Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM)

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.

Neurosarcoidosis: inicio con compromiso de múltiples sitios neurológicos / Neurosarcoidosis: Onset with involvement of multiple neurological sites

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.

Hipogonadismo masculino secundario a macroprolactinoma / Men with hypogonadism secondary to macroprolactinoma / Hipogonadismo masculino secundário a macroprolactinoma

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.

Galactorreia pós-mastopexia com prótese: relato de caso / Post-mastopexy galactorrhoea with a prosthesis: a case report

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.

Hyperprolactinemia and galactorrhea associated with the use of duloxetine to treat chronic neuropathic pain. Case report / Hiperprolactinemia e galactorreia associada ao uso de duloxetina para tratamento de dor neuropática crônica. Relato de caso

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.

Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia

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.

Hyperprolactinemia associated with psychiatric disorders / Hiperprolactinemia asociada con trastornos psiquiátricos

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.

Caracterización clínico-etiológica y bioquímica de pacientes con ginecomastia / Clinical- etiological and biochemical characterization of patients with gunecomastia

RESUMEN Introducción: La ginecomastia define el aumento benigno del tamaño de la glándula mamaria en el hombre. Objetivo: Determinar las características clínicas, etiológicas y bioquímicas de los pacientes con diagnóstico de ginecomastia atendidos en el servicio de Cirugía General. Método: Se realizó un estudio descriptivo de corte transversal en una muestra de 108 pacientes, mayores de 18 años, atendidos en el servicio de Cirugía General con diagnóstico de ginecomastia. El estudio se llevó a cabo en los Hospitales Mariano Pérez Balí y Celia Sánchez Manduley, entre septiembre 2015 y marzo 2017. Se determinó edad, características clínicas, etiología y perfil bioquímico de estos pacientes. Resultados: La edad media fue de 27,63 años siendo la afectación estética el principal motivo de consulta. Predominó la ginecomastia bilateral, el sobrepeso/obesidad, el grado IIa de la enfermedad, la etiología idiopática y el antecedente de ginecomastia puberal. La presencia de galactorrea, hiperprolactinemia, hipoandrogenismo e hiperestrogenemia fue mínima. Conclusiones: La ginecomastia bilateral de causa idiopática, en pacientes con sobrepeso/obesidad y niveles normales de hormonas hipofisarias y gonadales es la forma de presentación más frecuente de esta afección(AU)

ABSTRACT Introduction: Gynecomastia defines the benign increase of the mammary gland size in men. Objective: To determine the clinical, etiological and biochemical characteristics of patients diagnosed with gynecomastia attended at the General Surgery service. Methods: A descriptive cross-sectional study was conducted in a sample of 108 patients over the age of 18 years, attended at the service of General Surgery with a diagnosis of gynecomastia. The study was carried out in ´´Mariano Perez Bali´´ and ´´Celia Sánchez Manduley´´ Hospitals from September 2015 to March 2017. The age, clinical characteristics, etiology, and biochemical profile of these patients were determined. Results: The mean age was 27.63 years and the aesthetic affectations were the main reason for consultation. There was a predominance of bilateral gynecomastia, overweight/obesity, grade IIa of the disease, idiopathic etiology and the history of pubertal gynecomastia. The presence of hyperprolactinemia, galactorrhea, hypoandrogenism and hyperstrogenism was minimal. Conclusions: Bilateral gynecomastia of idiopathic cause, in patients with overweight/obesity and normal levels of gonadal and pituitary hormones is the most common presentation of this condition(AU)

Body self-image disturbances in women with prolactinoma

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Quiste de bolsa de Rathke e hiperprolactinemia, una causa infrecuente de amenorrea primaria / Rathke cleft cysts and hyperprolactinemia, an uncommon cause of primary amenorrhea

El quiste de la bolsa de Rathke es una lesión epitelial benigna de la región selar, formada a partir de remanentes embrionarios. La mayoría de los casos son asintomáticos, aunque pudiera presentarse con cefalea, disfunción hipofisaria y trastornos visuales, muy infrecuentemente como apoplejía hipofisaria. Se presenta el caso de una paciente que, habiendo presentado amenorrea primaria, se le realiza el diagnóstico de quiste de la bolsa de Rathke con hiperprolactinemia, logrando menarquia luego del tratamiento con cabergolina.

Rathke's cyst is a benign epithelial lesion of the sellar region, formed from embryonic remnants. Most cases are asymptomatic although it could present with headache, pituitary dysfunction and visual disorders, very infrequently as pituitary stroke. We present the case of a patient who, having presented primary amenorrhea, is diagnosed with Rathke's cyst with hyperprolactinemia, achieving menarche after treatment with cabergoline.

Alteraciones endocrinas asociadas al uso medicamentos en el Programa Distrital de Farmacovigilancia de Bogotá durante el periodo 2012 a 2016 / Medication-use related endocrine disruption reported to the local pharmacovigilance program in Bogota, during 2012- 2016 / Alterações endócrinas associadas ao uso de medicamentos no Programa Distrital de Vigilância farmacológica em Bogotá no período 2012-2016

Objetivos. Conocer las reacciones adversas tipo endocrino asociado al uso de medicamentos y reportado al Programa Distrital de Farmacovigilancia de Bogotá durante el periodo 2012 a 2016. Materiales y métodos. Los reportes analizados corresponden al periodo del 1º de enero de 2012 al 31 de diciembre de 2016 del Programa Distrital de Farmacovigilancia. Su análisis se hizo mediante algoritmos de causalidad y por tipo de evento. Resultados. Se analizaron 85 reportes. Uno de ellos relacionado con una sospecha de problema de calidad del medicamento, los otros 84 relaciona-dos con reacciones adversas sobre los cuales se centró la investigación. De los 84 reportes, 36 (42,9 %) corresponden a reacciones adversas a medicamento tipo A y 26 (31 %) a reportes de reacciones adversas a medicamentos de tipo fallo terapéutico. Los principales efectos secundarios a los medicamentos fueron el aumento de los niveles de hormona paratiroidea por uso de cinacalcet en 27 (34,1 %) reportes, seguidas por el síndrome de Cushing relacionado con la administración de prednisolona en 12 (14,1 %), bocio por uso de adalimumab en 12 (14,1 %), hiperprolactinemia por el uso de risperidona en 10 (11,8 %) e hipotiroidismo inducido por amiodarona en 3 (3,4 %). Conclusiones. El desarrollo de estos estudios permite conocer las principales reacciones adversas que se presentan durante el uso habitual de los medicamentos, así como su perfil de seguridad.

Objective. Becoming familiar with medication-use related endocrine disruption reported to the local pharmacovigilance program in Bogotá during 2012-2016.Tools and methods. Analyzed reports are dated between January 1st, 2012 and December 31st, 2016 and were gathered from the Pharmacovigilance Program in Bogotá. The analysis of the said reports was conducted through causality algorithms and event type.Results. Out of 87 analyzed reports, two were not included in the study due to lack of information for its classification in one case and, medication-related problems in another case. 36 reports (42.9 %) were found to have adverse reaction to type A medications, while 26 reports (34.1%) were found to have medication related problem type therapeutic failure. The main medication related problems were associated to the use of Cinacalcet with increased levels of parathormone in 27 out of 87 analyzed reports in this study. Other medication related problems found were: Cushing Syndrome, associated with the use of prednisolone in 12 reports; Goiter associated to the use of adalimumab in 12 reports; Hyperprolactinemia associated to the use of Risperidone in 10 reports and, Hypothyroidism associated to the use of Amiodarone in 3 reports. Conclusions: Carrying out such studies allows for the understanding of the main medication-use problems that are shown during common use of medications, as well as their safety profile.

Objetivo. O objetivo do artigo é conhecer as alterações endócrinas associadas ao uso de medicamentos reportadas pelo Programa Distrital de Vigilância farmacológica em Bogotá. Materiais e métodos. Os reportes analisados correspondem ao período de janeiro de 2012 a dezembro 2016 e a analise foi realizada com algoritmos de causalidade e por tipo de evento. Resultados. Foram analisados 87 reportes, embora no final dois deles foram desconsiderados, um por corresponder a um problema relacionado com o medicamento e o outro por falta de informações para classifica-lo. Encontraram-se 36 (42%) de reportes associados a reações adversas perante os medicamentos tipo A e 26 (31%) de reportes de RAM tipo falho terapêutico. As principais RAM foram por uso de cinacalcet com aumento dos níveis de parathormona em 27 reportes (34%), seguidas de Síndrome de Cushing relacionado com prednisolona em 12 reportes (14,1%), bócio por uso de adalimumab em outros 12 re-portes, hiperprolactinemia por uso de risperidona em 10 casos (11,8%) e hipotiroidismo induzido por amiodarona em 3 casos. Conclusoes. O desenvolvimento destes estudos, permite conhecer as principais reações adversas causadas pelo uso habitual dos medicamentos mesmo como seu perfil de segurança.

Primary amenorrhea associated with hyperprolactinemia in polyglandular autoimmune syndrome type II: A case report / Amenorreia primária associada com hiperprolactinemia em síndrome poliglandular autoimune tipo 2: relato de caso

Abstract Polyglandular autoimmune syndrome type II (PGA-II) is a rare immunoendocrinopathy syndrome characterized by the occurrence of autoimmune Addison disease along with diabetes mellitus type 1 and/or autoimmune thyroid disease. Here, we report the case of a 23-year-old female with PGA-II who was followed up at the dermatology and endocrinology clinics of the Universidade Federal do Triângulo Mineiro, located in the state of Minas Gerais, Brazil. First, the patient presented diffuse skin hyperpigmentation, vitiligo; and in sequence, due to vomiting, appetite and weight loss, hypoglycemia, amenorrhea, and galactorrhea, the patient was then diagnosed with PGA-II. The patient also presented intense hyperprolactinemia due to primary hypothyroidism. The late diagnosis of PGA-II is frequent because the disorder is uncommon and has non-specific clinical manifestations. This report emphasizes the significance of a timely diagnosis and appropriate treatment to reduce morbidity and mortality associated with these diseases, especially Addison disease. The present study reports a rare case of a patient with PGA-II with primary amenorrhea associated with hyperprolactinemia.

Resumo A síndrome poliglandular autoimune tipo 2 (SPGA-2) é uma síndrome de imunoendocrinopatia rara caracterizada por doença de Addison autoimune associada à diabetes mellitus tipo 1 e/ou doenças tireoidianas autoimunes. Relatamos aqui o caso de uma paciente de 23 anos de idade com SPGA-2 que foi acompanhada nos ambulatórios de dermatologia e endocrinologia da Universidade Federal do Triângulo Mineiro, localizada no estado de Minas Gerais, Brasil. Primeiramente, a paciente apresentou hiperpigmentação cutânea difusa e vitiligo; posteriormente, por apresentar vômitos, hiporexia, perda ponderal, hipoglicemia, amenorreia e galactorreia, foi diagnosticada com SPGA-2. A paciente apresentou também intensa hiperprolactinemia secundária apenas ao hipotireoidismo primário. É comum o diagnóstico tardio da SPGA-2, pois a doença é rara e apresenta manifestações clínicas inespecíficas. Este relato de caso enfatiza a importância do diagnóstico e tratamento precoces como objetivo de reduzir a morbimortalidade associada a essas doenças, especialmente à doença de Addison. O presente estudo descreve um caso raro de uma paciente com SPGA-2 com amenorreia primária associada a hiperprolactinemia.

Presentación atípica de un prolactinoma gigante en un adolescente de 15 años / Atypical presentation of a giant prolactinoma in a 15-year-old boy

El prolactinoma gigante es un adenoma pituitario poco frecuente caracterizado por su gran invasión local. Se reporta el caso de un varón de 15 años de edad con dolor retroocular izquierdo y exoftalmos ipsilateral de 4 meses de evolución secundario a un tumor en la base del cráneo que invadía la órbita. Los estudios hormonales revelaron prolactina sérica de 6913,7 ng/ml (valor normal < 20), que confirmó el diagnóstico de prolactinoma gigante. El paciente inició un tratamiento con el agonista dopaminérgico cabergolina en dosis crecientes. Luego de 7 meses de seguimiento, la prolactina había descendido a 349,8 ng/ml y el volumen del tumor se redujo un 70%, sin efectos adversos al tratamiento. El paciente se encontraba asintomático y había reiniciado la pubertad. La rápida remisión de los síntomas sin necesidad de tratamientos invasores subraya la importancia de considerar el diagnóstico de prolactinoma entre los posibles diagnósticos diferenciales de tumor de la base del cráneo.

Giant prolactinomas are rare pituitary adenomas characterized by their great local invasion. In this paper, we report a 15-year-old male with left retro-ocular pain and ipsilateral exophthalmos of 4 months of evolution, secondary to a tumour in the base of the skull that invaded the orbit. Hormonal studies revealed serum prolactin of 6913,7 ng/ml (normal value < 20), confirming the diagnosis of giant prolactinoma. The patient started treatment with the dopaminergic agonist cabergoline in increasing doses. After 7 months of follow-up the prolactin had decreased to 349.8 ng/ml and the tumor volume was reduced by 70%, without presenting adverse effects to the treatment. The patient was asymptomatic and had restarted puberty. The rapid remission of symptoms without the need for invasive treatments underlines the importance of considering the diagnosis of prolactinoma among the possible differential diagnoses of tumor of the skull base.

Características clínicas y manejo de la macroprolactinemia como causa de hiperprolactinemia / Clinical characteristics and management of macroprolactinemia as cause of hyperprolactinemia

La macroprolactinemia se define como la presencia de cantidades elevadas de esta isoforma de la prolactina en suero, en conjunto con concentraciones normales de prolactina monomérica. Se trata de una entidad bastante común, considerada entre las tres primeras causas de hiperprolactinemia. Su origen parece responder a mecanismos autoinmunes y el seguimiento de los pacientes afectos durante periodos de 10 años ha demostrado que es una condición crónica. La prueba de elección para el diagnóstico es la cromatografía líquida en columna de gel, pero este es un método costoso que generalmente es suplido por la prueba de precipitación con polietinglicol. Por mucho tiempo ha prevalecido el concepto de que estos pacientes son esencialmente asintomáticos, pero reportes recientes señalan la presencia de síntomas de hiperprolactinemia como parte significativa del cuadro, aunque la literatura actual muestra criterios divergentes. En estos pacientes la realización de resonancia magnética nuclear hipofisaria parece ser un procedimiento innecesario, basado en la escasa frecuencia de resultados positivos. El tratamiento farmacológico con agonistas dopaminérgicos muestran respuestas contradictorias en cuanto a la desaparición de los síntomas y la normalización de los niveles de prolactina. Por tanto, la inexistencia de un consenso en la literatura científica en lo referente a las manifestaciones clínicas y el manejo, obliga a una conveniente valoración individual de cada caso(AU)

Macroprolactinemia is defined as the presence of high quantities of this prolactin isoform in serum, together with normal concentrations of monomeric prolactin. It is a common entity, considered among the three first causes of hyperprolactinaemia. The origin seems to respond to autoimmune mechanisms and the affected patients follow-up during ten years periods has shown that it is a chronic condition. The standard gold test to the diagnostic is gel-filtration chromatography, but it is an expensive method that is generally supplied by the polyethylene glycol precipitation test. During a long time, the concept that these patients are essentially asymptomatic has prevailed, but recent reports stamps the presence of hyperprolactinemia symptoms as a significant part of the entity, although current literature shows divergent criteria. In these patients, performing pituitary magnetic resonance seems to be an unnecessary procedure, based on the rare frequency of positive results. Pharmacological treatment with dopamine agonists shows contradictory responses with regard to symptoms disappearance and prolactin levels normalization. Therefore, the lack of consensus in the scientific literature with regard to the clinical manifestations and the management, requires a convenient individual assessment of each case(AU)

Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

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.

Investigación electrónica del tratamiento de la hiperprolactinemia en Brasil: endocrinólogos contra ginecólogos / Electronic survey of management of hyperprolactinemia in Brazil: Endocrinologists versus gynecologists

Hyperprolactinemia is a frequent condition in clinical practice, responsible for 20-25% of secondary amenorrhea cases. We performed an electronic survey among members of the Brazilian Society of Metabolism and Endocrinology (SBEM) and the Brazilian Federation of Association of Gynecology and Obstetrics (FEBRASGO) to assess diagnostic and therapeutic preferences for management of hyperprolactinemia. Electronic addresses of SBEM and FEBRASGO members were obtained from the directories of these societies, and these members were invited, through electronic messages (e-mail), to answer an online questionnaire that included 10 questions about the treatment of micro and macropro-lactinomas, maximum dose of dopamine agonist, how to exclude primary hypothyroidism and macroprolactinemia, hyperprolactinemia and pregnancy. We received responses to the questionnaire by e-mail from 521 SBEM members and 233 FEBRASGO members. The results of this survey demonstrate that there are many area of agreement between SBEM and FEBRASGO members and most of their responses follow the latest Endocrine Society Guideline. Relative to a survey performed several years ago, our findings show that SBEM members have incorporated some of latest recommendations in this field. The principal issues of concern for both groups are duration of dopamine agonist treatment for patients with microprolactinoma and dopamine agonist withdrawal during pregnancy.

La hiperprolactinemia es una alteración frecuente, siendo responsable del 20 al 25% de los casos de amenorrea secundaria. Se realizó una investigación electrónica entre los miembros de la Sociedad Brasileña de Endocrinología y Metabología (SBEM) y de la Federación Brasileña de Ginecología y Obstetricia (FEBRASGO) para evaluar sus preferencias en el diagnóstico y el tratamiento de la hiperprolactinemia. Las direcciones electrónicas de miembros SBEM y de FEBRASGO se obtuvieron a partir de los directorios de esas sociedades. Se invitó a estos miembros a responder un cuestionario que incluía 10 cuestiones sobre el tratamiento de los micro y macroprolactinomas, dosis máxima del agonista dopaminérgico, hiperprolactinemia e hipotiroidismo primario, macroprolactinemia, prolactinoma y embarazo. Hemos recibido respuestas de 521 miembros de la SBEM y de 233 miembros FEBRASGO. Los resultados demuestran que hay bastantes áreas de concordancia entre los miembros de la SBEM y de la FEBRASGO y que la mayoría de las respuestas están de acuerdo con el último consenso de la Endocrine Society. En cuanto a una encuesta similar realizada hace años, nuestros resultados muestran que los socios de SBEM incorporaron algunas de las últimas recomendaciones propuestas en esa área. Los principales aspectos de interés en ambos grupos son la duración del tratamiento con el agonista dopaminérgico y la retirada del mismo durante el embarazo.

Pituicitoma hipofisario, un hallazgo diagnóstico inusual: reporte de caso / Pituitary pituicytoma, finding of an unusual diagnosis: a case report

Los pituicitomas son tumores infrecuentes de la región selar y supraselar, originados de la neurohipófisis, que suelen ser confundidos con otros tumores al compartir características imaginológicas. Se reporta el caso de una mujer de 36 años de edad, con un pituicitoma en la región selar, que fue diagnosticado como un adenoma hipofisario debido a los hallazgos clínicos e imaginológicos preoperatorios y se realiza una revisión de la literatura.

The Pituicytomas are rare tumors of the sellar and suprasellar region originated of the neurohypophysis and are usually confused with other tumors when sharing imagining features. It is reported a case of a 36 years old woman with pituicytoma in the sellar region that was diagnosed as a pituitary adenoma due to the presurgical clinical and imaging findings and, it is revised the literature.

Evaluación de los valores séricos de prolactina en lupus eritematoso sistémico / Assessment of serum prolactin levels in patients with systemic lupus erythematosus

El propósito del presente estudio fue determinar la relación entre los valores de prolactina sérica y las características clínicas de pacientes con lupus eritematoso sistémico (LES) asistentes a la consulta de Reumatología del Servicio Autónomo Hospital Universitario de Maracaibo, en Maracaibo, Venezuela. Se realizó un estudio descriptivo, correlacional y transversal en pacientes femeninas, mayores de 18 años, con diagnóstico de LES, quienes asistieron al Hospital Universitario de Maracaibo, durante los meses de noviembre 2012 a junio del 2013; se les realizó una historia clínica integral, basada en anamnesis y examen físico, con énfasis en la búsqueda de manifestaciones clínicas de actividad lúpica y se tomaron muestras sanguíneas para la determinación de las concentraciones séricas de prolactina, en el momento de la evaluación de la paciente. Se utilizaron como rangos normales, valores entre 2,1 y 25 ng/mL. La población consistió en un total de 50 pacientes y se clasificó en dos grupos: el primer grupo conformado por 28 mujeres con crisis lúpica y el segundo por 22 sin crisis al momento del estudio. La concentración promedio de prolactina sérica fue de 39,0 ± 59,5 ng/dL para el primer grupo y de 14,2 ± 7,2 ng/dL para el segundo grupo, con diferencias estadísticamente significativas (p=0,044). Las pacientes con crisis lúpica presentaron valores de prolactina más elevados que las pacientes en remisión, no obstante que solo la séptima parte de ellas tenían cifras de prolactina fuera del rango normal. Todas las pacientes asintomáticas presentaron niveles normales de prolactina, por el contrario, todas las pacientes con hiperprolactinemia estaban en crisis lúpica.

To determine the relationship between hyperprolactinemia levels and clinical features of patients with systemic lupus erythematosus (SLE), a descriptive, correlational and cross-sectional study, was performed in female patients over 18 years old, who attended the Rheumatology Clinic at the Hospital Universitario, in Maracaibo, Venezuela, from November 2012 to June 2013. They underwent a comprehensive medical history evaluation, based on interviews and physical examination, with emphasis on the search for clinical manifestations of lupus activity. Blood samples were taken in order to determine prolactin levels at the moment of the patient evaluation. Values from 2.1 to 47.6 ng/mL were considered as normal. The population was classified into two groups: a group formed by 28 women with lupus crisis and another group formed by 22 patients without crisis. The average prolactin serum level was 39.0 ± 59.5 ng/dL for the first group and 14.2 ± 7.2 ng/dL for the second group, indicating statistical significance (p = 0.044). Patients with lupus crisis had prolactin values higher than those of asymptomatic patients, although only oneseventh of them had absolute hyperprolactinemia. All asymptomatic patients had normal levels of prolactin. All patients with hyperprolactinemia were in lupus crisis.

Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension / Prolactinomas podem ter apresentações incomuns resultantes de maciça extensão tumoral extrasselar

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.