Incidentalomas o no incidentalomas: ¿cuál es la relevancia de los adenomas hipofisarios en el adulto? / Incidentalomas or Non-Incidentalomas: What is the Relevance of Pituitary Adenomas in the Adult?

Introducción: desde el punto de vista anatómico, los adenomas hipofisarios (AH) se observan en el 10% de la población. Son en su mayoría pequeños y no funcionantes. La mayoría de los incidentalomas descubiertos en estudios de imágenes con alta resolución pedidos en situaciones clínicas frecuentes, como el traumatismo craneoencefálico, el accidente cerebrovascular y las demencias, corresponden a AH indolentes. Nos preguntamos cuál es la relevancia clínica de los adenomas hipofisarios. Desarrollo: los AH clínicamente relevantes son tumores en su mayoría benignos que conllevan, en diferentes proporciones, aumento en la morbilidad y/o mortalidad de los pacientes por mecanismos relacionados con la hipersecreción hormonal, la insuficiencia hormonal y/o los efectos de masa ocupante. La prevalencia de los AH clínicamente relevantes es mayor de la que se suponía hace 20 años. Afecta aproximadamente a 1/1000 habitantes. Los más prevalentes son los prolactinomas y los adenomas no funcionantes. La acromegalia, la enfermedad de Cushing y los tumores agresivos se traducen en pacientes complejos con mayor morbimortalidad. El diagnóstico temprano y el tratamiento multimodal proveen una razonable mejoría de la sobrevida. El estudio epidemiológico de los AH clínicamente relevantes es importante para la estimación del impacto en los sistemas de salud. Conclusiones: los estudios por imágenes de mejor resolución continuarán señalando incidentalomas hipofisarios. Una evaluación cuidadosa de los pacientes podrá identificar aquellos AH clínicamente relevantes. (AU)

Introduction: from the anatomical point of view, pituitary adenomas (HA) are observed in 10% of the population. They are mostly small and non-functioning. Most incidentalomas discovered in high-resolution imaging studies ordered in frequent clinical situations, such as head trauma, stroke and dementia, correspond to indolent HA. We wonder what is the clinical relevance of pituitary adenomas. Development: clinically relevant HAs are mostly benign tumors that lead, in different degrees, to an increased morbidity and/or mortality in patients by mechanisms related to hormone hypersecretion, hormone insufficiency and/or occupying mass effects. The prevalence of clinically relevant HA is higher from what was assumed 20 years ago. It affects approximately 1/1000 of the population. The most prevalent are prolactinomas and non-functioning adenomas. Acromegaly, Cushing's disease and aggressive tumors make for complex patients with increased morbidity and mortality. Early diagnosis and multimodal treatment provide a reasonable improvement in survival. Epidemiological study of clinically relevant HAs is important for estimating the impact on health systems. Conclusions: Higher-resolution imaging studies will continue to highlight pituitary incidentalomas. Careful evaluation of patients will identify clinically relevant HAs. (AU)

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study / 亚洲男科学杂志(英文版)

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

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.

Adenoma hipofisário (prolactinoma) proveniente da disfunção hormonal da prolactina: revisão de literatura / Pituitary adenoma (prolactinoma) from prolactin hormonal dysfunction: literature review

Os adenomas hipofisários são, geralmente, tumores benignos com características de hipersecreção ou hipersecreção hormonal, diagnosticados conforme o crescimento tumoral, síndromes de hiperprodução, deficiência da secreção dos hormônios, alterações visuais e cefaleias. A hiperprolactinemia é a produção excessiva de prolactina (PRL), apresentando níveis elevados de prolactina sérica, o que resulta no aparecimento de adenomas lactotróficos (prolactinomas), predominante em mulheres com idade fértil. O prolactinoma é um adenoma hipofisário secretor de prolactina, classificado como adenoma hipofisário microadenoma, em mulheres, e macroadenoma, em homens. Nas mulheres, o prolactinoma apresenta indícios como galactorreia, amenorreia, disfunção sexual e infertilidade. Em homens, a sintomatologia pauta-se em ganho de peso, disfunção erétil e infertilidade. Os exames laboratoriais, como dosagem de prolactina sérica, e os exames de imagem, principalmente a ressonância magnética (RM), são importantes para confirmar o diagnóstico e a escolha da terapêutica ideal. O tratamento medicamentoso inicial dá-se por drogas agonistas dopaminérgicos (AD), sendo padrão-ouro a cabergolina (CAB), em razão da eficácia e dos efeitos colaterais reduzidos. Quando agonistas dopaminérgicos não surtem efeitos, indica-se submissão a tratamento cirúrgico. Em casos de tumores agressivos ou prolactinomas malignos, indica-se radioterapia. Sendo assim, este artigo corresponde a uma revisão bibliográfica que visa relacionar o adenoma hipofisário (prolactinoma) com a produção excessiva de prolactina (PRL).

Pituitary adenomas are generally benign tumors with characteristics of hypersecretion or hormonal hypersecretion, diagnosed according to tumor growth, hyperproduction syndromes, deficiency in hormone secretion, visual changes and headaches. Hyperprolactinemia is the excessive production of prolactin (PRL), with high levels of serum prolactin, resulting in the appearance of lactotrophic adenomas (prolactinomas), predominant in women of childbearing age. Prolactinoma is a prolactin-secreting pituitary adenoma, classified as pituitary adenoma microadenoma in women and macroadenoma in men. In women, prolactinoma shows signs such as galactorrhea, amenorrhea, sexual dysfunction and infertility. In men, the symptoms are based on weight gain, erectile dysfunction and infertility. Laboratory tests, such as serum prolactin levels, and imaging tests, especially magnetic resonance imaging (MRI), are important to confirm the diagnosis and choose the ideal therapy. The initial drug treatment is done by dopaminergic agonist drugs (AD), with cabergoline (CAB) being the gold standard, due to the reduced efficacy and side effects. When dopaminergic agonists have no effect, submission to surgical treatment is indicated. In cases of aggressive tumors or malignant prolactinomas, radiotherapy is indicated. Thus, this article corresponds to a bibliographic review that aims to relate pituitary adenoma (prolactinoma) with excessive prolactin production (PRL).

Hiperprolactinemia e infertilidad / Hyperprolactinemia and infertility

La prolactina es una hormona hipofisiaria implicada en diversas funciones tales como reproductivas, lactancia y metabólicas. El hallazgo de hiperprolactinemia es frecuente en mujeres que consultan por infertilidad, oscilando entre el 15 y el 20%. Sus manifestaciones clínicas incluyen trastornos del ciclo, galactorrea, infertilidad y osteoporosis. Cuando hay tumores que superan 1 cm de diámetro pueden asociarse a alteraciones visuales. Aunque la hiperprolactinemia puede ser producida por el embarazo, el consumo de algunos fármacos, los trastornos tiroideos, las alteraciones hepáticas y renales, su causa más frecuente es la presencia de adenomas hipofisiarios productores de prolactina. Pueden ser microadenomas cuando su tamaño es menor de 10 mm y que representan el 90% o macroadenomas cuando son de mayor tamaño. La prolactina se encuentra bajo un estrecho control de su secreción a través de un sistema de retroalimentación de asa corta que hace que se libere dopamina que frena su producción. También se han descrito péptidos liberados de prolactina entre los que se encuentra la TRH. El exceso en su producción inhibe directamente la pulsatilidad de la GnRH y disminución en los pulsos de LH. Este cambio conduce a ciclos anovulatorios. Para su manejo se encuentran aprobados en Colombia fármacos agonistas de la dopamina como bromocriptina y cabergolina, siendo este último más efectivo. El manejo con cirugía transesfenoidal se reserva para aquellos casos en los que el tratamiento farmacológico ha fallado.

Prolactin is an hypophyseal hormone implicated in various functions such as reproductive, lactation and metabolic. Finding hyperprolactinemia is frequent in women consulting for infertility, ranging between 15 and 20%. Its clinical manifestations include menstrual cycle irregularities, galactorrhea, infertility and osteoporosis. When tumors greater than 1 cm in diameter are present visual disturbances may appear. Although hyperprolactinemia may be produced by pregnancy, certain medications, thyroid disfunction, hepatic or renal disfunction, the most frequent cause is the presence of prolactin secreting adenomas. They can be micro adenomas when their diameter is less than 10 mm, representing 90% or macro adenomas when their size is greater. Prolactin secretion is under a close control through a short loop feedback system, that makes dopamine to be secreted which lowers its production. Releasing peptides have been described, including TRH. Excess in its production directly inhibits GnRH pulsatility lowering LH pulses. This change conducts to anovulatory cicles, For its treatment in Colombia dopamine agonists have been approved, including bromocriptine and cabergoline, the last one being mor effective. Surgical management with transesphenoidal approach is reserved for those cases in which pharmacological treatment has failed.

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.

Macroprolactinoma clival ectópico: una forma rara de presentación de adenoma hipofisario / Ectopic clival macroprolactinoma: a rare presentation of pituitary adenoma

Los adenomas pituitarios son los tumores hipofisarios más frecuentes siendo una entidad rara cuando se trata de adenomas ectópicos, es decir, sin conexión con la glándula pituitaria. Se cree que derivan de células residuales del tracto de migración embriológico desde la bolsa de Rathke. Su presentación clínica es muy variable porque depende de la producción hormonal y del efecto masa en estructuras adyacentes. Generalmente suponen un reto diagnóstico debido a su baja frecuencia, la clínica variable de presentación y que no presentan características específicas en las pruebas de imagen. Generalmente el diagnóstico se realiza de manera retrospectiva tras la resección quirúrgica. Presentamos el caso de un varón de 56 años que se presentó con unos valores de prolactina de 6647.5 ng/ml (2.2-17.7) con clínica de hipogonadismo aislada que se resolvió con tratamiento médico sin precisar resección quirúrgica, con una disminución de la densidad radiológica y estabilización del tamaño y sin clínica compresiva ni alteración visual.

Pituitary adenomas are the most common hypophyseal tumors being a rare entity when they are ectopic, without connection to the pituitary gland. They are thought to arise from residual cells in the migration tract from Rathke´s pouch. Its clinical presentation is variable depending on the hormonal production and the pressure effect on adjacent structures. They usually are a diagnostic challenge due to their low frequency, wide range of clinical presentation and not showing specific features on imaging techniques. The diagnosis is made usually retrospectively after surgical resection. We report the case of a 56 years old male that presented with a prolactine value of 6647.5 ng/ml (2.2-17.7) and isolated hypogonadism symptoms that resolved with medical treatment without surgery, diminishing the radiological density and stabilizing the size without having compresive symptoms nor visual disturbances.

Macroprolactinoma in a young man presenting with erectile dysfunction / 대한생식의학회지

Hyperprolactinemia due to a pituitary adenoma is a rare cause of erectile dysfunction (ED). The prevalence of clinically apparent prolactinomas is reported to be from 6–10 to 50 per 100,000. A few reports have been published of prolactinoma presenting with ED. Here, we report a rare case of a young man who presented with ED as a chief complaint and who was diagnosed with a huge prolactinoma, and we discuss a related fertility issue.

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.

Prolactinoma en una adolescente como causa de alteraciones visuales / Prolactinoma as the cause of visual alterations in a female adolescent

Introducción: los prolactinomas corresponden a la mitad de las causas etiológicas de los adenomas de presentación en la población pediátrica, lo cual les proporciona una gran importancia para tenerlos como diagnóstico diferencial ante el estudio de un tumor hipofisario. Las alteraciones visuales no corresponden al síntoma más común, sin embargo, es necesario tenerlo presente, especialmente ante la identificación de un macroadenoma. Presentación del caso: paciente femenina, de 16 años de edad, con un macroadenoma en estudio, que fue identificado como un macroprolactinoma. La sintomatología principal de consulta correspondió a alteraciones visuales y cefalea. Recibió tratamiento médico por Endocrinología Pediátrica con cabergolina, con estabilidad en el tamaño y características de la masa tumoral, y disminución de los niveles de prolactina sérica. Conclusiones: en la población pediátrica los prolactinomas que producen afectaciones visuales son más frecuentes en el sexo masculino, sin embargo, también puede ocurrir en el femenino; su diagnóstico implica la realización de estudios de laboratorio especializados y neuroimágenes, así como la participación activa de Endocrinología Pediátrica. Se resalta la importancia del tratamiento médico con agonistas dopaminérgicos, como la primera opción en esta entidad antes de plantear decisión quirúrgica, y es necesario un seguimiento médico cuidadoso al respecto(AU)

Introduction: prolactinomas account for half of the etiological causes of presentation adenomas in the pediatric population, hence their important role as differential diagnosis in the study of a pituitary tumor. Visual alterations are not their most common symptom, but they should be borne in mind, particularly in the identification of a macroadenoma. Case presentation: female 16-year-old patient with a macroadenoma under study which was identified as a macroprolactinoma. The main symptoms at presentation were visual alterations and headaches. She received medical treatment with cabergoline at the Pediatric Endocrinology service, achieving stability in the size and characteristics of the tumor mass, and a reduction in serum prolactin levels. Conclusions: in the pediatric population, prolactinomas causing visual alterations are more common in males, but they can also occur among females. Their diagnosis includes specialized laboratory tests and neuroimaging, as well as the active involvement of the Pediatric Endocrinology service. Mention must be made of the medical treatment with dopaminergic agonists as the first choice for this condition before indicating surgery, and careful medical follow-up is required in this respect(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.

Transtorno de Controle de Impulsos em pacientes portadores de prolactinoma em tratamento com agonistas dopaminérgicos / Impulse Control Disorder in carrier patients of prolactinoma under treatment with dopaminergics agonists

RESUMO Os prolactinomas são o tipo mais comum de tumores secretores da hipófise. Todos os pacientes portadores de prolactinoma sintomáticos ou com crescimento evidente requerem tratamento; sendo a principal terapia o uso de agonistas dopaminérgicos. O aumento da impulsividade e o surgimento de transtornos de controle de impulsos têm sido descritos na terapia com fármacos desta classe. O objetivo primário desse estudo é avaliar a frequência de TCI em pacientes portadores de prolactinoma em tratamento com agonistas dopaminérgicos e identificar possíveis fatores associados a patologia. Materiais e métodos: Trata se de um estudo transversal em que um questionário foi aplicado durante as consultas ambulatoriais, a fim de fazer rastreio de TCIs, e foram obtidos ainda informações médicas relativas a história e tratamento do tumor durante seguimento. Resultados: no grupo em uso de cabergolina tivemos prevalência de 12,5% de TCIs relacionado ao sexo e 12,5% relacionados a compras. No grupo controle não houveram casos de TCIs relacionados ao sexo e tivemos 66,66% de rastreio positivo para TCI para compras. Conclusão: Não foi possível caracterizar completamente o uso de AD com desenvolvimento de ambos os TCI. Há possibilidade de que os próprios tumores pituitários possam contribuir com um risco independente adicional para o desenvolvimento do TCI. Os médicos que prescrevem agonistas de dopamina devem ficar atentos a esses efeitos colaterais potenciais no início do tratamento e nas consultas subsequentes da clínica.

Risk factors and the prognosis of sexual dysfunction in male patients with pituitary adenomas: a multivariate analysis / 亚洲男科学杂志(英文版)

The impact of sexual dysfunction (SD) is distressing to many male patients with pituitary adenomas which affect both physical and psychological health. The research explored to identify risk factors affecting sexual function and the prognosis of male patients with pituitary adenomas. Two hundred and fifty-four male patients, who aged between 18 and 60 (mean ± s.d.: 44.16 ± 10.14) years and diagnosed with pituitary adenomas, were retrospectively analyzed. One hundred and fifty-nine patients (62.6%) complained of SD prior to surgery. The mean International Index of Erectile Function (IIEF-5) in patients with giant adenomas was 16.13 ± 2.51, much smaller than those with microadenomas or macroadenomas (P < 0.05). All the patients showed significant improvement in terms of erectile dysfunction (ED) following surgery (P < 0.05). In addition, complete resection achieved a higher degree of SD relief than partial resection. The incidence of SD in functioning pituitary adenomas (FPAs) was much higher than that in nonfunctioning pituitary adenomas (NFPAs) (P < 0.05). In addition, compared with NFPAs, males with prolactinomas (82.8%) had the higher prevalence of SD and significantly improvement following surgical intervention (P < 0.05). An inverse relationship was identified between decreasing testosterone levels and increasing incidence of SD before surgery (P < 0.05). There was no significant difference between 6 months and 12 months after surgery in serum testosterone level (P > 0.05). Our results indicated that surgical therapy could be optimized for improvements in SD and that testosterone levels can be used as a sensitive indicator to predict the recovery rate of sexual function in patients with pituitary adenomas following surgery and the serum testosterone level will stay stable in 6 months after surgery.

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.

Hiperprolactinemia idiopática / Idiopathic hyperprolactinemia

La hiperprolactinemia es uno de los trastornos neuroendocrinológicos más frecuentes; la causa común de la hiperprolactinemia es la presencia de un adenoma hipofisario productor de prolactina o prolactinoma. El país cuenta con escasa referencia bibliográfica sobre la patología presentada, por lo que resulta importante realizar la exposición de este caso. Objetivo: documentar el abordaje de hiperprolactinemia en el país. Caso clínico: paciente femenina de 22 años, con antecedentes familiares de macroprolactinoma; se presenta con historia de amenorrea de 6 años y caída de cabello de 2 años de evolución; prurito intenso en ambas mamas con predominio en la areola derecha desde hace 1 año; alteraciones en los niveles de prolactina presentando valores de 33.5ng/mL y ultrasonografía abdominal ausente de anormalidades. Tratada con cabergolina, sin éxito evidente en el tratamiento. Conclusión: en pacientes con hiperprolactinemia, su abordaje debe hacerse de manera ordenada, integral, secuencial y detallada con el fin de descartar previo al tratamiento, situaciones que secundariamente elevan los valores de prolactina. Esto lo demuestra el caso expuesto donde se integran diferentes pruebas clínicas y laboratoriales para descartar la etiología de la hiperprolactinemia en el país...(AU)

Progressão de Valvopatia Esquerda durante o Uso de Dopaminérgicos / Progression of Left Valve Disease during Use of Dopaminergic Drugs

A cabergolina e a bromocriptina são drogas dopaminérgicas derivadas do ergot e utilizadas para tratamento de distúrbios hiperprolactinêmicos idiopáticos ou adenomas hipofisários, cujo mecanismo de ação é decorrente da redução da secreção de prolactina. Alguns relatos na literatura demonstram que a cabergolina pode causar valvopatia após sua administração a longo prazo. Relatamos o caso de um paciente com diagnóstico de macroprolactinoma que fez uso intercalado de cabergolina e bromocriptina e desenvolveu alterações valvares antes inexistentes

Polimorfismos del receptor D2 / D2 receptor polymorphisms

Los prolactinomas son tumores bien diferenciados que se originan en las células lactotropas pituitarias, una línea celular que secreta fisiológicamente prolactina (PRL). A nivel hipofisario, la dopamina está implicada en la regulación de la secreción de PRL por las células lactotropas y este efecto inhibitorio está mediado por la activación del receptor de prolactina tipo 2 (DRD2). Hay varios polimorfismos del DRD2, el primero y más estudiado es TaqI A1; está demostrado que este alelo se encuentra asociado a una reducción de la actividad cerebral dopaminérgica, además de observarse una reducción en su capacidad de unión de aproximadamente un 30%. Este alelo se ha vinculado con una menor densidad de DRD2 en el cuerpo estriado, especialmente en el putamen y caudado ventral, y la cantidad de DRD2 en portadores del alelo A1 fue un 30-40% más bajo que en los no portadores (es decir, TaqI A2 homocigotos). En la literatura, hay evidencia que apoya la posible participación de los polimorfismos DRD2 en la regulación de la secreción hormonal.

Prolactinomas are well differentiated tumours that originate in the pituitary lactotrope cells, a cell line that physiologically secretes prolactin (PRL). At pituitary level, dopamine is involved in the regulation of PRL secretion by lactotropes, and this inhibitory effect is mediated by activation of prolactin type 2 receptor (DRD2). Of the several DRD2 polymorphisms, the first and most studied is TaqI A1. It has been demonstrated that this allele is associated with a reduced dopaminergic brain activity, and a reduction in its binding capacity of approximately 30% also being observed. This allele was associated with a lower density of DRD2 in the striatum, especially in the putamen and ventral caudate. The amount of DRD2 in A1 allele carriers was 30 - 40% lower than in non-carriers (this is, TaqI A2 Homozygotes). There is evidence in the literature, that supports the possible involvement of DRD2 polymorphisms in the regulation of hormonal secretion.

Recent Progress in the Medical Therapy of Pituitary Tumors

Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human Prolactinoma Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project. MATERIALS AND METHODS: Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. RESULTS: Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells. CONCLUSION: These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.

Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina

ABSTRACT Objectives The main purpose of this study was to estimate the incidence rate and prevalence of clinically relevant pituitary adenomas (PAs) within the Hospital Italiano Medical Care Program (HIMCP), a well-defined population of 150,000 members living in the urban and suburban area of the city of Buenos Aires. We defined clinically relevant PAs as those associated with endocrine dysfunction and/or mass effect. Subjects and methods A retrospective open cohort study was conducted, including all members of the HIMCP over 18 years old, with active memberships during the period of the study, from January 1st 2003, to January 1, 2014. The incidence rates (IRs) were standardized (SIR) to the World Health Organization (WHO) 2000 standard population and were expressed per 100,000 members/year. Prevalence was estimated at January 1, 2014, and was expressed per 100,000 persons. The clinical records have been electronically managed since 2001. All lab and imaging studies were done in-house. Results The overall SIR was 7.39/100,000/year (95% CI 4.47-10.31). Female patients had a specific IR significantly higher than male patients (5.85 vs.1.54) and represented 73% of the affected members. Regarding tumor size, 61.4% were microadenomas, and the mean age at diagnosis was 46.4 years. Prolactinomas had the highest SIR (5.41), followed by acromegaly (Acro) and non-functioning adenomas (NFAs) with overlapping 95% CIs (0.44-1.41 and 0.31-0.99, respectively). Microprolactinomas were more frequent in female (72.6%) (p < 0.01) and younger members (38 vs.60 years; p < 0.04). The overall prevalence rate was 97.76/100,000. Prolactinomas had the highest prevalence (56.29), followed by NFAs (21.48), Acro (14.07) and CD (5.93). Conclusion Our results demonstrate that clinically relevant PAs are more common than usually suspected, especially prolactinomas and growth-hormone secreting PAs. These data highlight the need to increase the awareness of PAs, thereby enabling early diagnosis and treatment.