RESUMO
Monotherapy is the recommended initial treatment for early Parkinson's disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson's disease.
Assuntos
Antiparkinsonianos , Agonistas de Dopamina , Levodopa , Doença de Parkinson , Humanos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologia , Antiparkinsonianos/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/administração & dosagem , Índice de Gravidade de DoençaRESUMO
ABSTRACT Monotherapy is the recommended initial treatment for early Parkinson´s disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson´s disease.
RESUMO
INTRODUCTION: Despite the inherent heterogeneity of the information derived from national registries, they are a useful tool to investigate the epidemiological, clinical, biochemical and treatment outcome characteristics of low prevalence conditions such as acromegaly. Although the information provided by single-center experiences is more homogeneous, these studies usually comprise a limited number of patients and thus, frequently lack statistical power. AREAS COVERED: Registry-based Information regarding the epidemiology, clinical presentation, biochemical and imaging diagnosis, as well as therapeutic outcome and mortality in acromegaly is critically analyzed. EXPERT OPINION: By gathering data from multiple centers in a specific Country, these registries generate important insights into the real-life behavior of this condition, that should be considered, both, in international consensus meetings and in the design of local, Country-specific diagnostic and therapeutic strategies.
Assuntos
Acromegalia , Adenoma , Hormônio do Crescimento Humano , Neoplasias Hipofisárias , Humanos , Acromegalia/diagnóstico , Acromegalia/epidemiologia , Acromegalia/terapia , Hormônio do Crescimento Humano/uso terapêutico , Adenoma/diagnóstico , Adenoma/tratamento farmacológico , Somatostatina/uso terapêutico , Resultado do Tratamento , Sistema de Registros , Fator de Crescimento Insulin-Like I , Neoplasias Hipofisárias/tratamento farmacológicoRESUMO
Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.
Assuntos
Endometriose , Neoplasias , Osteoartrite , Feminino , Humanos , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Endometriose/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias/metabolismo , Adjuvantes Imunológicos/uso terapêutico , Osteoartrite/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismoRESUMO
ABSTRACT Objective: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.
RESUMO
PURPOSE: To make a systematic review and meta-analysis of studies evaluating the effect of cabergoline (CBG) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: The primary outcome was tumor shrinkage, using as cut-off a reduction of at least 20% of the NFPA size from baseline. The secondary outcomes were prevention of tumor progression, clinically required additional interventions and adverse events (AE). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Random meta-analysis for the proportion of tumor shrinkage, prevention of tumor progression, clinically required additional interventions and frequency of AE were conducted. RESULTS: Five studies were included. The meta-analysis of proportion was 19% for tumor shrinkage (95% CI 8-38%, 4 studies, 108 participants), 50% for prevention of tumor progression (95% CI 35-64%, 5 studies, 187 participants), 14% for clinically required additional interventions (95% CI 6-30%, 4 studies, 128 participants) and 2% for adverse events (95% CI 1-6%, 3 studies, 157 participants). CONCLUSIONS: Effect of CBG to promote tumor shrinkage in NFPAs was low, while prevention of tumor progression after surgery was seen in half of the cases, with a low frequency of adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020206778.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Adenoma/patologia , Cabergolina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológicoRESUMO
Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.
Assuntos
Adenoma , Neoplasias Hipofisárias , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/tratamento farmacológico , Adenoma/patologia , Cabergolina/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Estudos RetrospectivosRESUMO
For a long time, dopaminergic treatment (DT) was the medication for restless legs syndrome. Although DT is effective and safe over the short-term, complications develop over longer periods, including augmentation, tolerance, and impulse control disorders. Nowadays, it is recommended that first-line treatment should be alpha-2 ligands, which are more effective in the absence of previous DT. As a second-line treatment, opioids, such as oxycodone extended-release with naloxone, are approved in Europe. Brain iron should be monitored before and during treatment and corrected if necessary. Two new promising non-DTs are being developed: perampanel and dipyridamole. More research is needed.
Assuntos
Síndrome das Pernas Inquietas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Dopamina/efeitos adversos , Dopamina/uso terapêutico , Humanos , Ferro/análise , Ligantes , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Abstract Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.
Resumen La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.
Assuntos
Humanos , Antipsicóticos/efeitos adversos , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/tratamento farmacológico , Transtornos Mentais/etiologia , Transtornos Mentais/tratamento farmacológico , Prolactina/metabolismoRESUMO
Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.
La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.
Assuntos
Antipsicóticos , Hiperprolactinemia , Transtornos Mentais , Antipsicóticos/efeitos adversos , Humanos , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Prolactina/metabolismoRESUMO
RESUMEN La enfermedad de Parkinson (EP) es principalmente una enfermedad de pacientes ancianos. Es un trastorno multifacético que comprende síntomas motores y no motores en todas las etapas de la enfermedad. Esta revisión busca integrar los datos de las opciones de tratamiento más recientes con los datos de las terapias establecidas, a fin de proporcionar una referencia actualizada basada en la evidencia para los médicos que tratan la EP temprana, con medicamentos que puedan usarse como alternativa a la levodopa. El enfoque de los médicos para el tratamiento de la enfermedad de Parkinson (EP) temprana debe tener en cuenta numerosos aspectos, entre ellos, cómo informar al paciente sobre el diagnóstico y la decisión crítica de qué terapia adoptar y cuándo iniciarla. El tratamiento del trastorno motor asociado con la EP temprana debe considerar varios factores cruciales, como la edad de inicio, las comorbilidades y los requisitos funcionales del paciente, y no se puede resumir en una fórmula simple. En pacientes más jóvenes (es decir, antes de la edad de 70 años) y en aquellos sin altos requisitos funcionales, el tratamiento generalmente se inicia con agonistas de dopamina y / o inhibidores de la enzima monoaminooxidasa-B (MAO- B I). En pacientes más jóvenes, la levodopa se debe agregar a los agonistas de la dopamina y / o MAO-B I, según lo requiera la progresión de la enfermedad, mientras que en los pacientes mayores, cuando la respuesta a la levodopa sola no es satisfactoria, los agonistas de la dopamina o los inhibidores de la catecol-O- metiltransferasa pueden posteriormente ser agregados.
SUMMARY Parkinson's disease (PD) is primarily a disease of elderly patients. Is a multifaceted disorder comprised of both motor and non-motor symptoms at all stages of the disease. This review seeks to integrate data from the newest treatment options with data from established therapies, so as to provide an up-to- date evidence-based reference for clinicians treating early PD, with medications that can be used as an alternative to levodopa. The clinicians' approach to the treatment of early Parkinson's disease (PD) should take into account numerous aspects, including how to inform a patient upon diagnosis and the critical decision of what therapy to adopt and when to start it. The treatment of the motor disorder associated with early PD needs to consider several crucial factors, such as age at onset, comorbidities, and the patient's functional requirements, and cannot be summarized in a simple formula. In younger patients (i.e., before the age of 70) and in those without high functional requirements, treatment is usually initiated with dopamine agonists and/or monoamine oxidase-B enzyme inhibitors (MAO-B I). In younger patients, levodopa should be added to dopamine agonists and/or MAO-B I, as required by disease progression, whereas in older patients, when response to levodopa alone is not satisfactory, dopamine agonists or catechol-O- methyltransferase inhibitors may subsequently be added.
Assuntos
Mobilidade UrbanaRESUMO
Two types of drugs have been extensively investigated for the treatment of restless legs syndrome (RLS)/Willis-Ekbom disease (WED): dopamine agonists and α2δ ligands to the α2δ subunit of calcium channels. Comparative studies show that both classes of drugs are similarly effective in treating RLS symptoms over the short- and long-term. While dopamine agonists are more effective in treating periodic limb movements (PLMs), α2δ ligands are more effective in consolidating sleep. However, given the fact that dopamine agonists cause high rates of augmentation of symptoms, recent international guidelines recommend that whenever possible the initial treatment of choice should be an α2δ ligand. In fact, the most effective preventive strategy involves not using dopaminergic agents unless absolutely necessary. Indeed, should dopaminergic treatment be needed to handle the symptoms effectively, then it is recommended that the dopaminergic load be reduced by using the lowest effective dose for the shortest possible period of time. However, it must be taken into account that the only α2δ ligand approved for RLS/WED is gabapentin enacarbil, which is not yet available in Europe. Furthermore, recent studies have also reported on the efficacy of opioids as a second-line treatment of RLS/WED, following treatment failure with dopamine agonists. Recent guidelines have taken these new data into account and highlight that a low dose of an opioid (prolonged-release oxycodone or methadone) may be considered in patients with very severe augmentation of symptoms. Alternative non-dopaminergic treatment concepts based on glutamatergic and adenosinergic mechanisms are currently in development, and are likely to provide encouraging therapeutic alternatives.
Assuntos
Dopaminérgicos/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Ligantes , Síndrome das Pernas Inquietas/fisiopatologia , Sono/fisiologiaRESUMO
ABSTRACT Neuropsychiatric disorders are common among patients with Parkinson's disease and may appear in any stage of the disease. However, these disorders often go undiagnosed and receive insufficient treatment. Observations in recent years have revealed that dopamine replacement therapy may lead to the development or worsening of conditions, such as gambling disorder, compulsive sexual behavior, compulsive buying and binge eating, in addition to punding and dopamine dysregulation syndrome. The pathophysiology of these disorders seems to be related to abnormal dopaminergic stimulation of the basal regions of the basal ganglia, especially via nigro-mesolimbic pathways. The aim of the present study was to perform a literature review on impulsivity, impulse control disorders and related conditions among patients with Parkinson's disease, with emphasis on their epidemiology, clinical characteristics and treatment.
RESUMO Alterações neuropsiquiátricas são comuns na doença de Parkinson e estão presentes em todas as fases da enfermidade. No entanto, frequentemente não são reconhecidas e recebem tratamento insuficiente. Ao longo dos últimos anos, observou-se que a terapia de reposição dopaminérgica pode levar ao desenvolvimento ou piora de condições como transtorno do jogo, compulsão por sexo, compras, e comida, além da síndrome de desregulação dopaminérgica e punding. Sua fisiopatologia parece estar relacionada à estimulação dopaminérgica anormal das regiões basais dos núcleos da base, sobretudo pelas vias nigro-mesolímbicas. O presente artigo tem como objetivo fazer uma revisão da literatura a respeito de impulsividade, transtornos do controle de impulso e condições relacionadas na doença de Parkinson, com foco na epidemiologia, características clínicas e tratamento.
Assuntos
Humanos , Doença de Parkinson/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Prognóstico , Fatores de RiscoRESUMO
ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.
Assuntos
Humanos , Masculino , Feminino , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/terapia , Prolactinoma/diagnóstico , Guias de Prática Clínica como Assunto , Prolactina/sangue , Brasil , Prolactinoma/terapia , Bromocriptina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Cabergolina , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by debilitating motor deficits, as well as autonomic problems, cognitive declines, changes in affect and sleep disturbances. Although the scientific community has performed great efforts in the study of PD, and from the most diverse points of view, the disease remains incurable. The exact mechanism underlying its progression is unclear, but oxidative stress, mitochondrial dysfunction and inflammation are thought to play major roles in the etiology. OBJECTIVE: Current pharmacological therapies for the treatment of Parkinson's disease are mostly inadequate, and new therapeutic agents are much needed. METHODS: In this review, recent advances in computer-aided drug design for the rational design of new compounds against Parkinson disease; using methods such as Quantitative Structure-Activity Relationships (QSAR), molecular docking, molecular dynamics and pharmacophore modeling are discussed. RESULTS: In this review, four targets were selected: the enzyme monoamine oxidase, dopamine agonists, acetylcholine receptors, and adenosine receptors. CONCLUSION: Computer aided-drug design enables the creation of theoretical models that can be used in a large database to virtually screen for and identify novel candidate molecules.
Assuntos
Antiparkinsonianos/uso terapêutico , Desenho de Fármacos , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/química , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica MolecularRESUMO
INTRODUCTION: Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood. This condition is preferentially treated with dopamine agonists. Resistance to these drugs is rare. CASE REPORT: We describe the case of a boy diagnosed with macroadenoma at the age of 9 and followed up for 21 years. He did not fully respond to treatment with dopamine agonists. His initial prolactin level was 2,400 ng/mL (in males, normal values are <16.0 ng/mL) and never normalized. At the last assessment, his prolactin level was 21.5 ng/mL, recorded after 21 years of treatment with the dopamine agonist cabergoline at a dose as high as 4.5 mg per week. Although the prolactin level remained elevated throughout the follow-up period, the patient never presented a low testosterone level and had normal pubertal development. An MRI of the sella turcica showed that the tumor became progressively cystic and disappeared, but a normal pituitary gland was observed. The pituitary gland retained its normal functions despite a partially empty sella. DISCUSSION: Long-term treatment with high doses of cabergoline may cause cystic degeneration of a prolactinoma considered to be resistant to this treatment, but we cannot rule out the possibility that this outcome represents the natural development of the tumor.
Assuntos
Agonistas de Dopamina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Ergolinas/administração & dosagem , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Cabergolina , Criança , Seguimentos , Humanos , Masculino , Neoplasias Hipofisárias/sangue , Prolactina/sangue , Prolactinoma/sangueRESUMO
Background: Restless legs syndrome (RLS) affects 10% of the general population. Aim: To analyze a series of patients with a minimum follow-up period of four years, treated during an interval of 14 years. Material and Methods: Retrospective analysis of medical records of 200 patients assessed and followed by the authors at a private outpatient clinic. Results: Fifty patients aged 25 to 90 years (34 females), who had a mean follow-up of 6,3 years (range 4-14 years), were selected. Sixty percent responded to therapy that initially consisted in dopamine agonists in 78% of cases. Thirty four percent remained symptomatic and 4% worsened. RLS severity scale improved from an initial score of 19,2 to 12,5 at the last follow-up visit (p < 0.05). Thirty-three patients (66%) experienced an overall worsening of symptoms beyond pretreatment levels during follow-up. The strategies to overcome this augmentation were the change to another agonist, use of ligands such as pregabalin and gabapentin, opioids and iron. Low ferritin was common in most of the patients in whom it was measured (24 of 45 results), mainly in those with augmentation (p < 0,05). Six percent of patients treated with dopamine agonist developed an impulse control disorder. Conclusions: RLS is a treatable condition during a long period of follow-up in most patients. We found a high rate of potentiation at presentation which can be explained by the inadequate use of high doses of dopaminergic agents.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Síndrome das Pernas Inquietas/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Índice de Gravidade de Doença , Estudos Retrospectivos , Seguimentos , Resultado do TratamentoAssuntos
Fármacos do Sistema Nervoso Central/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Frutose/análogos & derivados , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/etiologia , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Encéfalo/diagnóstico por imagem , Cabergolina , Criança , Agonistas de Dopamina/uso terapêutico , Ergolinas/efeitos adversos , Ergolinas/uso terapêutico , Frutose/uso terapêutico , Humanos , Masculino , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/metabolismo , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/cirurgia , Prolactinoma/diagnóstico por imagem , Prolactinoma/tratamento farmacológico , Prolactinoma/cirurgia , TopiramatoRESUMO
ABSTRACT The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18–54 years); median serum prolactin level was 4,562 ng/ml (1,543–18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41–60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7–84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.
RESUMO O objetivo desta série de casos é relatar oito pacientes com prolactinomas gigantes enfatizando as formas de apresentação e uma complicação do tratamento. O estudo incluiu seis homens e duas mulheres. A mediana de idade foi 29 anos (18–54); e dos níveis de prolactina foi 4.562 ng/ml (1.543–18.690); três pacientes (37,5%) apresentaram pan-hipopituitarismo; a mediana do máximo diâmetro tumoral foi 50 mm (41–60 mm). Cinco pacientes (62,5%) apresentaram alterações no campo visual e três tiveram melhora durante o tratamento; seis pacientes (75%) alcançaram normalização da prolactina em 10,5 meses (7–84) com dose mediana de cabergolina de 2,0 mg / semana (1,0 a 3,0). Um paciente se apresentou como um verdadeiro incidentaloma. Um paciente apresentou uma fistula liquórica durante o tratamento medicamentoso e recusou correção cirúrgica. No entanto a fistula foi resolvida com medidas conservadoras. Esta série de casos ilustra um subtipo raro de macroprolactinomas, a importância de considerar apresentações incomuns no diagnóstico, a eficácia do tratamento farmacológico e suas possíveis complicações.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/terapia , Prolactinoma/patologia , Prolactinoma/terapia , Neoplasias Hipofisárias/diagnóstico por imagem , Prolactina/sangue , Sela Túrcica/patologia , Fatores de Tempo , Imageamento por Ressonância Magnética , Prolactinoma/diagnóstico por imagem , Seguimentos , Resultado do Tratamento , Agonistas de Dopamina/uso terapêutico , Carga Tumoral , Ergolinas/uso terapêutico , Vazamento de Líquido Cefalorraquidiano/patologia , Cabergolina , Antineoplásicos/uso terapêuticoRESUMO
Abstract Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases.
Resumo Os mecanismos fisiopatológicos da miocardiopatia periparto ainda não são totalmente definidos, apesar de haver forte associação com vários fatores já conhecidos, incluindo a pré-eclâmpsia. O tratamento segue as mesmas recomendações para a insuficiência cardíaca com disfunção sistólica. Estudos clínicos e experimentais recentes sugerem que os produtos de degradação da prolactina podem induzir a miocardiopatia. A supressão farmacológica da produção de prolactina por agonista do receptor D2 da dopamina, bromocriptina ou cabergolina, vem demonstrando resultados satisfatórios na resposta terapêutica do tratamento. Apresentamos o relato de uma primigesta, adolescente, com miocardiopatia periparto que evoluiu para a normalização da função ventricular esquerda após a administração da cabergolina, utilizada como adjuvante na terapêutica da disfunção cardíaca. Subsequentemente, apesar do intervalo entre as gestações ser considerado curto, apresentou evolução satisfatória em uma nova gestação sem qualquer alteração cardíaca durante todo o período gestacional ou puerpério. Os agonistas dopaminérgicos, drogas de uso oral e de preço acessível para a maioria dos centros terciários, em particular em países subdesenvolvidos, não podem ser esquecidos frente a casos de miocardiopatia periparto.