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Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.
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Neoplasias Encefálicas/diagnóstico , Germinoma/diagnóstico , Granuloma/diagnóstico , Hipofisite/diagnóstico , Hipopituitarismo/diagnóstico , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
PURPOSE: Endocrinal insufficiency caused by vasculotoxic snake envenomation is under-recognized and is mostly confined to a specific geographic area. We conducted a prospective study to determine the prevalence and pattern of pituitary-target gland insufficiencies caused by snake envenomation. MATERIALS AND METHODS: The hormonal evaluation of patients who had suffered from vasculotoxic snake envenomation was done at baseline and at 6 months of follow-up. Those patients with a documented hormonal insufficiency underwent magnetic resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of envenomation was assessed by the acute physiology and chronic health evaluation II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score, and the snake bite severity score (SBSS) for all patients. RESULTS: Seventy-six patients were seen during the study period, of which 60 were available for a repeat hormonal evaluation at 6 months, with the majority of patients belonging to the middle age group (mean age, 37.6 ± 14.9 years). The mean lag period at presentation was 32 ± 20 h. Thirty-five patients (46.1%) had coagulopathy, 20 patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%) needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was in continuation with the acute hypopituitarism that they developed. Growth hormone and glucocorticoid deficiencies were the most common endocrinopathies observed. The occurrence of hypopituitarism was observed only in patients with a vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal insufficiency, or any of the scoring tools did not predict the occurrence of hypopituitarism. CONCLUSION: Acute asymptomatic and chronic symptomatic or asymptomatic hypopituitarism are important sequelae of viper bite in a small proportion of patients and can occur in the presence of normal pituitary imaging. Routine prospective pituitary hormone screening should be done in all patients within the first 6 months of envenomation by the vasculotoxic snakebite as chronic pituitary dysfunction can often occur in these patients.
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Hipopituitarismo/etiologia , Hipófise/fisiopatologia , Mordeduras de Serpentes/complicações , Adulto , Animais , Feminino , Humanos , Hipopituitarismo/diagnóstico por imagem , Hipopituitarismo/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipófise/diagnóstico por imagem , Estudos Prospectivos , Daboia , Mordeduras de Serpentes/diagnóstico por imagem , Mordeduras de Serpentes/fisiopatologia , Sobreviventes , Adulto JovemRESUMO
BACKGROUND: Growth hormone (GH) levels following oral glucose tolerance test (OGTT) at 12 weeks or later after surgery have been accepted as the most reliable parameter for defining remission and/or cure in patients with acromegaly. However, the role of random GH in predicting remission in the immediate postoperative period using modern criteria is not known. This study was undertaken to evaluate the role of random GH levels in first 5 postoperative days as an early predictive tool for long-term remission of patients with acromegaly following transsphenoidal pituitary surgery (TSS). PATIENTS AND METHODS: Seventy-five consecutive acromegaly patients with at least three postoperative OGTT values at 3, 6, and 12 months of follow-up were included in the study. GH levels were measured just before surgery, in the immediate postoperative period, at 6 h and on day 1 to day 5 after surgery. Remission was defined as normal age-specific insulin-like growth factor-1 and either basal fasting GH <1 ng/ml or a nadir GH following OGTT <0 .4 ng/ml at 3 months of surgery. RESULTS: Of the 75 patients with acromegaly who underwent TSS, long-term remission was achieved in 42 (56%) patients. GH values ≤1.55 ng/ml at 6 h of surgery showed the highest predictive power for long-term remission, with a sensitivity of 81.2% and a specificity of 83.3%. The duration of disease and tumor volume had no effect on the 6 h GH value-related prediction of cure. CONCLUSION: Early postoperative GH values may be used to predict long-term cure. A value of ≤1.5 ng/ml at 6 h following surgery may predict long-term cure in two-thirds of the patients with acromegaly who undergo TSS.
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Acromegalia/cirurgia , Hormônio do Crescimento Humano/análise , Teste de Tolerância a Glucose , Humanos , Fator de Crescimento Insulin-Like I/análise , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
BACKGROUND: Extra-pituitary birth defect (EPBD) in children with congenital hypopituitarism is largely unknown. OBJECTIVE: The study aims to evaluate the incidence and pattern of EPBD in children with congenital hypopituitarism and to evaluate whether it can serve as a clue to diagnose this condition. PATIENTS AND METHODS: Retrospective analysis of hospital record of patients of short stature due to various etiology from which patients with congenital hypopituitarism with age ≥18 years were recruited for the analysis. Clinical, hormonal, radiological and ocular electrophysiological studies were done in all patients and all EPBD were noted. RESULTS: Twenty seven patients (79%) had multiple pituitary hormone deficiency (MPHD) of which growth hormone was universal followed by gonadotropin (62%), TSH (59%), ACTH (44%) and prolactin (12%). Nineteen patients (56%) had multiple EPBD in various combinations. Twenty three ocular abnormalities were present in 12 patients (35%). Nine patients (26%) had other associated EPBD along with ocular abnormalities while 3 had ocular abnormalities without any other associated birth defect. Skeletal defects were present in 10 patients (29.5%). On the contrary, 5 patients in the EPBD group had total 15 visual defects. The most common abnormality of the visual system were abnormal visual evoke response (VER, 18%), followed by strabismus (15%), visual acuity (VA, 12%), electroretinogram (ERG) and electrooculogram (EOG) 8% each and visual field defect 6%. There was a trend towards early age at presentation with EPBD. CONCLUSIONS: Presence of EPBD in a short child is a sensitive marker to diagnose congenital hypopituitarism. Subtle abnormalities of visual pathway without absent septum pellucidum or midline brain defects were common.
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Traumatismos do Nascimento , Nanismo , Hipopituitarismo , Hipófise/diagnóstico por imagem , Hormônios Hipofisários , Sela Túrcica/diagnóstico por imagem , Adulto , Traumatismos do Nascimento/complicações , Traumatismos do Nascimento/epidemiologia , Nanismo/diagnóstico , Nanismo/epidemiologia , Anormalidades do Olho/diagnóstico , Feminino , Hormônio do Crescimento/análise , Humanos , Hipopituitarismo/congênito , Hipopituitarismo/diagnóstico , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Índia/epidemiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Hormônios Hipofisários/análise , Hormônios Hipofisários/deficiência , Estudos Retrospectivos , Displasia Septo-Óptica/diagnóstico , Displasia Septo-Óptica/epidemiologia , Estatística como Assunto , Tomografia Computadorizada por Raios X/métodosRESUMO
India aims to provide universal health coverage to all individuals and communities thus ensuring accessibility, promotive, curative, preventive, rehabilitative, and palliative health services to all. Healthcare technologies play a critical role in ensuring eliminating healthcare disparities and encouraging quality healthcare at all levels. Technology solutions such as indigenous medical devices and diagnostic products, telemedicine, artificial intelligence, and drone technology can best integrate rural needs, improve health outcomes, patient safety, and healthcare quality and experience for patients' values and strengths and can therefore be important contributors to advancing rural health equity. These technologies can transform India's healthcare system by providing quality care and mitigating the risk of catastrophic financial hardship.
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Background: The burden of communicable, non-communicable diseases and reproductive maternal, newborn, child & adolescent health in India, reflects the necessity to develop tailored solutions. The plethora of MedTech innovations has provided healthcare facilities with more effective, affordable and accessible healthcare for people across the country. However, in spite of the Make-in-India scheme in the country, the indigenously developed healthcare technology is far from making an impact on the healthcare system. Objective: To present a roadmap for MedTech innovations for their successful deployment into the public healthcare system. Methodology: In addition to the literature review, recommendations were included from several stakeholders such as innovators, manufacturers, policymakers, subject matter experts, funding organizations, State health officials etc. Results and conclusion: The journey of healthcare innovation from need identification to ideation, to prototyping and validation has paved the way towards the de novo design that caters to unmet needs. Innovations at the advanced technology readiness level (TRL 7/8 and above) demand a holistic and multidisciplinary approach which includes clinical validation, regulatory approval and Health technology assessment. The deployment of healthcare technology into the public healthcare system must consider resources (e.g., time, staff, budget, investment policies), ethical concerns (privacy, security, regulations, ownership), governance (policy, accountability, responsibility etc.), and Skills (capabilities, culture, etc.). The technologies are considered for field trials before the uptake in the public health system. Technology can be a key tool in achieving Universal Health Coverage but its use has to be strategic, judicious, and cognizant of issues around privacy and patient rights.
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Timely delivery of medical supplies is essential in the healthcare sector, which is hampered by factors such as poor transportation network, traffic and adverse environmental conditions. Alternatively, drone operations can leapfrog the last mile logistic solutions in hard-to-reach terrains. The present paper elucidates the implementation process of drone-based delivery of medical supplies, operational challenges and innovations adopted by scientists in Manipur and Nagaland. Three districts, Bishnupur, Imphal West and Churachandpur from Manipur and two districts, Mokokchung and Tuensang from Nagaland, were selected for the study. Regulatory and ethical approvals and coordination with state health and administrative authorities were accorded. Implementation and operational challenges faced by the research team were recorded elaborately in the field diaries and assessed qualitatively. The experiences encountered by the team for case-to-case based permission and coordination with the central and state aviation authorities, district administration and health authorities were observed. The drone-related technical and logistic challenges were identified as the deployment of suitable drones, payload capacity, time management for operations, and transportation of drones. The officials adopted mitigation strategies to overcome field-based challenges. Drone-based deliveries of medical supplies are proving to be time efficient, however, overcoming operational challenges could provide an effective long-term deployment strategy.
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Meios de Transporte , Dispositivos Aéreos não Tripulados , ÍndiaRESUMO
Context: Paediatric pituitary adenomas (PPAs) are uncommon, with evidence confined to small cohorts. Aim: We aimed to elucidate the baseline profile and outcomes of PPAs in a large, contemporary, monocentric cohort. Settings, Design: Pituitary clinic at PGIMER over 8 years (2010-2018). Subjects and Methods: PPAs in patients (≤20 years at diagnosis) were included. A retrospective review of their baseline clinico-biochemical and radiological profiles and outcomes post pituitary surgery/medical management was performed. Results: There were a total of 74 patients, of which 42 were female. The median age was 15 (IQR 13-18) years. Corticotropinomas (32.4%) and somatotropinomas (25.7%) were common, with 1 case of TSHoma and pituitary blastoma. The most common presentation was headache (57%) overall and menstrual irregularities (64.2%) in girls. Most (78%) had macroadenomas. Prolactinomas showed an excellent response to primary medical therapy (83.3%). Transsphenoidal surgery was performed in 81% of patients. Diabetes insipidus (30%) and hyponatremia (26.7%) emerged as common postoperative complications. Adjuvant medical management was required in 25%, and radiotherapy in 18%. Remission rates in Cushing's and acromegaly were 62.5% and 57.8%, respectively, with long-term hormone deficits noted in one-third of patients. Conclusion: PPAs have unique features and management challenges, including effects on growth and puberty. Functional tumours and macroadenomas are common. Remission can be achieved in more than half of the patients, with endocrine deficits persisting in about a third of cases, needing long-term surveillance.
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Acromegalia , Adenoma , Neoplasias Hipofisárias , Acromegalia/cirurgia , Adenoma/diagnóstico , Adenoma/patologia , Adenoma/cirurgia , Adolescente , Criança , Feminino , Humanos , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze pregnancy course and outcomes in women treated for acromegaly and compare outcomes based on disease activity at the time of conception. DESIGN: Retrospective study. PATIENTS: Women with acromegaly diagnosed prior to or during pregnancy from 2010 to 2019, representing cases (14 pregnancies in 12 cases), were later stratified based on active (n = 5) or controlled disease (n = 9) at time of conception. Female acromegalic patients over the same period constituted the 'acromegaly cohort' (AC) (n = 75). RESULTS: All cases had macroadenomas with nadir GH of 15.06 ng/ml (IQR 9-30), IGF-I index of 3.04 (1.96-3.82), for which they had undergone pituitary surgery; except two patients diagnosed during pregnancy, who received pharmacotherapy followed by surgery 4 months postpartum. Adjuvant pharmacotherapy was required in 71.4% patients and radiotherapy in 35.7%. Pregnancy occurred at a median of 2 (0.8-5.1) years after surgery and 21.4% required assisted reproduction. All had term delivery with normal APGAR except one case with gestational hypertension, who delivered a preterm baby. None had congenital malformations. Despite higher baseline IGF-I, GH and tumor volume in those with pre-conceptional active acromegaly, materno-fetal outcomes were not different from those with controlled disease (p > 0.05). Similar or greater proportion of cases had normal GH and no residual tumor postpartum, even in those with pre-conceptional active acromegaly. CONCLUSION: The current study showed conducive outcomes of gestation in women treated for acromegaly and no higher rates of pregnancy parameters or complications than non-acromegaly pregnancies in the same population. Active acromegaly does not seem to have an adverse bearing on outcomes.
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Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/metabolismo , Acromegalia/patologia , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Although low-and middle-income countries (LMIC) bear the burden of the pituitary adenomas, most research is conducted in developed countries. However, there has been significant growth in research on pituitary adenomas in India from 1995 to 2020. The cost of patient treatment, management, and surgery of pituitary lesions are comparatively lower in India in comparison to high income countries. OBJECTIVE: The intended goal is to highlight the current scenario of pituitary research in India with regards to prevalence/incidence, tumor size, treatment modalities, cost of pituitary surgery, and potential strategies for tackling pituitary adenoma disease burden in the country. METHODOLOGY: In addition to the literature review, recommendations were included from neurosurgeons, endocrinologists, and radiologists from various centers in India. RESULTS: There is an increasing evidence of pituitary adenoma heterogeneity compared to western populations. Although there has been significant increase in research on pituitary tumors from India, it is considerably less as compared to the data from the rest of the world. The major challenges for the treatment of this benign disease in India are lack of imaging facility in rural areas, poor patient follow up, and financial constraints for periodic imaging and biochemical assessment. CONCLUSION: A computerized pituitary registry and genetic screening and testing will significantly boost research and lead to better patient outcome in the country. Special emphasis should be laid on multimodal management to ascertain optimal long-term tumor control with best hormonal outcome.
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Adenoma , Neoplasias Hipofisárias , Radiocirurgia , Adenoma/epidemiologia , Adenoma/cirurgia , Seguimentos , Humanos , Índia/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The COVID-19 infection outbreak has aroused increasing attention and affected thousands of people nationwide. The long incubation period, high infectious rate, varied manifestation, and absence of effective treatment make it difficult to manage the disease transmission. OBJECTIVE: The intended goals are to encourage efficient management of neurological and neurosurgical patients, resource utilization, and protecting the healthcare provider during the COVID-19 epidemic. Herein, we present a consensus statement from various centers in India. METHODOLOGY: In addition to the literature review, recommendations were included from neurologists and neurosurgeons from various centers in India. RESULTS: Every patient presenting for treatment should be treated as a potential asymptomatic infected case. Patients should be categorized based upon the priority as acute (require immediate treatment/surgery within 24 h), sub-acute (requiring treatment within a maximum of 7-10 days), or chronic (requiring treatment within a month). Non-essential elective surgeries and outpatient clinics should be avoided after informing the patient(s). There is a high risk of aerosol dispersion during intubation and certain neurosurgical procedures particularly those involving drills and endoscopes. These procedures should be performed wearing full personal protective equipment. The workflow of the operating rooms should also be modified significantly. Minor modifications in personal and professional lifestyles and routine training to use the PPE will ensure efficient management of resources. CONCLUSION: These recommendations could be used to mitigate the risks and reduce exposure to other patients, public, and healthcare staff.
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Infecções por Coronavirus , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Infecções/normas , Neurologia/normas , Neurocirurgia/normas , Pandemias , Assistência ao Paciente/normas , Pneumonia Viral , COVID-19 , Consenso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Procedimentos Neurocirúrgicos , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissãoRESUMO
OBJECTIVE: The natural history of glucose intolerance (GI) in patients with acromegaly undergoing surgical treatment has not been fully understood. This study was aimed to unravel the prevalence and predictors of recovery from GI in these patients in a prospective multivariate model. MATERIALS AND METHODS: Patients with acromegaly treated between 2007 and 2016 were prospectively studied with respect to demographics, clinicoradiological features, comorbidities, and hormonal investigations before surgery and at regular follow-up. The independent predictors of recovery from diabetes were analyzed. RESULTS: There were a total of 151 patients with active acromegaly included in the study. The median baseline growth hormone (GH) and insulin-like growth factor (IGF)-1 levels were 25 and 811 ng/mL, respectively. Diabetes mellitus (DM) and pre-diabetes were noted in 93 (61.6%) and 20 (13.2%) patients, respectively. Following surgical treatment, the median HbA1c decreased significantly from 6.4% to 5.5% (P < 0.001), with 46.8% having complete recovery from DM or pre-diabetes. This glycemic recovery had significant association with both biochemical (P = 0.001) and radiological remission (P = 0.01). The recovery from DM had a greater association with post-operative IGF-1 than GH, especially among those with discordant GH and IGF-1 levels (60% in normal IGF-1 and high GH vs. 20% in high IGF-1 and normal GH). Post-operative IGF-1 had a significant impact on recovery from DM (P = 0.01) independent of age, body mass index, duration of DM, and pre-operative HbA1c. CONCLUSION: Nearly half of the patients with acromegaly with DM or pre-diabetes had glycemic recovery, influenced by biochemical and radiologic remission. Post-operative IGF-1 appears to be the strongest independent determinant of recovery from DM.
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Acromegalia/cirurgia , Complicações do Diabetes/diagnóstico , Acromegalia/complicações , Adolescente , Adulto , Idoso , Criança , Complicações do Diabetes/etiologia , Feminino , Intolerância à Glucose/etiologia , Hormônio do Crescimento Humano/análise , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
CONTEXT: Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma. CASE DESCRIPTION: The patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35âmm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated. CONCLUSION: Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.
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Adenoma/genética , Adenoma/terapia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/terapia , Protocolos Antineoplásicos , Bevacizumab/uso terapêutico , Pré-Escolar , Terapia Combinada , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Mutação , Octreotida/uso terapêutico , Hipófise/cirurgia , Radioterapia Adjuvante , Temozolomida/uso terapêuticoRESUMO
Apoplectic pituitary adenomas cause significant morbidity and even mortality. The pituitary apoplexy denotes a pituitary adenoma presenting with hemorrhage and/or infarction, implementation in remedial effects of various of drugs in pituitary apoplexy is a promising pharmacogenomic field in the near future adenoma treatment. Indisputably, this is an important horizon for complicated pituitary adenomas. In a pituitary adenoma, the interplay between genetic, cytokine, and growth factors promotes the pathogenic transformation into an apoplectic formation. However, till date, little is known about how all these factors together lead to the pathogenesis of apoplectic pituitary. The vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), pituitary tumor-transforming gene (PTTG), matrix metalloproteinase-2/9 (MMP-2/9), proliferating marker (Ki-67), as well as hypoxia-inducing factor are the major contributing factors involved in pituitary apoplexy. The molecular mechanism involved in pituitary apoplexy has never been described so far. In this review, we discuss the various proteins/cytokines/growth factors and signaling molecules which are involved in the pathogenesis of pituitary apoplexy and their potential role as biomarkers or as therapeutic targets.
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Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line. Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/ß) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways. Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-ß (PDGFR-ß; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-ß pathway. Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas.
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BACKGROUND: Angiogenesis and vascular endothelial growth factor (VEGF) have recently been implicated in animal and clinical models of radiation-induced optic nerve, retinal, and brain necrosis. Although there are isolated case reports of anti-VEGF therapy with bevacizumab for management of radiation-induced brain necrosis, there are little data defining its role in radiation-induced optic nerve damage. PATIENTS AND METHODS: This study included patients with a sellar-suprasellar tumor who underwent intensity-modulated or Gamma Knife radiotherapy and developed radiation-induced optic neuritis (RION) refractory to 3 weeks of glucocorticoid therapy who received bevacizumab 5 mg/kg intravenously as initial dose, followed by subsequent doses of 10 mg/kg. RESULTS: Here we report 3 patients with sellar-suprasellar lesions undergoing conventional radiation therapy (2 cases) or Gamma Knife surgery (1 case) who had benefitted from anti-VEGF therapy following radiation-induced optic nerve damage. CONCLUSIONS: Early bevacizumab therapy in steroid-refractory RION shows gratifying results.
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Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Recidiva Local de Neoplasia/radioterapia , Neurite Óptica/tratamento farmacológico , Lesões por Radiação/tratamento farmacológico , Adenoma/radioterapia , Adulto , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/radioterapia , Humanos , Masculino , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Pessoa de Meia-Idade , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/etiologia , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown. MATERIALS AND METHODS: This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples. The hormonal parameters were done at baseline, at the time of discharge and at three months of follow-up. RESULTS: A total of 14 patients out of 46 with the mean age of 30.1 ± 10.3 years were finally eligible for the study. Hormonal alterations at admission were similar to sick euhormonal syndrome. Overall 7 of them had nine hormonal deficits at three months of follow up, 4 having sub normal basal cortisol level and two each had low testosterone and growth hormone and only one had thyroxine deficiency. CONCLUSION: Acute organophosphate poisoning results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a small subset of patients, varying level of hormonal insufficiency may occur either at admission or later. These observations need re-validation in a larger group of patients with specific OPC.
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CONTEXT: Disorders of the prostate gland are more prevalent in patients with acromegaly. GH-insulin-like growth factor 1 (IGF1) axis plays an additive role in prostatic growth and development. OBJECTIVE: To correlate the structural and histopathological changes of the prostate and prostatic symptoms with GH/IGF1 in patients with acromegaly. DESIGN: Case-control study, from January 2012 to November 2013. SETTING: Tertiary referral centre university hospital in Northern India. PATIENTS: Fifty-three men with acromegaly and 50 healthy men matched for age and BMI. MAIN OUTCOME MEASURES: International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, dimensions of the prostate on trans-rectal ultrasonography, parameters on uroflowmetry, and immunopositivity with anti-IGF1 antibody in prostatic tissue biopsies. RESULTS: Despite low serum testosterone levels (8.9ânmol/l vs 14.3ânmol/l, acromegaly vs control), patients with acromegaly had marginally higher IPSS, PSA levels, and grades of enlarged prostate and obstructive features on uroflowmetry compared with controls. Dimensions of the prostate on ultrasonography were also significantly higher in patients. These changes were present irrespective of age, current gonadal status, and disease activity. Evidence of prostatic hyperplasia on biopsy was seen in six of 14 patients (42.8%) who underwent prostatic biopsy while it was absent in the controls. Immunohistochemistry with anti-IGF1 antibody showed moderate positivity in all the 14 patients who underwent biopsy with benign prostatic hyperplasia, compared with mild positivity in 21% of controls. Similarly, 14 control patients with prostatic malignancies showed variable positivity, four patients had strong, two each had mild and moderate positivity, while six were negative. CONCLUSIONS: In patients with acromegaly, there is a higher frequency of structural changes in the prostate, along with greater prostatic volume and obstructive features, compared with healthy controls, irrespective of age, gonadal status, and disease activity.