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)

Importancia de la anamnesis exhaustiva ante una ginecomastia unilateral inexplicada en un niño / Importance of the exhaustive anamnesis to an unexplained unilateral gynecomastia in a child

La ginecomastia es el crecimiento de la mama por un desequilibrio hormonal entre estrógenos y andrógenos. Un crecimiento importante y unilateral requiere descartar patologías subyacentes. Una causa poco frecuente es la traumática, que provoca aumento de tamaño por estimulación repetida. Se presenta el caso de un niño de 6 años con ginecomastia unilateral. Se destaca como único hallazgo en las pruebas complementarias hiperprolactinemia. Rehistoriando, se detecta una continua autoestimulación mamaria manual y oral a través de mordiscos de meses de evolución. Tras el cese del estímulo, se observa la involución de la mama y la normalización de los niveles de prolactina séricos.

Gynecomastia consists of breast enlargement due to a hormonal imbalance between estrogens and androgens. Unilateral and important breast growth requires ruling underlying pathologic disorders out. Mechanical cause is uncommon, causing enlargement by repeated stimulation. We report a 6-year-old boy with unilateral gynecomastia. Hyperprolactinemia is the only abnormal finding at laboratory tests. After repeated inquiries, a continuous breast selfstimulation is detected. Its relation with gynecomastia is verified because prolactin normalizes and breast regressed in further revisions, after stopping stimulus.

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.

Challenges and pitfalls in the diagnosis of hyperprolactinemia / Desafios e armadilhas no diagnóstico da hiperprolactinemia

The definition of the etiology of hyperprolactinemia often represents a great challenge and an accurate diagnosis is paramount before treatment. Although prolactin levels > 200-250 ng/mL are highly suggestive of prolactinomas, they can occasionally be found in other conditions. Moreover, as much as 25% of patients with microprolactinomas may present prolactin levels < 100 ng/mL, which are found in most patients with pseudoprolactinomas, drug-induced hyperprolactinemia, or systemic diseases. On the other hand, some conditions may lead to falsely low PRL levels, particularly the so-called hook effect, that is an assay artifact caused by an extremely high level of PRL, and can be confirmed by repeating assay after a 1:100 serum sample dilution. The hook effect must be considered in all patients with large pituitary adenomas and PRL levels within the normal range or only modestly elevated (e.g., < 200 ng/mL). An overlooked hook effect may lead to incorrect diagnosis and unnecessary surgical intervention in patients with prolactinomas. Another important challenge is macroprolactinemia, a common finding that needs to be identified, as it usually requires no treatment. Although most macroprolactinemic patients are asymptomatic, many of them may present galactorrhea or menstrual disorders, as well as neuroradiological abnormalities, due to the concomitance of other diseases. Finally, physicians should be aware that pituitary incidentalomas are found in at least 10% of adult population. Arq Bras Endocrinol Metab. 2014;58(1):9-22.

A definição da etiologia da hiperprolactinemia muitas vezes representa um grande desafio e um diagnóstico preciso é fundamental antes do tratamento. Embora níveis de prolactina > 200-250 ng/mL sejam altamente sugestivos de prolactinomas, ocasionalmente podem ser encontrados em outras condições. Além disso, até 25% dos pacientes com microprolactinomas podem apresentar-se com níveis de prolactina < 100 ng/mL, os quais são evidenciados na maioria dos pacientes com pseudoprolactinomas, hiperprolactinemia induzida por drogas ou doenças sistêmicas. Por outro lado, deve-se atentar às condições que podem levar a valores de prolactina falsamente baixos, particularmente o chamado efeito gancho. Este último é um artefato causado por um nível extremamente elevado de PRL e que pode ser confirmado pela repetição do exame após diluição do soro a 1:100. O efeito gancho deve ser considerado em todo paciente com grandes adenomas hipofisários e níveis de prolactina dentro da faixa normal ou apenas moderadamente elevados (p. ex., < 200 ng/mL). Um efeito gancho não detectado pode levar a diagnóstico incorreto e intervenção cirúrgica desnecessária em pacientes com prolactinomas. Outro desafio importante é a macroprolactinemia, um achado comum que precisa ser identificado visto que geralmente não requer tratamento. Ainda que a maioria dos pacientes seja assintomática devido à concomitância de outras doenças, muitos podem apresentar galactorreia ou distúrbios menstruais, bem como anormalidades neurorradiológicas. Finalmente, os médicos devem estar cientes de que incidentalomas hipofisários são encontrados em pelo menos 10% da população adulta. Arq Bras Endocrinol Metab. 2014;58(1):9-22.

A Case of Idiopathic Granulomatous Hypophysitis

Granulomatous hypophysitis is a rare pituitary condition that commonly presents with enlargement of the pituitary gland. A 31-year-old woman was admitted to the hospital with a severe headache and bitemporal hemianopsia. Magnetic resonance imaging (MRI) showed an 18 x 10-mm sellar mass with suprasellar extension and compression of the optic chiasm. Interestingly, brain MRI had shown no abnormal finding 4 months previously. On hormonal examination, hypopituitarism with mild hyperprolactinemia was noted. The biopsy revealed granulomatous changes with multinucleated giant cells. We herein report this rare case and discuss the relevant literature.

Diagnóstico diferencial de los prolactinomas / Differential diagnosis of prolactinomas

La hiperprolactinemia puede deberse tanto a adenomas hipofisarios que secretan prolactina (prolactinomas) como a tumores selares no funcionantes (denominados seudoprolactinomas). La relación entre el tamaño del tumor y el grado de prolactinemia habitualmente permite distinguir los prolactinomas de los seudoprolactinomas; este diagnóstico diferencial es esencial, dado que la terapia es completamente diferente (médica en el primer caso, quirúrgica en el último). La posible coexistencia de otras causas fisiológicas, patológicas o yatrogénicas de hiperprolactinemia, así como artefactos de laboratorio (efecto gancho) y la presencia de variantes de prolactina desprovistas de actividad biológica (macroprolactinas) puede dar origen a errores. Los médicos deben conocer estos trastornos, dado que cuando no se reconocen se pueden realizar tratamientos inapropiados.

Consumo materno de dois compostos bioativos da semente da linhaça sobre parâmetros bioquímicos e hormonais das mães e proles durante a lactação / Maternal consumption of two bioactive compounds from flax seed on biochemical and hormonal parameters of mothers and offspring during lactation

Avaliamos o efeito do consumo materno de SDG (Diglicosídeo Secoisolariciresinol) e de óleo de Linhaça+SDG sobre parâmetros bioquímicos e hormonais das ratas e das proles machos e fêmeas na lactação. As ratas lactantes foram separadas em: controle (C), ração controle cuja proteína foi caseína; (SDG): ração C com 400mg de SDG/Kg de ração; OLSDG: ração C com 400mg de SDG/Kg de ração e 7% de óleo de linhaça. No 14º e 20º dias de lactação as ratas foram ordenadas e no 21º dia foram sacrificadas por punção cardíaca. Leite e soro foram coletados para avaliação bioquímica e hormonal. Hormônios foram quantificados por radioimunoensaio. As proles machos e fêmeas foram sacrificadas aos 14 e 21 dias de idade. Os animais foram eviscerados para análise da composição corporal. Monitoramos a ingestão alimentar e a massa corporal (MC) durante o período experimental. As ratas SDG apresentaram maior gordura corporal (GC; +39%), enquanto as OLSDG menor conteúdo mineral (-20%) e trigliceridemia (TG) (-39%). As ratas SDG e OLSDG apresetaram hiperprolactinemia (+389% e 153%, respectivamente) sem alteração na concentração de estradiol. No 14º dia de lactação, o leite das ratas OLSDG apresentou menores teores de lactose (-17%) e de proteínas (-20%) e o das ratas SDG apenas menor teor de proteína (-21%). A partir do 13º dia de lactação tanto os machos quanto as fêmeas OLSDG apresentaram menor MC (-14%, -16%, respectivamente). No 14º dia de lactação os machos SDG e OLSDG apresentaram menor gordura corporal (-24%, -55%, respectivamente) e a prole SDG maior massa de gordura visceral (+39%). Os machos SDG apresentaram maiores concentrações de TG (+105%) e hipoprolactinemia (-41%). Os machos OLSDG também apresentaram hipoprolactinemia (-41%). As fêmeas SDG e OLSDG apresentaram maior estradiol aos 14 dias (+86% e +176%) que se normalizou aos 21 dias, maior colesterolemia (+16%) e as SDG apresentaram maior trigliceridemia (+74%). Aos 21 dias os machos e as fêmeas SDG e OLSDG...

We evaluated the mother's intake of SDG (Diglicoside secoisolariciresinol) and flaxseed oil + SDG upon biochemical and hormonal parameters of lactating female rats and the male and female offspring during lactation. The female lactating rats were divided into: Control (C): feeding a diet with casein; (SDG): feeding diet C added 400mg of SDG/Kg diet; (OLSDG): diet C added 400mg of SDG/Kg diet and 7% of flaxseed oil. Milk samples were obtained on the 14th and 20th days of lactation and the mothers were sacrificed and blood collected by cardiac puncture on the 21st day. Milk and serum were collected for biochemical and hormonal analysis. The male and female offsprings were sacrified on the 14th and 21th day. The hormonal dosages were measured by radioimunassay. The animals were completely eviscerated to analyze body composition. Body mass (BM) and food intake were monitored during all experimental period. The SDG rats showed higher fat mass (+39%) while the OLSDG rats showed lower mineral content (-20%) and triglycerides (TG) serum levels (-39%). The SDG and OLSDG rats showed higher prolactin levels (+339% and +153% respectively) without changes in serum estradiol. On the 14th day of lactation we observed lower lactose (-17%) and protein (-20%) content in the OLSDG rat's milk while in the SDG only lower protein (-21%). From the 13th day of lactation both the males and females OLSDG showed lower BM (-14%, -16%, respectively). On the 14th day the male SDG and OLSDG showed lower fat mass (-24%, -55%, respectively), and the SDG offspring showed higher visceral fat mass (+39%). The SDG male also showed higher TG levels (+105%) and lower prolactin levels (-41%). The OLSDG males also showed lower prolactin serum levels (-41%). The OLSDG female showed higher serum estradiol at 14 days (+86% e +176%), which normalized at 21 days and higher cholesterolemia (+16%) and the SDG female presented higher TG levels (+74%). On day 21th day the male and female SDG and OLSDG...

Effects of Olanazapine and haloperidol on serum malondialdehyde, prolactin level, blood glucose and lipid profilein schizophrenic patients

The association of the atypical antipsychotics with hyperglycemia, elevated lipids, and weight gain was recognized soon after the introduction of clozapine and has become of increased concern as the use and uses of atypical antipsychotics have been expanded. The aim of the present study was to investigate the prevalence of diabetes, dyslipidamia, lipid peroxidation and hyperprolactinemia in Olanzepine treated patients in comparison with patients treated with haloperidol. Fifty patients were selected randomly from psychiatric inpatient clinic in Erbil city in Iraqi Kurdistan Region between November 2007 and June 2008. All patients were diagnosed as schizophrenia, and none of them were in acute severe state. Thirty Schizophrenic patients received Haloperidol orally as typical antipsychotic and 20 patients received Olanazapine orally as atypical antipsychotic for a minimum of one month. Fasting blood samples for the assessment of serum malondialdehyde [MDA], lipid profile, fasting blood glucose [FBG] and prolactin levels were obtained after one month of the drug prescribing time. From those fifty patients, 16 patients were selected to follow them prospectively over a mean period of time of 112 days for olanzapine and 75 days for haloperidol. The prospective study includes FBG, lipid profile, BMI and serum MDA. The prevalence of hyperprolactinaemia and lipid peroxidation was higher in Haloperidol treated patients. Whereas, the prevalence of diabetes and dyslipidaemia were higher in Olanazapine treated patients, the mean level of BMI of the Olanazapine group was significantly higher than BMI of the Haloperidol group. There was 6.66% prevalence of D< in Olanazapine treated patients, but there was no prevalence of DM in Haloperidol treated patients. There was no incidence of diabetes mellitus in the prospective study for both Haloperidol and Olanazapine treated patients. No absolute evidence indicates that the atypical antipsychotic Olanazapine is the cause of diabetes, since the glucose levels of all patients were within normal range and there was no incidence of diabetes in the prospective study in spite of their higher weight and body mass index

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids: [revisão] / Gonadotrophic axis dysfunction in men with HIV-infection/Aids: [review]

A disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neoplasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de massa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisiopatológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento.

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.

Utilidad de la cabergolina en pacientes portadores de prolactinoma resistentes o intolerantes a bromocriptina / Usefulness of cabergoline in patients with prolactinemia and resistant or intolerant to bromocriptine

Introducción: La terapia de elección de los prolactinomas son los agonistas dopaminérgicos, cuyo principal exponente es la bromocriptina, sin embargo, hay pacientes que no responden o presentan severos efectos secundarios (resistentes o intolerantes a bromocriptina, respectivamente). El objetivo en este estudio fue valorar la respuesta al uso de cabergolina en pacientes con prolactinomas, intolerantes o resistentes a bromocriptina Material y métodos: Se estudiaron 27 pacientes (25 mujeres y dos varones) en quienes se realizó determinación basal de prolactina y cada mes hasta completar tres meses, registrando los datos asociados a hiperprolactinemia y los efectos secundarios. La dosis inicial fue de 0.25 mg los lunes y jueves durante la primera semana, y 0.5 mg a partir de la segunda. El análisis estadístico incluyó la prueba de Shapiro-Wilk, Kruskal-Wallis y Anova. Resultados: 22 pacientes presentaron microadenomas y cinco macroadenomas. En los intolerantes (n = 11) el valor inicial de prolactina de 61.45 ± 19.82 disminuyó al tercer mes a 4.94 ± 1.79 (p < 0.024). En los resistentes (n = 16), el valor basal fue 119.53 ± 11.52; 15 pacientes redujeron significativamente a 12.95 ± 3.66 (p < 0.005) al tercer mes de tratamiento. En ambos, los signos atribuibles a la hiperprolactinemia mejoraron significativamente, con poca incidencia de efectos secundarios. Conclusiones: La cabergolina es útil en la mayoría de los pacientes considerados intolerantes o resistentes a la bromocriptina.

BACKGROUND: Dopaminergic agonists are the treatment of choice for prolactinomas with bromocriptine (BCE) being the primary agent used. There is a group of patients who are not responders to such therapy or have severe side effects (resistant or intolerant to BCE, respectively). We undertook this study to evaluate the response to the administration of cabergoline (CBG) in patients intolerant or resistant to BCE. METHODS: Twenty seven patients (25 females and 2 males) were recruited with prolactin-pituitary tumors, obtaining basal serum prolactin (PRL) samples and again each month up to 3 months. We recorded signs associated with hyperprolactinemia and secondary effects of CBG. The initial dose was 0.25 mg twice weekly during the first week, with an increase to 0.5 mg twice weekly from the second week until the conclusion of the study. Statistical analysis included Shapiro-Wilk, Kruskal-Wallis and ANOVA tests. RESULTS: Twenty two patients had microadenomas and five had macroadenomas. In the intolerant group (n= 11), the initial PRL value (61.45 +/- 19.82) decreased by the third month to 4.94 +/- 1.79 (p<0.024). In the resistant group (n= 16), basal PRL values were 119.53 +/- 11.52. In 15 of these patients, the PRL value significantly decreased to 12.95 +/- 3.66 ng/ml (p<0.005) by the third month of treatment. In both groups the signs related to hyperprolactinemia significantly improved, with a low incidence of secondary effects due to CBG. CONCLUSIONS: CBG is useful in most patients considered as intolerant or resistant to BCE.

Hiperprolactinemia en la población infantojuvenil: un tema vigente / Hyperprolactinaemia in child an adolescent population: a current issue

La hiperprolactinemia constituye la altelaración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares, algunas de ellas con menor o ausente actividad biológica. Todo proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. Si bien la patología tumoral constituye el diagnóstico de mayor relevancia, los prolactinomas son poco frecuentes en nios y adolescentes, aunque tienen en general una particular presentación clínica: de acuerdo con nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50% de las pacientes de sexo femenino. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspención de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6% de la PRL total y la BB PRL contituyó el 40 y el 72% de çesta en este gruo de pacientes. En cuanto al tratamiento por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos.

Severe hyperprolactinemia associated with internal carotid artery aneurysm: differential diagnosis between prolactinoma and hypothalamic-pituitary disconnection / Hiperprolactinemia severa associada a aneurisma interno da artéria carótida: diagnóstico diferencial entre prolactinoma e desconexão hipotálamo-hipofisária

Sellar and parasellar masses blocking inhibitory hypothalamic dopaminergic tonus can produce hyperprolactinemia. One of these conditions, seldom reported, is internal carotid artery aneurysm causing pituitary stalk compression and hyperprolactinemia, the majority of which is related to small increases in serum prolactin levels. The aim of this study is to report the case of a patient with an internal carotid aneurysm and severe hiperprolactinemia. A 72 years old female patient, on oncology follow-up for clinically controlled cervical carcinoma, was evaluated due to worsening chronic headaches. During the investigation, computed tomography and magnetic resonance imaging (MRI) showed a sellar mass associated with high prolactin level (1.403 µg/L) that initially was considered a macroprolactinoma, and treated with bromocriptine. However, subsequent pituitary MRI suggested an internal carotid aneurysm, which was confirmed by an angioresonance imaging of cerebral vessels. On low bromocriptine dose (1.25 mg/day), there was a prompt normalization of prolactin levels with a great increase (> 600 µg/L) after withdrawal, which was confirmed several times, suggesting HPD. We report a patient with internal carotid artery aneurysm with severe hyperprolactinemia never reported before in patients with HPD, and the need for a differential diagnosis with macroprolactinomas even considering high prolactin levels.

Massas selares e parasselares podem produzir hiperprolactinemia por bloquear o tônus inibitório hipotalâmico de dopamina. Uma destas condições, raramente reportada, é o aneurisma de artéria carótida interna causando compressão da haste hipofisária e hiperprolactinemia, a maioria com pequenas elevações da prolactina. O objetivo deste estudo é descrever o caso de uma paciente com aneurisma de carótida interna e grave hiperprolactinemia. Paciente feminina, 72 anos, em acompanhamento oncológico por carcinoma de colo de útero clinicamente controlado, avaliada por causa da piora de cefaléia crônica. Durante investigação, tomografia computadorizada e ressonância magnética (RM) de hipófise mostraram massa selar associada com altos níveis de prolactina (1.403 µg/L), sendo avaliado como macroprolactinoma e tratado com bromocriptina. Entretanto, RM subseqüente sugeriu aneurisma de carótida interna que foi confirmado por angiorressonância de vasos cerebrais. Em uso de baixas doses de bromocriptina (1,25 mg/dia), houve pronta normalização da prolactina com grande elevação (> 600 µg/L) após a retirada do medicamento, sendo confirmado por várias vezes sugerindo DHH. Reporta-se uma paciente com aneurisma de artéria carótida interna com grave hiperprolactinemia, nunca descrita anteriormente em pacientes com DHH, e a necessidade do diagnóstico diferencial com macroprolactinoma, mesmo considerando altos níveis de prolactina.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean ± SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 ± 1.29 percent). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 ± 4 ng/mL), luteinizing hormone (control: 1.58 ± 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 ± 2.28 ng/mL), estradiol (control: 14.65 ± 3.22 pg/mL), and total testosterone (control: 138.41 ± 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Efectos de la menopausia sobre los niveles de prolactina en mujeres con hiperprolactinemia / Effects of menopause on the prolactin levels in women with hyperprolactinemia

Con el objetivo de determinar si la menopausia produce modificaciones en el cuadro hiperprolactinémico en pacientes menopáusicas con antecedentes de hiperprolactinemia en su etapa reproductiva, se realizó el presente trabajo. Se entrevistaron 65 mujeres con edades entre 41 y 59 años, distribuidas en 2 grupos: grupo 1 formado por 17 pacientes posmenopáusicas con antecedentes de hiperprolactinemia, y un grupo control (grupo 2) compuesto por 48 mujeres posmenopáusicas sin hiperprolactinemia. Se aplicó una encuesta que incluyó datos generales, valores de prolactina al diagnóstico (grupo 1) y la presencia o no de síntomas relacionados con el climaterio; además, se les extrajo sangre para determinar prolactina, hormona estimulante del folículo (FSH), hormona luteinizante (LH) y estradiol. El promedio de edad para el grupo 1 fue 53,1 años, y en el grupo 2 de 51,8 años, la edad promedio de la menopausia fue 47,5 y 48,5 años, respectivamente. La prolactina en el grupo 1 presentó una mediana de 623 mUI/l, mientras que en el grupo 2 fue de 239 mUI/l. Al analizar los valores de prolactina dentro del grupo 1 antes y después de la menopausia encontramos que el 47 por ciento de las mujeres normalizaron estas cifras. En conclusión, los niveles de prolactina en mujeres hiperprolactinémicas en etapa reproductiva disminuyen al llegar a la menopausia, y un por ciento significativo los normaliza. Los valores de prolactina en la posmenopausia en mujeres con antecedentes de hiperprolactinemia son mayores que en las mujeres sin este antecedente(AU)

The present work was aimed at determining wether or not menopause produces modifications in the hyperprolactinemic picture of menopausal patients with prolactinemia history in their reproductive stage. 654 females aged 41-59 were interviewed and divided into 2 groups: group 1 that was made up of 17 postmenopausal women with hyperprolactinemia history, and a control group (group 2) composed of 48 postmenopausal women without hyperprolactinemia. A survey tha included general data, prolactin values on the diagnosis (group 1) and the presence or not of symptoms related to the climaterium, was done. Blood was extracted to find out prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol. The average age for group 1 was 53.1 years old, and 51.8 for group 2. The average age for menopause was 47.5 years old and 48.5, respectively. Prolactine in group 1 presented a median of 623 mUI/l, whereas in group 2 it was 239 mUI/l. On analyzing the prolactin values in group 1 before and after menopause it was observed that 47 per cent of women normalized these figures. The prolactin values in postmenopause among women with hyperprolactinemia history were higher than in women wihtout it(AU)

Hiperprolactinemia en niños y adolescentes, conceptos e interrogantes actuales / Hyperprolactinemia in children and adolescents, current questions and concepts

La hiperprolactinemia constituye la alteración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares (PRL glicosilada, fosforilada, sulfatada, deaminada, BIG PRL, BIG BIG PRL, etc.), algunas de ellas con menor o ausente actividad biológica. El recién nacido presenta inmadurez fisiológica del eje prolactínico, alcanzando niveles de hasta 800 ng/mL en las primeras horas de vida. Posteriormente, cualquier proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. La patología tumoral constituye el diagnóstico de mayor relevancia. Los prolactinomas poco frecuentes tienen, por su presentación clínica en niños y adolescentes, algunas características destacables. De acuerdo a nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50 % de las pacientes de sexo femenino y en más del 25 % de los varones. La mayor prevalencia de macroadenomas en varones coincide con los hallazgos en adultos y no dependería de un mayor retraso en el diagnóstico. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspensión de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6 % de la PRL total y la BB PRL constituyó el 40 y el 72 % de la misma en este grupo de pacientes. Por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos. La adquisición de nuevos conceptos y la mejor comprensión de la fisiología y la fisiopatología de los estados hiperprolactinémicos en niños y adolescentes, han modificado las alternativas diagnósticas y terapéuticas

Hyperprolactinemia is the most common endocrine alteration of the pituitary-hypothalamic axis, although its prevalence in the pediatric and adolescent population is not clearly defined yet. Apart from native (23Kda) Prolactin (PRL), many molecular variants (glycosylated, phosphorilated, sulphated, deaminated PRL, BIG PRL, BIG BIG PRL, etc) have been described, some of them with less or no biological activity. Newborns have physiological immaturity of the prolactin axis, attaining levels of as much as 800 ng/mL during the first hours after birth. Subsequently, any process that discontinues dopamine secretion, interferes with its secretion to the pituitary portal vessels or blocks dopaminergic receptors of lactotrophic cells, may cause hyperprolactinemia. Tumor disease is the major diagnosis. Prolactinomas, though rare, have some noticeable features, given their clinical presentation in children and adolescents. Based on our experience, pubertal delay occurs in approximately 50 % of females and in over 25 % of males. The larger prevalence of macroadenomas in males is consistent with findings in adults and would not be related to a later diagnosis. In patients with asymptomatic hyperprolactinemia, the presence of altered proportions of PRL isoforms should be evaluated. G100 Sephadex column chromatography, precipitation with a protein A suspension or PEG and ultracentrifugation, are the most common methods for detection of PRL isoforms. In our experience, B PRL accounted for 6.6 - 32.6 % of total PRL and BB PRL accounted for 40 to 72 % of total PRL in this group of patients. Because of their effectiveness and tolerance, dopaminergic agonists are the initial therapy of choice in pediatric age patients. Bromocriptine and cabergoline have been used with similar results to those obtained in adults. The new concepts gained and the better insight into the physiology and pathophysiology of hyperprolactinemic conditions in children and adolescents have brought about a change in diagnostic and therapeutic alternatives

Prevalência da macroprolactinemia entre 115 pacientes com hiperprolactinemia / Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia

Macroprolactinemia caracteriza-se pelo predomínio no soro de uma prolactina (PRL) de alto peso molecular e baixa atividade biológica que não requer tratamento. A prevalência de macroprolactinemia foi avaliada em 115 pacientes consecutivos com hiperprolactinemia. Entre eles, 19 (16,5 por cento) tinham exclusivamente macroprolactinemia, 4 (3,5 por cento) síndrome dos ovários policísticos, 7 (6,1 por cento) acromegalia, 8 (6,9 por cento) hiperprolactinemia idiopática, 10 (8,7 por cento) hipotiroidismo primário, 14 (12,2 por cento) adenomas clinicamente não-funcionantes, 20 (17,4 por cento) hiperprolactinemia farmacológica e 33 (28,7 por cento) prolactinomas. O diagnóstico de macroprolactinemia foi estabelecido pela obtenção de uma recuperação da PRL < 30 por cento após tratamento do soro com polietilenoglicol. Dentre os 19 pacientes com macroprolactinemia isolada, 16 (84,2 por cento) eram mulheres e 12 (63,2 por cento) eram assintomáticos, enquanto 4 (21 por cento) tinham oligomenorréia e 3 (15,8 por cento), galactorréia. Em contraste, apenas 11,5 por cento dos indivíduos com outras causas de hiperprolactinemia eram assintomáticos (p< 0,001). Os níveis de PRL nos casos de macroprolactinemia variaram de 45,1 a 404 ng/mL (média de 113,3 ± 94,5), mas em 15 (78,9 por cento) foram < 100 ng/mL. Nossos achados demonstram que macroprolactinemia é uma condição freqüente e, assim, sugerimos que seja rotineiramente pesquisada em pacientes com hiperprolactinemia.

Macroprolactinemia is characterized by the predominance in the serum of macroprolactin, a prolactin (PRL) with high molecular mass and low biological activity that does not need treatment. The prevalence of macroprolactinemia was evaluated in 115 consecutive patients with hyperprolactinemia. Among them, 19 (16.5 percent) had solely macroprolactinemia, 4 (3.5 percent) polycystic ovary syndrome, 7 (6.1 percent) acromegaly, 8 (6.9 percent) idiopathic hyperprolactinemia, 10 (8.6 percent) primary hypothyroidism, 14 (12.2 percent) clinically non-functioning pituitary adenomas, 20 (17.4 percent) drug-induced hyperprolactinemia and 33 (28.7 percent) prolactinomas. The diagnosis of macroprolactinemia was established by the demonstration of a PRL recovery < 30 percent after treatment of sera with polyethylene glycol. Among the 19 patients with isolated macroprolactinemia, 16 (84.2 percent) were female and 12 (63.2 percent) were asymptomatic, while 4 (21 percent) presented with oligomenorrhea and 3 (15.8 percent) with galactorrhea. In contrast, only 11.5 percent of individuals with other causes of hyperprolactinemia were asymptomatic (p< 0.001). Prolactin levels in cases of macroprolactin ranged from 45.1 to 404 ng/mL (mean 113.3 ± 94.5) but in 15 (78.9 percent) were < 100 ng/mL. Our findings demonstrate that macroprolactinemia is a common condition and, therefore, we suggest that it should be routinely screened in patients with hyperprolactinemia.

A Case of McCune-Albright Syndrome with Associated Multiple Endocrinopathies

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).

Estados hiperprolactinémicos / Hyperprolactinemia

En el presente artículo revisamos los aspectos relevantes de la hiperprolactinemia, en los campos de la fisiología, fisiopatología, prevalencia, etiología, evaluación clínica y tratamiento; enfatizándose la problemática peruana.

Relación entre los valores plasmáticos de prolactina y las imágenes obtenidas en resonancia magnética / Relationship between plasma levels of prolactin and magnetic resonance imagery

Objetivo: Relacionar los valores de prolactina plasmática (PP) con las imágenes de hipófisis obtenidas mediante RM. Material y Métodos: Se analizaron retrospectivamente 164 RM de la región selar y se las relacionó con los valores plasmáticos de prolactina previos al tratamiento instituido. Se estudiaron 152 mujeres y 12 hombres con edades comprendidas entre 2 y 68 años, con un promedio de 31 años. Las exploraciones se realizaron utilizando un Magneto Signa 1,5 T (General Electric-Milwaukee, USA) con cortes sagitales y coronales ponderados en T1 sin y con contraste paramagnético. También se practicó la técnica de perfusión y coronal FLAIR. Resultados: El 20,73% presentó valores de PP menores a 25 ng/ml; de estos, el 47,05% tuvo diagnóstico de adenoma. En el 42,68%, los valores de PP estuvieron entre 25 y 100ng/ml. En estos casos la RM demostró la presencia de adenomas en aproximadamente el 62,85%. De los que tuvieron valores de PP entre 100 y 200 ng/ml (17,07%), la RM demostró adenomas en alrededor del 78,57%. El 18,29% tuvo valores de PP entre 200 y1000 ng%ml, siendo la RM positiva para adenomas en el 60% de estos pacientes. 2 pacientes (1,21%) presentaron valores de PP por encima de los 1000 ng/ml, demostrando la RM la presencia de un adenoma invasor en ambos casos (100%). Conclusión: La RM es el método imagenológico de elección par el estudio de la hipófisis gracias a su especificidad y sensibilidad en la anatomia y función, especialmente cuando se utilizan gadolino y la técnica de perfusión.Los valores de PP son predictores relativos del resultado de la RM; si bien, a mayores niveles, especialmente superiores a 100 ng/ml, las probabilidades de hallazgo de patología hipofisaria aumentan considerablemente. De cualquier manera, cabe destacar que no se trata de una relación lineal y que siempre, en caso de existir hiperprolactinemia, deben descartarse otras etiologías posibles (fisiológicas, drogas, trastornos metabólicos, tumores), aparte de las hipofisarias.