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Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.
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Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Brasil , Prolactina , Prolactinoma/diagnósticoRESUMO
Abstract Background: Hyperprolactinemia is increased in women with infertility and recurrent pregnancy loss; the prevalence of hyperprolactinemia in Mexican women with infertility is unknown. Objective: To know the prevalence of hyperprolactinemia and the clinical-biochemical characteristics in Mexican women with infertility. Methods: This cross-sectional study included infertile women attending in a third-level hospital. All women had prolactin determination and a complete hormonal profile. Women with TSH > 2.5 mlU/L or those taking dopaminergic drugs were excluded. The prevalence of hyperprolactinemia was calculated with a 95% confidence interval (95% CI). Results: A total of 869 women were included in the study. The prevalence of hyperprolactinemia was 9.6% (95% CI 7.7-11.7%). Of the 83 women with hyperprolactinemia, 52 (62.2%) had serum prolactin values between 25 and 40, 17 (20.4%) between 41 and 60, and 14 (16.8%) > 60 ng/m. The prevalence of one or more miscarriages in women with hyperprolactinemia versus those without hyperprolactinemia among women with secondary infertility was 19/20 (95%) versus 116/197 (58.9%), respectively, p = 0.002. The prevalence of anovulation and clinical hyperandrogenism was significantly higher in women without hyperprolactinemia. Conclusion: Hyperprolactinemia affects one of ten Mexican women with infertility. Women with hyperprolactinemia and secondary infertility showed a higher frequency of a history of one or more miscarriage.
Resumen Antecedentes: La hiperprolactinemia se incrementa en mujeres con infertilidad y pérdida gestacional recurrente. Se desconoce la prevalencia de hiperprolactinemia en mujeres mexicanas con infertilidad. Objetivo: Conocer la prevalencia de hiperprolactinemia y las características clínico-bioquímicas en mujeres mexicanas con infertilidad. Método: Estudio transversal que incluyó a mujeres con infertilidad en un hospital de tercer nivel. Todas las mujeres tenían determinación de prolactina y perfil hormonal completo. Se excluyeron mujeres con hormona estimulante de la tiroides > 2.5 mUI/l o que tomaban medicamentos dopaminérgicos. Se calculó la prevalencia de hiperprolactinemia con intervalo de confianza al 95% (IC95%). Resultados: En total se incluyeron 869 mujeres. La prevalencia de hiperprolactinemia fue 9.6% (IC95%: 7.7-11.7%). De 83 mujeres con hiperprolactinemia, 52 (62.2%) tenían valores de prolactina entre 25-40, 17 (20.4%) entre 41-60 y 14 (16.8%) > 60 ng/ml. La prevalencia de uno o más abortos espontáneos en mujeres con hiperprolactinemia vs. sin hiperprolactinemia entre mujeres con infertilidad secundaria fue: 19/20 (95%) versus 116/197 (58.9%), respectivamente (p = 0.002). La prevalencia de anovulación e hiperandrogenismo clínico fue significativamente mayor en mujeres sin hiperprolactinemia. Conclusiones: La hiperprolactinemia afecta a una de cada diez mujeres mexicanas con infertilidad. Las mujeres con infertilidad secundaria e hiperprolactinemia mostraron mayor frecuencia de antecedente de uno o más abortos.
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ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.
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Resumen Presentamos el caso de una mujer joven sana, que consultó por parálisis facial periférica izquierda asociada a fiebre, tos seca, disnea y astenia de dos semanas de evolución. Al examen físico se evidenció hipoestesia en dermatomas D6 a D12 izquierdos y galactorrea bi lateral. En el laboratorio presentaba serologías virales negativas, eritrosedimentación, títulos de anticuerpos antinucleares, prolactina y hormona tiroestimulante elevados, con anticuerpos antiperoxidasa positivos. La tomografía computarizada mostró múltiples adenopatías cervicales, mediastinales e hiliares bilaterales, sin com promiso del parénquima pulmonar. El cultivo de líquido cefalorraquídeo fue negativo para gérmenes comunes, micobacterias (Xpert MTB/RIF), y la citología no mostró atipia. Se realizó una resonancia magnética con con traste endovenoso de cerebro sin hallazgos patológicos y de columna con alteración de la señal centromedular de D6 a D9 de casi la totalidad del espesor del cordón, con refuerzo con contraste endovenoso. Durante la in ternación recuperó la sensibilidad en tronco izquierdo y no repitió episodios febriles o tusígenos. Se realizó mediastinoscopía con biopsia ganglionar con anatomía patológica con presencia de numerosos granulomas no caseificantes compatibles con sarcoidosis. Se clasificó como neurosarcoidosis probable e inició tratamiento con corticoides con mejoría de los síntomas neurológi cos restantes, realizándose una resonancia magnética a los tres meses, donde la alteración de la señal se limitaba desde D7 a D8. Nuestro objetivo es destacar la presentación neurológica en múltiples sitios que obligó a descartar otras entidades más frecuentes, así como la evolución favorable incluso previo al inicio de un esquema de tratamiento de primera línea.
Abstract We present the case of a healthy young woman who consulted for left peripheral facial palsy associated with fever, dry cough, dyspnea, and asthenia of two weeks' evolution. Physical examination revealed hypoesthesia in left T6 to T12 dermatomes and bilateral galactorrhea. In the laboratory, she presented negative viral serology, elevated erythrocyte sedimentation rate, antinuclear an tibody titers, prolactin and thyroid-stimulating hormone, with positive antiperoxidase antibodies. Computed to mography showed multiple bilateral cervical, mediastinal, and hilar adenopathies, without involvement of lung parenchyma. Cerebrospinal fluid culture was negative for common germs, mycobacteria, and Xpert MTB/RIF, and cytology did not show atypia. Contrast-enhanced magnetic resonance was performed on the brain without pathological findings and on the spine with alteration of the centromedullary signal from T6 to T9 of almost the entire thickness of the cord, with posterior enhancement with gadolinium. During hospitalization, she recovered sensitivity in the left trunk and did not repeat febrile or cough episodes. She was referred to another center for mediastinoscopy with lymph node biopsy revealing the presence of numerous non-caseating granulomas compatible with sarcoidosis. It was classified as probable neurosarcoidosis and started treatment with corticoste roids with improvement of the remaining neurological symptoms. A magnetic resonance was performed three months later where the signal alteration was limited from T7 to T8. Our objective is to highlight the florid neu rological presentation that made it necessary to rule out other more frequent entities and the favorable evolution even before starting a first-line scheme of treatment.
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We present the case of a healthy young woman who consulted for left peripheral facial palsy associated with fever, dry cough, dyspnea, and asthenia of two weeks' evolution. Physical examination revealed hypoesthesia in left T6 to T12 dermatomes and bilateral galactorrhea. In the laboratory, she presented negative viral serology, elevated erythrocyte sedimentation rate, antinuclear antibody titers, prolactin and thyroid-stimulating hormone, with positive antiperoxidase antibodies. Computed tomography showed multiple bilateral cervical, mediastinal, and hilar adenopathies, without involvement of lung parenchyma. Cerebrospinal fluid culture was negative for common germs, mycobacteria, and Xpert MTB/RIF, and cytology did not show atypia. Contrast-enhanced magnetic resonance was performed on the brain without pathological findings and on the spine with alteration of the centromedullary signal from T6 to T9 of almost the entire thickness of the cord, with posterior enhancement with gadolinium. During hospitalization, she recovered sensitivity in the left trunk and did not repeat febrile or cough episodes. She was referred to another center for mediastinoscopy with lymph node biopsy revealing the presence of numerous non-caseating granulomas compatible with sarcoidosis. It was classified as probable neurosarcoidosis and started treatment with corticosteroids with improvement of the remaining neurological symptoms. A magnetic resonance was performed three months later where the signal alteration was limited from T7 to T8. Our objective is to highlight the florid neurological presentation that made it necessary to rule out other more frequent entities and the favorable evolution even before starting a first-line scheme of treatment.
Presentamos el caso de una mujer joven sana, que consultó por parálisis facial periférica izquierda asociada a fiebre, tos seca, disnea y astenia de dos semanas de evolución. Al examen físico se evidenció hipoestesia en dermatomas D6 a D12 izquierdos y galactorrea bilateral. En el laboratorio presentaba serologías virales negativas, eritrosedimentación, títulos de anticuerpos antinucleares, prolactina y hormona tiroestimulante elevados, con anticuerpos antiperoxidasa positivos. La tomografía computarizada mostró múltiples adenopatías cervicales, mediastinales e hiliares bilaterales, sin compromiso del parénquima pulmonar. El cultivo de líquido cefalorraquídeo fue negativo para gérmenes comunes, micobacterias (Xpert MTB/RIF), y la citología no mostró atipia. Se realizó una resonancia magnética con contraste endovenoso de cerebro sin hallazgos patológicos y de columna con alteración de la señal centromedular de D6 a D9 de casi la totalidad del espesor del cordón, con refuerzo con contraste endovenoso. Durante la internación recuperó la sensibilidad en tronco izquierdo y no repitió episodios febriles o tusígenos. Se realizó mediastinoscopía con biopsia ganglionar con anatomía patológica con presencia de numerosos granulomas no caseificantes compatibles con sarcoidosis. Se clasificó como neurosarcoidosis probable e inició tratamiento con corticoides con mejoría de los síntomas neurológicos restantes, realizándose una resonancia magnética a los tres meses, donde la alteración de la señal se limitaba desde D7 a D8. Nuestro objetivo es destacar la presentación neurológica en múltiples sitios que obligó a descartar otras entidades más frecuentes, así como la evolución favorable incluso previo al inicio de un esquema de tratamiento de primera línea.
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Doenças do Sistema Nervoso Central , Sarcoidose , Feminino , Gravidez , Humanos , Tosse , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose/complicações , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/tratamento farmacológico , PulmãoRESUMO
The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia.
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Glândula de Harder , Hiperprolactinemia , Gravidez , Humanos , Camundongos , Feminino , Animais , Proteoglicanas/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Decorina/metabolismo , Prolactina/efeitos adversos , Prolactina/análise , Prolactina/metabolismo , Progesterona , Glândula de Harder/metabolismo , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Estrogênios/efeitos adversos , Estrogênios/análise , Estrogênios/metabolismoRESUMO
Hyperprolactinemia is a pathological condition resulting from increased prolactin that directly affects reproduction, as this condition inhibits the release of LH, FSH and gonadal steroidogenesis, bringing several negative clinical associations in reproduction. In contrast, melatonin (MEL) plays an important role in the regulation of steroidogenesis and modulates damages to the process of spermatogenesis. The objective was to analyze the protective effects of exogenous melatonin on the testis of hyperprolactinemic adult rats. Forty-eight male rats were used, divided into two treatment periods: 30 and 60 days, each treatment was subdivided into three groups: Control, Hyper (hyperprolactinemia), and Hyper+MEL (hyperprolactinemia and melatonin). Treatment with melatonin was 200 µg/100 g, subcutaneously. Induction of hyperprolactinemia was obtained with a dose of 4 mg/kg of domperidone, subcutaneously. The results of the histopathology demonstrated that the animals in the Hyper group presented degeneration of germ cells when compared to the control. In addition, the degenerations were presented in smaller quantities in the Hyper+MEL, in both treatment periods, evidencing the benefits of the melatonin in gonadal regeneration. The Hyper group of both treatment periods showed a decrease in tubular diameter, epithelium height, and tubular area, in addition to a decrease in Sertoli cells, when compared to the control and the Hyper+MEL group. In conclusion, the hyperprolactinemia can affect the germinal epithelium and testicular microstructure; the exogenous melatonin has a protective effect against hyperprolactinemia, reducing testicular damage.
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Hiperprolactinemia , Melatonina , Ratos , Masculino , Animais , Testículo , Melatonina/farmacologia , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/patologia , Domperidona/farmacologia , ProlactinaRESUMO
PURPOSE: Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline. METHODS: We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal. RESULTS: Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases. CONCLUSIONS: Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.
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Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Feminino , Humanos , Prolactinoma/tratamento farmacológico , Prolactinoma/complicações , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Cabergolina/uso terapêutico , Neoplasias Hipofisárias/patologia , Hiperprolactinemia/tratamento farmacológico , Bromocriptina/uso terapêutico , Ergolinas/efeitos adversosRESUMO
CONTEXT: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. OBJECTIVE: We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. DESIGN: Observational, retrospective, and cross-sectional study. SETTING: This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. PATIENTS AND METHODS: Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. RESULTS: We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001). CONCLUSIONS: The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets.
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Neoplasias Hipofisárias , Prolactinoma , Masculino , Humanos , Animais , Camundongos , Prolactinoma/tratamento farmacológico , Prolactinoma/genética , Agonistas de Dopamina/uso terapêutico , Cabergolina/uso terapêutico , Receptores da Prolactina , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Prolactina/genética , Ergolinas/farmacologia , Ergolinas/uso terapêutico , Estudos Retrospectivos , Estudos Transversais , Camundongos KnockoutRESUMO
Los prolactinomas son los tumores funcionantes de hipófisis más frecuentes. Se clasifican según su tamaño en microprolactinomas (menores a 1 cm) y macroprolactinomas (mayor o igual a 1 cm). Estos últimos tienen mayor frecuencia en hombres y en general se diagnostican más tardíamente, cuando aparecen síntomas compresivos. La hiperprolactinemia interfiere con la secreción pulsátil de la hormona liberadora de gonadotropinas (GnRH), lo que genera la inhibición de secreción de hormona luteinizante (LH) y de hormona foliculoestimulante (FSH), y en consecuencia produce hipogonadismo hipogonadotrófico. El presente artículo reporta un caso clínico de un paciente de 26 años, de sexo masculino, en el que se realiza el diagnóstico de hipogonadismo hipogonadotrófico secundario a un macroprolactinoma, en el contexto de una pubertad detenida.
Prolactinomas are the most common functioning pituitary tumors. According to size, they are classified into microprolactinomas (smaller than 1 cm) and macroprolactinomas (larger than or equal to 1 cm). The latter are more frequent among men and in general of late diagnosis upon compressive symptoms. Hyperprolactinemia interferes with the pulsatile secretion of the gonadotrophin releasing hormone (GnRH)) what results in inhibition of the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), what consequently produces hypogonadotrophic hypogonadism. The study reports the clinical case of a 26-year-old male who was diagnosed with hypogonadotrophic hypogonadism secondary to macroprolactinoma, within the context of detained puberty.
Os prolactinomas são os tumores hipofisários funcionantes mais comuns. São classificados de acordo com seu tamanho em microprolactinomas (menos de 1 cm) e macroprolactinomas (maior ou igual a 1 cm). Estas últimas são mais frequentes em homens e geralmente são diagnosticadas mais tarde, quando aparecem sintomas compressivos. A hiperprolactinemia interfere na secreção pulsátil do hormônio liberador de gonadotropina (GnRH), levando à inibição da secreção do hormônio luteinizante (LH) e do hormônio folículo-estimulante (FSH) e, consequentemente, hipogonadismo hipogonadotrófico. Este artigo relata o caso clínico de um paciente do sexo masculino de 26 anos, no qual é feito o diagnóstico de hipogonadismo hipogonadotrófico secundário a um macroprolactinoma, no contexto de puberdade interrompida.
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Puberdade Tardia , Prolactinoma , HipogonadismoRESUMO
[This corrects the article DOI: 10.3389/fendo.2021.727628.].
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A mastopexia é a cirurgia plástica responsável pela correção da ptose mamária, problema caracterizado pela discrepância entre o volume da mama e sua camada cutânea. As complicações mais relatadas no pós-operatório imediato são deiscência de suturas, seroma, edema e infecção, enquanto outras, como a galactorreia, são consideradas raras. O caso em questão consiste em uma paciente de 52 anos, que realizou a mastopexia bilateral com inclusão de prótese e desenvolveu após 30 dias do procedimento galactorreia com hiperprolactinemia. O diagnóstico foi suspeitado devido ao aumento de volume, associado a dor ou desconforto mamário no pós-operatório, seguido de saída secreção leitosa. A galactocele pósmastopexia com prótese pode ou não estar associada à hiperprolactinemia, porém pouco se sabe sobre a real fisiopatologia do desenvolvimento desse quadro. O tratamento foi feito com cabergolina 0,5mg em duas doses, com melhora do quadro.
Mastopexy is the plastic surgery responsible for correcting breast ptosis, a problem characterized by a discrepancy between the volume of the breast and its skin layer. The complications most commonly reported in the immediate postoperative period are suture dehiscence, seroma, edema and infection, while others such as galactorrhea are considered rare. The case in question consists of a 52-yearold patient who underwent bilateral mastopexy with prosthesis inclusion and developed galactorrhea with hyperprolactinemia 30 days after the procedure. The diagnosis was suspected of increased volume, associated with postoperative breast pain or discomfort, followed by milky discharge. Galactocele after mastopexy with a prosthesis may or may not be associated with hyperprolactinemia, but little is known about the real pathophysiology of the development of this condition. Treatment was done with cabergoline 0.5mg in two doses, improving the condition.
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ABSTRACT BACKGROUND AND OBJECTIVES: The association of the use of some drugs with hyperprolactinemia and galactorrhea has been reported in the literature, but information on the role of duloxetine in these alterations is scarce. Therefore, the aim of this study was to highlight this adverse effect and discuss the pathophysiological causes of galactorrhea associated with the use of duloxetine in a patient undergoing treatment for chronic pain. CASE REPORT: Female patient, 70 years old, with herpetic neuropathy diagnosis. She developed refractory pain after drug treatment and was referred to the pain clinic. Duloxetine (60mg) taken once a day was maintained and associated with blocks with local anesthetic in regions of herpetic pain. The patient complained of galactorrhea and changes in weight and showed an increase in serum prolactin. Then, the possibility of hyperprolactinemia due to duloxetine was raised. Duloxetine was suspended, and after one month, a significant reduction in serum prolactin levels and end of galactorrhea were observed. CONCLUSION: The treatment of patients with neuropathic pain is extremely challenging and the detailed understanding, especially of the pharmacological strategy and its possible adverse effects, is fundamental for the better management of patients and their well-being. Therefore, it is concluded that duloxetine, although rarely, can cause an increase in serum prolactin and galactorrhea in users.
RESUMO JUSTIFICATIVA E OBJETIVOS: A associação do uso de alguns fármacos com hiperprolactinemia e galactorreia tem sido relatada na literatura, mas são escassas as informações sobre o papel da duloxetina nestas alterações. Portanto, o objetivo deste estudo foi destacar este efeito adverso e discutir as causas fisiopatológicas da galactorreia associada ao uso de duloxetina no tratamento da dor crônica. RELATO DO CASO: Paciente do sexo feminino, 70 anos, com diagnóstico de neuropatia herpética. Evoluiu com refratariedade álgica após tratamento farmacológico, sendo encaminhada à clínica de dor. Optou-se por manter a duloxetina (60 mg) uma vez ao dia e associar bloqueios com anestésico local em regiões de dor herpética. A paciente queixou-se de galactorreia e alteração de peso e apresentou elevação da prolactina sérica. Foi aventada, então, a possibilidade de hiperprolactinemia pela duloxetina. Foi, então, realizada a suspensão da duloxetina e, após um mês, foi observada redução expressiva dos níveis séricos da prolactina e cessação da galactorreia. CONCLUSÃO: O tratamento de pacientes com dor neuropática é extremamente desafiador e a compreensão detalhada do processo, em destaque para a estratégia farmacológica e seus possíveis efeitos adversos é fundamental para o melhor manejo dos pacientes e manutenção do bem-estar. Diante disso, concluiu-se que a duloxetina, apesar de acontecer raramente, pode causar aumento da prolactina sérica e galactorreia em usuários.
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PURPOSE: Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic-pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians. We review the effects of opioids on hypothalamic-pituitary-target gland function and their implications for clinical practice. METHODS: Experts in hypothalamic-pituitary disorders and opioid pharmacology reviewed recently published literature and considered strategies for diagnosing and managing these opioid-induced endocrine effects. RESULTS: Opioid suppression of hypothalamic-pituitary axes can lead to hypogonadotropic hypogonadism, central adrenal insufficiency, and hyperprolactinemia. These important clinical manifestations are often under-estimated, poorly evaluated, and typically either untreated or not optimally managed. Data on biochemical testing for diagnosis and on the effect of hormone replacement in these patients is limited and prospective randomized controlled studies for guiding clinical practice are lacking. CONCLUSIONS: Patients should be informed about risks for hypogonadism, adrenal insufficiency, and hyperprolactinemia, and encouraged to report associated symptoms. Based on currently available evidence, we recommend clinical and biochemical evaluation for potential central adrenal insufficiency, central hypogonadism, and/or hyperprolactinemia in patients chronically treated with opioids as well as the use of current expert guidelines for the diagnosis and treatment of these conditions.
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Hiperprolactinemia , Hipogonadismo , Analgésicos Opioides/efeitos adversos , Prova Pericial , Humanos , Hipogonadismo/induzido quimicamente , Hipogonadismo/diagnóstico , Hipogonadismo/tratamento farmacológico , Estudos ProspectivosRESUMO
Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.
Assuntos
Animais , Feminino , Ratos , Hiperprolactinemia , Hiperplasia/patologia , Progesterona , Prolactina , Receptores da Prolactina , Receptores de Progesterona , Western Blotting/métodos , Secreções Corporais , Glândulas Mamárias Humanas/anatomia & histologia , Injeções Intramusculares/efeitos adversos , Injeções Intramusculares/instrumentação , MétodosRESUMO
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
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.