Atypical pituitary hormone-target tissue axis / 医学前沿

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.

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.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

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)

Two Cases of Hypovascular Pituitary Metastases and Literature Review / 中国医学科学院学报

Pituitary metastasis,a rare kind of intracranial malignant tumor,is characterized by metastasis from all parts of the body to the pituitary.The common tumors metastatic to pituitary are abundant with blood supply,located in the posterior pituitary lobe and/or the pituitary stalk.The lesion shows infiltrative growth,and mainly demonstrates low signal on T1 weighted imaging and high signal on T2 weighted imaging.It is usually enhanced significantly after iodinated contrast administration.The metastatic tumor with poor blood supply is similar to pituitary macroadenoma on magnetic resonance image,which makes it difficult to be differentiated.We reported two cases of pathologically diagnosed pituitary metastasis with poor blood supply and reviewed related papers,aiming to provide the imaging differentiation points of hypovascular pituitary metastasis.

Clinical characteristics of central nervous system involvement in IgG4 related diseases / 北京大学学报(医学版)

OBJECTIVE@#To improve the understanding of the clinical characteristics of immunoglobulin G4-related disease (IgG4-RD) with central nervous system (CNS) involvement, so as to contribute to the early diagnosis and treatment.@*METHODS@#In this study, 10 patients with IgG4-RD with CNS involvement were selected. Clinical data including demographic features, clinical manifestations, organ involvement, laboratory findings, radiological results, pathology, treatments and outcomes were collected retrospectively.@*RESULTS@#Among the 10 IgG4-RD patients complicated with CNS involvement, 6 cases manifested as pituitary involvement and 4 cases manifested as dural involvement. Only 2 patients had nervous system involvement alone, while the left patients were complicated with other organ involvement besides nervous system. Half of the patients presented nervous system involvement as the initial manifestation, and the main symptoms of nervous system included polydipsia, polyuria, headache, decreased vision and so on. In the laboratory examination, the serum IgG4 level was increased in 9 cases (90.0%), and the total serum IgE was increased in 7 cases (87.5%). At the same time, their IgG, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were increased, while complement (C) 3 and C4 were decreased in some patients. Eight patients underwent tissue biopsies in different parts, the pathological examination showed a large number of lymphocyte and plasma cell infiltration, accompanied by fibrous tissue proliferation in part. All the patients were treated with glucocorticoids, and 8 cases (80%) were given immunosuppressants at the same time, and 3 cases were treated with rituximab when they expe-rienced disease relapse. As a result, 2 cases (20%) achieved complete remission (CR), and 8 cases (80%) achieved partial remission (PR). The median follow-up time was 13.5 months, and 4 cases relapsed.@*CONCLUSION@#Pituitary and dura are common affected organs of IgG4-RD with CNS involvement. Most IgG4-RD patients with CNS involvement are combined with other organ involvement, but half of them presented nervous system involvement as the initial manifestation, and the symptoms are not typical. In order to make an early diagnosis, laboratory, imaging examination and tissue biopsy should be taken into consideration in combination if necessary.

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.

Profil épidémiologique et aspect à l'IRM des pathologies hypophysaires au CHU de Brazzaville / Epidemiological profile and MRI appearance of pituitary pathologies at Brazzaville University Hospital

Objectif :Décrire le profil épidémiologique et remnologique des pathologies retrouvées chez les patients adressés pour IRM hypophysaire dans le service d'imagerie médicale du CHU-B. Patients et Méthode :il s'agissait d'une étude transversale descriptive, réalisée au service d'imagerie médicale du CHU de Brazzaville de janvier 2014 à décembre 2018. Tous les patients adressés pour IRM hypophysaire étaient inclus. Les examens ont été réalisés sur une IRM de haut champ de 1,5 Tesla sans et avec injection de produit de contraste. Les données épidémiologiques, l'indication et les résultats retrouvés ont été traitées avec le logiciel Microsoft Excel 2013. Résultats :Cinquante-huit IRM étaient retenues durant la période d'étude. L'âge moyen des patients était de 38,24 ± 11,52 ans avec des extrêmes allant de 12 à 74 ans et un âge médian de 36 ans. Le sexe ratio (F/H) était de 4,8 avec 48 femmes (82,76%). La galactorrhée était le motif de consultation le plus fréquemment retrouvé (21,88% des cas), suivie des aménorrhées (18,75%). L'adénome hypophysaire était la pathologie la plus fréquente devant les selles turciques vides et les kystes de la poche de Rathke. Conclusion :La pathologie hypophysaire est l'apanage du sujet jeune de sexe féminin. Son mode de révélation le plus fréquent est celui de troubles gynécologiques et/ou endocriniens. Les adénomes constituent la quasi-totalité de la pathologie hypophysaire avec une nette prédominance de macroadénome. L'IRM apporte des informations essentielles au diagnostic de cespathologies malgré son accessibilité et sa disponibilité qui restent encore limité.

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 Apoplexy Presenting as Isolated Bilateral Oculomotor Nerve Palsy

PURPOSE: To report a case of pituitary apoplexy presenting as isolated bilateral oculomotor nerve palsy. CASE SUMMARY: A 46-year-old male presented with bilateral ptosis and acute severe headaches for 6 days. He underwent head surgery and bilateral vitrectomy 12 years prior to his visit because of ocular and head trauma. He mentioned that previous visual acuities in both eyes were not good. The initial corrected visual acuity was finger counting in the right eye and 20/500 in the left eye. Ocular motility testing revealed the limitation of adduction, supraduction, and infraduction with complete bilateral ptosis in both eyes, and his left pupil was dilated. He was diagnosed with an isolated bilateral oculomotor nerve palsy. Magnetic resonance imaging indicated pituitary gland hemorrhage with a tumor, which was suspicious of pituitary apoplexy. The patient was treated intravenous with 1.0 g methylprednisolone to prevent the corticotropic deficiency. In addition, he underwent surgical decompression using a navigation-guided transsphenoidal approach and aspiration biopsy. He was confirmed with pituitary adenoma using a pathological examination. The patient's ocular movements began to dramatically improve by the third day postoperatively. At 4 months postoperative follow-up, his ocular movement and double vision were completely recovered. CONCLUSIONS: This was a rare case of pituitary apoplexy with bilateral isolated oculomotor nerve palsy, which was the first report in the Republic of Korea. A full recovery was achieved after early surgical treatment.