RESUMO
Pituicytoma is a rare low degree tumor that arises from pituicytes in the infundibulum and posterior pituitary gland. As they do not have characteristic radiological features, they can be misdiagnosed as pituitary adenoma, meningioma, or craniopharyngioma. Clinically, patients can present with hormonal disturbances, headaches and visual field defects. A 46 year old male who presented with visual field defects and symptoms suggestive of panhypopituitarism for the past 3 years, is described. As a personal history, he had neurofibromatosis type 1 and his daughter, with the same disease, who has been operated of astrocytoma. Upon clinical assessment, the patient's ophthalmic examination was bitemporal hemianoptia, and hormonal evaluation confirmed hypopituitarism. Pituitary magnetic resonance imaging showed a suprasellar homogeneous enhancing post-gadolinium mass causing chiasmatic displacement. Transnasal transsphenoidal resection was performed. Postoperatively, the patient developed diabetes insipidus. Histopathology showed patterns consistent with pituicytoma. and immunohistochemistry confirmed it. Total resection remains the goal of treatment.
El pituicitoma es un tumor de bajo grado, infrecuente, surge de los pituicitos en el infundíbulo y la neurohipófisis. Al no tener rasgos radiológicos característicos, pueden diagnosticarse erróneamente como adenoma hipofisario, meningioma o craneofaringioma. Clínicamente los pacientes pueden presentar alteraciones hormonales, cefaleas y defectos del campo visual. Se describe el caso de un varón de 46 años que presentó defectos del campo visual y síntomas de panhipopituitarismo de 3 años de evolución. Como antecedentes personales presentaba neurofibromatosis tipo 1, y la hija, con la misma enfermedad, operada de astrocitoma cerebral. En el examen oftalmológico el paciente presentaba hemianopsia bitemporal y la evaluación hormonal confirmó hipopituitarismo. La resonancia magnética hipofisaria evidenció una masa selar con extensión supraselar con realce homogéneo post contraste, la cual generaba desplazamiento del quiasma óptico. Se realizó una resección transnasal transesfenoidal. Posterior a la cirugía, desarrolló diabetes insípida. La histopatología mostró patrones compatibles con pituicitoma confirmado por inmunohistoquímica. La resección total continúa siendo el objetivo del tratamiento.
Assuntos
Imageamento por Ressonância Magnética , Neurofibromatose 1 , Neoplasias Hipofisárias , Humanos , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Pessoa de Meia-Idade , Neurofibromatose 1/complicações , Hipopituitarismo/etiologia , Hipopituitarismo/diagnósticoRESUMO
Introduction: Congenital hypopituitarism (CH) is characterized by the deficiency of pituitary hormones. Among CH patients, 85% lack a molecular diagnosis. Whole Exome Sequencing (WES) identified a homozygous variant (c.865G>A, p.Val289Ile) in the CDH2 gene, responsible for N-Cadherin production, crucial for cell-cell adhesion. Predicted to be likely pathogenic, the variant was found in a patient deficient in GH, TSH, ACTH, and LH/FSH. Its impact on cell adhesion was confirmed in L1 fibroblast cell lines. Objective: Create a cdh2 knockdown in zebrafish for investigating its role in pituitary development through growth hormone and transcription factors expression. Methods: Utilized pET28B-RfxCas13d-His plasmid for Cas13 mRNA production via in vitro transcription, guiding Cas13 to cdh2 with three RNAs. Injected the complex into single-cell embryos for analysis up to 96 hpf. Assessed gene expression of cdh2, prop1, pit1, and gh1 using RT-qPCR. Evaluated cdh2 protein expression through the western blot technique. Results: Knockdown animals displayed developmental delay. The cdh2 expression decreased by 75% within 24 hours, rebounded by 48 hours, and reached wild-type levels by 96 hpf. gh1 expression decreased at 48h but increased by 96 hpf, aligning with WT. No significant differences in prop1 and pit1 expression were observed. Conclusion: Our findings underscore cdh2's role in pituitary development and hormonal regulation, offering insights for developmental biology research.
Assuntos
Sistemas CRISPR-Cas , Caderinas , Técnicas de Silenciamento de Genes , Hipófise , Fatores de Transcrição , Peixe-Zebra , Animais , Peixe-Zebra/genética , Caderinas/genética , Caderinas/metabolismo , Hipófise/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Humanos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hipopituitarismo/genética , Hipopituitarismo/metabolismoRESUMO
Hypopituitarism is a rare clinical condition that can present as a partial or complete absence of pituitary hormones. Hypopituitarism is most commonly caused by a sellar or parasellar mass, particularly a tumor, and the gold standard for its differential diagnosis is magnetic resonance imaging (MRI). Intrasellar aneurysm is an unusual cause of hypopituitarism. Indeed, about 0.17% of all cases of hypopituitarism are due to intrasellar aneurysms. We report the case of a 72-year-old man who was admitted to the hospital due to gastrointestinal symptoms and malnourishment. Due to persistent hyponatremia and spontaneous hypoglycemia in laboratory findings, the examination of the hypothalamic-pituitary-adrenal axis was eventually initiated, and the patient was later diagnosed with an unruptured aneurysm of the ophthalmic segment of the right internal carotid artery with sellar extension as a cause of panhypopituitarism. A combined endovascular treatment was performed with stent-assisted coil embolization of the aneurysm, and the patient was prescribed oral hormonal therapy. At the 1-year follow-up visit, no improvement in pituitary function was observed, and a pituitary MRI showed complete aneurysm occlusion and partial empty sella with significantly decreased pituitary volume. Aneurysms of the internal carotid artery are rare and may be associated with hypopituitarism and delayed diagnosis due to their unusual clinical presentation. Endovascular procedures, such as coil embolization of the aneurysm, could be the treatment of choice in these patients. Persistent hypopituitarism may occur even after successful treatment of the aneurysm.
Assuntos
Hipopituitarismo , Sela Túrcica , Humanos , Masculino , Hipopituitarismo/etiologia , Hipopituitarismo/diagnóstico por imagem , Idoso , Sela Túrcica/diagnóstico por imagem , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética , Embolização Terapêutica , Artéria Carótida Interna/diagnóstico por imagemRESUMO
BACKGROUND: Pituitary apoplexy (PA) is characterized by acute hemorrhage or infarction of the pituitary gland. Management can be either conservative or surgical. Evidence favoring either is still limited to observational studies. This meta-analysis evaluates the effectiveness of both approaches on patient outcomes. METHODS: A systematic search was performed until February 2024. We included cohort studies of patients with PA. Patients were divided into 2 groups: a conservative management group and a surgery group, including early and late surgery. Outcomes of interest were assessed categorically using risk ratio (RR) and Mantel-Haenszel's random effects model. RESULTS: Of the 273 published articles, 15 cohort studies comprising 908 patients were included. There was no statistically significant difference between groups in recovery of ophthalmoplegia (RR=1.09, confidence interval [CI]=1.00-1.18, P=0.05), visual field (RR=1.09, CI=0.91-1.3, P=0.35), visual acuity (RR=1.05, CI=0.87-1.26, P=0.61), hypopituitarism (RR=1.37, CI=0.81-2.32, P=0.25), and tumor recurrence (RR=0.74, CI=0.34-1.61, P=0.45). This was similar for conservative management versus early surgery in recovery of visual field (RR=0.92, CI=0.62-1.37, P=0.68), visual acuity (RR=1.01, CI=0.81-1.26, P=0.93), and ophthalmoplegia (RR=0.92, CI=0.53-1.61, P=0.77). CONCLUSIONS: Both interventions provide comparable outcomes. These findings, though, are drawn from observational studies, and more severe cases typically undergo surgery. Larger studies are necessary to provide conclusive evidence.
Assuntos
Apoplexia Hipofisária , Humanos , Tratamento Conservador/métodos , Hipopituitarismo/etiologia , Procedimentos Neurocirúrgicos/métodos , Oftalmoplegia/etiologia , Apoplexia Hipofisária/complicações , Apoplexia Hipofisária/cirurgia , Apoplexia Hipofisária/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). METHODS: The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. RESULTS: Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. CONCLUSIONS: The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.
Assuntos
Hipopituitarismo , Camundongos Knockout , Hipófise , Hipopituitarismo/genética , Animais , Humanos , Hipófise/metabolismo , Hipófise/anormalidades , Hipófise/patologia , Camundongos , Fenótipo , Feminino , Masculino , Modelos Animais de Doenças , Sequenciamento do Exoma , Displasia Septo-Óptica/genéticaRESUMO
CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction, with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes with high loss-of-function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (eg, PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.
Assuntos
Sequenciamento do Exoma , Hipopituitarismo , Humanos , Hipopituitarismo/genética , Hipopituitarismo/diagnóstico , Masculino , Feminino , Criança , Pré-Escolar , Adolescente , Lactente , Argentina/epidemiologia , Mutação , Estudos de Coortes , FenótipoRESUMO
Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.Diagnosis typically involves a thorough clinical evaluation, hormone level assessments, and neuroimaging studies to identify underlying causes. Treatment aims to replace deficient hormones and address the underlying cause and related complications when possible. In this special issue we address diagnosis, comorbidities, and management of hypopituitarism. We hope that it will help healthcare professionals to manage their patients.
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Hipopituitarismo , Humanos , Hipopituitarismo/terapia , Hipopituitarismo/diagnósticoRESUMO
INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.
Assuntos
Neoplasias de Cabeça e Pescoço , Hipopituitarismo , Neoplasias Pancreáticas , Adulto , Criança , Humanos , Incidência , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Neoplasias de Cabeça e Pescoço/radioterapia , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologiaRESUMO
Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.
Assuntos
Hipopituitarismo , Resistência à Insulina , Síndrome Metabólica , Humanos , Hipopituitarismo/etiologia , Hipopituitarismo/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/complicações , Terapia de Reposição Hormonal , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/metabolismoRESUMO
Retinitis pigmentosa (RP) is the most common retinal degeneration in humans and is characterized by the progressive degeneration of rods and cones and retinal pigment epithelium. We generated the IOCVi001-A induced pluripotent stem cell (iPSC) line from dermal fibroblast of a patient with a homozygous c.498_499insC (p.(Asn167Glnfsâ34) variant in the Membrane-type frizzled related protein (MFRP) gene, a genetic defect causing a syndrome characterized by RP and small eye size (nanophthalmos). IOCVi001-A displayed normal stemness, expressed pluripotent stem cell markers and displayed a normal karyotype. This iPSC line can be used for in vitro disease modeling for complex forms of RP.
Assuntos
Hipopituitarismo , Células-Tronco Pluripotentes Induzidas , Microftalmia , Retinose Pigmentar , Humanos , Microftalmia/genética , Microftalmia/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Proteínas de Membrana/genética , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , MutaçãoRESUMO
Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.
Assuntos
Hipopituitarismo , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/terapia , Criança , Hormônios Adeno-Hipofisários/deficiência , Hormônios Adeno-Hipofisários/metabolismoRESUMO
O linfoma de células B de mediastino é um linfoma não Hodgkin, uma neoplasia maligna do sistema linfático, com um comportamento agressivo. Este artigo é um estudo descritivo com o objetivo de relatar o caso de uma paciente feminina de 33 anos que, durante a investigação diagnóstica para imunodeficiência comum variável, foi diagnosticada com linfoma primário de mediastino associado à infiltração hipofisária e consequente pan-hipopituitarismo em um hospital de São Paulo. Esta paciente foi tratada com o esquema R-DA-EPOCH de quimioimunoterapia, que tem doses escalonadas das medicações de acordo com a tolerância, com remissão completa da doença após os seis ciclos previstos no esquema. Atualmente, a paciente mantém seguimento após quimioterapia e está em remissão. Realizou-se uma revisão de literatura desde os aspectos diagnósticos até a terapêutica. Os registros foram confrontados com a literatura médica, podendo assim qualificar a intervenção terapêutica instituída e os resultados alcançados. O estudo em questão ilustra a complexidade de casos de linfoma de células B primário de mediastino, quando se evoluem de forma disseminada, especialmente numa rara apresentação de infiltração hipofisária, se tornando um desafio clínico e demonstrando a importância de fomentar mais pesquisas na área, capazes de aprimorar a abordagem aos linfomas em diferentes níveis de assistência médica. Palavras-chave: Hipopituitarismo. Linfoma de Células B. Mediastino. Neoplasias do mediastino. Antineoplásicos - administração & dosagem.
Assuntos
Humanos , Feminino , Adulto , Terapêutica , Linfoma não Hodgkin , Células , Linfoma de Células B , Tratamento Farmacológico , Conduta do Tratamento Medicamentoso , Resposta Patológica Completa , Hipopituitarismo , Sistema Linfático , Linfoma , Neoplasias do Mediastino , Mediastino , Assistência Médica , Neoplasias , Antineoplásicos/administração & dosagemRESUMO
Introdução: A Displasia septo-óptica (DSO) é uma condição clínica relativamente rara, com uma prevalência de 1:10.000 a 20.000 nascidos vivos. O seu diagnóstico é clínico, sendo realizado quando há pelo menos 2 dos componentes da tríade clássica: hipoplasia de nervo óptico (HNO), malformação de linha média e disfunções hipofisárias. Até 70% dos pacientes com DSO podem apresentar deficiências hormonais. Apesar de relativamente rara, tem-se observado um aumento significativo da sua incidência ao longo dos anos, de maneira que cada vez mais estudos estão sendo elaborados para melhor entendimento de sua fisiopatologia. Estima-se uma maior prevalência de obesidade na síndrome, justificada pelos defeitos hipotalâmicos que podem levar a alterações metabólicas como hiperfagia e alterações de sensibilidade da leptina, favorecendo o ganho ponderal. Além disso, as deficiências hormonais hipofisárias, como a deficiência do hormônio de crescimento (GH), também contribuem para agravar o quadro. Objetivos: Avaliar o perfil metabólico, por meio da análise clínica, laboratorial e de bioimpedância elétrica (BIA) dos pacientes com DSO acompanhados no ambulatório de endocrinologia do IPPMG-UFRJ. Metodologia: Estudo transversal descritivo de coorte de pacientes com DSO acompanhados no ambulatório de endocrinologia do IPPMG-UFRJ. Resultados: Foram encontrados 48 indivíduos com DSO (50% do sexo feminino), sendo 28 com seguimento regular. As idades médias de diagnóstico e de encaminhamento ao ambulatório de endocrinologia foram de 3,90 ± 3,85 anos e 3,15 ± 3,30 anos, respectivamente, e a idade média atual daqueles que mantém acompanhamento foi de 7,46 ± 4,83 anos. A idade materna era ≤ 25 anos no momento do parto em 64% (25/39), sendo 44,44% (n=20/45) delas primigestas. Quanto aos critérios diagnósticos da DSO, em 92,6% (N=38/41) foi identificada HNO (78,9% bilateralmente); 95,3% (N=41/43) apresentaram alterações estruturais de linha média em exame de neuroimagem, 85,7% (N=24/28) alterações estruturais de sela túrcica e 73% apresentaram pelo menos uma deficiência hormonal, dos quais 2/3 apresentaram múltiplas disfunções hipofisárias. A disfunção mais frequente foi do hormônio tireotrófico (TSH), seguida pela de GH e hormônio adrenocorticotrófico (ACTH). Foram encontradas as medianas de valores de glicemia, colesterol total, LDL, HDL e triglicerídeos de 77 mg/dL,187 mg/dL, 112,7 mg/dL, 48 mg/dL e 107 mg/dL, respectivamente. Na avaliação da bioimpedância (BIA), foi encontrada uma mediana de 18,7% para massa gorda e uma mediana de 81,3% para massa magra. Na avaliação da distribuição da massa magra entre massa óssea e massa muscular, foi encontrada uma mediana de 4,3% e uma mediana de 28,4%, respectivamente. Dez participantes apresentaram percentual de massa óssea baixo e 9 participantes apresentaram percentual de massa muscular baixo. Onze participantes apresentaram pelo menos 1 destes percentuais abaixo dos valores de referência. Conclusão: Mais de 1/3 dos pacientes apresentava os 3 critérios da tríade clássica de DSO e 2/3 disfunções hipofisárias. Não houve alterações significativas de glicemia, TGO, TGP. A dislipidemia se mostrou presente na maioria dos pacientes, com mais da metade com LDL elevado e quase 2/3 com hipertrigliceridemia. A maioria dos pacientes foi classificada como eutrófica pelo índice de massa corporal (IMC), no entanto » apresentou percentual elevado de massa gorda e quase 80% percentual de massa magra baixo, sendo ¾ com baixo percentual de massa óssea. Recomendase que a BIA não seja substituída pela avaliação do IMC nos pacientes com DSO.(AU)
Background: Septo-optic dysplasia (SOD) is a rare clinical condition, with a prevalence of 1:10,000 to 20,000 live births. Its diagnosis is clinical, being made when there are at least 2 of the components of the classic triad: optic nerve hypoplasia (ONH), midline malformation and pituitary dysfunction. Up to 70% of patients with SOD may experience hormonal deficiencies. Despite being rare, a significant increase in its incidence has been observed over the years, so that more and more studies are being carried out to better understand its pathophysiology. A higher prevalence of obesity in the syndrome is estimated, justified by hypothalamic defects that can lead to metabolic changes such as hyperphagia and changes in leptin sensitivity, favoring weight gain. Furthermore, pituitary hormonal deficiencies, such as growth hormone (GH) deficiency, also contribute to aggravating the condition. Objective: To evaluate the metabolic profile, through clinical, laboratory and bioelectral impedance (BIA) analysis of cohort of patients with SOD followed at the endocrinology outpatient clinic at IPPMG-UFRJ. Methodology: Descriptive study of cohort of patients with SOD followed at the endocrinology outpatient clinic at IPPMG-UFRJ. Results: 48 individuals with SOD were found (50% female), 28 of whom had regular follow-up. The average ages at diagnosis and referral to the endocrinology outpatient clinic were 3.90 ± 3.85 years and 3.15 ± 3.30 years, respectively, and the current average age of those who maintain follow-up was 7.46 ± 4 .83 years. Maternal age was ≤ 25 years at the time of birth in 64% (25/39), with 44.44% (n=20/45) of them being primiparous. Regarding the diagnostic criteria for SOD, ONH was identified in 92.6% (N=38/41), 78.9% bilaterally; 95.3% (N=41/43) had midline structural changes on neuroimaging examination, 85.7% (N=24/28) had structural changes in the sella turcica and 73% had at least one hormonal deficiency, of which 2/3 had multiple pituitary dysfunctions. The most frequent dysfunction was thyrotropic hormone (TSH), followed by GH and adrenocorticotropic hormone (ACTH). A median of blood glucose level, cholesterol, LDL, HDL and triglycerides of 77 mg/dL, 187 mg/dL, 112.7 mg/dL, 48 mg/dL and 107 mg/dL were found, respectively. In the BIA assesment, a median of 18.7% was found for fat mass and a median of 81.3% for lean mass. When evaluating the distribution of lean mass between bone mass and muscle mass, a median of 4.3% and 28.4% were found, respectively. Ten participants had a low bone mass percentage, and 9 participants had a low muscle mass percentage. Eleven participants presented at least one of these percentages below the reference values. Conclusion: More than 1/3 of the patients presented the classic triad criteria of SOD and 2/3 had pituitary dysfunction. There were no significant changes in blood glucose, TGO, TGP. Dyslipidemia was present in most patients, with more than half having elevated LDL and almost 2/3 having hypertriglyceridemia. Most patients were classified as eutrophic based on body mass index (BMI), however » had a high percentage of fat mass and almost 80% a low percentage of lean mass, with ¾ having a low percentage of bone mass. We recommended that BIA not be replaced by BMI assessment in patients with SOD.(AU)
Assuntos
Lactente , Pré-Escolar , Criança , Adolescente , Composição Corporal , Impedância Elétrica , Displasia Septo-Óptica/metabolismo , Síndrome Metabólica , Endocrinologia , Obesidade Infantil/epidemiologia , Hipopituitarismo , Criança , Estudos de Coortes , AdolescenteRESUMO
La histiocitosis de células de Langerhans (HCL) es una rara afección histiocítica que se distingue por el crecimiento excesivo de células del sistema fagocítico mononuclear (macrófagos, células dendríticas, monocitos) en diversos órganos y sistemas. La afectación de la glándula hipófiisis se reporta en 5-50% de los pacientes con HCL, lo más frecuente la deficiencia de arginina vasopresina en 50% de los casos. Una minoria también presenta disfunción de hormonas de la adenohipófisis. Presentamos el caso de un paciente masculino de 33 años, diagnosticado de HCL en contexto de infecciones óticas a repetición, con tratamiento quimioterápico hasta en 3 ocasiones por recidiva tumoral. En el seguimiento se evidencia deficiencia de arginina-vasopresina. Asimismo, se diagnostica panhipopituitarismo. Nos enfocaremos en la definición, fisiopatología, epidemiología, y cómo realizar el seguimiento endocrinológico en pacientes adultos con HCL. La afectación de la hipófisis puede resultar un desafío diagnóstico. Es fundamental reconocer esta manifestación clínica para un diagnóstico y tratamiento adecuado, ya que sin tratamiento el paciente puede enfrentar un riesgo vital.
Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by the excessive proliferation of cells from the mononuclear phagocyte system (macrophages, dendritic cells, monocytes) in various organs and systems. Pituitary gland involvement is reported in 5-50% of patients with LCH, with the most common issue being arginine vasopressin deficiency in 50% of cases. A minority also present with adenohypophysis hormone dysfunction. We present the case of a 33-year-old male patient diagnosed with Langerhans cell histiocytosis (LCH) in the context of recurrent ear infections, with chemotherapy treatment administered up to three times due to tumor relapse. Follow-up reveals arginine-vasopressin deficiency. Additionally, the patient is diagnosed with panhypopituitarism. We will focus on the definition, pathophysiology, epidemiology, and how to conduct endocrinological follow-up in adult patients with LCH. Pituitary gland involvement can pose a diagnostic challenge. Recognizing this clinical manifestation is crucial for accurate diagnosis and appropriate treatment, as untreated patients may face life-threatening risks.
Assuntos
Humanos , Masculino , Adulto , Arginina Vasopressina/deficiência , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Otite , Hipopituitarismo/diagnósticoRESUMO
Presentamos el caso de una paciente con displasia septo-óptica (SOD), también conocida como síndrome de De Morsier, un desorden congénito raro. Se caracteriza por una combinación de alteraciones: hipoplasia del nervio óptico, disfunción hipofisaria y anormalidades de la línea media. Presentamos el caso de una paciente de 37 años con síndrome de De Morsier que consulta por infertilidad. Asocia hipopituitarismo, con déficit de hormona de crecimiento e hipogonadismo hipogonadotrófico, diagnosticada a los 11 años, en contexto de hipocrecimiento e impuberismo. También presenta complicaciones asociadas a estos déficits, como infertilidad, síndrome metabólico y compromiso óseo. Un diagnóstico y tratamiento temprano puede prevenir la morbimortalidad asociada a este síndrome, pero no así la infertilidad. Sin embargo, es posible lograr el embarazo mediante inducción de la ovulación.
The study presents the case of a patient with septo-optic dysplasia (SOD), also known as de Morsier syndrome, which is a rare congenital disorder. It is characterized by a combination of abnormalities, including optic nerve hypoplasia, pituitary dysfunction, and midline abnormalities. We present the case of a 37-year-old female patient with De Morsier syndrome, who seeks medical attention due to infertility. She presents with hypopituitarism, characterized by growth hormone deficiency and hypogonadotropic hypogonadism, diagnosed at the age of 11 in the context of short stature and delayed puberty. The patient also exhibits complications associated with these deficits, such as infertility, metabolic syndrome, and skeletal compromise. Early diagnosis and treatment can prevent morbidity and mortality associated with this syndrome, but unfortunately, infertility remains unaffected. Nevertheless, achieving pregnancy is possible through ovulation induction.
A síndrome de De Morsier, é uma doença congênita rara, caracterizada por uma combinação de alterações: hipoplasia do nervo óptico, disfunção hipofisária e anomalias da linha média. Apresentamos o caso de uma paciente de 37 anos com displasia septo-óptica (SOD), também conhecida como síndrome de De Morsier que consultou por infertilidade. Associado à SOD detectou-se hipopituitarismo, com deficiência de hormônio do crescimento e hipogonadismo hipogonadotrófico diagnosticado aos 11 anos de idade em um contexto de hipocrescimento e impuberdade. Foram observadas também complicações associadas a esses déficits como infertilidade, síndrome metabólica e envolvimento ósseo. O diagnóstico e tratamento precoces podem prevenir a morbimortalidade associada a esta síndrome, mas não a infertilidade. No entanto, a gravidez é possível através da indução da ovulação.
Assuntos
Displasia Septo-Óptica , HipopituitarismoRESUMO
Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.
Assuntos
Hipopituitarismo , Feminino , Humanos , Masculino , Alelos , Hipopituitarismo/diagnóstico , Hipopituitarismo/genética , Mutação , Proteínas Nucleares/genética , Fator de Transcrição Pit-1/genética , Fatores de Transcrição/genética , Proteína Gli2 com Dedos de Zinco/genéticaRESUMO
INTRODUCTION: Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded. METHODS: Twenty-eight patients (23 women), with PH were included. Median age: 37. RESULTS: The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonadism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous enhancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were diagnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immunosuppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients. DISCUSSION: In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe compressive symptoms, transsphenoidal surgery was the best option.
Introducción: La hipofisitis es una enfermedad infrecuente que plantea un desafío en el diagnóstico y tratamiento. El objetivo de este estudio multicéntrico y retrospectivo fue describir: a) características de pacientes con hipofisitis primaria (HP), b) métodos diagnósticos, y c) tratamientos realizados. Además, evaluar: a) presentación clínica, b) bioquímica, c) radiológica, d) oftalmológica al diagnóstico y evolución según el tratamiento recibido. Métodos: Estudio retrospectivo donde se estudiaron 28 pacientes (23 mujeres/5 varones) con HP, edad promedio de 38±11.1 años. Resultados. Los síntomas fueron: cefalea: 68%, poliuria- polidipsia: 50% y alteraciones visuales: 48%. El examen de laboratorio inicial informó disfunción adenohipofisaria en 71% de los pacientes, siendo el eje gonadal el más afectado. Los hallazgos radiológicos más frecuentes fueron: lesión simétrica:78.5%, aumento homogéneo post contraste: 78.5% y engrosamiento de tallo:70%. En 4/23 mujeres (17%) se relacionó con embarazos o puerperio La conducta inicial fue expectante (CE) en 14 pacientes, cirugía de resección/descompresión en 8 y tratamiento con inmunosupresores en 6. Quince pacientes tuvieron confirmación histológica, 9 resultaron hipofisitis linfocitaria, 5 hipofisitis por IgG4 y una xantomatosa. Trece fueron diagnosticados por criterios clínicos establecidos. El tamaño de la lesión disminuyó en 43% de pacientes con CE, 62.5% con cirugía y 50% con inmunosupresores. Los síntomas compresivos mejoraron en los 3 grupos, con escaso efecto sobre la función adenohipofisaria, sin resolución de la diabetes insípida. Discusión: En pacientes sin síntomas compresivos adoptamos CE. En aquellos pacientes sin certeza diagnóstica o con síntomas compresivos graves, se optó por cirugía transesfenoidal.
Assuntos
Hipofisite Autoimune , Hipofisite , Hipopituitarismo , Gravidez , Humanos , Feminino , Adulto , Estudos Retrospectivos , Hipofisite/diagnóstico , Hipofisite/terapia , Hipofisite/patologia , Hipófise/patologia , Hipopituitarismo/diagnóstico , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/terapia , Hipofisite Autoimune/patologia , Imageamento por Ressonância MagnéticaRESUMO
Objective: Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD. Design: Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment. Methods: Auxological, clinical, laboratory, and MRI data throughout follow-up were collected. Results: We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, p<0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, p<0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, p<0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, p<0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times. Conclusions: Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.
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Nanismo Hipofisário , Hormônio do Crescimento Humano , Hipopituitarismo , Adulto , Criança , Humanos , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/tratamento farmacológico , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Estudos RetrospectivosRESUMO
INTRODUCTION: Pituitary incidentalomas (PIs) are lesions found incidentally in the pituitary on imaging performed for reasons unrelated to pituitary disease. METHODS: A cross-sectional, retrospective and descriptive study was carried out with the aim of analyzing the clinical and evolutionary characteristics of a population of patients with PIs in the city of Córdoba. RESULTS: A total of 67 patients were included, 67% female, with a median age at diagnosis of 44 years. Among the reasons that led to requesting the first image, chronic or recurrent headache was the most prevalent (34%). The median tumor size was 12 mm. Fifty-eight percent were macroincidentalomas. Men had significantly larger lesions (p = 0.04). At diagnosis, including both sexes, 30% showed extrasellar extension and 45% invasion of the cavernous sinuses. Neuro-ophthalmological compromise was detected in 21%. A positive correlation was found between age at diagnosis and tumor size (r= +0.31, p = 0.001). Ninety-one percent were non-functioning tumors and at presentation, 21% of patients had one or more hormonal deficiencies. Of the total, 26% required surgery. Most of those who continued without treatment showed no change in tumor size at the end of follow-up (median 42 months). CONCLUSION: We highlight the high frequency of macroincidentalomas in our series, with visual field defects and hypopituitarism being frequent at diagnosis. Although most non-operated PIs remained stable, there was a high frequency of clinically significant lesions.
Introducción: Los incidentalomas hipofisarios (IH) son lesiones halladas fortuitamente en la hipófisis mediante imágenes realizadas por motivos no relacionados con enfermedad hipofisaria. Métodos: Se realizó un estudio transversal, retrospectivo y descriptivo con el objetivo de analizar las características clínicas y evolutivas de una población de pacientes portadores de IH en la ciudad de Córdoba. Resultados: Se incluyeron 67 pacientes, 67% del sexo femenino, con una mediana de edad al diagnóstico de 44 años. Entre los motivos que llevaron a solicitar la primera imagen, la cefalea crónica o recurrente fue el más prevalente (34%). La mediana del tamaño tumoral fue de 12 mm. El 58% fueron macroincidentalomas. Los hombres tuvieron lesiones significativamente más grandes (p = 0.04). Al diagnóstico, considerando ambos sexos, el 30% evidenció extensión extraselar y el 45% invasión a senos cavernosos. Se detectó compromiso neurooftalmológico en el 21%. Se halló correlación positiva entre la edad al momento del diagnóstico y el tamaño tumoral (r = +0.31, p = 0.001). El 91% fueron tumores no funcionantes y en su presentación, el 21% de los pacientes presentaron una o más deficiencias hormonales. El 26% del total requirió cirugía. La mayoría de aquellos que continuaron sin tratamiento no evidenciaron cambios en el tamaño tumoral al final del seguimiento (mediana 42 meses). Conclusión: Destacamos la elevada frecuencia de macroincidentalomas en nuestra serie, siendo los defectos del campo visual y el hipopituitarismo frecuentes al diagnóstico. Si bien la mayoría de los IH no operados permanecieron estables, existió una alta frecuencia de lesiones clínicamente significativas.
Assuntos
Adenoma , Hipopituitarismo , Neoplasias Hipofisárias , Masculino , Humanos , Feminino , Adulto , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Adenoma/diagnóstico , Hipopituitarismo/diagnósticoRESUMO
In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.