Treatment Of Pituitary Adenomas Research Articles

Analysis of neuroendoscopy forthe treatment of macroadenomas and giant pituitary adenomas.

ObjectiveThis study investigated the use and effectiveness of endoscopic transnasal, transsphenoidal surgery, a minimally invasive method for the treatment of macroadenomas and giant pituitary a denomas, in a medical setting. The surgical results of 429 patients who received neuroendoscopic treatment of macroadenomas or giant pituitary adenomas were evaluated, and the experiences and lessons learned from treatment complications were assessed.Patients and methodsFrom January 2012 to December 2021, 429 patients with macroadenomas or giant pituitary adenomas, including 60 patients with giant adenomas (diameter ≥4 cm) and 369 patients with macroadenomas (diameter 1–4 cm), received a 3D head CT, a MRI with contrast enhancement, and an endocrinology examination prior to surgery. Preoperative clinical and radiological features, visual measurements, hormone levels, length of stay, length of surgery, postoperative stay, visual and hormone outcomes, resection range, complication and recurrence rates, and routine patient information were recorded. The patients were followed up for 6–72 months (median = 40 months).ResultsOf 429 patients with macroadenomas or giant pituitary adenomas who received neuroendoscopic treatment, 348 (81.12%) had gross-total resections (GTR), 53 (12.35%) had near-total resections (NTR), and 28 (6.53%) had subtotal resections. There were 138 cases of post-operative diabetes insipidus (32.17%), including 7 cases of permanent diabetes insipidus (1.63%), 16 cases of nasal hemorrhage (3.73%), 39 cases of intraoperative cerebrospinal fluid leakage (9.09%), 4 cases of intracranial infection (0.9%), 16 cases of hypophysis (3.7%), and 15 cases of anosmia (3.50%). The clinical symptoms and endocrinology indices of the patients improved after surgery, and all patients were discharged 5–18 days (8.36 ± 2.65) postop.ConclusionNeuroendoscopy is a safe operation with a short recovery period and hospital stay and is thus an effective method to treat macroadenomas and giant pituitary adenomas. Preoperative evaluation and prediction can help to accurately address possible intraoperative situations and improve GTR.

Treatment of non-functioning pituitary adenoma with cabergoline: a systematic review and meta-analysis.

To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. PROSPERO CRD42020206778.

β-Catenin is reduced in membranes of human prolactinoma cells and it is inhibited by temozolomide in prolactin secreting tumor models.

Prolactinomas are the most frequent pituitary tumor subtype. Despite most of them respond to medical treatment, a proportion are resistant and become a challenge in clinical management. Wnt/β-Catenin pathway has been implicated in several cancers including pituitary tumors and other sellar region malignancies. Interestingly, Wnt/β-Catenin inhibition augments the cytotoxicity of the chemotherapeutic agent Temozolomide (TMZ) in different cancers. TMZ is now being implemented as rescue therapy for aggressive pituitary adenoma treatment. However, the molecular mechanisms associated with TMZ action in pituitary tumors remain unclear. Our aims in the present study were to evaluate differential β-Catenin expression in human resistant prolactinomas and Wnt/β-Catenin signaling activation and involvement in Prolactin (PRL) secreting experimental models treated with TMZ. We first evaluated by immunohistochemistry β-Catenin localization in human resistant prolactinomas in which we demonstrated reduced membrane β-Catenin in prolactinoma cells compared to normal pituitaries, independently of the Ki-67 proliferation indexes. In turn, in vivo 15 mg/kg of orally administered TMZ markedly reduced PRL production and increased prolactinoma cell apoptosis in mice bearing xenografted prolactinomas. Intratumoral β-Catenin strongly correlated with Prl and Cyclin D1, and importantly, TMZ downregulated both β-Catenin and Cyclin D1, supporting their significance in prolactinoma growth and as candidates of therapeutic targets. When tested in vitro, TMZ directly reduced MMQ cell viability, increased apoptosis and produced G2/M cell cycle arrest. Remarkably, β-Catenin activation and VEGF secretion were inhibited by TMZ in vitro. We concluded that dopamine resistant prolactinomas undergo a β-Catenin relocalization in relation to normal pituitaries and that TMZ restrains experimental prolactinoma tumorigenicity by reducing PRL production and β-Catenin activation. Together, our findings contribute to the understanding of Wnt/β-Catenin implication in prolactinoma maintenance and TMZ therapy, opening the opportunity of new treatment strategies for aggressive and resistant pituitary tumors.

Pasireotide-Induced Shrinkage in GH and ACTH Secreting Pituitary Adenoma: A Systematic Review and Meta-Analysis.

IntroductionPasireotide (PAS) is a novel somatostatin receptor ligands (SRL), used in controlling hormonal hypersecretion in both acromegaly and Cushing’s Disease (CD). In previous studies and meta-analysis, first-generation SRLs were reported to be able to induce significant tumor shrinkage only in somatotroph adenomas. This systematic review and meta-analysis aim to summarize the effect of PAS on the shrinkage of the pituitary adenomas in patients with acromegaly or CD.Materials and methodsWe searched the Medline database for original studies in patients with acromegaly or CD receiving PAS as monotherapy, that assessed the proportion of significant tumor shrinkage in their series. After data extraction and analysis, a random-effect model was used to estimate pooled effects. Quality assessment was performed with a modified Joanna Briggs’s Institute tool and the risk of publication bias was addressed through Egger’s regression and the three-parameter selection model.ResultsThe electronic search identified 179 and 122 articles respectively for acromegaly and CD. After study selection, six studies considering patients with acromegaly and three with CD fulfilled the eligibility criteria. Overall, 37.7% (95%CI: [18.7%; 61.5%]) of acromegalic patients and 41.2% (95%CI: [22.9%; 62.3%]) of CD patients achieved significant tumor shrinkage. We identified high heterogeneity, especially in acromegaly (I2 of 90% for acromegaly and 47% for CD), according to the low number of studies included.DiscussionPAS treatment is effective in reducing tumor size, especially in acromegalic patients. This result strengthens the role of PAS treatment in pituitary adenomas, particularly in those with an invasive behavior, with progressive growth and/or extrasellar extension, with a low likelihood of surgical gross-total removal, or with large postoperative residual tissue.Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022328152, identifier CRD42022328152

Second brain tumours after pituitary irradiation: lower risk than once thought

Since its first proposal in the treatment of pituitary tumours more than a century ago, indications for cranial radiotherapy have notably evolved. In rare pituitary carcinomas, indication of radiotherapy remains undisputable after surgical treatment in case of remnant tumour or recurrence. Until the availability of effective medical treatment, radiotherapy was the second-line treatment for many secreting pituitary adenomas after surgery. Thanks to the use of cabergoline, which controls prolactin secretion and is able to shrink even giant macroprolactinomas, nowadays, radiotherapy is hardly ever proposed. 1 Chanson P Maiter D Prolactinoma. in: Melmed S The pituitary. 5th ed. Academic Press, London2022: 495-543 Google Scholar In patients with acromegaly, with the availability of somatostatin receptor ligands and growth hormone receptor antagonists, the indication of radiotherapy in patients in whom surgery was unable to achieve cure of the disease, has also clearly decreased over time. 2 Maione L Chanson P National acromegaly registries. Best Pract Res Clin Endocrinol Metab. 2019; 33101264 Crossref PubMed Scopus (37) Google Scholar In patients with non-functioning pituitary adenomas, indications for radiotherapy have also evolved—while it was routinely administered after surgery some decades ago, it is now reserved to patients with a postoperative remnant, with its timing, immediately after, or only in case of remnant regrowth, being a matter of debate. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar Indeed, even if the efficacy of radiotherapy is remarkable for achieving local control of pituitary tumours (roughly 90% of cases), 4 Loeffler JS Shih HA Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab. 2011; 96: 1992-2003 Crossref PubMed Scopus (151) Google Scholar the issue of side effects and particularly late toxicities long after radiation exposure has somewhat dampened the enthusiasm for this technique. The main adverse effect of radiotherapy is the occurrence of anterior pituitary hormone deficiency in about 30% of individuals at 5 years and 50% at 10 years after fractionated radiotherapy, respectively. 3 Chanson P Dormoy A Dekkers OM Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas. Eur J Endocrinol. 2019; 181: 1-13 Crossref PubMed Scopus (15) Google Scholar , 5 Fernandez A Brada M Zabuliene L Karavitaki N Wass JA Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009; 16: 733-772 Crossref PubMed Scopus (68) Google Scholar Whether or not radiotherapy technical refinement (eg, use of fractionated stereotactic radiotherapy or radiosurgery) will decrease this rate remains to be determined. Optic neuropathy, another side effect of radiotherapy, is nowadays quite rare, thanks to the limited radiation dose administered to the optic chiasm, as a result of improvements in radiotherapy techniques. But one of the main concerns with radiotherapy was the potential occurrence of secondary brain tumours, 6 Yamanaka R Abe E Sato T Hayano A Takashima Y Secondary intracranial tumors following radiotherapy for pituitary adenomas: a systematic review. Cancers (Basel). 2017; 9: 103 Crossref Scopus (27) Google Scholar some being devastating (eg, glioblastomas) when radiotherapy had been used in these patients for treating a benign condition. However, in clinical practice, this adverse effect seemed to be much more exceptional than previously reported. Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillanceIrradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. Full-Text PDF Open Access

Pituitary adenoma & nuclear medicine: Recent outcomes and ongoing developments

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

Long-term hormonal and imaging outcomes of adjunctive gamma knife radiosurgery in non-functioning pituitary adenomas: a single center experience.

Gamma Knife Radiosurgery(GKRS) is an established modality for treatment of non-functioning pituitary adenomas(NFPA). The objective of the study was to assess long-term hormonal and imaging outcomes after adjunctive GKRS in patients with NFPA. A retrospective review of records of 109 patients with NFPA, from 1996 to 2020, who received adjunctive GKRS, was performed. Patients who had received GKRS as the primary modality of treatment for NFPA were not included. Sixty-three (57.8%) patients were available for follow up at our institute. The median follow-up period was 47months (range, 6-260). At a median time of 38months (range, 8-97), 25 (39.7%) patients developed ≥ 1 new pituitary hormone deficiency. Median time to cortisol deficiency was 38months (range, 8-55), thyroid hormone deficiency was 45.5months (range, 12-97) and gonadotropin deficiency was 45months (range, 21-75). The actuarial risk of developing a new pituitary hormone deficit at 1, 3, 5, 7, and 10years was 2.5%, 11%, 26.3%, 28% and 29.7%, respectively. Adenoma size decreased in 36 (57.1%) patients, remained unchanged in 19 (30.2%) patients, and increased in 8 (12.7%) patients. Overall tumor control rate was 87.3%. Endocrinopathy-Free Survival was 47.1%, and tumor Progression-Free Survival was 93.3%, at 5years. Five (4.6%) patients required additional treatment after GKRS. One (1.6%) patient each had worsening of headache, optic atrophy and cerebellar infarct after GKRS therapy. GKRS offers a safe adjunctive treatment modality, with satisfactory long-term preservation of hormone functions and a high rate of tumor control, in patients with NFPA.

Deep Learning model-based approach for preoperative prediction of Ki67 labeling index status in a noninvasive way using magnetic resonance images: A single-center study

ObjectivesKi67 is an important biomarker of pituitary adenoma (PA) aggressiveness. In this study, PA invasion of surrounding structures is investigated and deep learning (DL) models are established for preoperative prediction of Ki67 labeling index (Ki67LI) status using conventional magnetic resonance (MR) images. MethodsWe reviewed 362 consecutive patients with PAs who underwent endoscopic transsphenoidal surgery, of which 246 patients with primary PA are selected for PA invasion analysis. MRI data from 234 of these PA patients are collected to develop DL models to predict Ki67LI status, and DL models were tested on 27 PA patients in the clinical setting. ResultsPA invasion is observed in 46.8% of cases in the Ki67 ≥ 3% group and 33.3% of cases in the Ki67 < 3% group. Three deep-learning models are developed using contrast-enhanced T1-weighted images (ceT1WI), T2-weighted images (T2WI), and multimodal images (ceT1WI+T2WI), respectively. On the validation dataset, the prediction accuracy of the ceT1WI model, T2WI model, and multimodal model were 87.4%, 89.4%, and 89.2%, respectively. In the clinical test, 27 MR slices with the largest tumors from 27 PA patients were tested using the ceT1WI model, T2WI model, and multimodal model, the average accuracy of Ki67LI status prediction was 63%, 77.8%, and 70.4%, respectively. ConclusionPreoperative prediction of PA Ki67LI status in a noninvasive way was realized with the DL model by using MRI. T2WI model outperformed the ceT1WI model and multimodal model. This end-to-end model-based approach only requires a single slice of T2WI to predict Ki67LI status and provides a new tool to help clinicians make better PA treatment decisions.

Transsphenoidal Surgery of Giant Pituitary Adenoma: Results and Experience of 239 Cases in A Single Center.

BackgroundTranssphenoidal surgery (TSS) is first-line treatment for giant pituitary adenomas (PAs). Although PA is a benign neuroendocrine tumor that originates from adenohypophysial cells, the surgical outcomes and prognosis of giant PAs differ significantly due to multiple factors such as tumor morphology, invasion site, pathological characteristics and so on. The aim of this study was to evaluate surgical outcomes of giant PAs in a single-center cohort.MethodsThe clinical features and outcomes of 239 patients with giant PA who underwent sphenoidal surgery at the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2021 were collected from medical records. The basic clinical information (age, gender, function etc.), surgical procedure, imaging features (maximum diameter, invasion characteristics, tumor shape etc.) and histopathological characteristics (pathological results, Ki-67, P53 etc.) were retrospectively reviewed. SPSS 25.0 and Stata 12.0 software were used for statistical analysis.ResultsA total of 239 patients with giant PAs underwent TSS, of which 168 surgeries (70.29%) were endoscopic endonasal transsphenoidal (EETS) and 71 (29.71%) were microscopic transsphenoidal (MTS). The mean preoperative maximum diameter in the cohort was 45.64 mm. Gross-total resection was achieved in 46 patients (19.25%), near-total in 56 (23.43%), subtotal in 68 (28.45%), and partial in 69 (28.87%) patients. The maximum tumor diameter and Knosp grade were the significant factors that limited the extent of the resection of giant PAs. A total of 193 patients (80.75%) experienced surgical complications, and the most common complications were postoperative diabetes insipidus (DI) (91, 38.08%), intracranial infection (36, 15.06%) and cerebrospinal fluid (CSF) leaks (37, 15.48%). In addition, there was a significant difference in the incidence of CSF leaks between the neuroendoscopy group and the microscopic group (P < 0.05).ConclusionThe management of giant PAs remains a therapeutic challenge due to their large size and postoperative complications. The maximum diameter and Knosp grade of giant PAs significantly limited the extent of resection, which warrants a reasonable surgical plan.

Long non-coding RNA LINC01004 promotes malignant behaviors of pituitary adenoma via miR-323a-3p/136–5p/RCN2 axis

Pituitary adenoma (PA) is a common intracranial tumor, and its incidence has been on the rise in recent years. Pituitary tumor not only causes intracranial space occupying signs, but also produces endocrine disorders, such as infertility, sexual dysfunction, facial and limb changes. Moreover, it destroys the internal environment stability and even affects the appearance of a person. However, the mechanism of PA is not fully understood. Previous research has confirmed that the expression or role of long non-coding RNA is closely connected with the occurrence of human diseases. In this study, we discovered that long intergenic non-protein coding RNA 1004 (LINC01004) was aberrantly up-regulated in PA cells. Functional assays manifested that LINC01004 promoted malignant behaviors of PA cells in vitro and growth of PA in vivo. By using bioinformatics tools and a series of mechanism assays, LINC01004 was identified to sponge miR-323a-3p/miR-136–5p to enhance the expression of RCN2 in PA. In conclusion, the results provided in this study revealed a novel regulatory mechanism of LINC01004 in PA, which might be helpful for the treatment of PA and supply a new thought for further research of PA.

Results of Resection of Giant Pituitary Adenomas through Endoscopic Endonasal Approach

Background/Objective: A minimally invasive surgical method is in use to create endoscopic transsphenoidal surgery. Because of the intricate dissection of the sellar region, surgical treatment of large pituitary adenomas is challenging. The study focused to determine the frequency of complications after endonasal endoscopic transsphenoidal resection of giant pituitary macroadenomas.&#x0D; Materials and Methods: A descriptive case series study was conducted at the Neurosurgical Department of Lahore General Hospital, Lahore. A total of 70 patients fulfilling the selection criteria were enrolled. Major vascular injury was noted when there is an injury to the internal carotid artery or cavernous sinus. After discharge, patients were followed-up in OPD for 3 months. After 3 months, patients were evaluated for CSF leak and vision. The presence of complications was recorded. During surgery, operative time was noted.&#x0D; Results: Mean age of patients was 55.7 ± 6.5 years. 45.71% of patients were male while the remaining 54.29% of patients were female Total of 41.43% of patients had disease &lt; 2 years, whereas the duration of surgery was ? 3 hours in 64.3% of patients. A total 15.71% had complications which included diabetes insipidus (8.57%), infections (5.71%), pituitary dysfunction (4.29%), CSF leak (2.8%) and vascular injury (1.43%). The mortality rate was 1.43%.&#x0D; Conclusion: The complication rate after endonasal endoscopic transsphenoidal resection of giant pituitary macroadenomas was high.&#x0D; Keywords: Endonasal Endoscopic, Transsphenoidal Resection, Pituitary Macroadenomas, Complications

Growth hormone secreting pituitary adenomas show distinct extrasellar extension patterns compared to nonfunctional pituitary adenomas.

Patterns of extension of pituitary adenomas (PA) may vary according to PA subtype. Understanding extrasellar extension patterns in growth hormone PAs (GHPA) vis-a-vis nonfunctional PAs (NFPAs) may provide insights into the biology of GHPA and future treatment avenues. Preoperative MR imaging (MRI) in 179 consecutive patients treated surgically for NFPA (n = 139) and GHPA (n = 40) were analyzed to determine patterns of extrasellar growth. Extension was divided into two principal directions: cranio-caudal (measured by infrasellar/suprasellar extension), and lateral cavernous sinus invasion (CSI) determined by Knosp grading score of 3-4. Suprasellar extension was defined as tumor extension superior to the tuberculum sellae- dorsum sellae line, and inferior extension as invasion through the sellar floor into the sphenoid sinus or clivus. Categorical analysis was performed using Fisher's exact test. GHPAs were overall more likely to remain purely intrasellar compared to NFPA (50% vs 26%, p < 0.001). GHPAs, however, were 7 times more likely to exhibit isolated infrasellar extension compared to NFPA (20% vs 2.8%, p = 0.001). Conversely, NFPAs were twice as likely to exhibit isolated suprasellar extension compared to GHPA (60% vs 28%, p < 0.001), as well as combined suprasellar/infrasellar extension (25% vs 3%, p = 0.011). There were no overall differences in CSI between the two subgroups. GHPA and NFPA demonstrate distinct extrasellar extension patterns on MRI. GHPAs show proclivity for inferior extension with bony invasion, whereas NFPAs are more likely to exhibit suprasellar extension through the diaphragmatic aperture. These distinctions may have implications into the biology and future treatment of PAs.

Endoscopic approach for giant pituitary adenoma: clinical outcomes of 205 patients and comparison of two proposed classification systems for preoperative prediction of extent of resection.

Giant pituitary adenoma is considered a challenging pathology for surgery owing to its complications and low resection rate. In this study, the authors present their experience of using the endoscopic endonasal approach to treat patients with giant pituitary adenoma, and they aimed to develop a classification system for prediction of extent of resection. The institutional medical records of patients diagnosed with giant pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery between August 1997 and December 2019 were retrospectively reviewed. Surgical and clinical outcomes were evaluated in detail. The effects of tumor characteristics on extent of resection were analyzed. The findings were used to develop two classification systems that could preoperatively predict extent of resection. Morphological score was based on tumor characteristics, and landmark-based classification was defined according to surgical zones based on neurovascular landmarks. The effects of change in surgical strategy, which aimed to maximize tumor resection and capsule dissection, on rates of resection and complications were evaluated before and after 2017. This study included 205 patients, with a mean patient age of 46.95 years and mean preoperative tumor diameter of 46.56 mm. Gross-total resection (GTR) was achieved in 35.12% of patients, near-total resection (NTR) in 39.51%, and subtotal resection (STR) in 25.36%. Extent of resection differed significantly between the grades and zones of the classification systems (p < 0.001 for both). Among patients with grade 3 tumor, 75.75% of patients achieved STR, 21.21% achieved NTR, and 3.03% achieved GTR. Among patients with zone 3 tumor, 65.75% achieved STR, 32.87% achieved NTR, and 1.36% achieved GTR. Both grade 3 and zone 3 indicated limited extent of resection. The mean (range) follow-up duration was 50.16 (9-247) months. Postoperative recovery of at least one hormone axis was seen in 15.24% of patients with pituitary deficiency, and development of new hormonal deficiency was observed in 22.43% of patients. Complications included permanent diabetes insipidus (7.80%), cerebrospinal fluid leakage (3.90%), postoperative apoplexy (3.90%), meningitis (3.41%), and epistaxis (3.41%). The surgical mortality rate was 1.46%. Among 85 patients treated before 2017, 27.05% of patients achieved GTR, 37.64% achieved NTR, and 35.29% achieved STR; among 120 patients treated after 2017, 40.83% achieved GTR, 40.83% achieved NTR, and 18.33% achieved STR. Seven patients in the pre-2017 cohort had postoperative apoplexy versus only 1 patient in the post-2017 cohort. There were no statistically significant differences between the two periods in terms of the incidence rates of other complications. Capsule dissection and GTR are valuable for preventing serious complications and reducing recurrence of giant adenoma. Treatment of giant pituitary adenoma may be better managed with the help of a classification system that provides information about extent of resection that can be achieved with an endoscopic approach.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Demographic and socioeconomic disparities of pituitary adenomas and carcinomas in the United States

IntroductionGrowth of some pituitary tumors is driven by hormones which vary in concentration along the lines of patient socioeconomic status. Thus, pituitary tumors may exhibit disparities in incidence upon stratification by socioeconomic variables. Exploring for these disparities could provide direction in tumor etiology elucidation and identification of healthcare inequalities. MethodsTo investigate pituitary adenoma and carcinoma incidence (per 100,000) with respect to sex, age, income, residence, and race/ethnicity, we searched the largest American administrative dataset (1997–2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of United States (US) discharges. ResultsAnnual national incidence was 2.80 for adenomas and 0.046 for carcinomas. For adenomas, males had an incidence of 2.63, similar (p = 0.17) to females at 2.78; likewise, for carcinomas, males had a statistically equivalent (p = 0.24) incidence at 0.051 to females at 0.041. Amongst age groups, for adenomas incidence progressively rose, peaking 65–84 years old (6.12), before declining. For adenomas and carcinomas respectively, patients with low income had an incidence of 2.66 and 0.044, similar (p = 0.11; p = 0.72) to the 3.01 and 0.041 of middle/high income patients. Incidence was greatest for adenomas amongst urban centers (3.47), followed by rural (3.16) and suburban (3.01) communities. Examining race/ethnicity (p = 0.0000016), for adenomas, incidences amongst Blacks, Asian/Pacific Islanders, Hispanics, and Whites were as follows, respectively: 3.64, 2.57, 2.54, 2.44. Annually, incidence for adenomas was increasing (τ = 0.63, p = 0.00021), but decreasing (τ = −0.60, p = 0.00085) for carcinomas. Specifically, for carcinomas incidence was only decreasing for females and the middle/high income. ConclusionIn the US, time-enduring healthcare disparities were identified for pituitary adenomas and carcinomas, against the background of sociodemographic strata. For carcinomas, annual incidence was declining only for middle/high income patients and females, which supporting prior investigations that low income patients and males are experiencing barriers to definitive treatment for pituitary adenomas. Incidence was also found to be greatest Blacks and urban residents.

Stereotactic Radiosurgery for pituitary adenomas: A review of literature.

Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.

Pseudocapsule-Based Resection for Pituitary Adenomas via the Endoscopic Endonasal Approach.

IntroductionThe endoscopic endonasal approach (EEA) is a safe and effective treatment for pituitary adenomas (PAs). Since extracapsular resection (ER) of PAs improves tumor resection and endocrine remission rates, the interface between the pseudocapsule and gland draws increasing attention. However, it is difficult to precisely dissect the tumor along the exact boundary, and complete removal of the tumor increases the risks of normal tissue damage and cerebrospinal fluid (CSF) leakage. In this study, we investigated the extracapsular resection as well as the pseudocapsule histology to evaluate the effectiveness and safety of pseudocapsule-related surgical interventions.MethodsFrom December 2017 to December 2019, 189 patients of PAs via EEA in our single center were analyzed retrospectively. The images, operative details, and clinical follow-up of patients were collected. Sixty-four patients underwent pseudocapsule-based ER, and 125 patients also underwent traditional intracapsular resection (IR) with or without intensive excision for FPAs. The clinical characteristics, tumor resection, endocrinological outcomes, and postoperative morbidities of the two groups were compared. Informed consent for publication of our article was obtained from each patient. Histological examination of pseudocapsule was performed using hematoxylin and eosin and reticulin staining.ResultsThe gross total recession was 62 (96.9%) in the ER group and 107 (85.6%) cases in the IR group, whereas the endocrine remission rate was 29/31 (93.5%) and 40/53 (75.5%) cases, respectively. Anterior pituitary functions were not aggravated postoperatively in any patient, but transient diabetes insipidus (DI) occurred more in the IR group (64.0%) than in ER (48.4%). Pseudocapsule specimens were obtained in 93 patients, and clusters of small cell aggregation were detected in 11 pseudocapsule specimens (11.8%) whereas other patients showed no remarkable developed pseudocapsule. Intraoperative CSF leak occurred more in the ER group (28.1%) than in the IR group (13.6%), but no difference was seen between two groups postoperatively. No case of intracranial hematoma or pituitary crisis occurred in both groups. After a mean follow-up of 22.8 months, tumor recurrence was observed in 4 (2.1%) cases.ConclusionPseudocapsule-based extracapsular resection of PAs via EEA is an effective and safe procedure to achieve complete resection with high and sustained endocrine remission and without deteriorating pituitary function.

Успешный исход беременности и родов после хирургического лечения аденомы гипофиза в I триместре (клиническое наблюдение)

The authors present a clinical case of partial hypopituitarism developed in a 31-year-old patient during the first trimester of pregnancy after the surgical treatment of hemorrhagic pituitary adenoma. The onset of the diseases was recorded on the 12th week of pregnancy and was characterized by such specific clinical manifestations as severe headache, multiple spells of vomiting, diplopia and right-sided ptosis. The contrast-enhanced MRI revealed a pituitary adenoma with a "fresh" hemorrhage and the destruction of anterior wall and floor of the sella turcica, and the invasion into the sphenoid and right cavernous sinuses. The patient underwent emergency surgery – the endoscopic endonasal approach for total resection of pituitary adenoma. Hypopituitarism manifestations identified in the postoperative period were relieved by hormone replacement therapy. A timely diagnosis and prompt decision on the surgical treatment of pituitary adenoma, as well as a multidisciplinary team approach to patient care ensured the appropriate management of the underlying disease, successful pregnancy, childbirth outcome and high maternal quality of life. KEYWORDS: pituitary adenoma, pregnancy, management practices, hemorrhage, pituitary apoplexy, hypopituitarism, surgical treatment. FOR CITATION: Barakina O.V., Markova T.N., Ismailova S.G. et al. Successful pregnancy and delivery outcome after the surgical treatment of pituitary adenoma in the first trimester of pregnancy (a clinical case). Russian Journal of Woman and Child Health. 2022;5(4):326–331 (in Russ.). DOI: 10.32364/2618-8430-2022-5-4-326-331.

Surgical approaches to the treatment of pituitary adenomas in pregnant women (literature review and clinical observation)

Surgical approaches to the treatment of pituitary adenomas in pregnant women (literature review and clinical observation)

Modern Linear Accelerator–Based Radiotherapy Is Safe and Effective in the Treatment of Secretory and Nonsecretory Pituitary Adenomas

Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT. Institutional retrospective review of LINAC RT for PAs with minimum 3 years of magnetic resonance imaging follow-up was performed. Hormonal control was defined as biochemical remission in absence of medications targeting hormone excess. LC defined using Response Evaluation Criteria in Solid Tumors on surveillance magnetic resonance imaging. Progression-free survival defined as time alive with LC without return of or worsening hormonal excess from secretory PA. Kaplan-Meier and Cox proportional hazard models used. From 2003 to 2017, 140 patients with PAs (94 nonsecretory, 46 secretory) were treated with LINAC RT (105 fractionated RT, 35 radiosurgery) with median follow-up of 5.35 years. Techniques included fixed gantry intensity-modulated radiotherapy (51.4%), dynamic conformal arcs (9.3%), and volumetric modulated arc therapy (39.3%). Progression-free survival at 5 years was 95.3% for secretory tumors and 94.8% for nonsecretory tumors. Worse progression-free survival was associated with larger planning target volume on multivariable analysis (hazard ratio 2.87, 95% confidence interval 1.01-8.21, P= 0.049). Hormonal control at 5 years was 50.0% and associated with higher dose to tumor (hazard ratio 1.05, 95% confidence interval 1.02-1.09, P= 0.005) and number of surgeries (hazard ratio 1.74, 95% confidence interval 1.05-2.89, P= 0.032). Patients requiring any pituitary hormone replacement increased from 57.9% to 70.0% after RT. Modern LINAC RT for patients with PAs was safe and effective for hormonal control and LC. No difference in LC was noted for functional versus nonfunctional tumors, possibly owing to higher total dose and daily image guidance.