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)

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.

A Giant Prolactinoma: A Case Report

A 38-years-old woman presented to our hospital 2 years ago with 5-year history of reduced vision, chronic cephaleea and secondary amenorrhea. Her baseline prolactin level was 46504 ?IU/mL (reference range=127-637mUI/ml) with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (4 × 2.2 × 2.6 cm3) with suprasellar extension, optic chiasma and right cavernous sinus compression. She was initially treated with cabergoline in order to reduce the prolactin level and tumoral mass, but after 6 months of medical treatment she proceed to transsphenoidal tumor debulking surgery. Prolactin level dropped in the normal range only after the addition of cabergoline treatment after surgery (1 mg/day 3 times/per week). However, the extensive tumour was not completely resectable so she remained amenorrheic requiring hormone replacement therapy as well as thyroxine replacement due to the development of TSH deficiency (free T4 6.03 pmol/L)

Apoplejía hipofisaria durante el embarazo: reporte de un caso / Pituitary apoplexy during pregnancy: A case report

Resumen ANTECEDENTES: La apoplejía hipofisaria es un infarto o hemorragia súbita en un tumor o tejido sano de la glándula pituitaria. El 80% de los casos es en pacientes con un adenoma hipofisario. El cuadro clínico se caracteriza por: cefalea, alteraciones visuales, náuseas y vómito; además, insuficiencia hipofisaria, que puede ser potencialmente mortal para la madre y el feto. El tratamiento conservador incluye analgésicos, corticosteroides y agonistas dopaminérgicos en caso de prolactinoma. El tratamiento quirúrgico de elección es la resección transesfenoidal. CASO CLÍNICO: Paciente de 35 años, con antecedentes de tres embarazos, un aborto y prolactinoma diagnosticado a los 22 años, en tratamiento con cabergolina. Acudió a consulta debido a cefalea a las 17 semanas de embarazo que se exacerbó a las 28.4 semanas. En la resonancia magnética se observó que la hipófisis medía 17 x 12 x 7 mm, con datos de hemorragia subaguda; con base en ello se diagnosticó: apoplejía hipofisaria. Se indicó tratamiento conservador con antiinflamatorios no esteroideos, opioides y corticosteroides; sin embargo, ante el deterioro del cuadro clínico se decidió la resección transeptal-transesfenoidal endoscópica del adenoma hipofisiario, a las 30.5 semanas de embarazo. La paciente evidenció una mejoría significativa y permaneció asintomática hasta la finalización del embarazo a las 37.5 semanas. CONCLUSIONES: Si bien la apoplejía hipofisaria es de baja incidencia en el embarazo se torna en un factor de riesgo de muerte; por ello, el ginecoobstetra debe tener conocimiento de las posibles implicaciones en el embarazo, ofrecer atención multidisciplinaria y considerar que el tratamiento quirúrgico es una opción segura en el embarazo.

Abstract BACKGROUND: Pituitary apoplexy is a sudden infarction or hemorrhage in a tumor or healthy tissue of the pituitary gland. Eighty percent of cases are in patients with a pituitary adenoma. The clinical picture is characterized by headache, visual disturbances, nausea and vomiting, and pituitary insufficiency, which can be life-threatening for the mother and fetus. Conservative treatment includes analgesics, corticosteroids and dopaminergic agonists in case of prolactinoma. The surgical treatment of choice is transsphenoidal resection. CLINICAL CASE: 35-year-old female patient with a history of three pregnancies, one miscarriage and prolactinoma diagnosed at 22 years of age, under treatment with cabergoline. She came for consultation due to headache at 17 weeks of pregnancy that was exacerbated at 28.4 weeks. Magnetic resonance imaging showed that the pituitary gland measured 17 x 12 x 7 mm, with evidence of subacute hemorrhage; based on this, a diagnosis of pituitary apoplexy was made. Conservative treatment with non-steroidal anti-inflammatory drugs, opioids and corticosteroids was indicated; however, due to the deterioration of the clinical picture, endoscopic transseptal-transsphenoidal resection of the pituitary adenoma was decided at 30.5 weeks of pregnancy. The patient showed significant improvement and remained asymptomatic until the end of pregnancy at 37.5 weeks. CONCLUSIONS: Although pituitary apoplexy is of low incidence in pregnancy, it becomes a risk factor for death; therefore, the obstetrician/gynecologist should be aware of the possible implications in pregnancy, offer multidisciplinary care and consider that surgical treatment is a safe option in pregnancy.

The incidence and clinical characteristics of impulse control disorders in patients with prolactinoma receiving dopamine agonist / 中华内分泌代谢杂志

Objective:To understand the incidence and clinical characteristics of dopamine agonist(DA) therapy-related impulse control disorders(ICDs) in prolactinoma patients.Methods:Outpatients diagnosed with prolactinoma from the Department of Endocrinology in Huashan Hospital from December 2019 to June 2020 were consecutively included and clinical data were collected. Impulse control disorders were screened with Questionnaire for Impulsive-Compulsive Disorders in Parkinson′s Disease(QUIP). Barratt Impulsiveness Scale 11(BIS-11) was used to evaluate personality construct of impulsiveness from three sub-factors . Health related quality of life was evaluated by the MOS 36-Item Short Form Health Survey(SF-36).Results:Among the 111 cases included, 40 were male and 53 were female, with an average age of(34.74±9.05) years and an average disease duration of(66.69±50.70) months. The initial prolactin level was 147.25(89.97, 470) ng/mL and the percentage of macroadenoma was 46.8%. Ninety cases received DA while 21 cases didn′t. According to the QUIP, any ICD was screened positive in 22 cases(24.7%) in the DA group and 3 cases(14.3%) in the untreated group. The attention impulsiveness scores of BIS-11 in the DA group were higher than the untreated group(23.32±3.67 vs 21.71±2.55, P=0.022). Among the ICDs positive cases in the DA group, the most common disorders were pathological gambling(40.6%) and hypersexuality(40.6%). Compared with the negative group, the non-planning impulsiveness scores of BIS-11 in the positive group were higher, while the scores of social function(69.32±24.62 vs 83.08±17.11, P=0.021), role emotional(50.00±45.72 vs 71.10±40.68, P=0.043) and mental health(55.27±22.75 vs 64.59±17.53, P=0.048) in SF-36 scale were lower in the positive group. Besides, the percentage of male(68.2% vs 38.2%, P=0.014) and initial prolactin level[470.00(130.00, 3 770.00) vs 140.29(79.50, 465.59) ng/mL, P=0.028] in the positive group were higher. Male was an independent risk factor of the presence of ICDs( OR=3.46, 95% CI 1.24-9.61, P=0.017). No significant difference was found in the type of drugs, duration, maximal or cumulative dose of treatment with DA between the two groups. Conclusion:Impulse control disorders may occur in prolactinoma patients receiving DA treatment and affect the quality of life. Endocrinologists should screen impulse control disorders in this patient set.

Machine learning models based on radiomics in diagnosis of pituitary prolactin macroadenoma / 中华放射学杂志

Objective:To explore the effectiveness and feasibility of the machine learning models based on radiomics in the diagnosis of pituitary prolactin macroadenoma.Methods:Totally 122 histologically proven pituitary macroadenoma patients, including 70 cases of pituitary prolactin macroadenoma (PPM) and 52 cases of non-pituitary prolactin macroadenoma (NPPM), were retrospectively recruited. The differences of age, sex, serum prolactin value, bleeding, cystic degeneration and Knosp classification were compared between PPM and NPPM. The pre-processing, delineation of the region of interest and feature extraction of the preoperative axial contrast-enhanced T 1WI image were performed in the 3Dslicer software. The optimal feature set were selected by least absolute shrinkage and selection operator. All patients were randomly divided into the training group ( n=85) and the test group ( n=37) at a ratio of 7∶3. The models were established in the training group by logistic regression and support vector machine (SVM), and then verified by the test group. ROC curves were drawn respectively, and specificity, sensitivity, accuracy and area under the ROC curve (AUC) were calculated. Results:The age [(38±12) years vs . (43±11) years], gender ratio (male/female 50 cases/20 cases vs . 14 cases/38 cases) and prolactin value [366.00 (117.75, 1 156.25)μg/L vs . 47.25 (32.68, 62.40) μg/L] of patients with PPM and NPPM were statistically different ( P<0.05). The AUC values of logistic regression and SVM in the training group were 0.936 and 0.946, and the AUC values of the test group were 0.768 and 0.774, respectively. The diagnostic accuracy of logistic regression and SVM in the training group were 88.2% and 91.8%, and the accuracy of the test group were 73.0% and 77.8%. Conclusion:The machine learning models based on the radiomics can predict the pituitary prolactin macroadenoma well with a high accuracy.

Estudios clínicos y genéticos en tres miembros de una familia afectados con adenomas hipofisarios aislados con prolactinomas homogéneos / Clinical and genetic studies of a three-member familial isolated pituitary adenoma with homogeneous prolactinomas

La mayoría de los adenomas hipofisarios son esporádicos, pero un 3-5% puede ocurrir en un contexto familiar y hereditario. Este es el caso de la neoplasia endocrina múltiple de tipo 1 (NEM1), complejo de Carney (CNC) y adenomas hipofisarios aislados familiares (FIPA). El FIPA es una condición infrecuente, que ocurre en un contexto familiar, no asociada a NEM t ipo1 ni CNC. Los FIPA pueden ser homogéneos (todos los adenomas tienen el mismo fenotipo) o heterogéneos (diferente fenotipo tumoral). Describimos una familia congolesa en la que dos hermanas y una prima fueron diagnosticadas a los 29, 32 y 40 años, respectivamente, con un prolactinoma (FIPA homogéneo). Las pacientes presentaron macroadenomas no invasivos al momento del diagnóstico, con buena respuesta biológica y tumoral al tratamiento con cabergolina hasta una dosis máxima de 1.5 mg/semanal. De las dos hermanas, una cursó un embarazo sin complicaciones. Durante el seguimiento de 12 años, ninguna de ellas presentó elementos clínicos o biológicos compatibles con NEM1 o CNC, por lo que dichos genes no se estudiaron. El análisis genético en dos de las pacientes permitió descartar la posibilidad de una mutación germinal del gen aryl hydrocarbon receptor interacting protein (AIP). Se considera que el 80% de los pacientes con FIPA no presentan mutación del gen AIP, por lo que se requieren futuros estudios en este tipo de familias, para poder determinar otros genes afectados involucrados en su fisiopatología.

Most pituitary adenomas are sporadic, but 3-5% can occur in a family and hereditary context. This is the case of multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC) and familial isolated pituitary adenomas (FIPA). FIPA is an infrequent condition that occurs in a family context, not associated with MEN type1 or CNC. FIPA kindred can be homogeneous (all adenomas affected in the family having the same tumor phenotype) or heterogeneous (different tumor phenotypes in the affected members). We describe a Congolese family in which two sisters and a cousin were diagnosed with a prolactinoma (homogenous FIPA) at the ages of 29, 32 and 40 years, respectively. The patients presented with macroadenomas at the time of diagnosis, non-invasive tumors and good biological response to cabergoline treatment (maximum dose of 1.5 mg/weekly). Of these two sisters, one went through a pregnancy without complications. Because no MEN1 and CNC clinical and biochemical features were detected during the 12-year follow-up, these genes were not investigated. The genetic analysis of the aryl hydrocarbon receptor interacting protein (AIP) was normal. As nearly 80% of patients with FIPA do not have a mutation in the AIP gene, future studies in these families are required to identify other affected genes involved in their physiopathology.

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.

Bromocriptine promotes secretion of exosomes and drug resistance of rat prolactinoma MMQ cells in vitro / 肿瘤

Objective: To investigate the effect of bromocriptine on the secretion of exosomes and the role of exosomes in drug resistance of rat prolactinoma MMQ cells. Methods: The effect of different concentrations of bromocriptine on the proliferation of MMQ cells was detected by CCK-8 assay, and the half maximal inhibitory concentration (IC50) was calculated. MMQ cells were exposed to bromocriptine for 48 h, then the exosomes were isolated by differential centrifugation. The morphology of exosomes was observed by transmission electron microscopy, the particle size of exosomes was analyzed by nanoparticle tracking analysis (NTA), and the expression of exosomal marker CD63 was detected by Western blotting. MMQ cells uptaking PKH67-labeled exosomes were observed by laser confocal microscopy. Then the sensitivity of MMQ cells to bromocriptine was tested again by CCK-8 method. The expression level of PR domain zinc finger protein 2 (PRDM2) mRNA in MMQ cells treated with exosomes was detected by real-time fluorescent quantitative PCR. The expression levels of PRDM2, dopamine 2 receptor (D2R), extracellular signal-regulated kinase 1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) proteins in MMQ cells treated with exosomes were determined by Western blotting. Results: The IC50 of bromocriptine on MMQ cells was (52.91±1.48) µmol/L. Compared with the exosomes collected from MMQ cells not treated with bromocriptine, the particles and proteins in exosomes collected from MMQ cells treated with 50 µmol/L bromocriptine were significantly increased (both P < 0.01). The expression of CD63 was only observed in the exosomes. The exosomes collected from MMQ cells treated with bromocriptine were uptaken by MMQ cells. After the exosomes were absorbed by MMQ cells, the IC50 of bromocriptine [(73.74±1.17) µmol/L] was increased on MMQ cells (P < 0.01). In exosome-treated MMQ cells, the expression levels of PRDM2 mRNA and protein (both P < 0.05) and D2R protein (P < 0.05) were down-regulated, while the expression level of p-ERK1/2 was higher than that in the control group (P < 0.05). Conclusion: Bromocriptine can promote the secretion of exosomes in MMQ cells, and the exosomes may be involved in the transmission of information through intercellular communication of tumors, which can make MMQ cells to obtain drug resistance.

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)

Pedigree analysis of a osteogenesis imperfect and prolactinoma family caused by a newly found gene mutation in COL1A1 / 中华内分泌代谢杂志

Objective To explore the collagen, typeⅠ, α 1 chain ( COL1A1) gene mutation in a family with type 1 osteogenesis imperfect. Methods The medical records and DNA samples of an osteogenesis imperfect patient and her family members were collected, and their DNA sequencing were performed and compared with 50 non-relative healthy control from the same area. Results The proband and her three family members ( father, younger brother, and younger nephew) with clinical features of osteogenesis imperfect as well as prolactinoma were confirmed of COL1A1 gene mutation at the 24th intron with a shear mutation of c. 1669-1 G＞A which was not reported previously. Other family members were genetically normal compared with the normal. Conclusions We found a new COL1A1 gene mutation family and mutation site, but the relationship between osteogenesis imperfect and prolactinoma was unknown.

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)

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.

Effects of Different Dosages of Bromocriptine on Clinical Efficacy of Prolactinoma,Serum Level of PRL and Tumor Volume / 中国药房

OBJECTIVE:To investigate clinical efficacy and safety of different dosages of bromocriptine in the treatment pro-lactinoma,and its effects on serum prolactin(PRL)and tumor volume. METHODS:A total of 60 patients with prolactinoma were selected from our hospital during Jan.-Dec. 2015 as research objects,and then divided into group A and B according to random number table,with 30 cases in each group. Both groups were given Bromocriptine mesilate tablets orally during meal. Group A was given medicine with initial dose of 2.5 mg/d,increasing to 3.75 mg/d 3 d later,increasing by 2.5 mg every week after 2-3 d,and then recovering to 3.75 mg/d till serum PRL level had been controlled. Group B was given medicine with initial dose of 1.25 mg/d, increasing to 2.5 mg/d 3 d later,increasing by 1.25-2.5 mg every week after 2-3 d,and then recovering to 2.5 mg/d till serum PRL level recovered to normal. Both groups were treated for consecutive 3 months. Clinical efficacies as well as serum level of PRL and tumor size were observed in 2 groups,and the occurrence of ADR was recorded. RESULTS:The total response rate of group A (83.33％) was higher than that of group B (66.67％),without statistical significance (P>0.05). Before treatment,there was no statistical significance in serum level of PRL and tumor size between 2 groups (P>0.05). After 1,2 months of treatment,serum levels of PRL in 2 groups were decreased significantly,and the group A was significantly lower than the group B,with statistical significance(P0.05). After treatment,tumor size of 2 groups were decreased significantly,and large adenoma and giant adenoma size in group A were significantly smaller than group B,with statisti-cal significance(P0.05). The inci-dence of ADR in group A(12 cases,40.00％)was significantly higher than group B(5 cases,16.67％),with statistical signifi-cance(P<0.05). CONCLUSIONS:Increasing dosages of bromocriptine no significant influence on therapeutic effect of prolactino-ma,but it can shorten the time of serum PRL level back to normal,and reduce the tumor size. The incidence of adverse reactions in-crease with the dosage.

Analysis of the clinical curative effect of neural endoscopic nasal adjustment surgical treatment for pituitary ;adenomas / 中国基层医药

Objective To explore the clinical curative effect of neural endoscopic nasal adjustment surgical treatment for pituitary adenomas.Methods The clinical data of 176 patients with pituitary adenoma were retrospec-tively analyzed.82 patients in group A used microscopic surgery treatment,94 cases were treated by nerve endoscopic treatment(group B).The operation time,postoperative hospital stay time,the cutting rate,hormone levels,recovery rate and complications were compared between the two groups.Results In group A,the operation time,postoperative hospitalization time,the whole cut were (103.5 ±21.5)min,(7.8 ±1.1)d,78 cases,those of group B were (109.1 ±25.8)min,(5.2 ±1.0)d,91 cases,the operation time,whole cut of the two groups had no statistically significant differences(t=1 .55 1 ,χ2 =0.034,all P>0.05 ).The postoperative hospitalization time of group A was longer than that of group B,the difference was statistically significant(t=16.422,P0.05).In group A,the transient diabetes insipidus,nasal symptoms,complications were higher than those in the control group,the differences were statistically significant(χ2 =10.746,P 0.05 ).Conclusion Neural endoscopic nasal adjustment of surgical treatment of pituitary adenoma and the microscopic surgery has similar clinical curative effect,but has a lower incidence of complications and shorter postop-erative hospital stay.

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.