RESUMO
BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.
Assuntos
Artrite Reumatoide , Glicemia , Hiperprolactinemia , Prolactina , Humanos , Prolactina/sangue , Artrite Reumatoide/sangue , Feminino , Estudos Transversais , Glicemia/análise , Pessoa de Meia-Idade , Hiperprolactinemia/sangue , Adulto , Índice de Gravidade de Doença , Fadiga/sangue , Fadiga/etiologiaRESUMO
BACKGROUND: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. METHODS: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. RESULTS: The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. CONCLUSION: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.
Assuntos
Cabergolina , Clomifeno , Hipogonadismo , Neoplasias Hipofisárias , Prolactinoma , Humanos , Masculino , Adulto , Prolactinoma/tratamento farmacológico , Pessoa de Meia-Idade , Hipogonadismo/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hipofisárias/tratamento farmacológico , Cabergolina/uso terapêutico , Cabergolina/administração & dosagem , Clomifeno/uso terapêutico , Clomifeno/administração & dosagem , Resultado do Tratamento , Testosterona/sangue , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Ergolinas/uso terapêutico , Ergolinas/administração & dosagem , Prolactina/sangueRESUMO
INTRODUCTION: Cabergoline is the treatment of choice for prolactinomas. However, 10-20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. SUBJECTS AND METHODS: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26-61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38-386 ng/mL) under cabergoline treatment (2-7 mg/week) for at least 6 months (6-108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0-2.5 g v.o./day) was given according to patients' tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30-60 days) and long-term (120-180 days) metformin treatment. RESULTS: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30-60 days, and at 120-180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0-2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. CONCLUSION: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.
Assuntos
Cabergolina/farmacologia , Agonistas de Dopamina/farmacologia , Hiperprolactinemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Síndrome Metabólica/tratamento farmacológico , Metformina/farmacologia , Prolactina/efeitos dos fármacos , Prolactinoma/tratamento farmacológico , Adulto , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Resistência a Medicamentos/fisiologia , Quimioterapia Combinada , Feminino , Humanos , Hiperprolactinemia/sangue , Hipoglicemiantes/administração & dosagem , Síndrome Metabólica/sangue , Metformina/administração & dosagem , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Prolactina/sangue , Prolactinoma/sangue , Estudos ProspectivosRESUMO
Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Antineoplásicos Alquilantes/uso terapêutico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Agonistas de Dopamina/uso terapêutico , Feminino , Galactorreia/etiologia , Humanos , Hiperprolactinemia/etiologia , Hipogonadismo/etiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Gravidez , Prolactina/sangue , Prolactinoma/complicações , Prolactinoma/diagnóstico , Prolactinoma/epidemiologia , Prolactinoma/terapia , Sela Túrcica/diagnóstico por imagem , Temozolomida/uso terapêuticoRESUMO
Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.
Assuntos
Interpretação Estatística de Dados , Técnicas de Diagnóstico Endócrino , Artefatos , Análise Química do Sangue/normas , Análise Química do Sangue/estatística & dados numéricos , Técnicas de Diagnóstico Endócrino/normas , Técnicas de Diagnóstico Endócrino/estatística & dados numéricos , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Prolactina/sangue , Prolactina/fisiologia , Prolactinoma/sangue , Padrões de Referência , Testes de Função Tireóidea/normas , Testes de Função Tireóidea/estatística & dados numéricosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. METHODS: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA). RESULTS AND DISCUSSION: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA. WHAT IS NEW AND CONCLUSION: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.
Assuntos
Agonistas de Dopamina/uso terapêutico , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/epidemiologia , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Feminino , Galactorreia/epidemiologia , Humanos , Distúrbios Menstruais/epidemiologia , Metanálise em Rede , Prolactina/sangue , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The present study examined the effects of different photoperiods and melatonin treatment on plasma prolactin concentrations in guanacos, a South American camelid, in captivity. Fourteen adult female guanacos, not gestating or lactating and isolated from males, were studied. The control group was exposed to natural daylight, during short days (N = 7, 10L:14D) and long days (N = 7, 16L:8D). The treatment group (N = 7, 10L:14D) received melatonin implants every 23 days for 6 weeks during long days. Blood samples were taken at intervals of 1 week for 3 weeks, starting the third week of treatment. Prolactin concentrations were measured using competitive ELISA. Plasma concentrations of prolactin in non-lactating female guanacos have seasonal changes, with a higher concentration (p < .001) in short days (3.50 ± 2.24 ng/ml) than long days (1.10 ± 0.91 ng/ml). Melatonin treatment significantly decreases (p < .05) plasma concentrations of prolactin on the 21st day after the treatment. These findings are the first report of an endogenous circannual rhythm of plasma prolactin concentration and the action of melatonin treatment on prolactin secretion in this wild camelid.
Assuntos
Camelídeos Americanos/fisiologia , Melatonina/farmacologia , Fotoperíodo , Prolactina/sangue , Animais , Implantes de Medicamento , Feminino , Melatonina/administração & dosagem , Estações do AnoRESUMO
The lack of data on hepatic and hormonal markers for occupational exposure to most modern halogenated anesthetics has stimulated our research, which assessed liver enzymes, high-sensitivity C-reactive protein (hs-CRP) and neuroendocrine response. The study investigated 106 physicians who were categorized in an exposed group (primarily exposed to isoflurane and sevoflurane and less to desflurane and nitrous oxide) as well as as a control group. Anesthetic air monitoring was performed, and biological samples were analyzed for the most important liver enzymes, hs-CRP, adrenocorticotrophic hormone, cortisol and prolactin. No biomarkers were significantly different between the groups. Exposed males showed significant increases in cortisol and prolactin compared to unexposed males. However, values were within the reference ranges, and 22 % of exposed males versus 5 % of unexposed males exhibited higher prolactin values above the reference range. This study suggests that occupational exposure to the most commonly used inhalational anesthetics is not associated with hepatotoxicity or neurohormonal changes.
Assuntos
Anestésicos Inalatórios , Exposição Ocupacional , Médicos , Hormônio Adrenocorticotrópico/sangue , Adulto , Alanina Transaminase/sangue , Anestésicos Inalatórios/análise , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos Transversais , Desflurano/análise , Monitoramento Ambiental , Feminino , Humanos , Hidrocortisona/sangue , Isoflurano/análise , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/análise , Exposição Ocupacional/análise , Prolactina/sangue , Sevoflurano/análiseRESUMO
PURPOSE: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents. METHODS: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia. RESULTS: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (rs = 0.30; P = 0.010), cortisol (rs = 0.33; P = 0.003), prolactin (rs = 0.25; P = 0.03), IL-6 (rs = 0.35; P = 0.008) and with BMI-SDS (rs = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004). CONCLUSION: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.
Assuntos
Arginina Vasopressina/sangue , Glicopeptídeos/sangue , Hipoglicemiantes/sangue , Prolactina/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Y chromosome anomalies are closely associated with non-obstructive azoospermia (NOA), a major etiology in male infertility. Klinefelter syndrome (KS) and Y chromosome microdeletions are some of the well-identified genetic defects in this regard, while Y chromosome aneuploidies have been reported to be susceptive. We report the rare case of a patient presenting with three complex genetic defects: mosaic Y chromosome aneuploidy; loss of the heterochromatin region in the q arm of the Y chromosome (Yqh-); and azoospermia factor C subregion (AZFc) microdeletion. The patient reported he had been subfertile for five years. Semen analysis confirmed total azoospermia along with an unaffected hormonal profile for serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Since the microdeletion analysis of azoospermia factor (AZF) region revealed the presence of three microdeletions in the AZFc region, the patient was offered intracytoplasmic sperm injection (ICSI) upon the retrieval of sperm by testicular sperm extraction (TESE) as the best possible assisted reproductive treatment (ART) option. It was further suggested to carry out pre-implantation genetic screening (PGS) in order to facilitate the transfer of only female embryos, thus preventing the dissemination of Y chromosomal anomalies.