Benign Pituitary Tumors Research Articles

Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs orGCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55years, 44% were females, and median maximal tumor diameter at presentation was 2.1cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9cm vs. 2.2cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

RARE-16. Differential expression of miRNAs in adamantinomatous craniopharynngioma reveals dysregulation of pathogenic pathways

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of target mRNAs and can control whole gene networks. ACPs are benign pituitary tumours that can result in significant morbidity and premature mortality. ACPs harbour mutations in CTNNB1 and are driven by the activation of the WNT/beta-catenin pathway. We sought to explore the expression of miRNAS in adamantinomatous craniopharyngioma (ACP) in a cohort of samples previously subjected to RNA-Seq analysis (Apps et al, Acta Neuropathologica, 2018, May;135(5):757-777). Total RNA ACP samples (n=18), non-functioning pituitary adenomas (n=3) and normal foetal pituitaries (n=3) underwent miRNA sequencing using the Qiagen miRNA library prep kit on a NextSeq 500 to a depth of 16 million reads. Differential expression was performed using DESeq2 and functional analysis with mirPath v.3. Expression of miRNAs was correlated with previously published mRNA expression We found that 210 miRNA were upregulated and 275 down regulated in ACP compared with controls (adjusted p-value <0.1). MIR-205-5p was the most upregulated miRNA (619 fold) and its expression correlated with genes expressed within the tumour epithelium (e.g. TP63). miR-375 an inhibitor of the WNT pathway was the most down regulated miRNA (361 fold). KEGG Pathway analysis identified Glycosphingolipid synthesis as the most enriched pathway targeted by upregulated miRNAs. Pathways that were enriched by down regulated miRNAs included: ECM-receptor interaction, fatty acid biosynthesis, Hippo, TGF-beta, WNT, and ErbB pathways. Down regulation of miR-132 has previously been suggested as a marker of aggressiveness in ACP, and was 16 fold down regulated (adjusted p-value<0.001) in this cohort and expression was inversely correlated with genes relating to epithelial development. This data confirms previous studies indicating that miRNA expression is altered in ACP. In silico analysis suggest that the dysregulation of miRNA affects the expression of genes involved in pathogenic pathways in ACP.

Incidence and Prognostic Factors of Patients with Benign Pituitary Tumors Based on the Surveillance, Epidemiology, and End Results (SEER) Database

To study the incidence and prognostic factors of patients with benign pituitary tumors based on the Surveillance, Epidemiology, and End Results (SEER) database. This was a retrospective cohort study. Patients with benign pituitary tumors reported in the Surveillance, Epidemiology, and End Results database from 2004 to 2016, who presented completed demographic and clinical data, were included in our study. The age-adjusted incidence rate was calculated and stratified by year at diagnosis, age, gender, and the pathological type of benign pituitary tumor. We used Kaplan-Meier curves and multivariable Cox regressions to determine the factors associated with overall survival. A total of 29,967 patients were included in the study, of whom 26,691 (89.07%) survived and 3276 (10.93%) died. The age-adjusted incidence rate increased from 3.15 per 100,000 person-years in 2004 to 4.66 per 100,000 person-years in 2011 (annual percent change= 5.51, P < 0.001), and the subsequent growth trend from 2011 to 2016 was not statistically significant (annual percent change= 0.26, P= 0.711). Most patients were female, aged 60-79 years, and pituitary adenomas accounted for the main proportion of the incidence of benign pituitary tumors. Surgery was associated with the overall survival on the multivariable Cox regression model (hazard ratio= 0.677, 95% confidential interval: 0.629-0.727) and Kaplan-Meier curves, especially in pituitary adenoma. Radiation was not associated with the overall survival of benign pituitary tumor. The overall incidence of benign pituitary tumors was low but showed an increasing trend. Surgery may be beneficial to the prognosis. It should be noted that benign pituitary tumors may not require excessive treatment, such as radiation.

Pituitary Carcinoma: Rare Disease with Difficult Diagnosis and Treatment

Although pituitary tumours are common, pituitary carcinomas are very rare. They are defined as adenohypophyseal tumours with metastatic activity within and outside the boundaries of the central nervous system (CNS). They usually spread to the other parts of the body, by the time they are diagnosed. Because so few cases of pituitary carcinoma have been reported worldwide, it is difficult to learn much about them, and it is difficult to diagnose and treat them. Pituitary carcinomas cannot be distinguished from benign pituitary tumours only on the basis of clinical findings and imaging. Presence of metastases is indicative of carcinoma. Many molecular markers for pathogenesis have been proposed, but none so far is a reliable predictor of disease progression or outcome. Treatment for pituitary carcinomas includes surgery, radiotherapy, and chemotherapy. The paucity of reported cases and literature on pituitary carcinomas renders necessary further research into underlying mechanisms, diagnostic findings, and novel molecular targets for therapy.

Distinct Histopathology Characteristics in Empty Nose Syndrome.

Empty nose syndrome (ENS) is a controversial disorder and the change of histopathology has never been discussed. This study aimed to conduct a structured histological review to improve the diagnosis and understanding of ENS. Further immunohistochemical staining of transient receptor potential channel melastatin 8 (TRPM8) was performed. A prospective case-control study in a tertiary medical center. Consecutive patients with ENS who were diagnosed and received surgical intervention after failure of conservative management were included. Patients with benign pituitary gland tumor receiving transsphenoidal excision were enrolled as control group. Biopsy of inferior turbinate was obtained during surgery for histological review and immunohistochemical staining. Seventeen patients with ENS and six patients as a control group were established for structured histological review. Patients with ENS presented significantly more squamous metaplasia, a higher rate of submucosal fibrosis, and a lower submucosal gland number grading. Additionally, a unique histological change called goblet cell metaplasia was found in the ENS group. The respiratory epitheliums of ENS were mostly intact with preservation of ciliated cells and goblet cells. The ENS group had a significantly lower expression level of TRPM8. The nasal mucosa of ENS experienced some airway remodeling and thermoreceptors downregulation, which contribute to clinical symptoms. The distinct histology of ENS included preserved respiratory epithelium and goblet cell metaplasia, accompanying with characteristics similar to atrophic rhinitis. Biopsy of the inferior turbinate may help diagnose ENS. 4 Laryngoscope, 131:E14-E18, 2021.

Contemporary Management of Clinically Non-functioning Pituitary Adenomas: A Clinical Review.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.

P1253 A case report of acromegalic cardiomyopathy with severe left ventricular hypertrophy

Abstract Introduction Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting benign pituitary tumor, with an increased production of GH and insulin-like growth factor 1 (IGF-1). One hallmark feature of the disease is acromegalic cardiomyopathy, a syndrome of progressive cardiac dysfunction characterized by left ventricular hypertrophy, diastolic dysfunction, and combined systolic and diastolic dysfunction in the very advanced stage. Clinical case A 54-year-old male with history of arterial hypertension and abnormal electrocardiogram (ECG) for more than 10 years was diagnosed with active stage of acromegaly (IGF-1-1711ng/ml, cardiac magnetic resonance (CMR) – pituitary tumor). Surgical treatment was recommended. He was referred for preoperative cardiac evaluation preceding transsphenoidal resection of a pituitary adenoma. He denied syncope or any chest pain. The standard 12-lead ECG demonstrated sinus rhythm, left atrial enlargement and left ventricular (LV) hypertrophy with deep negative T waves in V3-V6 leads. Holter monitor demonstrated episodes of non-sustained ventricular tachycardia. Transthoracic echocardiography revealed severe asymmetric LV hypertrophy without LVOT obstruction at rest and maneuver Valsalva (max. grad. – 19mm. Hg) with mildly abnormal LV ejection fraction (48%, range ≥52%), severe reduced global longitudinal strain (-8,2%, range &amp;lt;-18%) and grade II diastolic dysfunction. CMR imaging was performed. According to CMR suggested hypertrophic cardiomyopathy (HCM) demonstrating area of myocardial fibrosis on extensive late gadolinium enhancement, maximal LV wall thickness of 40 mm, increased myocardial mass (index 277g/m2, range 68–103g/m2) and mildly reduced systolic LV function (LVEF - 54%, range 57-74%). Coronary angiography did not show significant stenosis. After cardiac examination, transsphenoidal adenomectomy was done. There are currently no algorithms sudden cardiac death (SCD) for patients with acromegalic cardiomyopathy, but he was recommended implantation of cardioverter defibrillator devices on a scale for HCM (Risc SCD – 4,17%). Acromegaly-induced cardiomyopathy can mimic HCM. He was also recommended genetic typing for HCM, considering the results of MRI. Conclusion/Discussion: Reduction GLS might be expected to result in a fall in LVEF, however this is often not the case in hypertrophic LV diseases. It is important to note that measures of regional function such as myocardial strain may actually reflect global systolic function better than the ejection fraction. The results may improve our ability to provide a more accurate prognosis and better assessment of actual systolic function. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival. Abstract P1253 Figure.

Single-fraction stereotactic radiosurgery for spindle cell oncocytoma: preliminary experience and systematic review of the literature.

Spindle cell oncocytoma (SCO) is a rare benign pituitary tumor. No patient series regarding stereotactic radiosurgery (SRS) for SCO has been published. We report the clinical outcomes of SCO treated with single-fraction SRS, as well as a systematic review of the literature. Retrospective cohort series and systematic literature review. Five patients (four male, one female) having single-fraction SRS for persistent or recurrent SCO between 2002 and 2018. Median age was 56 (range 54-79) years. Pre-SRS treatments included transsphenoidal resection (TSR) (n = 3), multiple TSR (n = 1), and TSR, radiotherapy, and craniotomy (n = 1). Median target volume was 4.7 (range 1.8-8.4) cm3, with a median tumor margin dose of 17 (range 14-20) Gy. Median follow-up was 24 (range 10-69) months. All radiation-naïve patients achieved tumor control after SRS; tumor progression was noted 24months after SRS in one patient who failed prior radiotherapy. No radiation-induced complications were observed after SRS. Systematic literature review of 43 cases in addition to the five cases presented here showed that tumor progression/recurrence was more frequent after STR compared to GTR (P < 0.001). Ten previous cases of radiotherapy for SCO have been reported, but most did not detail radiation volumes, doses, or outcomes. SCO are uncommon sellar lesions with a propensity for progression or recurrence. Based on the clinically aggressive course of these tumors, adjuvant SRS after STR or at the time of tumor recurrence should be considered. Further case accumulation and follow-up is required to better understand the long-term treatment outcomes after single-fraction SRS for these rare tumors.

Clinical and functional characteristics of giant pituitary adenomas in the population of patients in the Moscow region

The aim of this study was to identify the clinical and functional features of giant pituitary tumors with different hormonal activity. We analyzed data of clinical, laboratory, and instrumental examinations of 351 patients diagnosed with pituitary macroadenomas at the Moscow Regional Research Clinical Institute in the period between 2008 and 2017: there were 144 hormonally inactive pituitary adenomas and 207 hormonally active pituitary adenomas (65 prolactinomas and 142 somatotropinomas). Among 351 patients with pituitary macroadenomas, there were 32 (9.1%) giant adenoma cases: 18 (12.5%) 144 patients with hormonally inactive pituitary adenomas and 14 (6.8%) 207 patients with hormonally active pituitary adenomas 6 (3.9%) 65 prolactinomas and 6 (2.9%) 142 somatotropinomas. The volume of giant adenomas was somewhat larger among somatotropinomas 48 926 [35 067; 97 650] mm3 and prolactinomas 36 872 [15 281; 75 102] mm3 compared to that of hormonally inactive pituitary adenomas 26 933 [21 910; 42 895] mm3. Tumors had predominant suprasellar and posterosellar growth (31 (97.8%) and 29 (90.6%) cases, respectively). The most common first patient complaints were visual impairments (59.4%) and headache and/or dizziness (43.8%). Correspondingly, due to these complaints, 16 (50%) patients first consulted an ophthalmologist. Hypopituitarism detected before any treatment was present in 16 (50%) patients. In most cases, visual impairments and headaches/dizziness were the first manifestations of giant pituitary adenomas; therefore, ophthalmologists and neurologists should always refer patients with these complaints to MRI. Patients with identified giant pituitary tumors should be referred to an endocrinologist for exclusion of hypopituitarism and, if necessary, timely prescription of hormonal therapy.

The specific features of endonasal transsphenoidal approach in surgical treatment of pituitary adenoma

Benign pituitary gland tumors (or adenomas) constitute the vast majority of all chiasmosellar tumors. There are various approaches in surgical treatment of the sella turcica pathology. Endonasal transsphenoidal approach is the method of preference. Choosing the approach to the skull base, the surgeon should carefully study the results of magnetic resonance imaging and computer-aided tomography. If there are anatomic features preventing the approach to the operated area, first of all the patient undergoes the correction of these structures. The surgical excision of pituitary adenoma through endonasal access is conditionally divided into three stages: nasal, sphenoidal and sellar. The final stage of surgical treatment is the stage-by-stage plastic surgery of the bottom of sella turcica with the layer-by-layer implantation of glue compositions and sealing the intracranial space. 12 patients diagnosed with pituitary adenoma with infra- and suprasellar growth were examined at the Chairs of Otorhinolaryngology and Neurosurgery with the participation of cytological laboratories. All the patients were examined by an otorhinolaryngologist on the 7th, 30th and 90th days after surgery. Endoscopic visualization of the surgical intervention area was performed and cytological examination of the nasal cavity secretion was made at the indicated time intervals. Therefore, it has been found that the reactive inflammatory phenomena associated with irrigation therapy were stopped by the 30th-40th day after the surgery. In 8 patients the treatment was supplemented with local antibacterial therapy, which provided the removal of the reactive inflammatory phenomena in the surgical intervention area. Therefore, all patients after endonasal transsphenoidal removal of pituitary adenoma are recommended the 30-day otorhinolaryngologists’ follow-up with the purpose of control of regeneration processes dynamics.

Newly Diagnosed Sellar Tumors in Patients with Cancer: A Diagnostic Challenge and Management Dilemma.

The use of combined positron emission tomography/computed tomography for staging in patients with cancer and the widespread use of magnetic resonance imaging has led to increased detection of incidental sellar masses. The imaging findings can be suggestive of a benign pituitary tumor, but metastasis can never be completely ruled out with noninvasive work-up. Appropriate diagnosis of sellar masses is critical, as the treatment paradigm might change in the presence of a pituitary metastasis. Definitive tissue diagnosis might prevent unnecessary radiotherapy to the skull base or the need for systemic treatment when benign pituitary disease is confirmed. A retrospective chart review from 2010 to 2015 of all patients with recently diagnosed cancer and undergoing surgery for sellar region masses was performed. There were 9 patients (3 female and 6 male) identified. Lung cancer was the primary condition in 4 patients; the remaining 5 patients had breast cancer, follicular thyroid cancer, cutaneous melanoma, colorectal carcinoma, and renal cell carcinoma. On final pathology, the sellar mass was a benign pituitary adenoma in 5 patients, metastatic cancer in 3 patients, and a granular cell tumor in 1 patient. Surgical resection of a sellar mass in patients with known cancer helps in the definitive diagnosis, relieves compressive symptoms, and avoids unnecessary empiric radiotherapy in cases of confirmed benign pituitary disease.

Diagnostic criteria in invasive pituitary adenomas

AbstractPituitary adenomas are benign pituitary primary tumors, the most frequent type of tumor in the pituitary fossa. An important part, around 1/3 of the pituitary adenomas manifests an aggressive behavior, growing faster and invading into parasellar areas (cavernous sinus, neural tissues and bones). Objectives: the first aim of this paper is to review the last findings about invasiveness diagnostic criteria, imagistic and biomarkers, which can be used in the classification of pituitary tumors and also to predict the probability of invasiveness, tumor recurrence and suspicion of malignancy. The second aim is to highlight the morphological and clinic types of invasive pituitary adenomas. Materials and methods: we performed a systematic review and analysis of the published articles, searching PubMed between January 1985 and December 2015. There were selected articles published in English, reviews and abstracts. During the advanced search type in PubMed, combinations of the following keywords were used: “pituitary adenoma”, “invasive”, “aggressive”, “biomarkers”, “classification”, “histological subtypes”, ‘”immunohistochemical markers”. Results: 215 articles were selected, regarding diagnostic, prognostic and therapeutic aspects. There were some histological subtypes of pituitary adenomas known as having an aggressive clinical behavior. Several biomarkers were identified as being associated with the invasive feature: proliferation markers (Ki-67 index, number of mitoses, p53 &amp; p27 expression, microvascularization density, telomerase, topoisomerase 2 Alpha), matrix metalloproteinases, protein kinase C, cyclooxygenase-2, E-cadherin, transcription Factors, genetic alterations (PTTG gene, Galectin-3 protein/ LGALS3 gene), apoptosis markers. Based on their invasion and proliferation characteristics, pituitary tumors are proposed to be classified into five grades (1a, 1b, 2a, 2b, 3), the grade 2b tumor with high risk of recurrence being considered as tumor suspected of malignancy. Conclusions: Using a set of specific biological markers for invasive process, there is hope to establish an early diagnosis and prevention of invasive pituitary adenomas. Due to the fact that aggressive pituitary tumors are generally difficult to manage, unresponsive to therapy, quickly recurrent and associated with poor prognosis, the early diagnosis and the search for new therapeutic approaches is becoming mandatory. Instead of using “invasive” or “aggressive” adenoma, the term “tumor suspected of malignancy” would be used for more accuracy

Newly Diagnosed Sellar Tumors in Patients with Cancer. Advantages of Surgical Intervention Over Empiric Radiotherapy

Introduction: The use of imaging modalities like PET/CT and MRI for staging in cancer patients has led to increased incidence of incidental detection of sellar masses. Imaging findings can be suggestive of a benign pituitary tumor but metastasis can never be completely ruled out. Appropriate diagnosis of these sellar lesions is critical as the treatment paradigm might change in the presence of pituitary metastasis. Moreover definitive diagnosis might avoid radiotherapy to the skull base or even the need for systemic treatment when benign pituitary disease is confirmed.

Managing Prolactinomas during Pregnancy.

Prolactinomas are the most prevalent functional benign pituitary tumors due to a pituitary micro- or macroadenoma. The majority of patients presents with infertility and gonadal dysfunction. A dopamine agonist (DA) (bromocriptine or cabergoline) is the treatment of choice that can normalize prolactin levels, reduce tumor size, and restore ovulation and fertility. Cabergoline generally preferred over bromocriptine because of its higher efficacy and tolerability. Managing prolactinomas during pregnancy may be challenging. During pregnancy, the pituitary gland undergoes global hyperplasia due to a progressive increase in serum estrogens level that may lead to increase of the tumor volume with potential mass effect and visual loss. The risk of tumor enlargement may occur in 3% of those with microadenomas, 32% in those with macroadenomas that were not previously operated on, and 4.8% of those with macroadenomas with prior ablative treatment. Though both drugs appear to be safe during pregnancy, the data on fetal exposure to DAs during pregnancy have been reported with bromocriptine far exceeds that of cabergoline with no association of increased risk of pregnancy loss and premature delivery. It is advisable to stop the use of DAs immediately once pregnancy is confirmed, except in the case of women with invasive macroprolactinomas or pressure symptoms. This review outlines the therapeutic approach to prolactinoma during pregnancy, with emphasis on the safety of available DA therapy.

Pituitary gene expression differs in D-galactose-induced cell senescence and steroid-induced prolactinomas.

In general, pituitary tumors are benign with low mitotic activity. Premature senescence has been considered to be a significant mechanism underlying this uniquely benign pituitary tumor. The present study aims to compare the expression of the associated proteins involved in premature senescence pathways among normal, aging and pituitary adenoma cells. We successfully induced the aging pituitary using continuous D‑galactose (D‑gal) injection as well as a prolactin‑secreting pituitary tumor via diethylstilbestrol implants. Compared with normal pituitary cells, the aging pituitary tissues revealed increased expression of IL‑6, C/EBPβ, p53, p21 and p16 and decreased expression of pituitary tumor transforming gene. In contrast, the expression of IL‑6, p21 and p16 was decreased in pituitary tumor cells compared with normal pituitary tissues. Taken together, multiple pathways including IL‑6/C/EBPβ, p53/p21 and p16 were activated in aging pituitary cells in response to D‑gal treatment. However, all these pathways were immune to pituitary tumors treated by chronic estrogen. The findings and the involvement of cytokines in a highly prevalent natural disease model (pituitary adenomas) indicate a potential use of this pathway as a target for effective therapy for tumor silencing and prevention of adenoma progression towards malignancy.

Sca1+ murine pituitary adenoma cells show tumor-growth advantage

The role of tumor stem cells in benign tumors such as pituitary adenomas remains unclear. In this study, we investigated whether the cells within pituitary adenomas that spontaneously develop in Rb+/- mice are hierarchically distributed with a subset being responsible for tumor growth. Cells derived directly from such tumors grew as spheres in serum-free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor. Some cells within growing pituitary tumor spheres (PTS) expressed common stem cell markers (Sca1, Sox2, Nestin, and CD133), but were devoid of hormone-positive differentiated cells. Under subsequent differentiating conditions (matrigel-coated growth surface), PTS expressed all six pituitary hormones. We next searched for specific markers of the stem cell population and isolated a Sca1(+) cell population that showed increased sphere formation potential, lower mRNA hormone expression, higher expression of stem cell markers (Notch1, Sox2, and Nestin), and increased proliferation rates. When transplanted into non-obese diabetic-severe combined immunodeficiency gamma mice brains, Sca1(+) pituitary tumor cells exhibited higher rates of tumor formation (brain tumors observed in 11/11 (100%) vs 7/12 (54%) of mice transplanted with Sca1(+) and Sca1(-) cells respectively). Magnetic resonance imaging and histological analysis of brain tumors showed that tumors derived from Sca1(+) pituitary tumor cells were also larger and plurihormonal. Our findings show that Sca1(+) cells derived from benign pituitary tumors exhibit an undifferentiated expression profile and tumor-proliferative advantages, and we propose that they could represent putative pituitary tumor stem/progenitor cells.

Reconstructed bone chip detachment is a risk factor for sinusitis after transsphenoidal surgery

Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. Prospective cohort study. We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July 2011. All patients were followed up with nasal endoscopy for at least 6 weeks. Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis.

Cerebrovascular complications and utilization of endovascular techniques following transsphenoidal resection of pituitary adenomas: a study of the Nationwide Inpatient Sample 2001–2010

Cerebrovascular complications following transsphenoidal resection of pituitary tumors are rare and often evaluated and treated with endovascular techniques. We determined the utilization rate and outcomes of endovascular procedures in transsphenoidal pituitary resection patients using an administrative database. Using the Nationwide Inpatient Sample 2001-2010, patients receiving transsphenoidal resection of benign pituitary tumors were identified. The rate of cerebrovascular complications and utilization of endovascular repair procedures and cerebral angiography were compared between high (≥ 75 procedures/year) and low volume (<75 procedures/year) centers. Chi squared tests were used to compare categorical variables. 70,878 were patients included in this study. ICH/SAH occurred in 0.9 % of patients (652/70,878) and stroke occurred in 0.5 % of patients (327/70,878). Patients treated at high volume centers had significantly lower rates of stroke (0.5 % vs. 1.0 %, P = 0.04), and ICH/SAH (0.5 vs. 1.0 %, P = 0.05) when compared to patients treated at low-volume centers. Overall, 531 patients (0.7 %) received post-operative angiography and 83 patients (0.1 %) received endovascular repair procedures. High volume center patients underwent angiography in 0.4 % of cases compared to 0.9 % for low volume center patients (P = 0.02). There was no significant difference in endovascular repair procedure rates at high and low volume centers (0.1 vs. 0.2 %, P = 0.37). Cerebrovascular surgical complications requiring cerebral angiography and endovascular repair are rare among transsphenoidal pituitary resection patients. These occur with higher frequency at low volume centers and are associated with high mortality rates.

Hyperprolactinemia: Diagnosis and treatment principles

Prolactin (PRL) is a peptide hormone that consists of 198 aminoacids and synthesizes in lactotrophs which present about 20 % of cells in hypophysis. The levels of prolactin can be increased due to physical and psychological stress, temperature, increased physical activity, general anesthesia, acute coronary syndrome and meals. The secretion of prolactin is under tonic inhibitory control by hypothalamic dopamine. Prolactinomas are benign pituitary tumors of lactotrophs in adenohypophysis, with unknown etiology. Clinical symptoms and signs of hyperprolactinemia in women include amenorrhea, infertility, and galactorrhea, and decreased libido and visual impairment in men. Dopamine agonists decrease tumor mass in the majority of patients and are used as the primary therapy. The therapy should be initiated at a low dose, which should be increased slowly to minimize side effects, such as gastrointestinal symptoms and orthostatic hypotension. Pituitary function should be tested in patients with micro and macroadenomas until normalizing PRL level and recovering hypogonadism. Repeat MR of hypophysis and visual field testing are mandatory when tumors are adjacent to the optic chiasm. Dopamine agonists are not approved for use during pregnancy and should be discontinued once pregnancy occurs. A normal serum prolactin level is the goal in treating hyperprolactinemia, decreasing galactorrhea and symptoms of hypogonadism, as well as reduction of tumor mass. Dopamine agonists are recommended for first-line therapy and typically decrease both prolactin levels and tumor mass, thereby relieving symptoms.

Update on feline acromegaly

Feline acromegaly is a clinical syndrome resulting from excess growth hormone production (hypersomatotropism). In most cats, this is caused by a functional benign pituitary tumour. Although the condition was previously thought to be rare, recent studies suggest that its prevalence among diabetic cats has been underestimated, and it could therefore account for diabetes mellitus in a proportion of the cat population. This might be related to the existence of subtle phenotype variants of the disease. Small animal practitioners dealing with diabetic cats should therefore be aware of the condition and consider screening for it. Once treated successfully, diabetic remission might ensue. This article considers the aetiology, pathogenesis, diagnosis and treatment options of feline hypersomatotropism and acromegaly.