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17ß-Trenbolone (17-TB) is well documented as an environmental endocrine disruptor in aquatic biological studies, but its effects on mammals remain poorly understood. Furthermore, 17-TB acts as a hormone with properties similar to testosterone, and the consequences of juvenile exposure on adult social behavior remain uncertain. Bisphenol A (BPA) acts as an estrogen-like hormone, compared to 17-TB. Three-week-old male Balb/c mice were exposed orally to 17-TB (100 µg/(kg·day)) and BPA (4 mg/(kg·day)) for 28 days. Assessments of social interactions and a three-chamber test showed that 17-TB increased virility in male mice, intensified both male and female sexual behavior, and attracted and accepted female mice. It also increased social dominance through tube tests in male mice and markedly activated the c-Fos+ immune response in the medial prefrontal cortex (mPFC) and basal amygdala (BLA). ELISA data showed that 17-TB and BPA exposure significantly affected serum gonadotropin-releasing hormone (GnRH), growth hormone (GH), estradiol (E2), and luteinizing hormone (LH) levels, as well as testicular lesions and androgen receptor (ARß) and estrogen receptor (ERα) synthesis. Testicular transcriptomic analysis further confirmed that could disrupt steroid synthesis and linoleic acid-related biometabolic processes. These findings suggest the influence of 17-TB and BPA exposure on sexual behavior and fertility in male mice, possibly through modulation of the hypothalamic-pituitary-gonadal axis. This study provides insights relevant to human reproductive health and neuro-social behavioral research, and the potential risk of environmental disturbances should not be overlooked.
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Compostos Benzidrílicos , Disruptores Endócrinos , Sistema Hipotálamo-Hipofisário , Fenóis , Animais , Masculino , Compostos Benzidrílicos/toxicidade , Camundongos , Fenóis/toxicidade , Disruptores Endócrinos/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Predomínio Social , Acetato de Trembolona/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Eixo Hipotalâmico-Hipofisário-GonadalRESUMO
Objectives The lateral supraorbital (LSO) approach is a less-invasive alternative to the pterional craniotomy that provides rapid transsylvian access. Establishing familiarity with the LSO technique and its features as compared with other anterolateral approaches is an important component of advanced skull base training. We present a step-by-step demonstration of the LSO approach using cadaveric dissection in a manner that is digestible for trainees at various levels. Design This is anatomic step-by-step dissection and representative case series. Setting This study was carried out in the cadaveric dissection laboratory. Participants A formalin-fixed, latex-injected cadaveric head specimen was dissected under microscopic magnification by a neurosurgery resident under faculty supervision. Following dissection, representative case applications were reviewed. Main Outcome Measures Dissection and case illustration were the main outcome measures. Results A single-layer myocutaneous flap is developed, and a single-burr-hole technique is used, followed by extensive drilling of the sphenoid wing. The dura is opened in a C-shaped fashion centered on the Sylvian fissure, exposing the inferior frontal and superior temporal lobes. Labeled photographs of dissections with pertinent anatomical structures are presented. Three case examples illustrating the versatility of the LSO approach, including the resection of a large pituitary adenoma, an inferior frontal melanoma metastasis presenting to the Sylvian surface, and a frontoinsular low-grade glioma, are reviewed. Conclusion As compared with the pterional craniotomy, the LSO approach involves a shorter incision, smaller craniotomy, and faster exposure; it can be conveniently tailored to various indications. Understanding the step-by-step dissection and indications of the LSO approach is of paramount importance to neurosurgery trainees.
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Pathologies of pediatric pituitary adenomas are uncommon and challenging to diagnose. Pituitary adenomas cause mass effects and neurological disruption in children. Postoperative evaluations of endocrine functions are challenging. The present study categorized adenomas by size and type, and evaluated outcomes based on the surgical procedures adopted. In addition, the present study analyzed the demographic parameters of children as well as the factors supposed to be influencing remission. Clinical characteristics, treatment parameters and postoperative outcomes of curative surgeries in 135 children [80 (59%) females and 55 (41%) males; age 12 (11-13) years at the time of first diagnosis] with pituitary adenomas who underwent curative surgeries operated between 1998 and 2023 in the Yichang Central People's Hospital, (Yichang, China) were included in the present retrospective study. A total of 112 (83%) children had microadenomas (<10 mm adenomas), 6 (4%) had macroadenomas (≥10 mm adenomas) and 17 (13%) had invisible adenomas. Pathological examination revealed that 59 (44%) children had functional adenomas and 10 (7%) had non-functional adenomas. Among functional adenomas, acromegaly (excess secretion of insulin-like growth factor 1) was reported to be the most common [30 (22%)] pediatric adenomas, followed by prolactinomas [prolactin secretion ≥1,000 mIU/l; 20 (15%) and Cushing syndrome (9 (7%)]. A total of 23 (17%), 3 (2%), 4 (3%), 3 (2%) and 3 (2%) children were reported to have remission and underwent re-surgery. These patients (remission) underwent microscopic trans-sphenoidal resection, endoscopic endonasal trans-sphenoidal resection, trans-sphenoidal resection alone, bilateral adrenalectomy and gross total resection adopted curative surgeries initially, respectively. Postoperative diabetes insipidus, adrenal insufficiency and cerebrospinal fluid leaks have been reported in children who have undergone curative surgeries for macroadenomas or Cushing syndrome. Female pediatric patients with clinical manifestations were more likely to have pituitary adenomas. Pediatric patients generally have functional pituitary adenomas, particularly adreno-corticotropin-secreting adenomas. Microscopic trans-sphenoidal resection is associated with a lower risk of under-treatment. Postoperative outcomes and clinical benefits of curative surgeries are based on the complete type of surgical removal and size of the pituitary adenomas mass (Level of Evidence: 3; Technical Efficacy Stage: 4).
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BACKGROUND: Somatotroph neuroendocrine pituitary tumors (sPitNET) are a subtype of pituitary tumors that commonly cause acromegaly. Our study aimed to determine the spectrum of DNA copy number abnormalities (CNAs) in sPitNETs and their relevance. METHODS: A landscape of CNAs in sPitNETs was determined using combined whole-genome approaches involving low-pass whole genome sequencing and SNP microarrays. Fluorescent in situ hybridization (FISH) was used for microscopic validation of CNAs. The tumors were also subjected to transcriptome and DNA methylation analyses with RNAseq and microarrays, respectively. RESULTS: We observed a wide spectrum of cytogenetic changes ranging from multiple deletions, recurrent chromosome 11 loss, stable genomes, to duplication of the majority of the chromosomes. The identified CNAs were confirmed with FISH. sPitNETs with multiple duplications were characterized by intratumoral heterogeneity in chromosome number variation in individual tumor cells, as determined with FISH. These tumors were separate CNA-related sPitNET subtype in clustering analyses with CNA signature specific for whole genome doubling-related etiology. This subtype encompassed GNAS-wild type, mostly densely granulated tumors with favorable expression level of known prognosis-related genes, notably enriched with POUF1/NR5A1-double positive PitNETs. Chromosomal deletions in sPitNETs are functionally relevant. They occurred in gene-dense DNA regions and were related to genes downregulation and increased DNA methylation in the CpG island and promoter regions in the affected regions. Recurrent loss of chromosome 11 was reflected by lowered MEN1 and AIP. No such unequivocal relevance was found for chromosomal gains. Comparisons of transcriptomes of selected most cytogenetically stable sPitNETs with tumors with recurrent loss of chromosome 11 showed upregulation of processes related to gene dosage compensation mechanism in tumors with deletion. Comparison of stable tumors with those with multiple duplications showed upregulation of processes related to mitotic spindle, DNA repair, and chromatin organization. Both comparisons showed upregulation of the processes related to immune infiltration in cytogenetically stable tumors and deconvolution of DNA methylation data indicated a higher content of specified immune cells and lower tumor purity in these tumors. CONCLUSIONS: sPitNETs fall into three relevant cytogenetic groups: highly aneuploid tumors characterized by known prognostically favorable features and low aneuploidy tumors including specific subtype with chromosome 11 loss.
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Aneuploidia , Cromossomos Humanos Par 11 , Metilação de DNA , Humanos , Metilação de DNA/genética , Cromossomos Humanos Par 11/genética , Variações do Número de Cópias de DNA/genética , Feminino , Masculino , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Deleção Cromossômica , Regulação Neoplásica da Expressão Gênica , AdultoRESUMO
OBJECTIVE: Mixed gangliocytoma-pituitary adenomas (MGPAs) are very rare sellar neoplasms. Contemporary understanding of their natural history, clinical characteristics, optimal management strategies, and prototypical outcomes remains poorly understood. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, EMBASE, Web of Science, and Cochrane were searched to include studies of patients with histologically confirmed Mixed Gangliocytomas (MGPAs). Clinical features, management strategies, and outcomes were analyzed. RESULTS: 33 studies reporting 78 patients met study criteria and were included. Median age at diagnosis was 47 years, with a female predominance (71%). Common presenting symptoms included headache (49%), acromegaly (43%), and visual disturbance (20%). Growth hormone (GH) and prolactin were the most commonly elevated hormones. Magnetic resonance imaging (MRI) identified local infiltration in 86% of patients, most frequently in the cavernous sinus. Transsphenoidal resection was the primary treatment strategy, which achieved a gross total resection (GTR) in 43%. Postoperative pituitary function was normal in 92%. Median follow-up was 21 months, during which time 14% of patients required secondary intervention for persistent hormonal hypersecretion. Following these secondary interventions and as of last follow-up, radiographic and/or biochemical control was confirmed in all patients, with an overall survival rate of 97%. CONCLUSION: MGPAs are rare, slow-growing tumors that present with a combination of endocrinological and neurological symptoms. MGPAs are optimally managed with transsphenoidal resection, which appears to achieve favorable rates of symptomatic relief and local control, despite the high incidence of local infiltration and relatively low attendant GTR rate.
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OBJECTIVE: Endoscopic endonasal approaches (EEAs) specifically for procedures involving manipulation of the internal carotid artery (ICA), such as the transcavernous and translacerum approaches, confer a potential risk of carotid sympathetic plexus injury, potentially leading to postganglionic Horner syndrome. The primary aim of this study was to delineate the surgical anatomy of the carotid sympathetic plexus from an endoscopic endonasal perspective, offering insights to facilitate intraoperative anatomical identification and injury prevention. METHODS: A comprehensive dissection was conducted on 20 silicone-injected, lightly embalmed postmortem human heads. The segments, patterns, and surgical landmarks of the carotid sympathetic plexus were investigated in a stepwise manner. In addition, 3 illustrative cases highlighting the involvement of the carotid sympathetic plexus in EEAs are included to contextualize the anatomical findings. RESULTS: The carotid sympathetic plexus can be categorized into 3 segments: 1) the cavernous sinus (CS) segment, beginning at the upper surface of the petrolingual ligament and ascending anterosuperiorly along the inferior compartment of the CS (mean ± SD length 5 ± 0.5 mm); 2) the lacerum segment, starting at the exit of the petrous carotid canal and ascending laterally and vertically to the upper surface of the petrolingual ligament (mean ± SD length 10 ± 1 mm); and 3) the petrous segment, originating at the external opening of the carotid canal and terminating at the foramen lacerum (mean ± SD length 18 ± 1 mm). Two primary morphological patterns of the sympathetic plexus at the CS and lacerum segments were identified: a plexus-like pattern in 12 (30%) hemispheres, and a nerve-like pattern that was subcategorized as double (18 [45%] hemispheres) or single (10 [25%] hemispheres) trunks. Surgical strategies emphasize the importance of recognizing key landmarks when approaching the carotid sympathetic plexus, including the pterygosphenoidal triangle, lingual process, petrolingual ligament, lateral parasellar ligament, and abducens nerve. CONCLUSIONS: This article provides a comprehensive anatomical description of the carotid sympathetic plexus in EEAs, highlighting key anatomical segments and patterns for intraoperative identification. A better understanding of anatomical landmarks for the carotid sympathetic plexus could help reduce the incidence of postganglionic Horner syndrome, augmenting the safety and efficacy of endoscopic endonasal transcavernous surgery.
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Prolactinomas, the most common pituitary-secreting adenomas, can be effectively treated with dopamine D2 receptor (D2R) agonists. However, a subset of them (â¼20%) are resistant to dopamine (DA)-based therapies and require extirpation. The molecular mechanisms underlying their escape from dopaminergic regulation are not fully elucidated and may include alterations in D2R signaling. D2R can heteromerize with other G protein-coupled receptors, resulting in modulation of dopaminergic signaling. Since the bradykinin receptor type 2 (B2R) is overexpressed in prolactinomas, we interrogated whether this dopaminergic dysregulation observed in some prolactinomas may depend on a physical and functional interaction between D2R and B2R. The formation of B2R-D2R complexes in cultured cells transiently expressing both receptors was validated using NanoBiT technology. Interestingly, while D2R stimulation did not alter B2R-induced intracellular calcium mobilization, B2R stimulation abolished D2R signaling through modulation of cAMP. The existence of B2R-D2R complexes in pituitary adenomas (PitNet) biopsies was evaluated using an ALPHALisa approach. Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas (NFPA), but not in mixed (prolactin + growth hormone) secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists.
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BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology. RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety. CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.
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Ansiedade , Depressão , Modelos Animais de Doenças , Microbioma Gastrointestinal , Hipersecreção Hipofisária de ACTH , Animais , Camundongos , Hipersecreção Hipofisária de ACTH/microbiologia , Hipersecreção Hipofisária de ACTH/psicologia , Hipersecreção Hipofisária de ACTH/fisiopatologia , Depressão/microbiologia , Ansiedade/microbiologia , Humanos , Masculino , Comportamento Animal , Fezes/microbiologia , Feminino , Corticosterona/sangue , Bactérias/classificação , Bactérias/isolamento & purificação , Adulto , Pessoa de Meia-Idade , Transplante de Microbiota Fecal , Camundongos Endogâmicos C57BLRESUMO
Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neuropeptide and endocrine peptide precursors; it is expressed in neuroendocrine tissues as well as in immune cells. In response to endotoxemia, global PC1/3 knockout mice mount a cytokine storm and die rapidly. Further, immune cells isolated from these mice have a pro-inflammatory signature, suggesting that PC1/3 activates an unknown anti-inflammatory peptide precursor in immune cells. Here, we tested this hypothesis using tissue-specific PC1/3 ablation models. Knocking out PC1/3 in the myeloid or the hematopoietic compartment did not induce any phenotype. In contrast, proopiomelanocortin (POMC)-specific PC1/3 knockout mice phenocopied global PC1/3 knockout mice, including an enlarged spleen size and a hyperinflammatory sepsis phenotype in response to mild endotoxemia. This phenotype was prevented by steroid therapy and mimicked by blocking corticoid receptors in wild-type mice. Thus, our data suggest that sepsis hypersensitivity in PC1/3 deficiency is uncoupled from immune cell intrinsic PC1/3 expression and is driven by a lack of anti-inflammatory glucocorticoids due to an impairment in the hypothalamic-pituitary-adrenal axis.
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Introduction Social determinants of health (SDOH) are associated with differential outcomes after pituitary tumor treatment. However, the specific impact of SDOH is not well characterized. One reason may be the lack of collection and reporting of sociodemographic variables in the literature. This study aims to evaluate the frequency of reporting and distribution of participants' sex, race, ethnicity, income, and education level within pituitary surgery literature. We will compare the reported clinical research population demographics to the 2020 U.S. census. Methods A systematic review was performed by searching PubMed, Cochrane, and Embase databases for pituitary surgery clinical research published between July 1, 2021 to June 30, 2022. We excluded studies that lacked a comparison group, were not original research (i.e., systematic reviews, meta-analysis), or included national databases and registry data. Results The final analysis included 92 studies. A total of 99% of studies collected data on subject sex. On average 49% (range: 14-100%) of study populations were male. Only 4% ( n = 4) studies included racial demographic data. Two studies included information on participants' ethnicity and two included education background. No studies included income or insurance data. Four U.S. studies included demographic distribution, and the reported race and ethnicity percentages are similar to the U.S. 2020 census distribution. Conclusion Most clinical pituitary research collects and reports data on participant sex. However, very few studies collect and report data on other sociodemographic variables that can play a role in outcomes. The lack of sociodemographic information in clinical research literature makes it difficult to determine the role of SDOH on pituitary surgery outcomes.
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Objective Sellar repair techniques with varying complexity and effectiveness have been employed to reduce the incidence of postoperative cerebrospinal fluid (CSF) leaks following endoscopic transsphenoidal pituitary surgery. This study describes our institutional experience with a minimalistic, highly effective approach to sellar repair. Methods The authors performed a retrospective review of consecutive cases of transsphenoidal pituitary surgery performed at our institution. All included subjects underwent sellar repair with an epidural interlay graft. Relationships between patient and tumor characteristics, incidence of CSF leak, adjunct repair techniques, and endocrine outcomes were examined. Results Three hundred and thirty-four (334) cases were included. Intraoperative CSF leak was encountered in 116 cases (34.7%), and postoperative CSF leak occurred only once (0.3%) early in the series. Seventy intraoperative CSF leaks were successfully repaired with an epidural interlay alone, including 13 high-flow leaks. Our rate of fat graft use (1.2%), nasoseptal flap (3.0%), and lumbar drain placement (6.6%) in the second half of the series showed a significant decline compared with the first half, indicating increased reliance on the interlay graft over time. Our 65% functional macroadenoma remission rate compares favorably with large historical series. Conclusion Simple sellar repair using an epidural interlay graft is highly effective in preventing postoperative CSF leaks, including cases of high-flow intraoperative leaks. More complex repair techniques are reserved for select high-risk cases or those with inadequate sellar bony ledges. With this technique, there has been no postoperative CSF leak at our institution in over 300 consecutive transsphenoidal pituitary surgeries.
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OBJECTIVE: To elucidate the iron load in different organs of non-transfusion-dependent thalassemia (NTDT) patients using magnetic resonance imaging (MRI) T2* scan. METHODS: Thirty-four NTDT patients, including 28 NTDT iron chelation without and 6 NTDT with iron chelation, together with 15 normal controls, underwent MRI examination between December 2022 and July 2024 were enrolled in the study. Measured T2* of the pituitary gland, kidney cortex, heart, liver, pancreas, spleen. Liver and spleen volumes were evaluated. RESULTS: Of the 28 patients in NTDT without iron chelation group, 19 patients with iron overload in the liver, 9 patients with iron overload in the kidneys, and 4 patients with iron overload in the spleen. Most patients with abnormal kidney and spleen iron (76.9 %) had liver iron overload. Compared with the control group, NTDT without iron chelation patients had lower T2* in the liver, kidney, and spleen (p < 0.05). And heart T2* was correlated with kidney T2* (r = 0.480, p = 0.010) and pancreas (r = 0.411, p = 0.037). Liver T2* was correlated with spleen T2* (r = 0.479, p = 0.011). Pancreas T2* was correlated with pituitary T2* (r = -0.433, p = 0.031). CONCLUSIONS: NTDT patients exhibit significant organ-specific iron overload, particularly in the liver, kidneys, and spleen. The correlations between iron levels in different organs suggest interconnected mechanisms of iron accumulation. These findings highlight the importance of regular MRI screening to monitor and manage iron overload in NTDT patients.
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Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.
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Adenoma , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasia Endócrina Múltipla Tipo 1/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Adulto , Estudos Retrospectivos , Adenoma/epidemiologia , Adenoma/patologia , Pessoa de Meia-Idade , Seguimentos , Adulto Jovem , Prognóstico , Progressão da Doença , Adolescente , Resultado do Tratamento , Prolactinoma/tratamento farmacológico , Prolactinoma/patologia , Prolactinoma/epidemiologiaRESUMO
OBJECTIVE: Endoscopic endonasal surgery is a feasible approach to lesions of the pediatric skull base. Olfactory outcomes following endoscopic endonasal approach (EEA) have been reported in the adult literature, but pediatric outcome data is lacking. The purpose of this preliminary study is to evaluate post-operative olfactory outcomes in pediatric patients who underwent EEA through transsphenoidal and/or transclival corridors. METHODS: Retrospective chart review of patients < 18 years of age who underwent EEA with nasoseptal flap skull base reconstruction between March 2019-January 2022. Following their first post-operative debridement and 6 months following surgery, patients were administered the University of Pennsylvania Smell Identification Test (UPSIT) to assess olfactory function. RESULTS: Fifteen patients (7 female, 8 male) with a mean age of 14.9 years met inclusion criteria. Thirteen (86.7%) patients required a transsphenoidal approach and 2 (13.3%) patients underwent a combined transsphenoidal and transclival approach. Mean time between surgical resection and first olfactory testing was 6.3 weeks (range 4.6-7.3 weeks). Nine patients (60.0%) had normosmia following EEA while 3 (20.0%) had mild microsmia, and 3 (20.0%) had moderate microsmia at 6 weeks following surgery. Results improved at their 6 month follow up visits. No patients experienced post-operative severe microsmia or anosmia. CONCLUSIONS: Olfactory preservation is possible following pediatric EEA, though 40% of patients will develop some degree of microsmia in the immediate post-operative period and 20% will have some persistent dysfunction at 6 months. Long-term data is necessary to determine if microsmia continues to improve over time.
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OBJECTIVE: The management of refractory pituitary adenomas (RPA) presents significant challenges. This study aimed to evaluate the long-term treatment outcomes of patients with RPA managed with temozolomide (TMZ) and to identify potential biomarkers for predicting TMZ treatment response. METHODS: This retrospective case series included patients with RPA who underwent transsphenoidal surgery (TSS) or craniotomy at a comprehensive medical center in China between January 2014 and December 2021. RESULTS: Thirty-nine patients with RPA (median age 42 years; 23 males (59%)) were treated with TMZ for a median of 9 cycles. The median follow-up was 34.4 months. Complete response (CR) was observed in 2 patients, partial response (PR) in 11 patients, stable disease (SD) in 9, progressive disease (PD) in 11, and death in 6 patients. MGMT (O6-methylguanine DNA methyltransferase) levels were significantly lower in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 24.2% and 58.1, respectively. MSH6 (MutS homologs 6) levels were significantly higher in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 64.2% and 36.9%, respectively. Patients who received concomitant TMZ and external beam radiotherapy showed a significant tumor size reduction of 178,837mm3 (p<0.001) compared to those treated with TMZ alone. CONCLUSIONS: TMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. MGMT and MSH6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.
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Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is a rare disorder. The signs and symptoms of ectopic acromegaly are indistinguishable from acromegaly due to a somatotroph adenoma. A 35-year-old female presented with secondary amenorrhea for 10 years, intermittent headache, and reduced vision in both eyes for 4 years, which worsened over 4 months before presentation. Additionally, she was diagnosed with uncontrolled diabetes mellitus. On examination, she had coarse facial features, a fleshy nose, and acral enlargement. She had diminished visual acuity (left>right) and bitemporal hemianopia on perimetry. Biochemical investigations revealed elevated IGF-1 [588 ng/ml, reference range (RR) 100-242], markedly elevated basal growth hormone (>80 ng/ml; RR, 0.12-9.88), and hyperprolactinemia in the tumoral range (832 ng/ml; RR, 5-25). MRI sella demonstrated a 22×30×34mm sellar-suprasellar mass with T2 hypointensity. Chest imaging revealed a 75×87×106mm left lung mass, which was found to be a well-differentiated neuroendocrine tumor (NET) on biopsy. Plasma GHRH levels were elevated [38,088 ng/l; RR, <250-300], and a diagnosis of ectopic acromegaly secondary to lung neuroendocrine tumor was considered. During workup, the patient developed in-hospital pituitary apoplexy, which improved with medical management. After a left pneumonectomy, her clinical features of acromegaly improved, her diabetes underwent remission, and there was a marked reduction in plasma GHRH and pituitary size. Histopathology was suggestive of a neuroendocrine tumor, with immunohistochemistry positive for GHRH and negative for prolactin. Her final diagnosis was ectopic acromegaly due to GHRH secreting a lung NET with pituitary somatotroph and lactotroph pituitary hyperplasia and apoplexy in the hyperplastic pituitary.
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Acromegalia , Hiperplasia , Hiperprolactinemia , Apoplexia Hipofisária , Humanos , Feminino , Adulto , Acromegalia/complicações , Hiperprolactinemia/complicações , Hiperprolactinemia/etiologia , Hiperplasia/complicações , Hiperplasia/patologia , Apoplexia Hipofisária/complicações , Hipófise/patologia , Hipófise/diagnóstico por imagem , Hipófise/metabolismo , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologiaRESUMO
Introduction: Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis. Objective: to evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA. Methods: Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method. Results: The sample was mainly composed of women (69/117 - 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 - 62.4%), Acromegaly (24/117 - 20.5%) and Cushing's Disease (CD) (20/117 - 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p <0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD. Conclusion: The results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs.
Assuntos
Adenoma , Neoplasias Hipofisárias , Canal de Ânion 1 Dependente de Voltagem , Proteína Killer-Antagonista Homóloga a bcl-2 , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Feminino , Adenoma/genética , Adenoma/metabolismo , Adenoma/cirurgia , Adenoma/patologia , Pessoa de Meia-Idade , Masculino , Adulto , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Canal de Ânion 2 Dependente de Voltagem/genética , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Prognóstico , Idoso , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
The Hypothalamus-Pituitary axis (HPA) is a rare location for metastasis of non-Hodgkin's lymphoma. Lymphomas constitute less than 0.5% of reported HPA metastasis. This case is unique in that, in addition to the noted panhypopituitarism; initial diagnostics demonstrated marked hyponatremia, consistent with syndrome of inappropriate antidiuretic hormone (SIADH), which was subsequently complicated by sudden diabetes insipidus (DI), suggesting hypothalamic/stalk infiltration. Despite low sensitivity, CSF cytology/flow cytometry may serve as a less invasive diagnostic measure. Treatment includes systemic chemotherapy with agents that cross the blood-brain barrier. Surgical resection alone or associated radiotherapy did not show an increase in survival. The prognosis remains poor.
RESUMO
PURPOSE: Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNETs) are the most common cause of acromegaly. The endoscopic endonasal transsphenoidal approach (EEA) is commonly employed to remove them. Although morphological differences in the nasal cavity exist between acromegaly patients and those with other types of PitNET, few quantitative studies have been performed. This study aimed to evaluate the anatomical features of the nasal cavity and paranasal sinuses in patients with acromegaly. METHODS: Preoperative computed tomography images of the nasal cavity and paranasal sinuses were compared between 20 patients with a GH-secreting PitNET (acromegaly group) and 22 with a non-functioning PitNET (control group). In the acromegaly group, the relationships between preoperative GH and/or insulin-like growth factor 1 (IGF-1) levels and anatomical characteristics were assessed. RESULTS: In the acromegaly group, the distance between the nostril and dorsum sellae was significantly longer and the distance between the parasellar internal carotid arteries was significantly shorter (p = 0.0022 and 0.0092, respectively). Pneumatization volume in the nasal cavity did not differ between the groups. Nasal mucosa and bony hypertrophy were observed in the acromegaly group. Preoperative GH level was correlated with the width of the piriform aperture (p = 0.0171). CONCLUSION: The nasal and paranasal changes associated with acromegaly can make EEA challenging to perform. Widening the surgical corridor anterior to the sphenoid sinus is important in these patients.