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Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas are considered the gold standard treatment for Cushing disease (CD). Even with various recent advances in management, disease persistence and recurrence are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64% to 93%. This study aims to determine the various clinical, biochemical, radiological, and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-κB, and SHH pathway activation and to study the protein expression of activation markers of these pathways (i.e., c-Fos, c-Jun, GLI-1, pMEK, NR4A1, and p44) in functioning corticotroph pituitary adenomas. From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n = 174 surgeries) for CD with a median follow-up of 8.1 years (range, 1–13.29 years) were ambispectively analyzed. The preoperative clinical, biochemical, and radiological features, operative findings, postoperative clinical and biochemical data, and histopathological and molecular profiles were retrieved from the electronic medical records. The patients were followed up to assess their remission status. Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for pediatric patients, and 12 surgeries were for patients with Nelson syndrome. In the primary surgery cohort, 74.3% were female, and the average age was 28.73 ± 10.15 years. Of the primary surgery cohort, 75% of the patients experienced remission compared with 47.4% after revision surgery. The remission rate for the pediatric patients was 55.5%. The postoperative day 1 plasma cortisol (P < 0.001; area under the curve, 0.8894; range, 0.8087–0.9701) and adrenocorticotropic hormone (P < 0.001; area under the curve, 0.9; range, 0.7386–1) levels were seen to be strong independent predictors of remission in the primary surgery cohort. The remission rate after endoscopic TSS was greater than that after microscopic TSS in patients undergoing primary surgery (81.08% vs. 57.14%; P = 0.008). The presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (P = 0.020). On stratifying by surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of nonremission (odds ratio, 38.1; 95% confidence interval, 4.2–348.3) compared with endoscopically operated patients with adenoma found on HPE. A lower immunoreactivity score for NR4A1 was found to correlate with higher remission rates (P = 0.074). However, none of the molecular markers studied (i.e., c-Fos, c-Jun, GLI-1, pMEK, and p44) showed a significant correlation with the preoperative cortisol values. The remission rate after primary surgery is higher than that after revision surgery and is lower for pediatric patients than for adults. The postoperative day 1 plasma cortisol and adrenocorticotropic hormone levels are strong independent predictors of remission in the primary surgery cohort. An endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate; thus, endoscopy should be the approach of choice for these patients with the goal of identification of an adenoma on HPE. [ABSTRACT FROM AUTHOR]

Background: Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas. Method: We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach. Conclusion: A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury. [ABSTRACT FROM AUTHOR]

Cushing's disease (CD) is an uncommon yet serious disorder, linked to increased morbidity and mortality. Diagnosis of these patients are complex, and emphasis should be placed on early detection for better management of these patients. The objective of this case report is to evaluate the diagnostic elements in the identification of a subcentimeter adrenocorticotrophic hormone (ACTH)-dependent pituitary adenoma. We report a case of a 26-year-old man who presented with extensive superficial fungal infection of the skin, unintentional weight gain, hypertension, dyslipidaemia as well as cushingoid appearance suspicious of hypercortisolism. Raised midnight plasma cortisol and 24-hour urinary cortisol levels warranted further investigation. Overnight and 48-hour low-dose dexamethasone suppression test (LDDST) were non-suppressed. Subsequent bilateral inferior petrosal sinus sampling (BIPSS) was not only efficient in differentiating pituitary from ectopic Cushing's syndrome (CS) but was shown to be superior to magnetic resonance imaging (MRI) in lateralisation of the pituitary adenoma. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism secondary to ectopic parathyroid (in anterior mediastinum) is rare in children. We report the case of a 12-year-old girl with a history of multiple fractures, renal calculi and limb deformities. She was diagnosed with hyperparathyroidism secondary to an intrathymic parathyroid adenoma. Sestamibi scan showed a lesion in the anterior mediastinum. A biochemical evaluation revealed hypercalcaemia, elevated alkaline phosphatase and parathormone levels. The lesion was marked with radioisotope and confirmed intraoperatively using a gamma camera. The child underwent thoracoscopic left thymectomy with the adenoma. Immediate decrease in calcium and parathyroid hormone values were noted intraoperatively and serial monitoring showed a downward trend. On follow-up, the child is doing well. Ectopic parathyroid adenoma is very rare. CT with radioisotope scans is helpful in diagnosis. Thoracoscopic excision of ectopic adenoma is safe in children. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative magnetic resonance imaging (iMRI) improves the intraoperative detection of adenoma remnants in transsphenoidal surgery. iMRI might be redundant in endoscopic pituitary surgery in non-invasive tumors (Knosp 0–2) due to a superior visualization of anatomical structures in the periphery of the sella turcica compared to the microscopic technique. We identified the anatomical location of tumor remnants in iMRI and evaluated risk factors for secondary resection after iMRI and hereby selected patients with pituitary adenomas who may benefit from iMRI-assisted resection. Methods: We conducted a retrospective monocenter study of patients who underwent iMRI-assisted transsphenoidal surgical resection of pituitary adenomas at our department between 2012 and 2020. A total number of 190 consecutive iMRI-assisted transsphenoidal surgeries of pituitary adenomas graded as Knosp 0–2 were selected for analysis. Exclusion criteria were missing iMRI availability or pathologies other than adenomas. Of these 190 cases, 46.3% (N = 88) were treated with microscopic, 48.4% (N = 92) with endoscopic, and 5.3% (N = 10) with endoscopic-assisted technique. Volumetric measurement of preoperative, intraoperative, and postoperative tumor extension was performed. Demographic data, tumor characteristics, and MRI features were evaluated. Additionally, analysis of adenoma remnants identified by iMRI was performed. Results: An additional resection after iMRI was performed in 16.3% (N = 31). iMRI helped to reach gross total resection (GTR) in 83.9% (26/31) of these cases. False-positive resection was found in 1 patient (0.5%). Multivariable logistic analysis identified tumor volume (OR = 1.2, p = 0.007) recurrence (OR = 11.3, p = 0.002) and microscopic technique (OR = 2.8, p = 0.029) as independent risk factors for additional resection. Simultaneously, the endoscopic technique was significantly associated with GTR as evaluated by iMRI (OR = 2.8, p = 0.011) and postoperative MRI (OR = 5.8, p = 0.027). The detailed analysis of adenoma remnants on iMRI revealed the suprasellar location in a diaphragm fold, penetrating tumor above the diaphragm, or undetected invasion of cavernous sinus as well as in case of microscopic resection tumor location outside the line of sight as the main reasons for incomplete resections. Conclusion: Tumor volume, recurrence, and microscopic technique were identified as independent predictors for additional resection in patients with Knosp 0–2 adenomas. iMRI might increase the extent of resection (EOR) safely even after the endoscopic visualization of the sella with very low risk for false-positive findings. Remnants of tumors hidden within the diaphragmic folds, intrathecally, or behind the infiltrated wall of cavernous sinus not recognized on preoperative MRI were the most common findings in iMRI. [ABSTRACT FROM AUTHOR]

This document is an erratum for an article titled "Mutational landscape of non-functional adrenocortical adenomas" published in the journal Endocrine-Related Cancer. The erratum acknowledges an error in Table 3 of the original paper, where the units for Aldosterone were incorrectly given as ng/dL instead of pg/mL. The corrected table is provided in the erratum. The article is authored by Luming Wu, Jing Xie, Yan Qi, Tingwei Su, Lei Jiang, Weiwei Zhou, Yiran Jiang, Cui Zhang, Xu Zhong, Yanan Cao, and Weiqing Wang. [Extracted from the article]

Purpose: We aim to more fully understand the incidence and natural history of spontaneously resolving non-functioning pituitary adenomas (NFPAs). Methods: We report a case of spontaneous complete resolution of a NFPA revealed by preoperative magnetic resonance imaging. In addition, we searched all major databases and neurosurgery journals to perform a comprehensive literature review of all previously reported cases of spontaneously resolving NFPAs. We discuss how these cases may contribute to our understanding of the natural course for non-functional pituitary adenomas. Results: To date, only twelve cases of spontaneously resolving nonfunctional pituitary adenomas have previously been reported. The presented case is the first reported spontaneously resolved nonfunctioning pituitary adenoma to recur. In all cases, apoplexy resulted in resolution of mass effect, obviating the need for surgical decompression. Conclusions: In all NFPA cases, the preoperative MRI should always be studied closely before surgery is initiated. Additionally, because we have demonstrated that the adenoma may regrow after spontaneous regression following apoplexy, these patients should be followed with regular serial MRIs to monitor for recurrence. [ABSTRACT FROM AUTHOR]

Pituitary adenoma surgeries are common in neurosurgical setup. Majority are tackled by a transsphenoidal route either by endoscopic or microscopic aid. Complications such as cerebrospinal fluid (CSF) leak, meningitis, diabetes insipidus, hematoma, and loss of vision are known, but midbrain infarct is rarely reported. We report and discuss the possible mechanism of this rare and unusual complication in transsphenoidal surgery. A 36‑year‑old nulliparous female with no comorbidities suffering from primary infertility presented with intermittent headache for 9 months with bitemporal vision disturbances for 3 months, pigmentation around the neck and nape, oligomenorrhea with an established diagnosis of plurihormonal secreting pituitary tumor (predominantly adrenocorticotropic hormone and prolactin), hyperparathyroidism, and diabetes. The whole symptom fitted into the diagnosis of multiple endocrine neoplasia 1 (MEN‑1) syndrome. Molecular genetic testing was done with full gene sequencing analysis of MEN‑1 gene using polymerase chain reaction. Furthermore, Sanger DNA sequencing was done, and two novel variations, namely IVS 9c.1364 + 99C>G and EXON 10 c.1813 C>T (p. L605 L), were detected. Radiology detected a microadenoma in the right lobe of the pituitary with mild deviation of the pituitary stalk on dynamic contrast‑enhancing magnetic resonance imaging. Gross total excision of the tumor was done through transsphenoidal approach. The surgery was uneventful other than some blood‑mixed CSF leak. Post excision, fat and tissue glue was packed. The patient did not wake up from anesthesia and had bilateral dilated pupil with no oculocephalic reflex. Investigations revealed bilateral thalamic and midbrain infarct. The patient subsequently expired. This case is reported in view of its unusual complication and to create awareness for such a fatal complication following transsphenoidal surgery for pituitary microadenoma and the importance of diligent approach to transsphenoidal surgery and to report novel genetic mutation of MEN‑I gene. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are the most common lesion of the sellar region. Very few cases in the literature have described their association with craniopharyngiomas in the same anatomic compartment, an entity defined as collision tumors of the sella. A 35-year-old man presented with headaches and progressive visual disturbances. Radiographic imaging initially highlighted the presence of a pituitary craniopharyngioma. An endoscopic transsphenoidal pituitary approach was performed, during which the tumor was partially resected. The pathology report was positive for 2 entities: a nonfunctioning pituitary adenoma and a papillary craniopharyngioma. This was an unexpected diagnosis based on the surgical and initial radiologic findings. To our knowledge, this is the first documented case of a collision tumor of the sella comprising a pituitary adenoma and a craniopharyngioma of the papillary type. [ABSTRACT FROM AUTHOR]

Background: The coexistence of two morphologically different tumors attached to each other creates a very rare type of tumor called a collision tumor. Collision tumors containing pituitary adenoma-sellar meningioma have only been described in four cases to date; we discuss a fifth case harboring a collision tumor comprising a pituitary corticotroph adenoma and a sellar meningioma in the same anatomic position.Case Presentation: A 34-year-old Caucasian woman presented with menstrual irregularity, severe weakness of the proximal muscles, and 10-15 kg weight gain within a year. Basal plasma cortisol and adrenocorticotrophic hormone levels were 17.7 mg/dL and 58 pg/mL, respectively. Her diurnal cortisol rhythm was impaired (plasma cortisol at 23:00, 18.2 mg/dL) and after a 48-hour, 2-mg dexamethasone suppression test, plasma cortisol level was 13.6 mg/dL. The results were consistent with a diagnosis of Cushing's syndrome. We then performed a nocturnal 8-mg dexamethasone suppression test and the suppression of cortisol was not greater than 50% (21.4 to 19.3). A pituitary magnetic resonance imaging revealed a tuberculum sellae meningioma arising from within the sellar region. An operation was chosen in order to examine whether the tumor was an adrenocorticotrophic hormone/corticotropin-releasing hormone-secreting lesion or if there were any microadenomas that could be observed during the operation. Via an extended endoscopic endonasal approach the meningioma was resected successfully. Unexpectedly, our patient complained of nausea and vomiting postoperatively. Plasma cortisol was 2.6 mg/dL and orally administered hydrocortisone treatment was initiated immediately. Histopathological examination revealed that the tumor generally consisted of a pituitary corticotroph adenoma infiltrated by meningioma. Our patient maintained hydrocortisone treatment for 11 months. At the latest visit, she had lost 12 kg, and her hypertension, menstrual irregularity, and weakness of the proximal muscles had disappeared. Her mental and physical wellbeing were restored.Conclusions: To the best of our knowledge, this is the first report of Cushing's disease due to a pituitary corticotroph adenoma adjacent to a meningioma. Even if a high-dose dexamethasone suppression test fails to suppress basal cortisol level, the importance of considering a suprasellar/sellar meningioma a possible component of a collision tumor presenting as adrenocorticotrophic hormone-dependent Cushing's syndrome is highlighted here. [ABSTRACT FROM AUTHOR]

Pituitary apoplexy (PA) is a rare, usually vision-threatening and occasionally life-threatening entity. The exact incidence of PA in large series of pituitary adenomas is variable; however, it is more common in macroadenomas and nonfunctioning adenomas though it has been reported rarely in microadenomas. There are several well-known precipitating factors for PA including the use of anticoagulants, surgery, head trauma, pregnancy, etc. The typical clinical presentation is characterized by the near universal presence of headache with or without the following: visual disturbances, extraocular palsies, altered sensorium. MRI is the imaging modality of choice. Most patients have hormonal and/or electrolyte disturbances at the time of presentation which needs to be quickly corrected. Both conservative and surgical treatment modalities have been advised for the management of this condition. However, on the basis of the evidence available in the literature, the treatment should be individualized for each patient with PA. If conservative management is chosen, close clinical monitoring is necessary for early identification of deterioration. Surgery generally is through the trans-sphenoidal route. Most patients have a good recovery in visual function and extraocular palsy. There is some evidence in the literature that surgical intervention, when necessary, should be undertaken early as it is associated with better visual outcome. The majority of the patients will have residual hormonal deficits which will require prolonged hormone replacement therapy. There is a small but significant risk of recurrent PA in patients with residual tumors, especially, in those with large tumor residues. There is also a small risk of tumor recurrence following PA and hence all patients should undergo surveillance imaging periodically to detect the possible recurrence of tumor. In recent years, the mortality from PA has decreased significantly. A high index of suspicion and prompt multidisciplinary management will often lead to an overall good outcome. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are benign tumors arising in the adenohypophysis and comprise 8%-20% of all reported primary brain tumors in the west. Transsphenoidal surgery with an aim to achieve complete tumor resection is the recommended first-line treatment for nonfunctioning as well as secretory pituitary adenoma. External beam radiation therapy (RT) has been demonstrated to be an effective treatment modality for pituitary adenoma, uncured by surgery and/or medical therapy, providing excellent long-term local control (>90%), but lower and variable rates (50%-80%) of biochemical remission in secretory tumors. The adoption of pituitary RT in the community has been limited due to concerns regarding potential late toxicity and long latency in normalization of hormonal hypersecretion. Over the years, technological advances in RT planning and delivery have resulted in progressive conformation of high doses to the target tissues while sparing adjacent neurovascular structures providing a favorable therapeutic index. The choice of RT technique should be based on size, site, and availability of infrastructure and expertise, with no significant differences between fractionated approaches and stereotactic radiosurgery (SRS). In contemporary clinical practice, the recommended dose of fractionated RT for pituitary adenoma is 45-50.4Gy in 25-28 fractions delivered over 5-6 weeks using modern high-precision techniques. The recommended dose of SRS given in a single fraction is 12-14Gy for nonfunctioning adenomas and 16-20Gy for secretory tumors. Late toxicity of pituitary RT includes hypopituitarism, neurocognitive impairment, neuropsychological dysfunction, optic neuropathy, cerebrovascular accidents, and second malignant neoplasms. Hence, RT in pituitary adenoma should be offered only to patients with residual, recurrent, progressive, or high-risk tumors with careful assessment of the benefit-risk ratio by an experienced multidisciplinary neurooncology team. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression levels of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in pituitary adenomas (PAs), and to analyze the relationship of the expressions of the two with the prognosis of patients.Methods: A total of 108 patients with PAs diagnosed in our hospital from May 2010 to May 2012 were selected and divided into the invasive PA (IPA) group (n = 58) and the non-IPA group (n = 50) according to the invasiveness of PAs. Hematoxylin and eosin (H&E) staining was used to observe the pathological state of patients. The expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry and western blotting at protein level and reverse transcription-polymerase chain reaction at gene level, respectively. The expression levels of MMP-9 and TIMP-1 in serum of patients before operation were tested using enzyme-linked immunosorbent assay, and patients with PAs after operation were followed up.Result: The positive expression rate of MMP-9 in IPAs was significantly higher than that in non-IPAs, whereas that of TIMP-1 was relatively high in non-IPAs, and the differences were statistically significant (p < 0.05). At both protein and gene levels, MMP-9 was highly expressed in IPAs, whereas TIMP-1 was highly expressed in non-IPAs, and the differences were statistically significant (p < 0.05 in all comparisons). Before operation, the expression level of MMP-9 in serum of patients with IPAs was relatively high, whereas that of TIMP-1 in serum of patients with non-IPAs was relatively high, and the differences were statistically significant (p < 0.05 in all comparisons).Conclusion: The postoperative survival rate of patients with highly expressed MMP-9 was relatively low, whereas that of patients with highly expressed TIMP-1 was relatively high. The abnormal expressions of MMP-9 and TIMP-1 play important roles in the invasion process of PAs. The prognoses of patients with low expression MMP-9 and high expression TIMP-1 are more positive. [ABSTRACT FROM AUTHOR]

Aim: To establish the value of early contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in differentiating residual pituitary adenoma from postoperative surgical changes.Materials and Methods: Thirty patients with non-functioning pituitary macroadenomas, who were undergoing trans-sphenoidal adenomectomy, were prospectively studied. Patients were imaged with both MRI and DWI in the early postoperative period, as well as 6-months post-surgery. Patterns of postoperative contrast enhancement were described (non-enhancement, peripheral enhancement, and nodular enhancement). Apparent diffusion coefficient (ADC) maps were utilised to select the region of interest (ROI) for ADC calculations.Results: Seventeen patients had postoperative surgical granulation tissue and 13 had residual adenoma based on the 6 months follow-up imaging. Mean ADC values of postoperative granulation tissue and residual adenoma were 1.476±0.476×10-3 mm2/s and 0.855±0.190×10-3 mm2/s, respectively, in the early postoperative period, and 1.357±0.416×10-3 mm2/s and 0.829±0.201×10-3 mm2/s, respectively, at the 6-month follow-up. ADC values of granulation tissue were significantly different from that of residual adenoma at both time points (p<0.001). Sensitivity, specificity, positive and negative predictive values of early MRI were 84.6%, 94.1%, 91.7%, and 88.9% respectively, and of early DWI were 91%, 97%, 94.3%, and 93%, respectively.Conclusion: Early postoperative DWI after trans-sphenoidal resection of pituitary macroadenomas may be more helpful than early MRI in differentiating residual adenoma from post-surgical changes. [ABSTRACT FROM AUTHOR]

Background: Microscopic transsphenoidal surgery (mTSS) is a well-established method to address adenomas of the pituitary gland. Endoscopic transsphenoidal surgery (eTSS) has become a viable alternative, however. Advocates suggest that the greater illumination, panoramic visualization, and angled endoscopic views afforded by eTSS may allow for higher rates of gross total tumor resection (GTR). The aim of this meta-analysis was to determine the rate of GTR using mTSS and eTSS.Methods: A meta-analysis of the literature was conducted using PubMed, EMBASE, and Cochrane databases through July 2017 in accordance with PRISMA guidelines.Results: Seventy case series that reported GTR rate in 8257 pituitary adenoma patients were identified. For all pituitary adenomas, eTSS (GTR=74.0%; I2 = 92.1%) was associated with higher GTR as compared to mTSS (GTR=66.4%; I2 = 84.0%) in a fixed-effect model (P-interaction < 0.01). For functioning pituitary adenomas (FPAs) (n = 1170 patients), there was no significant difference in GTR rate between eTSS (GTR=75.8%; I2 = 63.9%) and mTSS (GTR=75.5%; I2 = 79.0%); (P-interaction = 0.92). For nonfunctioning pituitary adenomas (NFPAs) (n = 2655 patients), eTSS (GTR=71.0%; I2 = 86.4%) was associated with higher GTR as compared to mTSS (GTR=60.7%; I2 = 87.5%) in a fixed-effect model (P-interaction < 0.01). None of the associations were significant in a random-effect model (all P-interaction > 0.05). No significant publication bias was identified for any of the outcomes.Conclusion: Among patients who were not randomly allocated to either approach, eTSS resulted in a higher rate of GTR as compared to mTSS for all patients and for NFPA patients alone, but only in a fixed-effect model. For FPA, however, eTSS did not seem to offer a significantly higher rate of GTR. These conclusions should be interpreted with caution because of the nature of the included non-comparative studies. [ABSTRACT FROM AUTHOR]

Objective. Pituitary adenomas can be classified as clinically functional or silent. Depending on the reviewed literature, these are the first or second place in frequency of the total pituitary adenomas. Even rarer is the presence of a functional gonadotropinoma since only very few case reports exist to date. The conversion of a clinically silent to functional pituitary adenoma is extraordinarily rare; the mechanisms that explain these phenomena are unknown or not fully understood. Methods. We report the case of a woman who initially had a nonfunctional gonadotropinoma and in the course of her medical condition showed biochemical changes in her hormonal pituitary profile compatible with a functional gonadotropinoma. Results. We considered that the patient had a functional gonadotropinoma due to the hyperestrogenemia in the context of secondary amenorrhea, resolving the hyperestrogenemia after almost complete resection of the tumor. Conclusion. It is necessary to point out from a clinical and/or biochemical point of view the change in functionality that a nonfunctional pituitary adenoma may have. In the case of our patient, the suspicion of this change in functionality became evident when we found an increase in the FSH/LH ratio and a progressive increase in serum estradiol concentrations when the patient had amenorrhea. [ABSTRACT FROM AUTHOR]

Background. Treatment of aggressive pituitary adenomas typically involves a multimodality approach based on histopathological features and may include pharmacotherapy, surgery, and occasionally radiation therapy. In cases of treatment-refractory tumor progression, chemotherapy may be considered; however, no standard chemotherapeutic regimen has been established. Literature review suggests that temozolomide may have a beneficial role in a subset of cases. To understand the efficacy of temozolomide in progressive pituitary tumors, we reviewed the outcomes of cases at our center. Methods. We performed a retrospective chart review to report the outcome and unique features of 7 patients with aggressive functioning pituitary adenomas or carcinomas treated with temozolomide. Tumor pathology included somatotroph (n = 1), corticotroph (n = 3), and lactotroph (n = 3) tumors. Results. Four of the 7 patients had at least 2 prior resections, and all had prior radiation and surgery before treatment with temozolomide. Notably, all patients showed response to therapy, defined as either stable disease (43%) or partial response (57%). Median progression-free survival was 1.66 years, and median overall survival was 4 years. Conclusion. Our data suggest that temozolomide has an important role in the management of aggressive functioning pituitary tumors that are resistant to standard therapies, and that optimization of therapy with temozolomide may involve individualized regimens. Future prospective clinical trials should be considered. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the function of the prolactin/adenoma maximum diameter (PRL/MD) and the prolactin/adenoma volume (PRL/V) in the differential diagnosis of prolactinomas and other types of pituitary adenomas. A total of 118 patients with pituitary adenoma, hyperprolactinemia and a plasma PRL <250 µg/l were enrolled. Clinical data from these patients were retrospectively analyzed. A receiver operating characteristic curve was plotted. The function of PRL, PRL/MD and PRL/V in the differential diagnosis of prolactinomas and other types of pituitary adenomas was compared. The results revealed that a PRL of 55.65 µg/l was the most accurate [sensitivity (SE), 0.800; specificity (SP), 0.716; positive predictive value (PPV), 0.857; negative predictive value (NPV), 0.933; and Youden index (YI), 0.516]. The PRL/MD with the highest diagnostic value was 4.03 µg/(l x mm) (SE, 0.800; SP, 0.898; PPV, 0.727; NVP, 0.929; and YI, 0.698). The PRL/V with the highest diagnostic value was 54.00 µg/(l x cm³) (SE, 0.900; SP, 0.966; PPV, 0.900; NVP, 0.966; and YI, 0.866). The PRL/MD tended to be of higher diagnostic accuracy than PRL, but this difference was not statistically significant (P=0.097). The differentiation ability of PRL/V was significantly stronger than that of PRL (P=0.028). Thus, serum PRL, PRL/MD and PRL/V levels may be able to differentiate prolactinomas from other types of hyperprolactinemia-causing pituitary adenomas prior to treatment. PRL/V may be better than the PRL level in achieving a differential diagnosis, and the optimal PRL/V ratio for differentiating prolactinomas from other types of hyperprolactinemia-causing pituitary adenomas was 54.00 µg/(l x cm³). [ABSTRACT FROM AUTHOR]

Pituitary adenomas, the most common tumors of all intracranial neoplasms, may cause either symptoms of mass effect or symptoms of hormone abnormal production. Besides physical damages, patients with pituitary adenomas always suffer from cognitive impairments, mainly in memory and executive functions. 18 beta-glycyrrhetinic acid (GA) has been found to exhibit anti-tumor effects in rat pituitary adenoma-derived cells. The aim of this paper was to investigate the effect of GA in postoperative clinical application. In this study, we recruited 647 patients with pituitary adenoma and 135 patients who dropped out were excluded from analysis. Thus, altogether 512 patients with pituitary adenoma completed the study, of whom 268 were treated with GA, and 244 were treated with placebo. Cognitive assessments, eyesight, tumor size, and hormone secretion levels were examined before and after surgery in both groups. All patients underwent surgeries by single-nostril transsphenoidal approach for their firsttime medical treatment. Hormone secretion levels were measured by blood samples and Magnetic resonance imaging (MRI) was used for examining the status of tumor excision. Compared with placebo group, the scores in orientation, language (expression), memory (recall), practice, abstract thinking, and MiniMental State Examination (MMSE) were significantly improved (p < 0.05) in GA treated group after one month of surgery. After six months, there was still a significant increase in abstract thinking scores. Moreover, GA did not impact the overall survival percentage of patients enrolled during our five-year follow-up, but significantly reduced the recurrence rate than that of the placebo group. GA significantly improved the cognitive functions at the early stage after surgery and had a long-termed efficacy on abstract thinking. Notably, GA inhibited the five-year recurrence rate of the recruited pituitary adenomas patients. [ABSTRACT FROM AUTHOR]

Background: Pituitary macroadenoma is a common tumor of middle-aged people. Magnetic resonance imaging (MRI) is the investigation of choice for its evaluation. Various parameters regarding the extent, consistency, and contrast uptake can be studied and a noninvasive diagnosis is possible. Aims and Objectives: To study the MRI features and extent of pituitary macroadenomas. Materials and Methods: We studied clinical and MRI features of 33 patients of all age groups and both sexes with pituitary macroadenomas who presented to Dayanand Medical College and Hospital, Ludhiana from January 2014 to June 2015. MRI was carried out on MAGNETOM Avanto 18 Channel 1.5 Tesla Machine by Seimens India Ltd. The dedicated sellar protocol consisted of sagittal and coronal T1-weighted image (TI-WI) and T2-WI without intravenous contrast using thin slices (3 mm) and a field of view of <200 mm. Results: On analysis of the 33 cases, we observed that patients of pituitary macroadenoma showed an almost equal sex incidence and average age group of 50-60 years. The common presenting complaints were headache and decreased vision. Superior and inferior extent of the lesion was beyond the defined boundaries of sella in most cases, but the lateral extent was limited, resulting in characteristic "snowman-like" appearance. The imaging characteristics showed solid to predominantly solid consistency, appearing mostly heterogeneously hyperintense on T2-WI, and hypo to isointense on T1-WI with intense postcontrast enhancement. Hemorrhage is less common. Pituitary apoplexy is rare and can result in spontaneous resolution. Conclusions: We conclude that the knowledge of clinical and imaging profile of pituitary macroadenoma can help the radiologists to diagnose these sellar lesions, and hence their therapeutic approach can be defined timely. [ABSTRACT FROM AUTHOR]

The present study investigated the use of cell‑cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin‑embedded tissues obtained by surgery, with all tissues stained for cell‑cycle regulatory proteins p16, p15, p21, cyclin‑dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin‑protein ligase mib1 (MIB‑1) antigen and p53. The primary end‑point was to investigate the expression of cell‑cycle regulatory proteins in SPA. The secondary end‑point was to estimate the progression‑free survival of patients with SPA following surgical resection and to identify its association with the expression of cell‑cycle regulatory proteins. Of the 127 SPA samples, 44 (34.6%) were from patients with progression during a mean follow‑up period of 62.4 months (range, 24.2‑118.9 months). Immunohistochemical overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%) for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples (13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin D1. Multivariate analysis revealed that null cell adenoma [95% confidence interval (CI), 0.276‑0.808], somatotroph SPAs (95% CI, 1.296‑3.121), corticotroph SPAs (95% CI, 1.811‑4.078), pluripotent SPAs (95% CI, 2.264‑5.194), decreased expression of p16 (95% CI, 2.724‑5.588), overexpression of pRb (95% CI, 2.557‑5.333), cyclin D1 (95% CI, 1.894‑4.122) and MIB‑1 (95% CI, 1.561‑4.133), increased mitotic index (95% CI, 1.228‑4.079), increased p53 expression (95% CI, 1.307‑4.065) and invasion into the cavernous sinus (95% CI, 3.842‑7.502) predicted SPA progression following resection. The results of the present study suggested that specific cell‑cycle regulators, including p16, cyclin D1 and pRb, were associated with SPA progression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. Materials and Methods: We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients' age was 56 years (24–82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15–25) and the median tumor volume size was 3.4 cm3 (0.06–16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. Results: During the median follow-up period of 72 months (range 6–144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. Conclusions: In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia (MEN) refers to a group of autosomal dominant disorders with generally high penetrance that lead to the development of a wide spectrum of endocrine and non-endocrine manifestations. The most frequent among these conditions is MEN type 1 (MEN1), which is caused by germline heterozygous loss-of-function mutations in the tumor suppressor gene MEN1. MEN1 is characterized by primary hyperparathyroidism (PHPT) and functional or nonfunctional pancreatic neuroendocrine tumors and pituitary adenomas. Approximately 10% of patients with familial or sporadic MEN1-like phenotype do not have MEN1 mutations or deletions. A novel MEN syndrome was discovered, initially in rats (MENX), and later in humans (MEN4), which is caused by germline mutations in the putative tumor suppressor CDKN1B. The most common phenotype of the 19 established cases of MEN4 that have been described to date is PHPT followed by pituitary adenomas. Recently, somatic or germline mutations in CDKN1B were also identified in patients with sporadic PHPT, small intestinal neuroendocrine tumors, lymphoma and breast cancer, demonstrating a novel role for CDKN1B as a tumor susceptibility gene for other neoplasms. In this review, we report on the genetic characterization and clinical features of MEN4. [ABSTRACT FROM AUTHOR]

In contrast to the clear indication for surgical treatment in symptomatic patients with clinically nonfunctioning pituitary adenomas (NFPA), there are no randomized controlled studies comparing therapeutic strategies such as watchful waiting, irradiation or medical therapy for the management of NFPA after surgery. Further, no medical therapy is currently approved for the treatment of NFPA. In this review, we summarize accumulating data on medications currently approved for secreting pituitary adenomas, used off-label in patients with NFPA. Perspectives on overall treatment optimization and potential future therapies are also detailed. [ABSTRACT FROM AUTHOR]

Objective: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. Material and Method: The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. Results: TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). Conclusion: This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas. [ABSTRACT FROM AUTHOR]

Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X 2 = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs. [ABSTRACT FROM AUTHOR]

Objective: The aim was to assess the factors influencing the visual outcome following trans-sphenoidal excision of pituitary adenomas. Materials and Methods: One hundred consecutive patients of pituitary adenomas with suprasellar extension (SSE) were operated by trans-sphenoidal approach from July 2003 to December 2006. There were 52 male and 48 female patients with a mean age of 42.47 years. The visual impairment score, which was used to evaluate the visual outcome was produced by adding the scores for visual acuity and visual field defects of each patient (from the tables of the German Ophthalmological Society). The mean diameter, the SSE and the parasellar extension of the lesion were noted in the magnetic resonance imaging study. The average follow-up was 43.5 months. Results: The mean diameter of the tumor was 32.97 mm, and the mean SSE was 14.95 mm. The parasellar extension was present in 27 patients. The vision improved in 61 of the 71 patients (85.91%). The shorter the duration of visual symptoms and smaller the size of the lesion resulted in better visual outcome. The age and the preoperative visual impairment did not show any correlation with the visual outcome. Conclusions: Patients with visual symptoms of <1-year duration (P < 0.01) and adenomas of <36.5 mm diameter (P < 0.009) have better visual outcome. [ABSTRACT FROM AUTHOR]

Background The aim of this study is to report the results of pure endoscopic endonasal transsphenoidal surgery (EETSS) for pituitary adenomas (PAs) and to evaluate the efficacy and safety of this procedure. In addition, we tried to determine the predicting factors for progression of PAs. Methods We reviewed the medical records of 331 consecutive patients who underwent pure EETSS of newly diagnosed PAs between April 1998 and December 2014. Demographic, endocrinologic, and radiologic features and their outcomes, complications, and hospital stay durations were retrospectively assessed in these patients. Results There were 157 (47.4%) nonfunctioning adenomas and 174 (52.6%) hormone-secreting adenomas. Fifty-one (15.4%) complications were present in 39 patients postoperatively. The frequent complications were temporary and permanent diabetes insipidus (14 and 3 cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (9 cases), and cerebrospinal fluid leaks (6 cases). There was only 1 death (0.3%) related to the procedure in this series. The patient's age ( P = 0.047), the tumor size ( P = 0.003), and the parasellar growth ( P <0.001) were associated with the occurrence of complications on multivariate analysis. Progression occurred in 92 (27.8%) patients and the mean time-to-progression was 23.7 months (range, 3.7–52.4 months) after a mean follow-up period of 68.5 months. In the multivariate analysis, the tumor size ( P = 0.021), the extent of surgery ( P = 0.012), the Knosp classification ( P = 0.002), and the MIB-1 index ( P = 0.019) were associated with progression-free survival. The mean duration of hospitalization was 4.4 (±1.6) days. Conclusions The pure EETSS of PA provides acceptable and reasonable results representing a safe alternative procedure to the traditional transsphenoidal microscopic approach. [ABSTRACT FROM AUTHOR]

Pituitary incidentalomas are lesions which are detected incidentally in the pituitary gland during imaging procedures for unrelated causes, such as headache, trauma or symptoms involving the neck or central nervous system. The wide application of sensitive brain imaging techniques (CT, MRI) has led to an increasing recognition of such lesions. Although the etiology of pituitary incidentalomas covers a wide range of pathologies, most of them (∼90%) are benign adenomas; nonetheless, they may result in visual and/or neurologic abnormalities. By definition, micro-incidentalomas have maximum diameter of less than 1cm, while macro-incidentalomas are at least 1cm. Micro-incidentalomas have a reported mean prevalence in normal individuals of around 10%. The endocrinologist facing a pituitary incidentaloma has to solve two main diagnostic problems: (i) the nature and extent of the lesion, and (ii) whether hormonal excess or deficits result from the lesion. The former is achieved by the use of pituitary MRI and visual field (VF) examination and the latter by basal or dynamic hormonal assessments. The answers to these two questions will guide the treatment and follow-up. VF deficits or neurological disturbances due to compression of the optic chiasm or nerve by the incidentaloma are the strongest recommendations for surgery. Furthermore, hormonally active incidentalomas, with the exception of prolactinomas, should be treated by surgery. Most cases of pituitary incidentalomas do not meet criteria for surgical excision, but may require follow-up. The follow-up strategy consists of clinical evaluation, pituitary MRI, VF examination and hormonal assessments. Macro-incidentalomas require more extensive initial investigation, as well as closer MRI surveillance, than micro-incidentalomas. Diagnostic, treatment and follow-up strategies should be in alignment with the optimal personalized clinical benefit. [ABSTRACT FROM AUTHOR]

The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20. [ABSTRACT FROM AUTHOR]

Object, The aim of this study was to analyze a series of 28 patients with acromegaly who underwent a multimodal surgical, medical and radiosurgical therapy, with a special attention to the advantages, complications, and predictive factors of a successful outcome. Methods. 28 consecutive cases of GH-secreting pituitary adenomas, who underwent transsphenoidal endoscopic or microscopic surgery, between 1 January 2014 and 31 December 2014 were retrospectively reviewed. Tumors were classified according to the diameter, measured on MRI, as micro- or macroadenomas, and parasellar (cavernous sinus) tumor extension was analyzed based on the Knosp grading score. The mean follow-up period was of 18.4 months. Criteria justifying the complete hormonal remission were preoperative basal serum GH < 2.5 pg/ L, preoperative nadirGH < 1 ng/ L after OGTT and normal preoperative IGF-I levels age and sex-matched. Results. An overall complete hormonal remission rate was achieved in 64.3% of the patients. The remission rate was higher in patients with microadenomas (77.8%) than in those with macroadenomas (57.9%). A number of predictive factors, which might have interfered with the hormonal remission rate from a statistical, clinical and paraclinical point of view, were identified: tumor size (r = 0.625), preoperative GH serum levels (r = -0.517), cavernous sinus extension was quantified according to Knosp grading score (r = 0.469) and the degree of tumor subtotal resection (r = 0.598). Conclusions. Favorable hormonal and visual remission rates can be achieved after transsphenoidal resection of GH-secreting pituitary adenomas: however, the management remains challenging, the increased surgical experience being important for higher cure rates. If a biochemical hormonal cure is not achieved postoperatively, adjuvant medical or radio surgical therapy can be recommended. [ABSTRACT FROM AUTHOR]

Background: A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation. Method: Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [ $$ \frac{4}{3}\pi\ (a.b.c) $$], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume). Results: Ellipsoid and perimeter methods of tumour volume estimation strongly correlated ( R = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were −0.11 (95 % CI, −0.35, 0.14), −0.74 (95 % CI, −2.2, 0.74) and −1.4 (95 % CI, −6.4, 3.7) for micro-tumours, macro-tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, following a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong. Conclusions: Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities. [ABSTRACT FROM AUTHOR]

Background The goal of this study was to identify preoperative risk factors associated with increased perioperative morbidity after endoscopic pituitary surgery. Methods A retrospective review of patients undergoing endoscopic pituitary adenoma surgery between 2002 and 2014 at 6 international centers was performed. Standard demographic and comorbidity data, as well as information regarding tumor extent and treatment were collected. Logistic regression was used to examine risk factors for the following 30-day outcomes: systemic complications, intracranial complications, postoperative cerebrospinal fluid (CSF) leaks, length of hospital stay, readmission, and reoperation. Results Data was collected on 982 patients with a mean age of 52 years. The median body mass index (BMI) for all patients was 30.9 kg/m2 with 56% female. The median hospital stay was 5 days and 23.8% of patients suffered a postoperative adverse event. Systemic complications occurred in 3.2% of patients and intraventricular extension was a risk factor (odds ratio [OR] 8.9). Intracranial complications occurred in 7.3% of patients and risk factors included previous radiation (OR 8.6) and intraventricular extension (OR 7.9). Reoperation occurred in 6.5% of patients and intraventricular extension (OR 7.3) and age (<40 years, OR 3.5; 40 to 64 years, OR 3.2) were risk factors. Postoperative CSF leaks occurred in 5.5% of patients and risk factors included female gender (OR 2.4), BMI ≥ 30 (OR 2.1), age (<40 years, OR 5.3; 40 to 64 years, OR, 7.9), and intraventricular extension (OR, 9.5). Conclusion Postoperative endoscopic pituitary adenoma surgery complications are associated with tumors with intraventricular extension, preoperative radiation, as well as common patient comorbidities. Identification of these factors may permit implementation of strategies to reduce postoperative complications. [ABSTRACT FROM AUTHOR]

Objective To evaluate the safety and efficacy of the endoscopic endonasal transsphenoidal approach (EETA) for nonfunctioning pituitary adenoma (NFPA) in the elderly population. Methods We performed a retrospective review of operative cases over a 7-year period, in which 158 elderly patients (age 65 years and older) who underwent a pure EETA to remove a pituitary adenoma were identified and compared with a series of 155 younger patients (age 40–55 years) who underwent the same procedure during the same period. The medical charts of the patients were reviewed to collect demographic information, such as age, sex, clinical symptoms, tumor size, the extent of tumor resection, clinical outcome, and complications. Results In the elderly group, total resection was achieved in 120 patients (75.9%), and 124 patients (78.5%) achieved significant postsurgical visual remission. In the younger group, total resection was achieved in 119 patients (76.8%), with 126 patients (81.2%) achieving significant postsurgical visual remission. Regarding surgical complications in the elderly group, transient diabetes insipidus occurred postoperatively in 28 (17.8%) patients, and permanent diabetes insipidus occurred in 7 (4.4%) patients. Six (6.4%) patients experienced postoperative cerebrospinal fluid leakage, and new developments of anterior hypopituitarism occurred in 15 (9.5%) cases. In the younger group, 21 (13.6%) patients developed transient diabetes insipidus postoperatively, and 5 (3.2%) patients experienced permanent diabetes insipidus. Six (3.9%) patients reported postoperative cerebrospinal fluid leaks, and 13 (8.4%) patients developed a new anterior hypopituitarism. There were no cases of either carotid artery injury or death in either group. During the follow-up (mean, 32 months), 11 (6.9%) patients experienced tumor recurrence in the elderly group compared with 24 (15.5%) patients in the younger group. Of the 15 elderly patients who developed new hypopituitarism, 13 (86.7%) recovered without hormone replacement; accordingly, the rate of hypopituitarism remission was 84.6% in the younger patients. Conclusions NFPAs in the elderly can be resected via a pure endoscopic technique with low morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective: Pituitary adenomas (PA) are among the most common human neoplasms. To describe the epidemiology and assess the disease burden of clinically significant PAs, population-based studies are needed. Iceland has a small well-defined population. The aim of this study is to describe the epidemiology of PAs in Iceland over an expanded period of time. Design: This is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012. Methods: Extensive clinical information was gathered in a database. Prevalence rates for all PA subtypes were calculated along with standardized incidence rates (SIR). Sex ratios and relationships with adenoma size, age, and symptoms were assessed. Results: We identified 471 individuals: 190 men and 281 women. Total prevalence in 2012 was 115.57/100 000, prolactinomas were most prevalent (54.37/100 000) followed by non-functioning adenomas (NFPAs) (42.32/100 000). Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas (39.9%) and 11.3% had acromegaly and 5.7% Cushing's disease. Women are diagnosed younger with smaller adenomas. Total SIR has increased significantly and is now 5.8/100 000 per year. Conclusion: In this nationwide study spanning six decades, we have confirmed PAs rising prevalence and incidence rates noted in recent studies. We demonstrated higher overall prevalence and incidence rates than ever previously recorded with an increasing predominance of NFPAs, which is not explained by incidental findings alone. There is a relationship with the introduction of imaging modalities, but the vast majority of patients are symptomatic at diagnosis. This underlines the importance of increased awareness, education, and appropriate allocation of resources for this growing group of patients. [ABSTRACT FROM AUTHOR]

Background Coexisting complex visual field defects and serious ophthalmologic comorbidities make the management of the pituitary macroadenomas more challenging. Diffusion tensor imaging (DTI) magnetic resonance imaging that tracks neural fibers in the white matter has been used recently to visualize the impact of different pathologies on cranial nerves. This study explains application of anterior optic pathway tractography for patients with ophthalmologic comorbidities and pituitary adenoma. Methods Two patients with atypical visual field defects caused by nonfunctional pituitary macroadenoma and simultaneous ophthalmologic morbidities (one glaucoma and the other giant cell arteritis) were selected for surgical decompression of the anterior optic apparatus. Standard perimetry and optic pathway DTI were done preoperatively, intraoperatively, and 3 months after surgery. Results The nontypical pattern of visual field defect could not differentiate between the ophthalmologic disease and the chiasmatic compression attributable to pituitary macroadenoma as the main cause. Preoperative visual pathway DTI tractography showed lack of decussating chiasmatic fibers in both of the patients. DTI tractography revealed the reappearance of these fibers intraoperatively in one and postoperatively in the other one. Three months after surgery, the visual field and acuity improved and DTI tractography confirmed presence of crossing chiasmatic fibers. Conclusion Visual pathway DTI tractography is a promising adjunct to the standard perimetry in preoperative assessment of pituitary macroadenoma with serious ophthalmologic comorbidities. It also may be useful in the intraoperative determination of the optic pathway decompression and for following the visual outcome of these patients after surgery. [ABSTRACT FROM AUTHOR]

Introduction. Invasive tumours in Nelson’s syndrome need aggressive therapy. Recent reports have documented the efficacy of temozolomide (TMZ) in the treatment of adenomas resistant to conventional management. Objective. The review of the literature concerning TMZ treatment of atypical corticotroph adenomas and a case study of 56-year-old woman who developed Nelson’s syndrome. Treatment Proceeding. The patient with Cushing’s disease underwent transsphenoidal adenomectomy followed by a 27-month-long period of remission. Due to a regrowth of the tumor, she underwent two reoperations followed by stereotactic radiotherapy. Because of treatment failures, bilateral adrenalectomy was performed. Then she developed Nelson’s syndrome. A fourth transsphenoidal adenomectomy was performed, but there was a rapid recurrence. Five months later, she underwent a right frontotemporal craniotomy. Due to a rapid regrowth of the tumour, the patient did not receive gamma-knife therapy and was treated with cabergoline and somatostatin analogue for some time. Only TMZ therapy resulted in marked clinical, biochemical, and radiological improvement. To date, this is the first case of invasive corticotroph adenoma in Nelson’s syndrome treated with temozolomide in Poland. Conclusion. In our opinion, temozolomide can be an effective treatment option of invasive adenomas in Nelson’s syndrome. [ABSTRACT FROM AUTHOR]

Aim: To report the results of a series of patients undergoing pure endoscopic endonasal pituitary surgery and to evaluate the efficacy and safety of this procedure. Materials and methods: The data of 1,166 patients that underwent endoscopic endonasal transsphenoidal adenoma removal between December 2006 and June 2013 were retrospectively reviewed. Pre- and postoperative hormonal status (3 months after surgery) were analyzed and compared with the clinical parameters originally presented by the patients. The incidences of tumor removal, hormonal control, and tumor removal complications were retrospectively analyzed. Result: Out of 577 nonfunctioning adenomas, 180 were growth hormone (GH) secreting, 308 prolactin (PRL) secreting, 26 mixed GH/PRL adenomas, 68 adrenocorticotropin secreting, and 7 thyroid-stimulating hormone-secreting adenomas. The gross total removal of pituitary adenomas was achieved in 98 % of microadenomas, 92 % of macroadenomas, and 76 % of giant adenomas. Hormonal control was achieved in 47 (69 %) cases of ACTH adenomas, 119 (66 %) GH adenomas, 262 (85 %) PRL adenomas, and 6 (86 %) TSH adenomas. Postoperative complications were observed in 168 (14.4 %) patients. The most frequent complications were diabetes insipidus (7 %), epistaxis (1.7 %), hyposmia (1.5 %), anterior lobe insufficiency (1.3 %) ,and CSF leaks (0.6 %). Conclusion: The pure endoscopic approach is a safe, efficacious, and minimally invasive technique for the removal of pituitary adenomas. A higher gross total resection rate is vital for non-functional and functional adenomas. For patients with functional adenomas, while hormonal remission is unlikely to be achieved by surgery, the use of adjuvant therapy is advocated to obtain long-term hormonal control. [ABSTRACT FROM AUTHOR]

This study investigated quantitated expression of dopamine 2 receptor (D2R) and somatostatin receptors of the five types (SSTR1-SSTR5) in a large series of clinically non-functioning pituitary adenomas (CNFAs). Co-expression of these receptors in individual adenomas was studied as well as correlation between receptor types. Adenoma tissue from 198 patients who underwent surgery for CNFAs was analyzed by immunohistochemistry and quantitative real-time PCR. D2R and SSTR1-3 mRNA was expressed in all 198 adenomas. SSTR4 and SSTR5 were detectable in 85% and 61% of adenomas, respectively. Expression of D2R was significantly higher than that of the somatostatin receptors. The median relative expressions were as follows from highest D2R >> SSTR3 > SSTR2 > SSTR1 > SSTR5 > SSTR4. High relative expression (ratio to β-glucuronidase mRNA > 1) of D2R was found in 60% of tumors, high expression of SSTR1 in 7.5%, SSTR2 in 7%, SSTR3 in 4% and SSTR5 in 0.5%. The quantity of D2R correlated positively with expression of SSTR2 and SSTR3, and negatively with SSTR1 and SSTR5. Among histological adenoma types, SSTR1 was significantly higher in null-cell adenomas and SSTR3 was lower in silent corticotroph adenomas. In conclusions, in CNFAs, high expression of somatostatin receptors is much less common than that of D2R, and co-expression of both these receptors is exceptional. D2R and SSTR3 seem to be the most promising targets for pharmacological treatment. [ABSTRACT FROM AUTHOR]

Pituitary adenomas comprise a heterogenous group of adenohypophyseal tumours with distinct clinicopathological features across both the clinically functioning and silent groups. although, predicting a clinically aggressive course remains challenging, accurate subtyping of pituitary adenomas offers valuable prognostic information that together with other clinical and radiological information serves as a platform for tailored treatment and follow-up. For instance, silent subtype 3 pituitary adenomas, silent corticotroph adenomas, acidophil stem cell adenomas, Crooke cell adenomas, and sparsely granulated somatotroph adenomas show more invasive growth. This review has been formulated as a set of practical questions that address the distinct clinical behaviour of a selected group of pituitary adenoma subtypes. [ABSTRACT FROM AUTHOR]

Background and Objective: In 2004, the World Health Organization defined atypical pituitary adenomas as those with a Ki-67 expression >3%, an excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed typical and atypical pituitary adenomas to compare the clinical and prognostic features. Patients and Methods: We retrospectively reviewed 343 consecutive pituitary adenomas. Atypical pituitary adenomas represented 18.7% of cases. All patients were operated on at the Department of Neurosurgery of our institution and were followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. The median follow-up time was 75 months (range 7-345). Results: Younger age at diagnosis as well as immunohistochemical positivity for adrenocorticotropic hormone and prolactin correlated with a higher risk of atypical pituitary adenomas, whereas typical and atypical pituitary adenomas did not differ with regard to gender, tumor size, recurrence risk and disease-free survival time (DFST). Among the 219 patients who underwent radical surgery, a Ki-67 expression ≥1.5% was associated with a higher risk of recurrence and a worse DFST, even after correction for age at diagnosis, gender, immunohistochemical classification, tumor size, invasiveness and Knosp classification [p = 0.01; hazard ratio (HR) 2.572; 95% confidence interval (CI) 1.251-5.285). Pituitary adenomas with a Ki-67 expression ≥1.5% showed a worse DFST as compared to pituitary adenomas with a Ki-67 expression <1.5% (HR 2.166; 95% CI 1.154-4.064). Conclusion: In this series, atypical and typical pituitary adenomas did not differ with regard to recurrence and DFST. Pituitary adenomas with a Ki-67 expression ≥1.5% showed a higher recurrence risk and a worse DFST as compared to those with a Ki-67 expression <1.5%. We suggest that a Ki-67 expression ≥1.5% may be useful as a prognostic marker, though this will need to be confirmed by prospective, multicenter data. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Concomitant pituitary adenoma (PA) and Rathke’s cleft cyst (RCC) are rare. In some cases, such PA is known to produce pituitary hormones. A 53-year-old man was admitted to our hospital with a diagnosis of lacunar infarction in the left basal ganglia. Magnetic resonance imaging (MRI) incidentally showed a suprasellar mass with radiographic features of RCC. When he consulted with a neurosurgical outpatient clinic, acromegaly was suspected based on his appearance. A diagnosis of growth hormone- (GH-) producing PA was confirmed from hormonal examinations and additional MRI. Retrospectively, initial MR images also showed intrasellar mass that is compatible with the diagnosis of PA other than suprasellar RCC. The patient underwent endonasal-endoscopic removal of the PA. Since we judged that the RCC of the patient was asymptomatic, only the PA was completely removed. The postoperative course of the patient was uneventful and GH levels gradually normalized. Only 40 cases of PA with concomitant RCC have been reported to date, including 13 cases of GH-producing PA. In those 13 cases, RCC tended to be located in the sella turcica, and suprasellar RCC like this case appears rare. In a few cases, concomitant RCCs were fenestrated, but GH levels normalized postoperatively as in the cases without RCC fenestration. If radiographic imaging shows typical RCC, and PA is not obvious at first glance, the possibility of concomitant PA still needs to be considered. In terms of treatment, removal of the RCC is not needed to achieve hormone normalization. [ABSTRACT FROM AUTHOR]

A 29-year-old male patient with a functioning pituitary macroadenoma is discussed. The pituitary mass was detected by MRI after the patient presented with sudden onset of headache, suggestive of an apoplectic event. The headache resolved with analgesic medications. Within a follow-up period of one week, the pituitary mass had spontaneously regressed to nearly half its original size without any therapy. The patient never reported any visual complaints and displayed no signs of hypopituitarism. Elevated prolactin levels were present. Seven weeks after the initial event, the pituitary mass showed continued regression on MRI. Prolactin levels remained elevated. This case provides a unique look at the rapid spontaneous regression of mass effect that may occur following apoplexy of a pituitary adenoma. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor gene underlying the pituitary adenoma predisposition. Thus far, the exact molecular mechanisms by which inactivated AIP exerts its tumor-promoting action have been unclear. To better understand the role of AIP in pituitary tumorigenesis, we performed gene expression microarray analysis to examine changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in signaling cascades associated with developmental and immune-inflammatory responses. In vitro experiments showed that AIP deficiency increases intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell lines. Based on knockdown of various G protein α subunits, we concluded that AIP deficiency leads to elevated cAMP concentrations through defective Gαi-2 and Gαi-3 proteins that normally inhibit cAMP synthesis. Furthermore, immunostaining of Gαi-2 revealed that AIP deficiency is associated with a clear reduction in Gαi-2 protein expression levels in human and mouse growth hormone (GH)-secreting pituitary adenomas, thus indicating defective Gαi signaling in these tumors. By contrast, all prolactin-secreting tumors showed prominent Gαi-2 protein levels, irrespective of Aip mutation status. We additionally observed reduced expression of phosphorylated extracellular signal-regulated kinases 1/2 and cAMP response element-binding protein levels in mouse and human AIP-deficient somatotropinomas. This study implies for the first time that a failure to inhibit cAMP synthesis through dysfunctional Gαi signaling underlies the development of GH-secreting pituitary adenomas in AIP mutation carriers. [ABSTRACT FROM AUTHOR]

Background. Nonfunctioning pituitary adenomas (NFPAs) are the most common benign lesions of the pituitary gland. Objective. To describe our experience with the management of NFPA. Study Design and Methods. Retrospective evaluation of NFPA patients managed between 2008 and 2013. We analyzed data regarding clinical presentation, imaging diagnosis, hormonal status, surgical, radiotherapeutic, and pharmacological treatment, and outcome. Results. 485 patients (54% men, mean age 53±14 years) were followed for a median of 6.5 years. Visual field abnormalities and headaches were the presenting complaints in 87% and 66%, respectively. The diagnosis of NFPA was made incidentally in 6.2%, and 8% presented with clinical evidence of apoplexy. All patients harbored macroadenomas, with a median volume of 10306 mm3; 57.9% had supra- or parasellar invasion and 19.6% had tumors larger than 4 cm. Central hypothyroidism, hypogonadism, and hypocortisolism were present in 47.2%, 35.9%, and 27.4%, respectively. Surgical resection was performed at least once in 85.7%. Tumor persistence was documented in 27% and was related to the size and invasiveness of the lesion. In selected cases, radiotherapy proved to be effective in controlling or preventing tumor growth. Conclusions. The diagnosis and treatment of NFPA are complex and require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Pituitary adenoma is one of the most common intracranial neoplasms, usually presenting with endocrinopathies or visual field defects. Granulomatous hypophysitis, one of the subtypes of primary hypophysitis, is a rare neurological entity presenting as a sellar lesion with mass effect symptoms and endocrinological dysfunction. Majority of cases of primary hypophysitis are misdiagnosed as pituitary adenomas preoperatively, and histopathology is required for a definitive diagnosis. Granulomatous hypophysitis can be primary/idiopathic or secondary to a variety of causes such as infection, foreign body reactions, and systemic inflammatory conditions. The presence of tumoral microgranulomas in pituitary adenoma is exceedingly rare, having been documented only twice previously. We present a unique case of recurrent pituitary macroadenoma in a 59-year-old woman with histopathological features of idiopathic intratumoral noncaseating granulomatous inflammation. The presence of a granulomatous response in the absence of a systemic infectious or inflammatory disorder is suggestive of a local tumoral response to an as-yet unidentified antigen. [ABSTRACT FROM AUTHOR]

Abstract: Background: Very little literature exists on frequency of MGMT methylation status in pituitary adenoma. We assessed the frequency of MGMT methylation and protein expression in pituitary adenoma and correlated with patients’ age group and prognosis. Methods: Tumor tissues from 30 patients with pituitary adenoma were evaluated for MGMT promoter methylation status by methylation specific PCR method. All tumors were also immunostained with MIB-1, anti-p53 and anti-MGMT antibodies. Results: MGMT methylation status was noted in 40% of cases (7/20 non-functioning adenomas and 5/10 functioning adenomas). MGMT protein expression on IHC was noted in 72.2% of unmethylated tumors, while only 41.6% of methylated tumors demonstrated protein expression. The mean labeling index of MGMT protein was higher in unmethylated tumors as compared to the methylated group, though the difference was not statistically significant (18.6% vs 8.8%; p =0.131). Tumor regrowth occurred in four unmethylated tumors as compared to none in methylated group. Even though there was no correlation between patient age and MGMT methylation status (p =0.823), we noted that the frequency of methylation in middle age patients (between 30 and 59 yrs) was 64.7%, which was higher compared to other age groups. Conclusion: This is the first study from India showing MGMT promoter methylation status with protein expression in pituitary adenoma. We noted that tumor regrowth was higher in unmethylated tumors. [Copyright &y& Elsevier]

Pituitary adenomas are common tumors arising in adenohypophysial cells or their precursors. For improving control of the disease an early diagnosis is important. Initially considered sporadic tumors, some of them are associated with familial syndromes and their recognition and classification is also required. Morphologically, pituitary adenomas represent a heterogeneous group of tumors with several subtypes and different clinical behavior thus a precise pathological diagnosis is crucial. The simple diagnosis of pituitary adenoma is not satisfactory and the correct classification of histological subtypes may predict aggressiveness in the majority of cases. Although considered not malignant, some of them are clinically aggressive and their recognition remains a challenge. In this paper we present the recent advances in the event of improving early recognition and differential diagnosis of pituitary tumors. [ABSTRACT FROM AUTHOR]