormone-secreting adenomas, 31 growth hormone-secreting adenomas, 17 prolactin-secreting adenomas, and 4 thyroid-stimulating hormone-secreting adenomas; 23 microadenomas, 174 macroadenomas, and 11 giant adenomas). Two neurosurgeons and a neuroradiologist independently measured the degree of parasellar extension on the preoperative sellar MRI according to the modified Knosp's classification. Inter-rater reliability was statistically assessed by measuring the intraclass correlation coefficient. The extents of resection were evaluated by comparison of the pre- and post-operative MR images; the neurovascular complications were assessed by reviewing the patients' medical records. The extent of resection was measured in each parasellar extension grade; thereafter, their statistical differences were calculated.ResultsThe intraclass correlation coefficient value of reliability across the three raters amounted to 0.862. The gross total removal (GTR) rates achieved in each grade were 70.0, 69.8, 62.9, 21.4, 37.5, and 4.3% in Grades 0, 1, 2, 3A, 3B, and 4, respectively. A significant difference in the extent of resection was observed only between Grades 2 and 3A. In addition, significantly higher complication rates were observed in the groups above Grade 3A.ConclusionAlthough the modified Knosp's classification system appears to be complex, its inter-rater reliability proves to be excellent. Regarding the clinical validity of the parasellar extension grading system, Grades 3A, 3B, and 4 have a negative predictive value for the GTR rate, with higher complication rates.

Sellar Masses: An Epidemiological Study.

Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. To determine the epidemiology of SM in the province of Nova Scotia, Canada. Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke's cyst (6.5%; 0.5), growth hormone-secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone-secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at <1 cm, and 11 (1.1%) had functioning pituitary adenomas without discernible tumor, whereas tumor size data were unavailable in 150 (14.9%) patients. The specific pathologies and their most common presenting features were: nonfunctioning adenoma (incidental, headaches, and vision loss), prolactinomas (galactorrhea, menstrual irregularity, and headache), growth hormone-secreting adenomas (enlarging extremities and sweating), adrenocorticotropic hormone-secreting adenoma (easy bruising, muscle wasting, and weight gain) and nonpituitary lesions (incidental, headaches, and vision problems). Secondary hormonal deficiencies were common, ranging from 19.6% to 65.7%; secondary hypogonadism, hypothyroidism, and growth hormone deficiencies constituted the majority of these abnormalities. This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.

Outcome of Transsphenoidal Surgery for Cushing Disease

Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness. To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children. Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 μg/dL; type 2 = morning cortisol normal). Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths. Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Pituitary-Targeted Dynamic Contrast-Enhanced Multisection CT for Detecting MR Imaging-Occult Functional Pituitary Microadenoma.

Although resection of a tumor by trans-sphenoidal surgery is considered the criterion standard for successful surgical treatment of functional pituitary microadenoma, MR imaging occasionally fails to visualize and identify the tumor and supplementary imaging modalities are necessary. We tested the possibility of dynamic contrast-enhanced multisection CT of the pituitary gland accompanying image reconstruction of contrast agent dynamics to identify the localizations of microadenomas and compared the diagnostic performance with conventional pituitary-targeted MR imaging. Twenty-eight patients with surgically confirmed functional pituitary microadenomas (including growth hormone-, adrenocorticotropic hormone-, and prolactin-secreting adenomas) who underwent pituitary-targeted dynamic contrast-enhanced multisection CT were retrospectively investigated. We undertook image reconstruction of the dynamics of the contrast agent around the pituitary gland in a voxelwise manner, visualizing any abnormality and enabling qualification of contrast dynamics within the tumor. Fifteen cases were correctly diagnosed by MR imaging, while dynamic contrast-enhanced multisection CT correctly diagnosed 26 cases. The accuracy of localization was markedly better for adrenocorticotropic hormone-secreting microadenomas, increasing from 32% on MR imaging to 85% by dynamic contrast-enhanced multisection CT. Compared with the normal pituitary gland, adrenocorticotropic hormone-secreting adenoma showed the least difference in contrast enhancement of the different functional microadenomas. Images acquired at 45-60 seconds after contrast agent injection showed the largest difference in contrast enhancement between an adenoma and the normal pituitary gland. Dynamic contrast-enhanced multisection CT combined with image reconstruction of the contrast-enhanced dynamics holds promise in detecting MR imaging-occult pituitary microadenomas.

Endoscopic endonasal transsphenoidal surgery for pituitary adenomas.

The objective of this study was to report the efficacy, safety, and outcomes of endoscopic endonasal transsphenoidal techniques for pituitary adenomas. A retrospective data analysis of 32 patients who underwent endoscopic endonasal transsphenoidal surgery for pituitary adenoma between February 2011 and December 2013 was performed. The patients' demographic data, clinical presentations, radiologic findings, recurrence rates, and complications were analyzed. There were 14 men and 18 women with age ranging from 23 to 74 years (mean age, 48.6 y). Functioning and nonfunctioning tumors were present in 22 (68.8%) and 10 patients (31.2%), respectively. Among the functioning adenomas, 8 patients (25%) had growth hormone-secreting adenomas, 6 patients (18.8%) had prolactinomas, 5 patients (15.6%) had adrenocorticotropic hormone-secreting adenomas, 2 patients (6.2%) had follicle-stimulating hormone/luteinizing hormone-secreting adenomas, and 1 patient (3.1%) had thyroid-stimulating hormone-secreting adenomas. Of the 32 patients, 20 (62.5%) had pituitary macroadenomas and 12 patients (37.5%) had microadenomas. Total-subtotal tumor resection was achieved in 75% and 45% of the microadenomas and macroadenomas, respectively. Radiologically, 60% of the macroadenomas had suprasellar and carvenous sinus extension. Postoperative cerebrospinal fluid leaks occurred in 3 patients. Two patients developed temporary diabetes insipidus. Endoscopic transsphenoidal surgery is an effective and safe treatment for most patients with pituitary adenoma and could be considered the first-choice therapy in these patients.

Role of gamma knife radiosurgery in the management of functioning pituitary adenomas

Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, fractionated radiotherapy, and, recently, gamma knife surgery (GKS). The objective of this study was to evaluate the efficacy, safety, and role of GKS in the treatment of secretory pituitary adenomas as regards hormonal and adenoma size control. Between January 2010 and January 2014, a prospective analysis of 40 consecutive patients who underwent GKS for secretory pituitary adenomas at the International Medical Center, Cairo, Egypt, was carried out. Eight patients had adrenocorticotropic hormone-secreting adenoma, 16 patients had prolactin-secreting adenoma, and 16 had growth hormone-secreting adenoma. In 19 patients, GKS was the secondary treatment to a prior surgery with failure of hormonal control along with medical treatment. In the remaining 21 patients, the secretory pituitary adenomas were not controlled with medical treatment alone. The follow-up period ranged between 12 and 60 months. Hormonal control was achieved with either normalization or a marked decline in abnormal hormone level of more 50%. Radiological tumor size control was carried out with either tumor size stabilization or reduction. Among the 40 patients, 21 had microadenoma of 1 cm 3 volume or less. Overall, 24 patients (60%) had hormonal control and 38 patients (95%) had tumor size control after GKS. There was a direct correlation between tumor size, prescription radiation dose, and hormonal and size control after GKS. Twenty out of the treated 21 microadenoma cases showed both hormonal and size control. In conclusion, GKS is a safe and effective treatment method for secretory pituitary adenomas that have failed to respond to medical treatment alone or have postsurgical residual tumor, or recurrence, especially microadenomas.

Clinical value of 68Ga-DOTATATE PET/CT in pituitary adenoma: a pilot study

Objective To investigate the correlation between the uptake of 68Ga-DOTATATE in pituitary adenoma and clinical parameters such as hormonal hypersecretion, and to evaluate the curative effect with 68Ga-DOTATATE imaging after octreotide therapy in patients with growth hormone-secreting adenoma (GH adenoma). Methods A total of 34 patients (15 males, 19 females) with pituitary adenoma were recruited, including 5 adrenocorticotropic hormone-secreting adenoma (ACTH adenoma), 17 GH adenoma, and 12 non-functioning adenoma (NF adenoma). In the 17 patients with GH adenoma, there were 13 patients treated by octreotide intramuscular injection 3 times with a total dose of 60 mg for 3 months. The finial diagnosis was based on histology. 68Ga-DOTATATE imaging was performed, and SUVmean, tumor volume and density index (DI) were recorded in all patients. The DI was the ratio of tumor SUVmean to tumor volume. The effective therapy was defined as more than 50% of hormonal suppression or more than 20% of tumor shrinkage. Non-parametric Mann-Whitney u test was used. Results NF adenoma showed greater tumor volume than secretory adenoma, ((9.10±7.00) cm3vs (2.92±1.60) cm3,u=43.0, P<0.05), whereas DI of secretory adenoma was higher than that of NF adenoma (7.16±4.52 vs 1.08±1.40, u=48.5, P<0.05). Additionally, DI was significantly higher(3.55±0.91 vs 1.38±0.69, u=2.0, P<0.05) in patients (n=8) with effective treatment than that in patients without effective treatment (n=5). Conclusion 68Ga-DOTATATE may be a useful probe for PET imaging in patients with pituitary adenoma, and may be valuable for predicting the therapeutic effect of somatostatin analog treatment. Key words: Pituitary neoplasms; Gallium radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; DOTATATE

Early promising results for the endoscopic surgical treatment of Cushing's disease.

High levels of endogenous cortisol due to Cushing's disease cause significant mortality and morbidity. Treatment of Cushing's disease is challenging. For many years, transsphenoidal microsurgical resection of the adenoma has been the treatment of choice. However, recently, neuroendoscope has taken its place in the neurosurgeon's armamentarium, and the endoscopic transsphenoidal resection of pituitary tumors has become a familiar approach. Our aim was to present the results of pure endoscopic surgery in the treatment of corticotropinomas for comparison with the results of previous endoscopic and microsurgical series. We present a retrospective analysis of 90 patients with diagnosis of Cushing's disease who were operated between 2006 and 2012. Among 90 patients, a total of 81 (90.0%) had a remission (28 out of 29 macroadenomas (96.6%) and 53 out of 61 microadenoma patients (86.9%)). Of note is that 66 out of 69 (95.7%) primary patients (i.e., those who were operated in our center) and 15 out of 21 (71.4%) patients previously operated in other centers reached a hypo/eucortisolemic state. A remission rate comparable with previous endoscopic series was achieved. In nine patients, it was not possible to achieve remission at all. On the other hand, only four of our cases (5.6%) had a recurrence, and with reoperation, all of these patients entered a re-remission. To our knowledge, our series is the largest series studying endoscopically operated adrenocorticotropic hormone-secreting adenomas. Our results suggest that the endoscopic approach has opened a new avenue in the treatment of Cushing's disease, previously a therapeutic challenge for both the clinician and the neurosurgeon. Endoscopic approach in the treatment of Cushing's disease is clearly better for patients because of its low morbidity rates and short duration of hospital stay. On the other hand, long-term follow-up of our patients will show whether these favorable observations will persist.

Childhood Onset Pituitary Adenoma: Clinical Presentations and Outcomes of 24 Cases

Purpose: Our purpose was to evaluate the clinical presentations at diagnosis and treatment outcomes of functional pituitary adenoma (PA) and nonfunctional PAs (NFPA) in childhood and adolescence. Methods: We performed a retrospective review of the medical records of patients diagnosed with PA before 18 years of age. Results: The mean age at diagnosis of 24 patients (9 males, 15 females) was 12.3 years, and the mean follow-up period was 4.5 years. PAs were categorized as follows: prolactinoma (n=7, 29.2%), adrenocorticotropic hormone secreting adenomas (n=4, 16.7%), growth hormone secreting adenomas (n=3, 12.5%), and NFPAs (n=10, 41.7%). The proportion of macroadenoma (n=13, 54.2%) was similar to that of microadenoma (n=11, 45.8%). Sixteen patients (66.7%) who were diagnosed with functional PA (including all prolactinomas), and two NFPAs underwent surgery due to mass effects. The patients who received surgery had a higher risk for hypopituitarism than those who did not (75.0% vs. 12.5%; P=0.008). Recurrence occurred in five patients, all of whom had residual tumors after surgery for macroadenoma. The degree of obesity at latest follow-up was associated with that at diagnosis (P<0.001). Conclusion: The prevalence of NFPAs was higher than that of previous reports, which was explained by higher detection of incidentalomas. Prolactinoma was the most common functional PA. Thorough investigation of symptoms related to hormone excess and hormone profiles is important for differential diagnosis and decision regarding treatment plan. Additionally, the regular follow up for relapse and endocrine deficit is mandatory in patients with PA, especially those who had received pituitary surgery.

Endoscopic Endonasal Transclival Approach to the Jugular Tubercle

The jugular tubercle is a rounded bony prominence that arises from the inferolateral margin of the clivus. In a previous publication, we described the surgical anatomy of the expanded endonasal approach to the jugular tubercle. To illustrate the translation of laboratory work to the operating room describing the anatomic and technical nuances of the endonasal approach to the jugular tubercle. We review the relevant surgical anatomy needed to perform an endonasal approach to the jugular tubercle, and we select 4 different lesions to illustrate the application of our laboratory findings. In the first case, exposure and partial drilling of the jugular tubercle was critical to gain an adequate corridor to the meningioma, particularly to its inferolateral margin. This allowed for early devascularization, safe extracapsular dissection, and preservation of surrounding neurovascular structures. In addition, the jugular tubercle was hyperostotic and its resection, along with generous dural removal, provided a grade I Simpson tumor resection. In the second (chondrosarcoma) and third (chordoma) cases, the jugular tubercle was infiltrated by tumor, and consequently its complete resection was essential to achieve total tumor removal. In the last case, an unusual adrenocorticotropic hormone-secreting adenoma recurrence at the jugular tubercle region, the technical modification of the transclival approach presented here was successfully applied to achieve complete resection and Cushing disease remission. The transjugular tubercle variant of the expanded endonasal transclival approach allows for direct access to ventrolateral lesions in the inferior clival/petroclival region with no cerebral or cerebellar retraction, or cranial nerve manipulation during the approach.

The Incidence of Stroke in Pituitary Adenoma Patients Treated with Postoperative Radiotherapy vs. Surgery Alone

To assess and compare the incidence of stroke in pituitary adenoma patients treated with postoperative radiotherapy (PORT) or surgery alone. PORT results in excellent local tumor control and improvement of excessive hormonal secretion where (repeated) surgery was unsuccessful. Nevertheless, concerns related to possible long-term side effects are often quoted to delay or reject this treatment. In previous studies, the incidence of stroke in PORT patients was compared with a normal reference population. However, such comparisons are biased by imbalances in the presence of other stroke risk factors that are related to pituitary adenoma disease and surgery. A cohort of 462 pituitary adenoma patients (non-functioning adenoma n = 256, growth-hormone secreting n = 139 and adrenocorticotropic-hormone secreting adenoma n = 67) treated between 1959 and 2008 at the University Medical Center Groningen in The Netherlands was studied. PORT was administered in 236 patients. Most patients received a total radiation dose of 45 Gy in 25 fractions of 1.8 Gy in 5 weeks. Stroke was classified into hemorrhagic and ischemic stroke. The TOAST and Oxfordshire classification methods were used to compare differences of causative mechanism and anatomic distribution of ischemic infarcts. Age at pituitary adenoma diagnosis was transformed to median life expectancy (MLE) using the annual life tables of the Central Office of Statistics according to gender. MLE was used in order to account for differences in life expectancy due to differences in follow-up, gender and birth cohort effects. The data were analyzed by log-rank test for investigating the risk of stroke in patients treated with PORT vs. surgery alone. Stroke risk factors were analyzed in univariate-and multivariate analysis by log-rank test. The median follow-up time was 14 years (range, 1 – 49 years) in patients treated with PORT and 6 years (range, 1 – 34 years) in patients treated with surgery alone. Thirteen PORT patients (5.5%) were diagnosed with a stroke (ischemic n = 10) compared to 12 patients (5.3%; ischemic n = 10) treated with surgery alone (univariate RR, 0.62; 95% CI, 0.28 – 1.35; p = 0.23). Stroke risk factors were coronary-and peripheral artery disease (univariate and multivariate RR, 10.4; 95% CI, 4.7 – 22.8; p < 0.001) and hypertension (univariate RR, 3.9; 95% CI, 1.6 – 9.8; p = 0.002). No difference was seen in TOAST and Oxfordshire classification of ischemic stroke between the two treatment groups. Postoperative radiotherapy in pituitary adenoma patients was not associated with an increased incidence or causative mechanism of stroke compared to patients treated with surgery alone. Coronary and peripheral artery disease on the other hand was associated with higher risk of stroke.

Clinical/disease sites: CNS and haematology

Purpose: Postoperative radiotherapy (PORT) results in excellent local tumour control and improvement of excessive hormonal secretion in pituitary adenoma patients where (repeated) surgery was unsuccessful. Despite this benefit, concerns related to possible long term side effects are often quoted to delay or reject this treatment. In previous studies. the incidence of second tumours and mortality in pituitary adenoma patients treated with PORT were compared with a normal reference population. For proper evaluation however, a direct comparison with similar patients treated with surgery alone should be made. The purpose of this study was to assess the impact of PORT on developing second tumours and mortality in pituitary adenoma patients by comparing the incidence with patients treated with surgery alone. Materials: A retrospective study was performed in 462 pituitary adenoma patients (non-functioning adenoma n=256. growth-hormone secreting n=139 and adrenocorticotropic-hormone secreting adenoma n= 67) treated between t959 and 2008 at the University Medical Center Groningen. PORT was performed in 236 pituitary adenoma patients. The different radiotherapy techniques used in this period were divided into techniques with (n=80) or without (n=153) a beam configuration directed into the central body axis of the patient. Most patients received a radiation fractionation scheme of 25 daily fractions of 1.8 Gy in 5 weeks.After pituitary adenoma diagnosis the incidence of tumours and death were investigated using median life expectancy (MLE). MLE was used to correct for year of birth and gender and with the application of years of follow up as a time base for a left-censored log-rank test. Results: Median age at diagnosis was 47 (range 10-83) years and median overall follow-up time was 9 (range 1-49) years. The median follow-up time of patients treated with PORT was 14 (range 1-49) years and 6 (range 134) years in patients treated with surgery alone. Four patients developed an intracranial tumour, 3 of them were treated with PORT. Twenty-one patients treated with PORT developed an extracranial tumour compared to 11 patients treated with surgery alone (RR 1.04 CI 95%, 0.50-2.17, P = 0.917). In 11 out of the 21 patients treated with PORT and diagnosed with an extracranial tumour a central body axis radiotherapy technique was used (RR 1.43 CI 95%, 0.60-3.41, P = 0.425).Forty-five patients treated with PORT died compared to 24 patients treated with surgery alone (RR 1.26 CI 95%, 0.77-2.08, P = 0.358). Conclusions: Postoperative radiotherapy did not increase the incidence of second tumours and mortality in pituitary adenoma patients. Central body axis radiotherapy technique was not associated with an increase in extracranlal tumours.

Endoscopic endonasal transsphenoidal approach for pituitary adenomas invading the cavernous sinus

In this report, the authors describe their experience with surgical access to the cavernous sinus via a fully transnasal endoscopic approach in 20 cases. Clinical and endocrinological follow-up are discussed. The authors used an endoscopic transsphenoidal approach in 192 patients with pituitary adenomas between September 1997 and January 2008, adding a cavernous sinus approach in 20 patients with invasive tumors during the last 5 years of this period [corrected]. Parasellar extension of the tumor was measured according to the Knosp Scale. Radical tumor removal was achieved in 13 (65%) of 20 patients, and subtotal removal in 7 (35%). The authors used recently defined cavernous sinus approaches in the first 14 cases, including the paraseptal approach in 6, middle turbinectomy in 7, and contralateral middle turbinectomy in 1 case. Combined approaches rather than defined standard cavernous sinus approaches were used in 4 cases and an extended approach in 2. The tumors included nonsecretory adenomas in 5 cases (25%), growth hormone-secreting adenomas in 7 (35%), prolactin-secreting adenomas in 4 (20%), and adrenocorticotropic hormone-secreting adenomas in 4 cases (20%). Normal growth hormone and insulin-like growth factor 1 levels were achieved in 4 patients (57%) with growth hormone adenomas, and remission criteria were obtained in 3 patients with prolactinomas and 3 patients with adrenocorticotropic hormone-secreting adenomas. Compared with transcranial and microscopic transsphenoidal surgery, endoscopic transsphenoidal surgery offers a wide exposure for cavernous sinus medial wall adenomas that enables removal of the adenoma from the medial cavernous sinus wall. Because of the necessity for multidisciplinary treatment to achieve satisfactory results, Gamma Knife surgery and medical therapy should be supplementary treatment options after endoscopic transsphenoidal surgery.

KAPOSI SARCOMA RELATED TO AN ECTOPIC HYPOTHALAMIC ADRENOCORTICOTROPIC HORMONE-SECRETING ADENOMA

We aim to report a case of Kaposi sarcoma (KS) with Cushing's syndrome caused by endogenic glucocorticoid-induced immunosuppression. A 43-year-old woman presented with delirium, hirsutism, fatigue, and hypertension. At the time of presentation, physical findings showed a Cushingoid appearance, with moon-like facies, hirsutism, and hyperpigmentation. Laboratory findings showed the following: adrenocorticotropic hormone, 86.7 pg/mL (normal range, 0-46 pg/mL); baseline cortisol level, 50 microg/dL (normal range, 6.2-19 microg/dL); potassium, 2.2 mEq/L (normal range, 3.5-5 mEq/L); and midnight cortisol level, 33 microg/dL. Serum cortisol levels failed to suppress after low and high doses of dexamethasone; these findings confirmed the diagnosis of ectopic adrenocorticotropic hormone production. Magnetic resonance imaging revealed a 12 x 15-mm, round, hypothalamic mass lesion in the center of the median eminence. Endoscopic biopsy from the floor of the third ventricle was performed, and pathological examination of the lesion showed a diffuse adrenocorticotropic hormone-secreting adenoma. The patient developed diffuse skin lesions that were proven to be a KS by skin biopsy while she was prepared for transcranial surgery. After surgical removal of the adenoma, she became hypocortisolemic and required cortisol replacement. Within 1 month after surgery, all KS lesions disappeared spontaneously. Excessive cortisol may induce immunosuppression. KS is one of the most common malignant tumors of patients with immunosuppression. To the best of our knowledge, this is the first case of Cushing's syndrome with KS caused by endogenous glucocorticoid-induced immunosuppression.