Adenomas gigantes de hipófisis: análisis de variables relacionadas con resultados visuales, endocrinológicos y de resección en cirugía endoscópica transesfenoidal / GIANT PITUITARY ADENOMAS: ANALYSIS OF VARIABLES RELATED TO VISUAL, ENDOCRINOLOGICAL AND RESECTION RESULTS IN TRANSSPHENOIDAL ENDOSCOPIC SURGERY

Introducción. Los adenomas gigantes de hipófisis (AGHs) son aquellos tumores con un diámetro máximo ≥4 cm en cualquier dirección, representando del 5% al 14% del total de los adenomas que se tratan quirúrgicamente. Su manejo terapéutico es desafiante ya que, debido a su extensión hacia otras estructuras cerebrales,está asociado a un riesgo mayor de complicaciones quirúrgicas, con una menor tasa de resección total. El objetivo de este trabajo fue evaluar el impacto de la cirugía endoscópica transesfenoidal en AGHs, analizando las variables asociadas a resultados visuales, endocrinológicos y según el grado de resección. Pacientes y Métodos. Se evaluó en 44 pacientes con AGHs(diámetro ≥4 cm y/o volumen ≥10 ml) la presentación visual, endocrinológica e imágenes. Se analizaron estadísticamente resultados visuales, endocrinológicos, grado de resección y complicaciones quirúrgicas. Resultados. Edad promedio de 48.8 años, 24 mujeres y 20 hombres. Presentación: déficit del campo visual (93.1%), hipopituitarismo (61.3%), cefalea (54.5%). Diámetro, volumen y extensión supraselar promedios: 4.8 cm, 20.3 ml, 1.8 cm, respectivamente. Campo visual: mejoría: 83.3%, sin cambios: 9.5%, mayormente en síntomas bilaterales (p<0.0001). Desmejoríavisual: 0%. En resección total: mayor posibilidad de mejoría visual (p=0.040). Buenos resultados endocrinológicos: 85.7%. Tasa de resección total: 52.3%. Resección subtotal: más frecuente con invasión del seno cavernoso (p=0.014). Sin diferencias en el grado de resección según diámetro, volumen, extensión supraselar, forma ni aspecto. Hipopituitarismo: 4.2%. Diabetes insípida: 9.5%, asociada a mayor diámetro (p=0.038) o extensión supraselar (p=0.010) y aspecto sólido (p=0.023). Fístula de LCR: 7.1%. Conclusión. La resección total puede lograrse en la mitad de los casos, siendo la limitante principal el grado de invasión del seno cavernoso y no el aspecto morfológico del AGH per se. Aun así, los resultados visuales y endocrinológicos son muy buenos. En resecciones incompletas se logra el control de la enfermedad mediante tratamientos complementarios

Introduction. Giant pituitary adenomas (sGAs) are those tumors with a maximum diame- ter ≥4 cm in any direction, representing 5% to 14% of all adenomas that are treated surgi- cally. Its therapeutic management is challenging since, due to its extension to other brain structures, it is associated with a higher risk of surgical complications, with a lower rate of total resection. Te objective of this work was to evaluate the impact of transsphenoidal endoscopic surgery on AGHs, analyzing the variables associated with visual and endocri- nological results and according to the degree of resection. Patients and Methods. Visual, endocrinological and imaging presentation were evaluated in 44 patients with sHAA (dia- meter ≥4 cm and/or volume ≥10 ml). Visual and endocrinological results, degree of resection and surgical complications were statistically analyzed. Results. Average age of 48.8 years, 24 women and 20 men. Presentation: visual field deficit (93.1%), hypopituitarism (61.3%), headache (54.5%). Average diameter, volume and suprasellar extension: 4.8 cm, 20.3 ml, 1.8 cm, respectively. Visual field: improvement: 83.3%, no changes: 9.5%, mostly in bilate- ral symptoms (p<0.0001). Visual impairment: 0%. In total resection: greater possibility of visual improvement (p=0.040). Good endocrinological results: 85.7%. Total resection rate: 52.3%. Subtotal resection: more frequent with invasion of the cavernous sinus (p=0.014). No differences in the degree of resection according to diameter, volume, suprasellar exten- sion, shape or appearance. Hypopituitarism: 4.2%. Diabetes insipidus: 9.5%, associated with greater diameter (p=0.038) or suprasellar extension (p=0.010) and solid appearance (p=0.023). CSF fistula: 7.1%. Conclusion. Total resection can be achieved in half of the cases, the main limitation being the degree of invasion of the cavernous sinus and not the morphological appearance of the HGA per se. Even so, the visual and endocrinological results are very good. In incomplete resections, disease control is achieved through com- plementary treatments

Hiperplasia de hipófise secundária a hipotireoidismo primário - relato de caso / Pituitary hyperplasia secondary to primary hypothyroidism - case report

A hiperplasia hipofisária é definida como um aumento não neoplásico no número de um dos tipos de células presentes na hipófise. Ela pode ocorrer por um processo fisiológico ou patológico. O hipotireoidismo primário prolongado é uma das causas patológicas desta condição, e ocorre devido a perda do feedback negativo. O objetivo desse relato foi demonstrar a presença de hiperplasia hipofisária em um paciente masculino com características corporais sugestivas de acromegalia. A investigação laboratorial confirmou a presença de hipotireoidismo primário e descartou a acromegalia. Foi instituído tratamento com levotiroxina, levando a regressão da hiperplasia hipofisária. Esse caso ilustra a importância de uma investigação apropriada em pacientes com hiperplasia hipofisária, bem como discute a fisiopatologia e o tratamento dessa doença.

Pituitary hyperplasia is defined as a non-neoplastic increase in the number of one of the cell types present in the pituitary gland. It can occur by a physiological or pathological process. Prolonged primary hypothyroidism is one of the pathological causes of this condition and occurs due to the lack of negative feedback. The objective of this report was to demonstrate the presence of pituitary hyperplasia in a male patient with body characteristics suggestive of acromegaly. Laboratory investigation confirmed the presence of primary hypothyroidism and ruled out acromegaly. Treatment with levothyroxine was instituted, leading to regression of pituitary hyperplasia. This case illustrates the importance of an appropriate investigation in patients with pituitary hyperplasia, as well as discussing the pathophysiology and treatment of this disease.

Endonasal Endoscopic Pituitary Adenoma Resection in light of the COVID-19 Pandemic: A Technical Report

Introduction The endoscopic endonasal transsphenoidal approach (EETA) is routinely used to treat sellar and suprasellar tumors. It provides safe and direct access to tumors in these locations, with wide visualization of anatomical landmarks and great surgical results. With the COVID-19 pandemic, despite the high risk of transmission involved, various surgical procedures cannot be postponed due to their emergency. Case Report A 62-year-old female presented in the previous two months with headaches, followed by bilateral severe visual loss. In 2016, she was submitted to subtotal resection of a non-secretorymacroadenoma. Because of the progressive visual deficits, the EETA was used to the resect the pituitary adenoma. Technical Note We developed a low-cost adaptation to the surgical fields, covering the patient's head and superior trunk with a regular surgicalmicroscope bag with a tiny slit to enable the endoscope and surgical instruments to enter the nose, thus protecting the personnel in the operating room from the aerosolization of particles. This makes surgery safer for the surgical team and for the patient. Conclusion In view of the lack of literature on this subject, except for some reports of experiences from some services around the world, we describe the way we have adjusted the EETA in the context of the COVID-19 pandemic.

Co-Occurrence of Pineal-Region and Pituitary-Stalk Hemangioblastomas in a Patient Presenting with Von Hippel-Lindau Disease ­ A Case Report

Introduction Hemangioblastomas of the pineal region or pituitary stalk are extremely rare. Only two cases of hemangioblastomas involving the pineal region have been reported, and four involving the pituitary stalk. The purpose of the present manuscript is to describe an unusual case of supposed hemangioblastoma found concomitantly in the pineal region and pituitary stalk of a patient diagnosed with Von Hippel-Lindau (VHL) disease. Case Report A 35-year-old female patient with a previous diagnosis of VHL complaining of occipital headaches and balance disturbances for three weeks, who previously had a cerebellar hemangioblastoma resected. The visual characteristics of the tumor suggested a friable vascular lesion with a reddish-brown surface, and an incisional biopsy was performed. The tumor consisted of a dense vascular network surrounded by fibrous stroma abundant in reticulin and composed by both fusiform and dispersed xanthomatous cells; the immunohistochemistry was immunopositive for neuronspecific enolase and immunonegative for epithelial membranous antigen. The patient has been monitored closely for 2 years, and the supratentorial masses have not presented any volume alteration. Conclusion This rare association must be taken into account in patients with VHL disease, or at least be suspected in patients who present a thickening of the pituitary stalk and a pineal-region mass. We believe a biopsy of our asymptomatic patient could have been dangerous due to inherent complications like intraoperative bleeding. We recommend close observation of asymptomatic lesions with MRIs every six months or until the lesions become symptomatic. If the pineal-region tumor does become symptomatic, gross resection via a transcallosal approach would be ideal.

Doença de cushing e hipertensão arterial: relato de caso / Cushing disease and hypertension: a case report

Caso clínico de VNS, 23 anos, sexo feminino, branca, solteira, estudante, natural e procedente de São Paulo- SP com queixa de "pressão alta" há 4 anos. A paciente foi encaminhada para consulta ambulatorial após ter sido atendida em pronto-socorro (PS) com cefaleia, tonturas e pressão arterial (PA) 210x110 mm Hg e medicada com losartana 50 mg a cada 12 horas e hidroclorotiazida 25 mg ao dia. Na avaliação ambulatorial relatava episódios prévios de cefaleia holocraniana de forte intensidade, latejante, de início gradual há 4 anos com piora há 2 anos, que a levava ao pronto-socorro (PS) com muita frequência. Além disso, referia aumento de peso e fraqueza generalizada. Ao exame físico apresentava-se com níveis elevados da PA 160x100 mm Hg em uso das medicações prescritas no PS, obesidade grau III (IMC 41), adiposidade localizada (giba), acantose nigricans e estrias violáceas abdominais. Foi diagnosticada a doença de Cushing associada à hipertensão arterial não controlada, realizados ajustes dos agentes anti-hipertensivos (associado anlodipino 5 mg a cada 12 horas) e solicitados exames laboratoriais. A monitorização ambulatorial da PA (MAPA) de 24 horas caracterizou a hipertensão resistente, as dosagens de cortisol (cortisol salivar = 8h:172; após 23h:280, supressão com dexametasona =<2,5) e a ressonância nuclear magnética evidenciou um macroadenoma da hipófise confirmando o diagnóstico da doença de Cushing com base nos achados do exame físico, laboratorial e de imagem. A paciente foi tratada clinicamente com cetoconazol via oral sem sucesso e após isso submetida a ressecção transesfenoidal do macroadenoma de hipófise. Após o tratamento cirúrgico, houve perda de peso e resolução da hipertensão confirmada pelas medidas ambulatoriais de consultório e pela MAPA.

Clinical case of VNS, 23 years old, female, white, single, student, born and living in São Paulo-SP, complaining of "high blood pressure" 4 years ago. The patient was referred to an outpatient clinic after being seen in the emergency room (ER) with headache, dizziness and blood pressure (BP) 210x110 mm Hg and medicated with losartan 50 mg every 12 hours and hydrochlorothiazide 25 mg daily. In the outpatient evaluation, she reported previous episodes of severe, throbbing holocranial headache, which started gradually over 4 years and worsened over 2 years ago, which took her to the ER very often. In addition, she reported weight gain and generalized weakness. On physical examination, he presented with high BP levels 160x100 mm Hg using the medications prescribed in ER, obesity grade III (BMI 41), localized adiposity (gib), acanthosis nigricans and abdominal violet streaks. Cushing's syndrome was diagnosed associated with uncontrolled arterial hypertension, adjustments were made to antihypertensive agents (associated with amlodipine 5 mg every 12 hours) and laboratory tests were requested. 24-hour ambulatory BP monitoring (ABPM) characterized resistant hypertension, cortisol levels (salivary cortisol = 8:00 am: 172; after 11:00 pm: 280, dexamethasone suppression = <2.5) and magnetic resonance imaging revealed a macroadenoma of the pituitary gland confirming the diagnosis of Cushing's disease based on the findings of the physical, laboratory and imaging exam. The patient was clinically treated with oral ketoconazole and underwent transphenoid resection of the pituitary macroadenoma. After the surgery the patient was no longer hipertensive, without use of antihypertensive medications, outpatient office measurements were normal, as were measurements outside the office by ABPM

Identification and sequence analysis of prolactin receptor and its differential expression profile at various developmental stages in striped hamsters

Prolactin (PRL) plays critical roles in regulation of biological functions with the binding of specific prolactin receptor (PRLR). Revealing the expression patterns of PRLR at different developmental stages is beneficial to better understand the role of PRL and its mechanism of action in striped hamsters. In this study, the cDNA sequence of PRLR (2866-base-pairs) was harvested from the pituitary of mature female striped hamsters (Cricetulus barabensis) that contains an 834-base-pair 5′-untranslated region (1-834 bp), a 1848-base-pair open reading frame (835-2682 bp), and a 184-base-pair 3′-untranslated region (2683-2866). The 1848-base-pair open reading frame encodes a mature prolactin-binding protein of 592 amino acids. In the mature PRLR, two prolactin-binding motifs, 12 cysteines, and five potential Asn-linked glycosylation sites were detected. Our results showed that the PRLR mRNA quantity in the hypothalamus, pituitary, ovaries, or testis was developmental-stage-dependent, with the highest level at sub-adult stage and the lowest level at old stage. We also found that PRLR mRNAs were highest in pituitary, medium level in hypothalamus, and lowest in ovaries or testis. PRLR mRNAs were significantly higher in males than in females, except in the hypothalamus and pituitary from 7-week-old striped hamsters. Moreover, the PRLR mRNAs in the hypothalamus, pituitary, and ovaries or testis were positively correlated with the expression levels of GnRH in the hypothalamus. These results indicated that the PRLR has conserved domain in striped hamster, but also possesses specific character. PRLR has multiple biological functions including positively regulating reproduction in the striped hamster.

The role of prostaglandin F2α on ovulation and LH release in cows / A função da prostaglandina F2α na ovulação e na liberação de LH em vacas

This study aimed to evaluate the role of prostaglandin F2α (PGF) on ovulation. In Experiment 1, cows were randomly allocated to two treatments to receive 150 µg of d-Cloprostenol (PGF Group, n = 12) or 2 mL of NaCl 0.9% (Control Group, n = 11) and CIDRs, were removed 4 days later. No cow ovulated in Control and PGF groups. In Experiment 2, cows were randomly separated into two experimental groups to receive 4 injections of 150 µg of d-Cloprostenol (n = 9) or 2 mL of NaCL 0.9% (n = 9). In this experiment, ovulation was not observed in any cows. In Experiment 3, ovariectomized cows receive three injections of 300µg of PGF analog (PGF Group, n = 5), 100µg of Lecirelin (GnRH Group, n = 5) or 2 mL of PBS (Control Group, n = 4). The LH concentration was higher (P <0.0001) in cows from the GnRH group than in the PGF and Control groups. In experiment 4, cows with preovulatory follicles (>11.5 mm) were treated with Saline (Control Group, n = 6); Lecirelin (GnRH Group, n = 7) or Cloprostenol Sodium (PGF Group, n = 6). There was a significant increase in the vascular area of follicles from 0 to 24 h in GnRH and PGF treatments. In conclusion, PGF was not able to induce ovulation in cows with high or low plasma progesterone concentration. Additionally, PGF alone was not able to induce LH release and follicle luteinization, but increased follicular vascularization.(AU)

O objetivo deste estudo foi avaliar o papel da prostaglandina F2α (PGF) na ovulação. No Experimento 1, as vacas foram alocadas aleatoriamente em dois tratamentos para receber 150 µg de d-Cloprostenol (Grupo PGF, n = 12) ou 2 mL de NaCl 0,9% (Grupo Controle, n = 11) e os CIDR, foram removidos 4 dias depois. Nenhuma vaca ovulou nos grupos Controle e PGF. No Experimento 2, as vacas foram separadas aleatoriamente em dois grupos experimentais para receber 4 injeções de 150 µg de d-Cloprostenol (n = 9) ou 2 mL de NaCL 0,9% (n = 9). Não foi observada ovulação em nenhum dos animais deste experimento. No Experimento 3, vacas ovariectomizadas receberam três injeções de 300µg de análogo de PGF (Grupo PGF, n = 5), 100µg de Lecirelina (Grupo GnRH, n = 5) ou 2 mL de PBS (Grupo Controle, n = 4). A concentração de LH foi maior (P <0,0001) nas vacas do grupo GnRH do que nos grupos PGF e Controle. No Experimento 4, vacas com folículos pré-ovulatórios (> 11,5 mm) foram tratadas com solução salina (Grupo Controle, n = 6), Lecirelina (Grupo GnRH, n = 7) ou Cloprostenol Sódico (Grupo PGF, n = 6). Houve um aumento significativo na área vascular dos folículos de 0 a 24h nos tratamentos com GnRH e PGF. Em conclusão, a PGF não foi capaz de induzir ovulação em vacas com alta ou baixa concentração plasmática de progesterona. Além disso, a PGF sozinha não foi capaz de induzir a liberação de LH e a luteinização do folículo, mas aumentou a vascularização folicular.(AU)

Prostaglandin E2 induces ovulation in prepubertal mice / Prostaglandina E2 induz ovulação em camundongos pré-púberes

The objective of this study was to determine the ability of prostaglandin E2 (PGE2) to induce ovulation and expression of PGE2 receptor (EP2 and EP4) and COX genes (COX-1 and COX-2) in the ovary and pituitary of prepubertal mice. The positive control consisted of the application of 5 µg of gonadotropin-releasing hormone (GnRH, n = 29); the negative control applied 0.5 mL of phosphate buffered saline (PBS, n=31); the treatment tested the application of 250 µg of PGE2 (n = 29), making a total of 89 prepubertal mice (BALB/c). Mice were euthanized 14 to 15 h after treatments to detect ovulation and tissue collection. A Chi-square test was used to compare the proportion of animals ovulating. Gene expressions and number of ovulation were analyzed by one-way ANOVA and Tukey's test was used to compare means among groups. A greater proportion of mice (P < 0.001) ovulated after receiving GnRH (89.7%, 26/29) compared to PGE2 group (58.6%, 17/29). However, the proportion was higher compared to those treated with PBS (0%, 0/31). Ep2gene expression in the pituitary was > two-fold higher (P < 0.05) in the PGE2 group compared to the PBS and GnRH groups. Further, PGE2 stimulated Cox1 (2.7 fold, P < 0.05) while GnRH stimulated Cox2 expression (6.5 fold, P < 0.05) in the pituitary when compared to the PBS group. In conclusion, our results support the hypothesis that PGE2 can induce ovulation in prepubertal mice with a concomitant increase in Ep2 and Cox1 gene expression in the pituitary gland.(AU)

O objetivo deste estudo foi determinar a capacidade da prostaglandina E2 (PGE2) em induzir a ovulação e expressão do receptor PGE2 (EP2 e EP4) e genes COX (COX-1 e COX-2) no ovário e na hipófise de camundongos pré-púberes. O controle positivo consistiu na aplicação de 5 µg de hormônio liberador de gonadotrofina (GnRH, n = 29); o controle negativo aplicação 0,5 mL de tampão fosfato-salino (PBS, n=31); o tratamento testado aplicação de 250 µg de PGE2 (n = 29), perfazendo um total de 89 camundongos (BALB/c) pré-púberes. Os camundongos foram sacrificados 14 a 15 h após os tratamentos para detectar ovulações e coleta de tecido. O teste do qui-quadrado foi usado para comparar a proporção de animais ovulando. As expressões gênicas e o número de ovulação foram analisados por ANOVA e o teste de tukey foi usado para comparar as médias entre os grupos. Uma maior proporção de camundongos (P <0,001) ovulou após receber GnRH (89,7%, 26/29) em comparação com o grupo PGE2 (58,6%, 17/29). No entanto, a proporção foi maior em comparação com aqueles tratados com PBS (0%, 0/31). A expressão do gene Ep2 na hipófise foi duas vezes maior (P <0,05) no grupo PGE2 em comparação com os grupos PBS e GnRH. Além disso, a PGE2 estimulou a Cox1(2,7 vezes, P <0,05) enquanto o GnRH estimulou a expressão de Cox2 (6,5 vezes, P <0,05) na pituitária em comparação com o grupo PBS. Em conclusão, nossos resultados suportam a hipótese de que PGE2 é capaz de induzir ovulação em camundongos pré-púberes com aumento concomitante na expressão dos genes Ep2 e Cox1 na glândula pituitária.(AU)

Primary pituitary tuberculosis

Tuberculosis is an infectious disease that involves any organ. However, the primary pituitary tuberculosis is an extremely rare disease. Intracranial tuberculomas account for 0.15-5% of intracranial space-occupying lesions, of which, pituitary as the primary site is unusual, and easily misdiagnosed as pituitary adenoma. In this setting, the late diagnosis can result in permanent endocrine dysfunction. We report the case of a 50-year-old woman who presented to the neurosurgery outpatient department with complaints of progressively increasing headache and diminished vision over the last year. On the clinical examination, the patient was conscious and oriented. The routine hematological and biochemical workup showed an increased erythrocyte sedimentation rate (ESR) and increased prolactin levels. The radiological working diagnosis was consistent with pituitary macroadenoma. No other radiological and/or clinical clue that could elicit the suspicion of pulmonary or extrapulmonary lesions of tuberculosis was found. The transsphenoidal endonasal tumor excision was done. The histopathology showed numerous epithelioid cell granulomas, Langhans giant cells along with scant necrosis. Ziehl Neelsen staining demonstrated acid-fast bacilli, and the final diagnosis of pituitary tuberculoma was made. We report this rare case of pituitary lesion that may be included in the differential diagnosis of sellar lesions to avoid unnecessary surgical interventions, especially in regions where the disease is endemic.

Tratamiento quirúrgico de los adenomas hipofisarios en el Noroeste Argentino / Surgical treatment of pituitary adenomas in the Argentine Northwest

Introducción: Los tumores de hipófisis representan aproximadamente un 10% de los tumores intracraneales. Los adenomas hipofisarios son ampliamente la lesión selar más frecuente. Es fundamental que se conformen equipos capaces de tratar holísticamente esta patología en las distintas regiones de nuestro vasto territorio. El propósito del presente trabajo es presentar nuestra experiencia en el manejo quirúrgico de los adenomas hipofisarios en el Noroeste Argentino. Materiales y métodos: Estudio retrospectivo de pacientes operados por adenomas selares, desde enero de 2013 hasta abril de 2019, en la provincia de Tucumán, por el autor Senior. Resultados: Se analizaron 211 pacientes operados de adenomas pituitarios. En el 75% (n=158) las resecciones fueron totales y en el 25% (n=53) fueron resecciones subtotales. De los 88 pacientes con macroadenomas no funcionantes y déficit visual, el 94% (n=83) presentó mejoría visual en el postoperatorio. De los 52 pacientes con acromegalia, un 75% (n=39) presentó remisión bioquímica completa postquirúrgica. De los 26 pacientes con enfermedad de Cushing, un 81% (n=21) presentó remisión bioquímica completa postquirúrgica. De los 21 pacientes con prolactinomas, un 71% (n=15) normalizaron los niveles de prolactina en el postoperatorio. Conclusión: Los resultados en el tratamiento quirúrgico de los adenomas hipofisarios de la presente serie son comparables a los reportados por centros especializados internacionales. Debemos formar equipos capaces de tratar esta patología en las distintas regiones de la Argentina.

Background: Pituitary tumors account for 10% of intracranial tumors. Pituitary adenomas are the most common selar lesion. It is essential that teams be formed capable of treating this pathology holistically in the different regions of our vast territory. The purpose of this article is to present our experience in the surgical management of pituitary adenomas in the Northwest of Argentine. Materials and methods: A retrospective analysis was done studding patients operated from pituitary adenomas, from January 2013 to April 2019, in Tucumán, by the Senior Author. Results: We analyzed 211 patients operated from pituitary adenomas, of which 75% (n=158) had gross total resections and 25% (n=53) had subtotal resections. Of the 88 patients with non-functioning macroadenomas and visual deficit, 94% (n=83) presented visual improvement after surgery. Of the 52 patients with acromegaly, 75% (n=39) presented complete biochemical remission after surgery. Of the 26 patients with Cushing's disease, 81% (n=21) presented complete biochemical remission after surgery. Of the 21 patients with prolactinomas, 71% (n=15) normalized prolactin levels after surgery. Conclusion: Our results in the surgical treatment of pituitary adenomas are comparable to those reported by international specialized centers. We must form teams capable of treating this pathology in the different regions of Argentina

Hereditary pituitary tumor syndromes: genetic and clinical aspects

ABSTRACT The pituitary gland is responsible for the synthesis and secretion of various hormones that play a key role in regulating endocrine function and homeostasis. Pituitary adenomas (PA) are benign epithelial tumors arising from the endocrine cells of the anterior pituitary gland. Clinically relevant PA are relatively common and they occur in 0.1% of the general population. They are mostly benign monoclonal neoplasms that arise from any of the five hormone-secreting cell types of the anterior pituitary gland. PA are categorized as either functioning or non-functioning, depending on whether or not they produce a hormonal hypersecretion syndrome. Both functioning and non-functioning adenomas can produce symptoms or signs resulting from compression of the optic chiasm or invasion of cavernous sinuses. Only 5% of PA occur within the context of hereditary syndromes with reasonably well-defined oncogenic mechanisms. The vast majority of PA are sporadic, and their etiopathogenesis remains largely unknown. Pituitary tumor oncogenesis involves several mechanisms that eventually lead to abnormal cell proliferation and dysregulated hormone production. Among these factors, we found inactivating mutations of tumor suppressor genes, activating mutation of oncogenes and the participation of hormonal signals coming from the hypothalamus, all resulting in cell-cycle regulation abnormalities. In this review, we summarize the clinical and pathophysiological aspects of the different hereditary pituitary tumor syndromes.

Metodología para la elaboración de la Guía de práctica clínica / Methodology for the development of the Clinical guideline for the diagnosis and treatment of precocious puberty

Resumen Introducción: La Sociedad Mexicana de Endocrinología Pediátrica presenta recomendaciones para el diagnóstico y el tratamiento de la pubertad precoz (PP), condición definida como el desarrollo de caracteres sexuales por incremento en la secreción hipofisiaria de gonadotropinas antes de los 8 años en las niñas y de los 9 años en los niños. Métodos: Se realizaron tres revisiones sistemáticas de ensayos clínicos controlados sobre intervenciones para el tratamiento de la PP, pruebas diagnósticas y estudios observacionales sobre efectos a largo plazo de la PP. La evaluación de la calidad de los estudios y la extracción de datos se realizó por pares. La evidencia se graduó con el sistema de la Scottish Intercollegiate Guidelines Network (SIGN) y del Oxford Centre for Evidence-Based Medicine (OCEBM) para las recomendaciones sobre la intervención y el diagnóstico, respectivamente. Las recomendaciones generadas se sometieron a un consenso por el método Delphi y fueron validadas por otros 143 endocrinólogos pediatras certificados mediante un cuestionario en línea. Resultados: Mediante consenso se generaron 12 recomendaciones para el diagnóstico de PP, siete sobre diagnóstico de causas secundarias de PP, ocho sobre intervenciones para inhibición de la pubertad, cinco sobre otras intervenciones en PP y 14 para la monitorización del tratamiento y el seguimiento de estos pacientes. Se obtuvo más del 90% de aprobación para cada una de las recomendaciones por el grupo de endocrinólogos certificados que respondieron el cuestionario en línea. Conclusiones: Si bien se logró un alto grado de consenso para las recomendaciones para el diagnóstico, el tratamiento y la monitorización de la PP entre los endocrinólogos pediatras, el nivel de evidencia para la mayoría de estas recomendaciones resultó bajo.

Abstract Background: The Mexican Society of Pediatric Endocrinology presents recommendations for the diagnosis and treatment of precocious puberty (PP), a condition defined as the development of sexual characteristics due to an increase in pituitary gonadotropin secretion before 8 or 9 years of age in girls and boys, respectively. Methods: Three systematic reviews were conducted: controlled clinical trials on interventions for PP treatment, diagnostic tests, and observational studies on the long-term effects of PP. The quality evaluation and data extraction from the studies were conducted by two independent reviewers. The Scottish Intercollegiate Guidelines Network and the Oxford Center for Evidence-Based Medicine systems were used for grading the quality of evidence for recommendations on intervention and diagnosis, respectively. Recommendations were submitted to a consensus by a Delphi method and were validated by another 143 certified pediatric endocrinologists through an online questionnaire. Results: The group generated 12 recommendations on the diagnosis of PP, seven on the diagnosis of secondary causes of PP, eight on interventions for inhibition of puberty, five on other interventions for PP treatment, and 14 for the monitoring and follow-up of these patients. The online questionnaires submitted to certified pediatric endocrinologists showed more than 90% of approval for each one of the recommendations. Conclusions: Although a high degree of consensus for the recommendations for diagnosis, treatment, and monitoring of PP among pediatric endocrinologists was achieved, most of these recommendations showed a low level of evidence.

Morphological and immunohistochemical comparison of the pituitary gland between a tropical Paracheirodon axelrodi and a subtropical Aphyocharax anisitsi characids (Characiformes: Characidae)

Cardinal tetra Paracheirodon axelrodi and bloodfin tetra Aphyocharax anisitsi are two species of characids with high trade value as ornamental fish in South America. Although both species inhabit middle water layers, cardinal neon exhibits a tropical distribution and bloodfin tetra a subtropical one. Generally, these species are difficult to grow, so it becomes essential to know some key components of the neuroendocrine system to achieve their reproduction in captivity. Considering the importance of deepening the knowledge of the reproductive physiology through functional morphology, for the first time in this work we performed an anatomical, morphological and immunohistochemical analysis of the pituitary gland of these two species. In both species, a leptobasic type pituitary is found in the ventral zone of the hypothalamus and it is characterized by a neurohypophysis which has a well-developed pituitary stalk and a globular adenohypophysis. The pituitary components, characterized by histochemistry and immunohistochemistry, shows a distribution pattern of cells types similar to other teleost species, with only slight differences in the distribution of βFSH and βLH for P. axelrodi.(AU)

El cardenal tetra Paracheirodon axelrodi y el tetra Aphyocharax anisitsi son dos especies de carácidos con alto valor comercial como peces ornamentales en América del Sur. Aunque ambas especies habitan en las capas medias de agua, el neón cardenal exhibe una distribución tropical, mientras que el tetra cola roja una distribución subtropical. En general estas especies son difíciles de cultivar, por lo que es esencial conocer algunos componentes clave de los sistemas neuroendocrinos para lograr su reproducción en cautiverio. Considerando la importancia de profundizar en el conocimiento de la fisiología reproductiva a través de la morfología funcional, en este trabajo realizamos, por primera vez, un análisis anatómico, morfológico e inmunohistoquímico de la glándula pituitaria de estas dos especies. En ambas especies, la hipófisis, del tipo leptobásica, se encontró en la zona ventral del hipotálamo y se caracteriza por una neurohipófisis con un tallo hipofisario bien desarrollado y una adenohipófisis globular. Los componentes hipofisarios, caracterizados por la histoquímica y la inmunohistoquímica, mostraron un patrón de distribución de tipos de células similares a otras especies de teleósteos, con solo pequeñas diferencias en la distribución de βFSH y βLH para P. axelrodi.(AU)

Serie de Casos Clínicos: Acromegalia, Presentación Clínica y Evolución en los Pacientes del Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, Mayo 2015 - Abril 2017 / Case Series: Acromegaly, Clinical Presentation and Evolution in Patients of Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, May 2015 - April 201

INTRODUCCIÓN:La acromegalia es una enfermedad sistémica caracterizada por la elevada producción de hormona del crecimiento, su etiología más común es el adenoma hipofisiario. En Ecuador existe una prevalencia de 18.7 casos por millón de habitantes y una incidencia de 1.3 casos por millón de individuos cada año. Se considera que existe un retraso de aproximadamente una década entre el inicio de los síntomas y el reconocimiento de los mismos por parte del equipo de salud. CASO CLÍNICO: Se presentan a continuación tres pacientes con acromegalia, atendidos por el servicio de Endocrinología del Hospital Vicente Corral Moscoso desde Mayo del 2015 hasta Abril del 2017. En esta serie, la edad de diagnóstico fue alrededor de los 34 años. Los motivos de consulta fueron molestias visuales, dolores articulares y complicaciones microvasculares. En todos los casos, la etiología fue un adenoma hipofisario productor de hormona del crecimiento en los que era necesaria la corrección quirúrgica; sin embargo, la paciente del caso 3 rechazó este tratamiento. EVOLUCIÓN: Se presentan a continuación tres pacientes con acromegalia, atendidos por el servicio de Endocrinología del Hospital Vicente Corral Moscoso desde Mayo del 2015 hasta Abril del 2017. En esta serie, la edad de diagnóstico fue alrededor de los 34 años. Los motivos de consulta fueron molestias visuales, dolores articulares y complicaciones microvasculares. En todos los casos, la etiología fue un adenoma hipofisario productor de hormona del crecimiento en los que era necesaria la corrección quirúrgica; sin embargo, la paciente del caso 3 rechazó este tratamiento. CONCLUSIÓN: Es importante reconocer la característica insidiosa de la acromegalia y sus variables manifestaciones clínicas, puesto que un diagnóstico oportuno permite mejorar el pronóstico y la calidad de vida. Hay diversas opciones terapéuticas, siendo el tratamiento quirúrgico complementado con terapia farmacológica, el de mayor eficacia. El manejo debe ser multidisciplinario e individualizado(au)

BACKGROUND: Case Series: Acromegaly, Clinical Presentation and Evolution in Patients of Hospital "Vicente Corral Moscoso". Cuenca - Ecuador, May 2015 - April 2017. CASE REPORTS: Three patients with acromegaly are presented, attended by the Endocrinology service of the Hospital Vicente Corral Moscoso from May 2015 to April 2017. In this series, the diagnosis age was around 34 years. Patients consulted because of visual discomfort, joint pain and microvascular complications. In all cases, the etiology was a pituitary adenoma producing growth hormone, in which surgical correction was necessary; however, patient number 3 rejected surgical treatment. EVOLUTION: In the present series, case 1 is undergoing treatment with Octreotide-Cabergoline and hormone replacement therapy, case 2 achieved biochemical remission with postoperative adjuvant treatment based on somatostatin analogues and case 3 has poor expectation of cure due to her medical history and lack of adherence to treatment. CONCLUSIONS: It is important to recognize the insidious characteristic of acromegaly and its varia-ble clinical manifestations, because a timely diagnosis allows a better prognosis and quality of life. There are several therapeutic options, being the surgical treatment supplemented with pharmacological therapy, the most effective. The management must be multidisciplinary and individualize(au)

Pituitary gland volumes in patients with obsessive-compulsive disorder before and after cognitive-behavioral therapy

Objective: The beneficial effects of psychopharmacological and cognitive behavioral therapy (CBT) on the brain are not well understood. In a previous study, we found smaller pituitary volumes in patients with obsessive-compulsive disorder (OCD). The purpose of this study was to examine the effect of CBT on pituitary gland volume. Methods: A total of 81 patients with various anxiety disorders and the same number of healthy controls underwent magnetic resonance imaging, and their pituitary gland volumes were compared at baseline. Pituitary gland volumes were also measured before and after CBT in the patient group. Results: OCD patients had smaller pituitary gland volumes at baseline than healthy controls (0.54±0.29 cm3 for OCD patients vs. 0.82±0.30 cm3 for healthy controls; p < 0.001). We found no significant changes in OCD patient pituitary gland volume after the 16-week treatment period, with mean pre- and post-treatment values of 0.54±0.29 cm3 and 0.56±0.32 cm3, respectively (p > 0.05). Conclusion: Our results indicate an absence of post-CBT volumetric changes in the pituitary gland of OCD patients.

Morphology and ultrastructure of the hypophysis in bactrian camels ( Camelus bactrianus ) / Morfología y ultraestructura de la hipófisis en camellos bactrianos ( Camelus bactrianus )

The morphology of the hypophysis in Bactrian camel has not been described in the literature, despite it being the master of endocrine organs in vertebrates. In the present study, we examined the morphological features of the hypophysis in Bactrian camel by means of gross anatomy, light and electron microscope. Our findings showed that the gland was a protrusion of the bottom of the hypothalamus at the base of the brain with about 1.54 g in weight and 2 cm3 in volume. The hypophysis consists of two major parts: fully developed adenohypophysis and underdeveloped neurohypophysis, the adenohypophysis consists of pars distalis and pars intermedia. Seven type cells of the pars distalis could be distinguished with immunohistochemical techniques and electron micrographs: somatotroph, mammotroph, thyrotroph, corticotroph, gonadotroph, chromophobe and stellate cells which is in accordance with most mammals. Notably, the stellate cells could be obviously distinguished from chromophobe cells in histological oberservation. Moreover, the corpusculum neurosecretorium (Herring bodies) were rare in the external neurohypophysis, and mainly distributed in the internal neurohypophysis, this was different from most mammals. Results from this study would provide a necessary theoretical basis for ongoing investigations for Bactrian camels and their good adaptability in arid and semi-arid circumstances.

La morfología de la hipófisis en el camello bactriano no ha sido descrita en la literatura, a pesar de ser el maestro de los órganos endocrinos en los vertebrados. En el presente estudio, examinamos las características morfológicas de la hipófisis del camello bactriano por medio de anatomía general, microscocopía de luz y microscopía electrónica. Nuestros hallazgos mostraron que la hipófisis es una protuberancia ubicada en la porción inferior del hipotálamo, en la base del cerebro, con aproximadamente 1,54 g de peso y 2 cm3 de volumen. La hipófisis consta de dos partes principales: adenohipófisis, completamente desarrollada, y neurohipófisis, poco desarrollada; además, la adenohipófisis consta de una pars distalis y una pars intermedia. Con técnicas inmunohistoquímicas y micrografías electrónicas en la pars distalis se pudieron distinguir siete tipos de células: somatotrofas, mamotróficas, tirotrofas, corticotrofas, gonadotrofas, cromófobas y estrelladas, lo que es similar a la mayoría de los mamíferos. En la observación histológica las células estrelladas se pueden distinguir naturalmente de las células cromófobas. Además, es rara la presencia de corpusculum neurosecretorium (Cuerpos de Herring) en la neurohipófisis externa, hallándose distribuidos principalmente en la neurohipófisis interna, esto es diferente a lo encontrado en la mayoría de los mamíferos. Los resultados de este estudio proporcionarían una base teórica necesaria para las investigaciones en curso de los camellos bactrianos y su buena adaptabilidad en circunstancias áridas y semiáridas.

Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Síndrome de interrupción del tallo pituitario: Relaciones clínicas, bioquímicas y neurorradiológicas / Pituitary stalk interruption syndrome: Clinical, biochemical and neuroradiological relationships

El síndrome de interrupción del tallo pituitario (PSIS) se caracteriza por la demostración neurorradiológica de un tallo pituitario ausente, interrumpido o hipoplásico, adenohipófisis aplásica/hipoplásica o neurohipófisis ectópica. Este síndrome se ha relacionado con formas severas de hipopituitarismo congénito (HPC), asociado a múltiples deficiencias de hormonas pituitarias (MPHD). Evaluamos a pacientes con HPC y PSIS, analizando los signos y los síntomas neonatales al diagnóstico, relacionándolos con las deficiencias hormonales pituitarias y signos neurorradiológicos presentes. Estudiamos retrospectivamente a 80 pacientes asistidos en el Hospital de Niños de Córdoba, con diagnóstico de HPC, de los cuales 42 (52%) presentaron PSIS; 22 mujeres y 20 varones, EC: 5 días-9,5 años. El 62% presentó MPHD y el 38% insuficiencia somatotrófica aislada (IGHD). El análisis de las variables perinatales demostró antecedentes de parto natural en el 52% (11/21) de las MPHD vs. 13% (2/15) de las IGHD. Cuatro pacientes, 2 con MPHD y 2 con IGHD presentaban antecedentes obstétricos consistentes en presentación podálica y transversa respectivamente, todos ellos resueltos mediante operación cesárea. Los signos y los síntomas perinatales fueron hipo- glucemia: 61% en MPHD vs. 19% en IGHD, p: 0,0105; ictericia: 38% en MPHD vs. 25% en IGHD; micropene: 77% en MPHD y colestasis: 19% en MPHD. Convulsiones neonatales se presentaron en el 75% de los niños con MPHD e hipoglucemia. EC media de consulta: 2,1 años en MPHD (30% en el período neonatal, 70% antes de 2 años) y 3,6 años en IGHD (44% en menores de 2 años). Los pacientes con MPHD presentaban: tallo no visible 81% (n: 21/26) vs. tallo hipoplásico: 19% (n: 5/26), p: 0,0001; en IGHD 56% (n: 9/16) vs. 44% (n: 7/16), p: 0,5067, respectivamente. El 100% de los neonatos con HPC tenían tallo pituitario ausente. Concluimos que la demostración de PSIS en niños con HPC proporciona información valiosa como predictor de la severidad fenotípica, la presencia de MPHD y de la respuesta al tratamiento. La baja frecuencia de antecedentes obstétricos posicionales potencialmente distócicos, como parte de los mecanismos fisiopatogénicos responsables de PSIS, indicaría la necesidad de analizar la importancia de posibles factores genéticos y epigenéticos involucrados. El diagnóstico precoz de HPC debe sospecharse en presencia de signos y síntomas clínicos, tales como hipoglucemia, colestasis, micropene y defectos asociados en la línea media facial. La resonancia magnética cerebral debe formar parte de los estudios complementarios en pacientes con esta presunción diagnóstica, especialmente a edades tempranas. El reconocimiento tardío de esta entidad puede aumentar la morbilidad y la mortalidad con efectos potenciales deletéreos y permanentes.

Pituitary stalk interruption syndrome (PSIS) is characterised by the combination of an interrupted or thin pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia. It is manifested as isolated (IGHD) or combined pituitary hormone deficiencies (CPHD) of variable degrees and timing of onset, with a wide spectrum of clinical phenotypes. PSIS may be an isolated morphological abnormality or be part of a syndrome. A retrospective evaluation is presented of clinical signs and symptoms present at early life stages, as well as an analysis of their relationship with hormone laboratory tests and diagnostic imaging in children with congenital hypopituitarism (CHP), and PSIS. This study was performed in a single centre on a sample of 42 children out of a total of 80 CHP patients, with a chronological age range between 5 days and 9.5 years from a database analysed over a period of 26 years. The study included 26/42 (62%) with CPHD and 16/42 (38%) with IGHD. The analysis of perinatal variables showed a natural delivery in 52% (11/21) of CPHD vs 13% (2/15) of IGHD. Four patients, two with CPHD and two IGHD had breech and transverse presentation respectively. All of them were resolved by caesarean section. The perinatal histories showed hypoglycaemia (61% CPHD vs 19% IGHD, P=.0105), jaundice (38% CPHDvs25% IGHD), micropenis (75%CPHD), hypoglycaemic seizures (75% CPHD), and cholestasis (19% CPHD). The mean CA of consulting for CPHD patients was 2.1 years, 30% in neonatal period and 70% before 2 years. The mean chronical age (CA) was 3.6 years in IGHD patients, with 44% of them less than 2 years. MRI showed that 81% of CPHD patients had absence of pituitary stalk vs 19% with thin pituitary stalk (P=.0001); Patients with IGHD presented 56% absence of pituitary stalk vs 44% with thin pituitary stalk (P=.5067). All (100%) of the patients diagnosed in the neonatal stage had absent pituitary stalk. The characterisation of GH deficient patients by presence and type of hypothalamic-pituitary imaging abnormality provides valuable information as a predictor of phenotypic severity, treatment response, and the potential to develop additional hormonal deficiencies. We conclude that demonstrating PSIS in children with HPC provides valuable information as a predictor of phenotypic severity, presence of MPHD, and response to treatment. The low frequency of potentially dysfunctional positional obstetric history, as part of the pathophysiological mechanisms responsible for PSIS, would indicate the need to analyse the importance of possible genetic and epigenetic factors involved. Early diagnosis of HPC should be suspected in the presence of clinical signs and symptoms, such as hypoglycaemia, cholestasis, micropenis, and associated facial midline defects. MRI should be part of complementary studies in patients with this diagnostic suspicion, especially at an early age. Late recognition of this entity may increase morbidity and mortality with potential permanent deleterious effects.

An activating mutation in the CRHR1 gene is rarely associated with pituitary-dependent hyperadrenocorticism in poodles

OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The present study aimed to investigate mutations in the CRHR1 coding region in poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing. RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine residue, located in the amino-terminal extracellular domain, exhibits high affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic analysis revealed structural rearrangements in the mutant protein, with a 17% increase in the surface binding affinity between CRHR1 and CRH. In vitro functional studies showed that mutant CRHR1 induced higher ACTH secretion than the wild type after stimulation with human CRH. CONCLUSION: These results suggest that germline activating mutations in CRHR1 may be a rare cause of pituitary hyperadrenocorticism in poodles.

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.