Nonfunctioning Pituitary Adenomas Research Articles

The Knosp Criteria Revisited: 3-Dimensional Volumetric Analysis as a Predictive Tool for Extent of Resection in Complex Endoscopic Pituitary Surgery.

The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery. To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas. Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined. One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46). Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods.

Evaluation of autoantibody signatures in pituitary adenoma patients using human proteome arrays.

To identify the specific diagnostic biomarkers related to pituitary adenomas (PAs), we performed serological antibody profiles for three types of PAs, namely Acromegaly, Cushing's and Nonfunctional Pituitary Adenomas (NFPAs), using the human proteome (HuProt) microarray. This is the first study describing the serum autoantibody profile of PAs. We performed serological autoantibody profiling of four healthy controls, four Acromegaly, three Cushing's and three NFPAs patient samples to obtain their autoantibody profiles, which were used for studying expression, interaction and altered biological pathways. Further, significant autoantibodies of PAs were compared with data available for glioma, meningioma and AAgAtlas for their specificity. Autoantibody profile of PAs led to the identification of differentially expressed significant proteins such as AKNAD1 (AT-Hook Transcription Factor [AKNA] Domain Containing 1), NINJ1 (Nerve injury-induced protein 1), L3HYPDH (Trans-3-hydroxy-L-proline dehydratase), RHOG (Rho-related GTP-binding protein) and PTP4A1 (Protein Tyrosine Phosphatase Type IVA 1) in Acromegaly. Protein ABR (Active breakpoint cluster region-related protein), ST6GALNAC6 (ST6 N-acetylgalactosaminide alpha-2, 6-sialyltransferase 6), NOL3 (Nucleolar protein 3), ANXA8 (Annexin A8) and POLR2H (RNA polymerase II, I and III subunit H) showed an antigenic response in Cushing's patient's serum samples. Protein dipeptidyl peptidase 3 (DPP3) and reticulon-4 (RTN4) exhibited a very high antigenic response in NFPA patients. These proteins hold promise as potential autoantibody biomarkers in PAs.

Giant Non-Functioning Pituitary Adenomas: Treatment Considerations.

Giant pituitary adenomas are a subgroup of pituitary adenomas defined by a diameter greater than 4 cm, and they account for 5–14% of adenomas in surgical series. Because of their growth patterns and locations, often involving critical neurovascular structures, they represent a true surgical challenge, and gross total resection is difficult to achieve. There is no consensus on the optimal surgical strategy for giant pituitary adenomas, and, often, integrated multi-staged treatment strategies have been considered. Transcranial or transsphenoidal approaches, alone or combined, according to tumor and patient features are the two main routes. Each of these strategies has pros and cons. The conventional transcranial approach has for a long time been considered the first choice for the removal of giant pituitary adenomas. Currently, with endoscopic techniques, it is also possible to remove lesions that involve the intradural compartment and the adjacent neurovascular structures with the use of extended approaches. Our policy for the management of these lesions is to adopt the endoscopic endonasal approach as the first choice unless the tumor presents significant intracranial extension that results in it being outside the visibility and maneuverability of the endoscopic endonasal route. In these latter cases, we agree that the transcranial approach is more appropriate. However, accurate preoperative evaluation and refined treatment plans for each patient are mandatory to define a proper strategy in order to achieve the most effective long-term result.

Expression pattern of non-coding RNAs in non-functioning pituitary adenoma.

Non-functioning pituitary adenoma (NFPA) is a benign tumor arising from the adenohypophyseal cells. They can be associated with symptoms arising from mass effect. Although these tumors are regarded to be benign tumors, they are associated with increased comorbidity and mortality. Several studies have indicated abnormal expression of genes in these tumors. In the current study, we have used existing methods to identify differentially expressed genes (DEGs) including DE long non-coding RNAs (DElncRNAs) and DE microRNAs (DEmiRNAs) in NFPAs compared with normal samples. Then, we have assessed the relation between these genes and important signaling pathways. Our analyses led to identification of 3131 DEGs, including 189 downregulated DEGs (such as RPS4Y1 and DDX3Y) and 2898 upregulated DEGs (such as ASB3 and DRD4), and 44 DElncRNAs, including 8 downregulated DElncRNAs (such as NUTM2B-AS1 and MALAT1) and 36 upregulated DElncRNAs (such as BCAR4 and SRD5A3-AS1). GnRH signaling pathway, Tight junction, Gap junction, Melanogenesis, DNA replication, Nucleotide excision repair, Mismatch repair and N-Glycan biosynthesis have been among dysregulated pathways in NFPAs. Taken together, our study has revealed differential expression of several genes and signaling pathways in this type of tumors.

Identifying risk factors for postoperative diabetes insipidus in more than 2500 patients undergoing transsphenoidal surgery: a single-institution experience.

Diabetes insipidus (DI) following transsphenoidal surgery can adversely impact quality of life and be difficult to manage. This study sought to characterize pre- and perioperative risk factors that may predispose patients to DI after pituitary surgery. A retrospective review of patients treated at a single institution from 2007 to 2019 was conducted. DI was defined as postoperative sodium > 145 mEq/L and urine output > 300 ml/hr and/or postoperative desmopressin (ddAVP) use. DI was further characterized as transient or permanent. Uni- and multivariate analyses were performed to determine variables associated with postoperative DI. The authors identified 2529 patients who underwent transsphenoidal surgery at their institution. Overall, DI was observed in 270 (10.7%) of the 2529 patients, with 114 (4.5%) having permanent DI and 156 (6.2%) with transient symptoms. By pathology type, DI occurred in 31 (46.3%) of 67 craniopharyngiomas, 10 (14.3%) of 70 apoplexies, 46 (14.3%) of 322 Rathke's cleft cysts, 77 (7.7%) of 1004 nonfunctioning pituitary adenomas (NFPAs), and 62 (7.6%) of 811 functioning pituitary adenomas (FPAs). Final lesion pathology significantly affected DI rates (p < 0.001). Multivariate analysis across pathologies showed that younger age (odds ratio [OR] 0.97, p < 0.001), intraoperative CSF encounter (OR 2.74, p < 0.001), craniopharyngioma diagnosis (OR 8.22, p = 0.007), and postoperative hyponatremia (OR 1.50, p = 0.049) increased the risk of DI. Because surgery for each pathology created specific risk factors for DI, the analysis was then limited to the 1815 pituitary adenomas (PAs) in the series, comprising 1004 NFPAs and 811 FPAs. For PAs, younger age (PA: OR 0.97, p < 0.001; NFPA: OR 0.97, p < 0.001; FPA: OR 0.97, p = 0.028) and intraoperative CSF encounter (PA: OR 2.99, p < 0.001; NFPA: OR 2.93, p < 0.001; FPA: OR 3.06, p < 0.001) increased DI rates in multivariate analysis. Among all PAs, patients with DI experienced peak sodium levels later than those without DI (postoperative day 11 vs 2). Increasing tumor diameter increased the risk of DI in FPAs (OR 1.52, p = 0.008), but not in NFPAs (p = 0.564). In more than 2500 patients treated at a single institution, intraoperative CSF encounter, craniopharyngioma diagnosis, and young age all increased the risk of postoperative DI. Patients with postoperative hyponatremia exhibited higher rates of DI, suggesting possible bi- or triphasic patterns to DI. Greater vigilance should be maintained in patients meeting these criteria following transsphenoidal surgery to ensure early recognition and treatment of DI.

Predictive factors for recovery from adult growth hormone deficiency after transsphenoidal surgery for nonfunctioning pituitary adenoma.

Recovery from adult growth hormone deficiency (AGHD) after transsphenoidal surgery (TSS) has not been well discussed because of the lack of examinations including pituitary provocation tests (PPTs) before and after the procedure. This study aimed to evaluate the growth hormone (GH) axis function of patients with nonfunctioning pituitary adenoma (NFPA) via pre- and postoperative PPTs. Moreover, the predictive factors for recovery from AGHD after TSS were validated to facilitate surgery for AGHD in patients with NFPA. In total, 276 patients (median age 60.0 years) who underwent TSS for NFPA were included in this study. PPTs were performed before and 3 months after TSS. Then, the relationships between recovery from AGHD after TSS and clinical, surgical, and hormonal factors, including peak GH level based on PPTs, were evaluated statistically. In this study, 114 patients were diagnosed with preoperative AGHD. Approximately 25.4% recovered from AGHD after TSS. In contrast, among the 162 patients without preoperative AGHD, 13 (8.0%) had newly developed postoperative AGHD. The predictive factors for recovery from AGHD were younger age, female sex, initial TSS, and high peak GH level based on preoperative PPT. According to the receiver operating characteristic curve analysis, patients who were aged ≤ 62.2 years and had a peak GH level of ≥ 0.74 μg/L based on preoperative PPT were likely to recover from AGHD (sensitivity: 82.8%, specificity: 72.9%, and area under the curve: 0.8229). AGHD caused by NFPA can improve after initial TSS among young patients with certain peak GH levels assessed by preoperative PPT. Whether TSS for NFPA can promote recovery from AGHD is worth considering in some patients.

Impact of surgical factors on delayed hyponatremia in patients with nonfunctioning pituitary adenoma after endonasal endoscopic transsphenoidal procedure

PurposeDelayed hyponatremia can occur after pituitary surgery, resulting in prolonged hospitalization. However, the influence of surgical factors after such a procedure has not been well established. The impact of surgery and related factors on delayed hyponatremia was investigated.MethodsThis was a retrospective analysis of 137 consecutive patients who underwent transsphenoidal surgery for a nonfunctioning pituitary adenoma between 2008 and 2019. Preoperative (demographics, comorbidities), intraoperative (resection extent, operation time, blood loss volume, cerebrospinal fluid leak, tumor consistency), and postoperative [hematoma, meningitis, diabetes insipidus (DI), hormonal assessment] data were collected, with statistical analysis of each factor performed.ResultsAmong the 137 patients, delayed hyponatremia occurred in 31 (22.6%). Multivariate analysis revealed that those with hypertension had a significantly higher likelihood of avoiding delayed hyponatremia (p = 0.004). Although no correlations of direct surgical factors with delayed hyponatremia were found, multivariate analysis of indirect surgical factors showed that presence of a firm tumor, transient DI, and meningitis were significantly associated with delayed hyponatremia (p = 0.014, 0.001, and 0.047, respectively). There was also a significant association of severe hyponatremia with appearance of symptoms (p = 0.002).ConclusionThere was a tendency for hypertension to be associated with delayed hyponatremia avoidance, with indirect surgical factors including tumor consistency, transient DI, and meningitis found to have an influence on delayed hyponatremia. It was concluded that attention should be given to non-hypertensive patients with a firm tumor, transient DI, or meningitis after pituitary surgery, as delayed hyponatremia may occur.

Metabolomics Profiling of Pituitary Adenomas by Raman Spectroscopy, Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy, and Mass Spectrometry of Serum Samples.

To date, no studies are available in which pituitary adenomas (PAs) have been studied using techniques like confocal Raman spectroscopy, attenuated total reflection-Fourier transform infrared (FT-IR), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the same serum samples. To understand the metabolomics fingerprint, Raman spectra of 16 acromegaly, 19 Cushing's, and 33 nonfunctional PA (NFPA) and ATR-FTIR spectral acquisition of 16 acromegaly, 18 Cushing's, and 22 NFPA patient's serum samples were acquired. Next, Principal component-based linear discriminant analysis (PC-LDA) models were developed, Raman spectral analysis classified acromegaly with an accuracy of 79.17%, sensitivity of 75%, and specificity of 81.25%, Cushing's with an accuracy of 66.67%, sensitivity of 100%, and specificity of 52.63%, and NFPA with an accuracy of 73.17%, sensitivity of 75%, and specificity of 72.73%. ATR-FTIR spectral analysis classified acromegaly with an accuracy of 95.83%, sensitivity of 100%, and specificity of 93.75%, Cushing's with an accuracy of 65.38%, sensitivity of 87.5%, and specificity of 55.56%, and NFPA with an accuracy of 70%, sensitivity of 87.5%, and specificity of 43.75%. In either of the cases, healthy individual cohorts were clearly segregated from the disease cohort, which identified differential regulated regions of nucleic acids, lipids, amides, phosphates, and polysaccharide/C-C residue α helix regions. Furthermore, LC-MS/MS-based analysis of sera samples resulted in the identification of various sphingosine, lipids, acylcarnitines, amino acids, ethanolamine, choline, and their derivatives that differentially regulated in each tumor cohort. We believe cues obtained from the study may be used to generate the metabolite-based test to diagnose PAs from serum in addition to conventional techniques and also to understand disease biology for better disease management, point of care, and improving quality of life in PA patients.

Increased Risk of Ocular Hypertension in Patients With Cushing's Disease.

An increased risk of ocular hypertension was seen in Cushing's disease. Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown. The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP. A total of 52 patients (38.4±12.4y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4mmHg and right 20.0±7.1mmHg) than in patients with acromegaly (left 17.5±2.3mmHg and right 18.6±7.0mmHg, P =0.033) and patients with NFPA (left 17.8±2.6mmHg and right 17.4±2.4mmHg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery. An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.

Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas.

BackgroundCathepsin K (CTSK) is a protease that degrades type I collagen and extracellular matrix, thereby contributing to bone resorption and tumor invasion. Some pituitary adenomas (PAs) could invade the sphenoid sinus (SS) and cavernous sinus (CS).PurposeThis retrospective cohort study aimed to study the expression of tumoral biomarkers (CTSK, MMP9, MMP2, TIMP2, and PTTG1) and evaluate their clinical significance in non-functioning pituitary adenomas (NFPAs) with different invasion patterns.MethodsWe assessed the expression levels of candidate invasion-specific protein biomarkers CTSK, MMP9, MMP2, TIMP2, and PTTG1 by immunohistochemical staining in paraffin-embedded NFPA tumor tissues. Variations in staining intensity were analyzed in cases with SS and CS invasion and non-invasive NFPAs.ResultsWe found that the levels of CTSK were higher in PA cases with SS invasion than that in PA cases with CS invasion (95.57 ± 31.57 vs. 65.29 ± 29.64, P < 0.001), and the expression of MMP9 and MMP2 was higher in CS-invasive cases than that in SS-invasive cases (145.02 ± 49.25 vs. 111.80 ± 51.37, P = 0.002, and 138.67 ± 52.06 vs. 108.30 ± 41.70, P = 0.002). Multiple Cox regression demonstrated that higher CTSK expression (P=0.011), subtotal resection (P<0.001), invasion (P=0.037), and larger tumor diameter (P=0.001) were independent risk factors for recurrence. A positive correlation was observed between CTSK expression and tumor size (r=0.671, p<0.001). There was no significant difference in TIMP2 and PTTG1 levels between CS-and SS-invasive cases (97.42± 39.80 vs. 102.10± 43.22, P = 0.58 and 13.89 ± 4.59 vs. 12.56 ± 3.96, P = 0.14).ConclusionOur data indicated that CTSK has the potential as a marker for SS invasion of PAs, whereas MMP9 and MMP2 may be markers for CS invasion. And CTSK may play an important role in tumor relapse.

Anesthetic Management in a Patient with Recurrent Pituitary Macroadenoma

Introduction: Tumours of the pituitary gland and sellar region represent 10-15% of all brain tumours. Pituitary macroadenoma is the most common suprasellar mass in adults and is the commonest indication for transnasal trans-sphenoidal hypophysectomy. Case Report: A 41-year-old patient presented with right-sided loss of vision and right-sided headache for 3 months and posted for the Transnasal Trans-sphenoidalhypophysectomy. The patient previously underwent a similar surgery for an invasive non-functioning pituitary adenoma 2.5 years back. He is a known hypothyroid, with normal vitals and class III Mallampati. The possibility of a difficult airway was considered because of the enlarged tongue. Other system examinations were normal. The hemogram and biochemistry measurements were normal. MRI brain showed a mass lesion measuring 5.2 x 5.6 x 4.7 cm in the sellar, supra, and parasellar regions. We were prepared for all the intraoperative complications of pituitary macroadenoma that can happen. Difficult airway cart was made available. 18-gauge IV cannula secured. Pre-oxygenated and premedicated with IV Glycopyrrolate 0.01mg/Kg and IV Fentanyl 2 mcg/Kg. Induced with Propofol 2mg/Kg, checked ventilation and Vecuronium 0.1mg/Kg was administered. Intubated with 8.5 mm cuffed endotracheal tube using Video laryngoscope. Right Subclavian vein cannulated and Invasive BP monitored through Radial artery cannulation. Anesthesia was maintained with Oxygen-Nitrous oxide, Isoflurane, Vecuronium, and Dexmedetomidine infusion. The patient was hemodynamically stable throughout the procedure. At the end of the procedure, reversal was given and extubated after ensuring adequate recovery. Conclusion: Appropriate assessment before anesthesia and perioperative adequate monitoring and preparation are important in the management of anesthesia of patients with pituitary macroadenoma. Keywords: Anesthetic concerns in pituitary adenoma, Neurosurgical Anesthesia, Pituitary Tumours, Pituitary Macroadenomas. Key Messages: Patients coming for recurrent pituitary macroadenoma need appropriate preoperative assessment and perioperative anesthesia management. This surgery requires a multidisciplinary team that includes an anesthesiologist, an endocrinologist, a neurosurgeon and a radiologist for better patient care and outcome. We are presenting a case report of recurrent pituitary macroadenoma and its successful management.

Endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: Learning curve and surgical results in a prospective series during initial experience.

BackgroundTo report the initial experience of surgery for non-functioning pituitary adenoma (NFPA) from a neurosurgeon in a dedicated residency training endoscopic transsphenoidal (ETS) program, and detail the surgical and clinical outcomes during this period.MethodsA prospective series of all patients operated for NFPA, using an ETS approach, during the three first years of experience of a newly board-certified neurosurgeon was analysed. Clinical, radiological and peri-operative data were collected. Extent of resection (EOR) was determined by formal volumetric analysis. Impact of the learning curve and predictive factors of gross total resection (GTR) were determined.ResultsFifty-three patients with NFPA were included in this prospective cohort which was divided in two periods of time (“First period”: 30 first cases, and “second period”: 23 following cases). Baseline characteristics of the patients in the two periods were similar. Overall occurrence of complication was 22% and was not significantly different in the two periods of time. No patient had severe neurological complication. Gross total resection was achieved in 70% of patients. Mean Extent of resection was 96%. In a multiple linear regression model, a higher EOR was positively correlated with experience (p = 0.018) and negatively correlated with Knosp Score equal to 4 (p < 0.001). Predictive factors for GTR were Higher Knosp grade (p = 0,01), higher pre-operative volume (p = 0.03), and second period of time (p = 0.01).ConclusionNFPA surgery can be safe and efficient during the learning period. Dedicated intensive learning, careful patient selection and multidisciplinary work are key to shorten the learning curve and achieve satisfactory results.

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.

Frequency of Functional and Non-Functional Pituitary Adenomas in Patients Presented at Ayub Teaching Hospital, Abbottabad

Objective: Pituitary lesions cause morbidity and mortality in all age groups due to their hormonal hypersecretion, its mass effects, and post-surgery complications. The present study determined the frequency of functional and non-functional pituitary adenomas.&#x0D; Materials &amp; Methods: The study included patients (n = 114) presenting with functional and non-functional pituitary adenoma. Pituitary adenomas were diagnosed based on MRI brain with contrast and the size of the tumor was noted a tumor having a size of 10 mm or more was labeled as macro adenoma and a tumor having a size less than 10 mm was labeled as microadenoma. Pituitary adenomas were stratified among age, gender, duration of symptoms, types of adenomas, types of functional adenoma, and type of the tumor on a size basis.&#x0D; Results: Most of the patients had TSH- secreting adenoma (21.9%). 52.6% were found with microadenoma and 47.4% had macro adenoma. Patients with functional adenoma were 30.7% and with non-functional adenoma 32.5% were male while patients with functional adenoma were 26.3% and with non-functional adenoma 10.5%were female (p = 0.018). Patients with functional adenoma (43.9%) and non-functional adenoma (8.8%) were found to have microadenoma, whereas patients with functional adenoma (13.2%) and non-functional adenoma (34.2%) were found to have macroadenoma (p = 0.000). Patients with functional adenoma having a duration of symptoms below 1 year were 11 (9.6%), 1 to 3 years were 25 (21.9%), 17 (14.9%) were 4 to 6 years, and 12 (10.5%) above 6 years duration of symptoms.&#x0D; Conclusion: Patients with pituitary adenomas should be diagnosed early to receive successful therapy.

Risk factors for delayed postoperative hyponatremia in patients with non-functioning pituitary adenomas undergoing transsphenoidal surgery: A single-institution study.

PurposeWe aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery (TSS) in patients with a non-functional pituitary adenoma (NFPA).MethodsWe retrospectively collected the clinical data of patients who underwent TSS for NFPA between January 2016 and January 2021. The pituitary region was preoperatively scanned with 3.0 T magnetic resonance imaging. The risk factors for delayed postoperative hyponatremia for NFPA were identified by univariate and multivariable logistic regression analysis.ResultsWe selected 166 patients with NFPA who fulfilled the inclusion criteria. Delayed postoperative hyponatremia occurred in 28 patients and did not in 138. Multivariable logistic regression analyses demonstrated that higher odds of developing delayed postoperative hyponatremia were independently associated with larger craniocaudal dimension (OR = 1.128, P = 0.034), as well as preoperative hyperprolactinemia (OR = 2.618, P = 0.045) and larger preoperative pituitary stalk deviation angle (OR = 3.033, P = 0.022).ConclusionWe identified the independent risk factors for delayed hyponatremia after TSS for NFPA; these included preoperative hyperprolactinemia, craniocaudal diameter, and preoperative pituitary stalk deviation angle.

Surgical Planning and Simulation of Endonasal Endoscopic Surgery for Pituitary Adenoma With Cavernous Sinus Invasion.

Transsphenoidal endoscopic endonasal surgery (EES) provides effective treatment for patients with lesions of the sella turcica. The endoscopic technique requires different instrumentation, which depends on the gross anatomy of the nasal cavity. The treatment of lateral lesions is more challenging in EES. To evaluate the effect of preoperative simulation using multiple anatomic landmarks. Pre- and postoperative tumor volumes were analyzed in 33 patients with nonfunctioning pituitary adenomas who underwent EES (Knosp grades 3 and 4). The surgical working angle and space were three-dimensionally simulated at the plane of the anterior/posterior surgical field (tuberculum sellae/posterior clinoid process) using multiple anatomic landmarks of high-resolution computed tomography scans, such as nasal piriform aperture (proximal surgical corridor), and the width of bilateral vidian canals or lamina perpendicularis of palatine bone (distal surgical corridor). Receiver operating characteristic curves for the removed tumor volume were used to determine the cutoff value for the simulated working angle and space. Simulated working space at the plane of tuberculum sellae using piriform aperture and lamina perpendicularis of palatine bone was associated with the removed tumor volume in the cavernous sinus. Patients with a larger working space (≥42.7 mm) significantly showed a higher removed tumor volume ( P = .023). There was no relationship between other parameters and the removed tumor volume. A new method to predict the surgical field for cavernous sinus lesions around sella turcica was successfully established. Further studies are needed to define and expand applications of this simulation method.

Metabolic Characteristics and M2 Macrophage Infiltrates in Invasive Nonfunctioning Pituitary Adenomas.

ObjectiveThe aim of this study was to investigate the metabolic differences between invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs), determine the expression of an M2 macrophage marker in NFPAs, and analyze the effects of metabolic changes in invasive NFPAs on M2 macrophage infiltrates.MethodsTissue samples of NFPAs from patients who underwent transsphenoidal or craniotomy surgery from January 2021 to August 2021 were collected. NFPA tissues were analyzed based on a gas chromatography-mass spectrometry non-targeted metabolomics platform, and immunohistochemical staining for M2 macrophage marker CD206 was performed.ResultsWe evaluated 15 invasive and 21 non-invasive NFPAs. A total of 22 metabolites were identified through non-targeted metabolomics analysis. Among them, the expression of 1-octadecanol, inosine 5’-monophosphate, adenosine 5’-monophosphate, guanosine 5’-monophosphate, creatinine, desmosterol, taurine, hypotaurine, lactic acid, and succinic acid was upregulated in invasive NFPAs, while that of 1-oleoylglycerol, arachidonic acid, cis-11-eicosenoic acid, docosahexaenoic acid, glyceric acid, hypoxanthine, linoleic acid, lysine, oleic acid, uracil, valine, and xanthine was downregulated. Immunohistochemical analysis suggested that the number of CD206-positive cells was higher in invasive NFPAs than in non-invasive NFPAs.ConclusionInvasive and non-invasive NFPAs showed distinct metabolite profiles. The levels of succinic acid and lactic acid were higher in invasive NFPAs, and the high expression of the M2 macrophage marker was verified in invasive NFPAs.

Primary hypothyroidism and postmenopause as the causes of delayed diagnosis of panhypopituitarism in a patient with nonfunctional pituitary adenoma

Hypopituitarism is a state of complete or partial deficiency of pituitary hormones, including adrenal insufficiency, hypothyroidism, hypogonadism, growth hormone deficiency, and, rarely, diabetes insipidus.The article describes a clinical case of hypopituitarism due to a pituitary tumor in a postmenopausal woman. Difficulties in diagnosing hypopituitarism were due to a history of primary hypothyroidism. The first identified component of panhypopituitarism in the patient, (central hypothyroidism) had previously been seen as laboratory indications of medication-induced hyperthyroidism.The non-specific nature of the clinical symptoms, as well as a relatively rare combination of endocrine diseases, led to a long examination period and delayed diagnosis of the pituitary tumor.Whether the development of hypopituitarism in a patient with a nonfunctional pituitary tumor is an indication for transsphenoidal pituitary surgery remains a controversial issue. The decision for surgery is made taking into account the characteristics of the course of the disease in a particular patient. In this clinical case, a conservative tactic was chosen with hormone replacement therapy for glucocorticoid and thyroid deficiency.

Preoperative Magnetic Resonance Imaging Localization of the Normal Pituitary Gland in Nonfunctioning Pituitary Adenoma Patients Using the Radiological Sign of “Internal Carotid Artery Notch”

Asymmetric features of nonfunctioning pituitary adenoma (NFPA) are poorly understood. We investigated the asymmetry in NFPA on magnetic resonance imaging. We reviewed preoperative magnetic resonance imaging findings of patients initially treated for NFPA. The internal carotid artery (ICA) often seemed to cause an indentation in the external shape of the tumor (i.e., the ICA notch). Two cases with a normal pituitary gland located at the midline were excluded. The remaining 66 cases were examined. The side where the normal gland was located was defined as the normal pituitary side and the opposite side as the cavernous sinus side. The Knosp grade was significantly higher on the cavernous sinus side (P<0.001), and the vertical distance of the ICA was significantly greater on the cavernous sinus side (P<0.001). The ICA notch was found in 87.9% of all cases on the normal pituitary side, but in only 45.5% on the cavernous sinus side (P<0.001). In cases with a single-side ICA notch (34 of 68), the ICA notch was found in 91.2% of cases and on the cavernous sinus side in 8.8% (P<0.001). Magnetic resonance imaging of NFPA frequently shows asymmetry. The tumor does not extend laterally on the normal pituitary side but extends laterally more freely on the cavernous sinus side. The ICA notch is often found on the normal pituitary side where the position of ICA does not move. This may be useful as a preoperative sign to indicate the normal pituitary side.

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