Evaluation of the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Changes of macular retinal structure and microcirculation in patients with pituitary adenoma observed by optical coherence tomography and optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes of macular retinal structure and microcirculation in patients with pituitary adenoma(PA)by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 40 PA patients treated at the department of neurosurgery, Affiliated Hospital of Guangdong Medical University from September 2021 to March 2023 were included as PA group, and 42 age- and gender-matched healthy volunteers were selected as normal control group. All patients underwent visual field, OCT and OCTA examinations, and the correlation of ocular parameters in PA patients was analyzed.RESULTS:The vessel density(VD)of each retinal layer in the macular area of the PA group was lower than that of the normal control group, and the superficial vascular complex(SVC)-VD in the macular area was positively correlated with the thickness of the macular ganglion cell complex(mGCC)(except the nasal side of the inner ring and the lower part of the outer ring; P&#x0026;#x003C;0.05). The thickness of mGCC in each quadrant of the macular area and the thickness of the circumpapillary retinal nerve fiber layer(CP-RNFL)in each quadrant were negatively correlated with the mean defect(MD)value of the visual field(P&#x0026;#x003C;0.05), and the area of the foveal avascular zone(FAZ)was positively correlated with the MD value(P&#x0026;#x003C;0.05).CONCLUSION:The combination of OCT and OCTA can fully understand the microscopic changes of retinal structure and microcirculation function in PA patients, which is of great value in evaluating the preoperative visual function of PA patients.

Hipofisitis primaria: diagnóstico y tratamiento. estudio multicéntrico / Primary hypophysitis: diagnosis and treatment multi-center study

Resumen Introducción : La hipofisitis es una enfermedad in frecuente que plantea un desafío en el diagnóstico y tratamiento. El objetivo de este estudio multicéntrico y retrospectivo fue describir: a) características de pa cientes con hipofisitis primaria (HP), b) métodos diag nósticos, y c) tratamientos realizados. Además, evaluar: a) presentación clínica, b) bioquímica, c) radiológica, d) oftalmológica al diagnóstico y evolución según el tratamiento recibido. Métodos : Estudio retrospectivo donde se estudiaron 28 pacientes (23 mujeres/5 varones) con HP, edad pro medio de 38±11.1 años. Resultados . Los síntomas fueron: cefalea: 68%, po liuria-polidipsia: 50% y alteraciones visuales: 48%. El examen de laboratorio inicial informó disfunción ade nohipofisaria en 71% de los pacientes, siendo el eje gonadal el más afectado. Los hallazgos radiológicos más frecuentes fueron: lesión simétrica:78.5%, aumento homogéneo post contraste: 78.5% y engrosamiento de tallo:70%. En 4/23 mujeres (17%) se relacionó con em barazos o puerperio La conducta inicial fue expectante (CE) en 14 pacientes, cirugía de resección/descompresión en 8 y tratamiento con inmunosupresores en 6. Quince pacientes tuvieron confirmación histológica, 9 resulta ron hipofisitis linfocitaria, 5 hipofisitis por IgG4 y una xantomatosa. Trece fueron diagnosticados por criterios clínicos establecidos. El tamaño de la lesión disminuyó en 43% de pacientes con CE, 62.5% con cirugía y 50% con inmunosupresores. Los síntomas compresivos mejora ron en los 3 grupos, con escaso efecto sobre la función adenohipofisaria, sin resolución de la diabetes insípida. Discusión : En pacientes sin síntomas compresivos adoptamos CE. En aquellos pacientes sin certeza diag nóstica o con síntomas compresivos graves, se optó por cirugía transesfenoidal.

Abstract Introduction : Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded. Methods : Twenty-eight patients (23 women), with PH were included. Median age: 37. Results : The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonad ism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous en hancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were di agnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immuno suppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients. Discussion : In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe com pressive symptoms, transsphenoidal surgery was the best option.

Cryptococcoma hipofisiario: un extraño caso de hipofisitis granulomatosa secundaria / Pituitary cryptococcoma: a strange case of secondary granulomatous hypophysitis

Resumen La hipofisitis es una afección con baja incidencia y prevalencia. Asimismo, las infecciones profundas por hongos en pacientes inmunocompetentes también re presentan un fenómeno infrecuente. Más raro aún es el caso que se describe a continuación, en donde se conjugan estos dos elementos mencionados, a saber: cryptococcoma hipofisario o hipofisitis granulomatosa causado por dicho patógeno en un huésped sin altera ción de la respuesta inmune. Luego de una búsqueda realizada en PubMed, existen limitados casos en la literatura médica de hipofisitis granulomatosa por Cryptococcus spp., que simuló por manifestaciones clínicas e imagenológicas un macro adenoma hipofisario. No encontramos informes en los que no haya evidencia de afectación del tejido meníngeo. La etiología micótica está escasamente descrita en las guías de referencia para hipofisitis y creemos que Cryp tococcus spp. debe ser tenido en cuenta en el diagnóstico diferencial de las hipofisitis granulomatosas secundarias dado que es un patógeno ubicuo y el tratamiento es sustancialmente diferente a otras entidades. Cobra mayor relevancia ante la tendencia actual al uso de glucocorticoides sistémicos a altas dosis para el tratamiento de la hipofisitis, que podría haber gene rado mayor daño de no haberse hecho el diagnóstico correcto.

Abstract Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immuno competent patients also represent a rare phenomenon. Even rarer is the case described below, where these two mentioned elements are combined, namely: pituitary cryptococcoma or granulomatous hypophysitis caused by said pathogen in a host without altered immune response. After research in PubMed, there are limited cases in the medical literature of granulomatous hypophysitis caused by Cryptococcus spp., which simulated a pituitary macroadenoma by clinical and imaging manifestations. We did not find reports in which there is no evidence of involvement of the meningeal tissue. The fungal etiology is scarcely described in the reference guidelines for hypophysitis and we believe that Cryptococcus spp. it should be taken into account in the differential diagnosis of secondary granuloma tous hypophysitis since it is a ubiquitous pathogen and the treatment is substantially different from other entities. It becomes more relevant given the current trend towards the use of high-dose systemic glucocorticoids for the treatment of hypophysitis, which could have generated greater damage if the correct diagnosis had not been made.

Endoscopic Orientation of Juxta-pituitary Carotid in Transsphenoidal Approaches: Critical Considerations for Clinical Applications

Abstract Introduction In sphenoid sinuses with ill-defined carotid bony landmarks, accidental injury of the internal carotid artery (ICA) remains one of the most challenging complications, which is particularly reported in the endoscopic endonasal transsphenoidal approaches (EETAs). Objectives To describe an anatomical model for the endoscopic orientation of the juxta-pituitary segment of the ICA in relation to the lateral opticocarotid recess (OCR) as a nearby bony landmark. Methods Dissection was performed progressively, simulating the EETA, in twenty fresh adult cadavers. After reducing the posterior and lateral walls of the sphenoid sinuses, various measurements were taken from both lateral OCRs to "contact points" on the juxta-pituitary segment of the ICA and lateral margins of the pituitary gland. Results The current results have enabled us to divide the region between the lateral OCRs into 3 compartments: 2 lateral parasellar compartments contain juxta-pituitary segments of the ICA with a mean width of 8 mm and a narrow range from 7 mm to 10 mm; and a central intercarotid sellar compartment represents the safe region for bone drilling, showing widely variable widths ranging from 9 mm to 20 mm. In all specimens, the variation in the width of the intercarotid compartment correlated with the distance between both lateral OCRs. Conclusion The present study improves surgeon awareness of the variations in the course of the ICA through the EETA along sphenoid sinuses with ill-defined bony landmarks. An appreciation of the measurements taken in the present study can help in operative training, and can also provide a base for future studies to confirm ICA courses associated with a higher risk of injury.

A unique coexistence of a plurihormonal pituitary adenoma with granulomatous hypophysitis

Dual pathology in the pituitary gland is a unique phenomenon. Coexistence of a pituitary adenoma with primary hypophysitis has been reported rarely with very few cases in the literature. Among the primary hypophysitis, primary granulomatous subtype has been proposed to be idiopathic and autoimmune in nature. Plurihormonal pituitary adenomas produce hormones of more than one different pituitary cell lineage. Pituitary adenoma with a single hormonal content has been documented with concurrent primary granulomatous hypophysitis. The present case describes the unique coexistence of a plurihormonal adenoma showing somatotroph, lactotroph, and corticotroph lineage with primary granulomatous inflammation in the sellar region in a 36-year-old woman.

Características clínicas y evolutivas de adenomas hipofisarios incidentales: estudio multicéntrico retrospectivo / Clinical and evolutionary characteristics of incidental pituitary adenomas: retrospective multicenter study

Resumen Introducción : Los incidentalomas hipofisarios (IH) son lesiones halladas fortuitamente en la hipófisis mediante imágenes realizadas por motivos no relacionados con enfermedad hipofisaria. Métodos : Se realizó un estudio transversal, retros pectivo y descriptivo con el objetivo de analizar las características clínicas y evolutivas de una población de pacientes portadores de IH en la ciudad de Córdoba. Resultados : Se incluyeron 67 pacientes, 67% del sexo femenino, con una mediana de edad al diagnóstico de 44 años. Entre los motivos que llevaron a solicitar la primera imagen, la cefalea crónica o recurrente fue el más prevalente (34%). La mediana del tamaño tumoral fue de 12 mm. El 58% fueron macroincidentalomas. Los hombres tuvieron lesiones significativamente más grandes (p = 0.04). Al diagnóstico, considerando ambos sexos, el 30% evidenció extensión extraselar y el 45% invasión a senos cavernosos. Se detectó compromi so neurooftalmológico en el 21%. Se halló correlación positiva entre la edad al momento del diagnóstico y el tamaño tumoral (r = +0.31, p = 0.001). El 91% fueron tumores no funcionantes y en su presentación, el 21% de los pacientes presentaron una o más deficiencias hormonales. El 26% del total requirió cirugía. La ma yoría de aquellos que continuaron sin tratamiento no evidenciaron cambios en el tamaño tumoral al final del seguimiento (mediana 42 meses). Conclusión : Destacamos la elevada frecuencia de macroincidentalomas en nuestra serie, siendo los de fectos del campo visual y el hipopituitarismo frecuentes al diagnóstico. Si bien la mayoría de los IH no operados permanecieron estables, existió una alta frecuencia de lesiones clínicamente significativas.

Abstract Introduction : Pituitary incidentalomas (PIs) are le sions found incidentally in the pituitary on imaging performed for reasons unrelated to pituitary disease. Methods : A cross-sectional, retrospective and descrip tive study was carried out with the aim of analyzing the clinical and evolutionary characteristics of a population of patients with PIs in the city of Córdoba. Results : A total of 67 patients were included, 67% fe male, with a median age at diagnosis of 44 years. Among the reasons that led to requesting the first image, chron ic or recurrent headache was the most prevalent (34%). The median tumor size was 12 mm. Fifty-eight percent were macroincidentalomas. Men had significantly larger lesions (p = 0.04). At diagnosis, including both sexes, 30% showed extrasellar extension and 45% invasion of the cavernous sinuses. Neuro-ophthalmological compromise was detected in 21%. A positive correlation was found between age at diagnosis and tumor size (r= +0.31, p = 0.001). Ninety-one percent were non-functioning tumors and at presentation, 21% of patients had one or more hormonal deficiencies. Of the total, 26% required surgery. Most of those who continued without treatment showed no change in tumor size at the end of follow-up (median 42 months). Conclusion : We highlight the high frequency of mac roincidentalomas in our series, with visual field defects and hypopituitarism being frequent at diagnosis. Al though most non-operated PIs remained stable, there was a high frequency of clinically significant lesions.

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

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

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

Pituitary Apoplexy in Pregnancy: What do We Know? / Apoplexia hipofisária na gravidez: o que sabemos?

Abstract Pituitary apoplexy refers to a rare clinical syndrome consisting of signs and symptoms that occur due to rapid expansion of the contents of the sella turcica. It can occur spontaneously or associated with pituitary tumors. It can have a broad clinical spectrum, but usually presents with severe headache, visual impairment and hypopituitarism. Sudden onset of symptoms associated to imagiologic confirmation makes the diagnosis. Surgical treatment is advised when there is important compression of the optic tract. We present a case report and a review of the literature on pituitary apoplexy in pregnancy. The cases were reviewed to obtain information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities and maternal and fetal outcomes. Our review found 36 cases of pituitary apoplexy in pregnancy. Most of the cases occurred in the second trimester of pregnancy and headache was the most frequent symptom at presentation. Surgical therapy was required in more than half of the patients. In what respect maternal and fetal outcomes, there were 3 cases of preterm delivery and one case of maternal death. Our clinical case and literature review reinforces the importance of an early diagnosis to avoid potential adverse consequences.

Apoplejía pituitaria e infección por SARS-COV-2 (COVID-19) / Pituitary apoplexy and SARS-CoV-2 (COVID-19) infection

Resumen La infección por coronavirus (SARS-CoV-2/COVID-19) es responsable de un diverso rango de manifestaciones extrapulmonares entre las cuales se destaca el compromiso neurológico directo o indirecto. La apoplejía hipofisaria es una entidad médica y neuroquirúrgica de gravedad variable que suele asociarse a la presencia de un adenoma subyacente. Un escaso número de reportes han vinculado estas dos enfermedades entre sí. Este trabajo describe un caso de apoplejía hipofisaria manifestada clínicamente en for ma concomitante al diagnóstico de COVID 19, en un paciente con macroadenoma hipofisario desconocido y su manejo terapéutico, revisando los mecanismos potencialmente subyacentes al nexo entre ambas entidades.

Abstract Coronavirus disease (SARS-CoV-2/COVID-19) is responsible for a wide variety of extrapulmonary manifestations, among which direct or indirect neurological compromise stands out. Pituitary apoplexy is a clinical and neurosurgical entity of variable severity, usually associated with a pituitary adenoma. Literature is scarce regarding the association between these diseases. This paper reports a case of pituitary apoplexy, manifested concomitantly to the diagnosis of COVID 19 in a patient with unknown pituitary macroadenoma, and its therapeutic management, reviewing the mechanisms potentially underlying the link between both entities.

The effect of COVID-19 process on patients with endocrinological disease in a pandemic hospital: What happened to the others?

ABSTRACT Objective: To evaluate the effects of the pandemic process on those with an endocrinological disease that will require close follow-up from the last visit before the pandemic. Materials and methods: Patients of 3,903 with thyroid, calcium-bone metabolism, adrenal gland, pituitary diseases, and neuroendocrine tumor (NET) were retrospectively scanned. The remaining 855 (656 females and 199 males) patients with active disease or who still needed multidisciplinary approaches were included. The number of patients who continued the disease-related medical procedures and could complete these procedures on time in the pandemic period was determined, and medical deprivation rate (MDR) was calculated. Results: The prepandemic period of our patients with thyroid disease (n = 594), calcium-bone metabolism disorder (n = 130), adrenal disease (n = 85), pituitary disease, and NET (n = 46) had MDRs of 85%, 56%, 81%, and 89%, respectively. For each subgroup of patients, the lowest MDR (67%) was in medullary thyroid carcinoma, the highest MDR (89%) was in differentiated thyroid carcinoma; the lowest MDR (6%) was in osteoporosis, the highest MDR (100%) was in the active Paget's disease; the lowest MDR (0%) was in primary adrenocortical insufficiency, the highest MDR (100%) was in hyperfunctional adrenal adenomas; the lowest MDR (81%) was in pituitary nonfunctional adenomas, and the highest MDR (100%) was in Cushing's disease, active prolactinoma, TSHoma, and NET, respectively. Conclusion: This study showed that not only those who had COVID-19 but also those who had medical deprivation due to their current endocrinological disease were not to be underestimated during the pandemic period.

Papiledema bilateral por síndrome do pseudotumor cerebral em paciente com achado fortuito de microadenoma hipofisário / Bilateral papilledema by cerebral pseudotumor syndrome in a patient with a fortuitous finding of pituitary microadenoma

RESUMO O presente relato descreve um raro caso de papiledema bilateral decorrente da síndrome do pseudotumor cerebral relacionado com achado de microadenoma hipofisário. Relatamos um caso de paciente do sexo feminino, 21 anos, referindo baixa acuidade visual para longe, associada à cefaleia de início há 2 meses. Ao exame oftalmológico, a fundoscopia mostrou presença de papiledema bilateral significativo. A ressonância magnética de encéfalo evidenciou imagem nodular na hipófise, medindo 7 mm, sem qualquer evidência de compressão intracraniana, insuficiente para causar os sintomas do quadro clínico. Após diagnóstico de síndrome do pseudotumor cerebral, instituiu-se tratamento clínico com acetazolamida e orientou-se perda de peso, com evolução satisfatória. A descrição de ambas as patologias presentes de forma mútua foi citada apenas uma vez durante extensa revisão da literatura. Dessa forma, chamamos a atenção para essa ocorrência incomum, enfatizando as características de ambas as patologias, a fim de facilitar o diagnóstico diferencial, bem como elucidar a melhor abordagem terapêutica. Ressaltamos que o achado de pequenos adenomas hipofisários não deve confundir o diagnóstico etiológico em pacientes com queixas visuais e papiledema bilateral.

ABSTRACT The present report describes a rare case of bilateral papilledema due to cerebral pseudotumor syndrome (CPT) related to an occasional finding of pituitary microadenoma. We report the case of a 21-year-old female patient presenting low far visual acuity, associated with headache beginning 2 months ago. On ophthalmological examination, fundoscopy showed significant bilateral papilledema. Magnetic resonance imaging of the brain showed symmetrical and normal-sized ventricles, besides a nodular imaging in the pituitary, measuring 7 mm, without any evidence of intracranial compression, insufficient to cause the symptoms of the clinical presentation. After the diagnosis of cerebral pseudotumor syndrome, clinical treatment with acetazolamide was instituted and weight loss was advised, with satisfactory evolution. The description of both pathologies mutually present was mentioned only once during extensive literature review. Thus, we call attention to this unusual occurrence, emphasizing the characteristics of both pathologies in order to facilitate the differential diagnosis, as well as to elucidate the best therapeutic approach. We emphasize that the finding of small pituitary adenomas should not confuse the etiological diagnosis in patients with visual complaints and bilateral papilledema.

La meningoencefalitis bacteriana que era en realidad una apoplejía hipofisaria

Introducción: La apoplejía hipofisaria es un síndrome que se produce como consecuencia de una lesión isquémica o hemorrágica en la glándula pituitaria dando lugar a un déficit de hormonas hipofisarias. Se manifiesta en forma de deterioro neurológico con cefalea en trueno como síntoma prínceps, siendo la irritación meníngea una manifestación infrecuente. Métodos: Presentamos el caso de una mujer de 53 años con antecedente de madroadenoma productor de prolactina que comienza con cefalea, náuseas y deterioro de nivel de consciencia. Se detecta un hipopituitarismo incompleto con nivel de cortisol normal. El líquido cefalorraquídeo (LCR) es consistente con una pleocitosis aséptica sin respuesta a terapias antibióticas. Asocia paresia oculomotora y una RM craneal revela sangrado en el adenoma hipofisario con compromiso de seno cavernoso. Resultados: la sospecha inicial es una meningoencefalitis bacteriana por la fiebre, estupor y LCR con pleocitosis, si bien no se identifica microorganismo y no hay respuesta a antibióticos. El LCR de la apoplejía muestra una pleocitosis aséptica por irritación meníngea del espacio subaracnoideo por el sangrado y la necrosis de la glándula. El hipopituitarismo puede ser parcial o completo, siendo más frecuente el déficit selectivo. Especial atención merece el déficit de ACTH por la morbimortalidad que conlleva el fallo adrenal. La oftalmoparesia traduce implicación de seno cavernoso por incremento en la presión selar. Conclusiones: Destacamos la importancia de tener una sospecha diagnóstica de apoplejía ante un cuadro neurológico agudo para dirigir las investigaciones pertinentes con determinación hormonal y así iniciar una terapia sustitutiva temprana y una actitud neuroquirúrgica en caso de ser necesaria; precisando un manejo multidisciplinar.

Introduction: Pituitary apoplexy is a syndrome that occurs as a result of an ischemic or hemorrhagic lesion in the pituitary gland, leading to a deficiency of pituitary hormones. It manifests in the form of neurological deterioration with thunderclap headache as the main symptom, with meningeal irritation being an infrequent manifestation. Methods: We present the case of a 53-year-old woman with a history of prolactin-producing madroadenoma that began with headache, nausea and impaired level of consciousness. Incomplete hypopituitarism with normal cortisol level is detected. Cerebrospinal fluid (CSF) is consistent with an aseptic pleocytosis unresponsive to antibiotic therapy. It is associated with oculomotor paresis and a cranial MRI reveals bleeding in the pituitary adenoma with involvement of the cavernous sinus. Results: the initial suspicion is bacterial meningoencephalitis due to fever, stupor and CSF with pleocytosis, although no microorganism is identified and there is no response to antibiotics. CSF from stroke shows aseptic pleocytosis due to meningeal irritation of the subarachnoid space from bleeding and necrosis of the gland. Hypopituitarism can be partial or complete, selective deficiency being more frequent. ACTH deficiency deserves special attention due to the morbidity and mortality that adrenal failure entails. Ophthalmoparesis translates involvement of the cavernous sinus due to an increase in sellar pressure. Conclusions: We emphasize the importance of having a suspected diagnosis of apoplexy in case of an acute neurological condition, to direct the pertinent investigations with hormonal determination and thus initiate early replacement therapy and a neurosurgical approach if necessary; requiring a multidisciplinary management.

Long-term Recovery Patterns of Olfactory Function after Trans-sphenoidal Approach with Nasoseptal Flap Elevation

Abstract Introduction Nasoseptal flap is widely used in reconstruction of the skull base to prevent cerebrospinal fluid leakage after surgery for skull base lesions. There has been a debate on whether more severe olfactory dysfunction occurs after nasoseptal flap elevation than the conventional trans-sphenoidal approach. Objective To compare the long-term recovery patterns associated with nasoseptal flap and the conventional trans-sphenoidal approach. Methods The subjects were divided into the conventional trans-sphenoidal approach group and the nasoseptal flap elevation group. We followed up self-reported olfactory score using the visual analogue scale and threshold discrimination identification (TDI) score of the Korean Version of the Sniffin Stick test II for 12 months, with olfactory training. Results The study included 31 patients who underwent the trans-sphenoidal approach. Compared with preoperative status, the mean visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group recovered 2 months postoperatively, while in the nasoseptal flap elevation group the visual analogue scale and TDI scores recovered 6 months and 3 months after surgery, respectively. Twelve months after surgery, the visual analogue scale and TDI scores in the conventional trans-sphenoidal approach group were 9.3 ± 0.5 and 28.5 ± 4.3, while those from the nasoseptal flap elevation group were 8.9 ± 1.5 and 27.2 ± 4.7 (p = 0.326; 0.473). Only one of the patients in the nasoseptal flap elevation group had permanent olfactory dysfunction. Conclusion The olfactory function recovered more gradually in the nasoseptal flap elevation group than in the conventional trans-sphenoidal approach group, but there was no difference between the two groups after 6 months.

Metastatic diffuse follicular variant papillary thyroid cancer without cervical lymph node metastasis presenting with symptoms related to hypopituitarism

ABSTRACT In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.

Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice / 解剖学报

Objective To explore the effect of melatonin ( MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases ( PI3K)/protein kinase B ( Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the frypothalamus. Methods Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1 mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone (LH)were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in frypothalamus were detected by Real-time PCR and Western blotting. Results Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time ( P < 0. 05 ) , decreased significantly ovarian and uterine volume and index (P<0. 05) , decreased significantly serum LH levels (P<0. 05) , and decreased significantly mRNA and protein expression levels of the frypothalamic PI3K/Akt/mTOR pathway (P<0. 05). Conclusion Melatonin delays puberty initiation in mice by a mechanism that ma)' be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway.

Research progress on effects of intergenerational transmission on allergic disease susceptibility in offspring / 中国药理学通报

Allergic diseases are diseases caused by abnormal immune responses to antigens. Recently the prevalence of allergic diseases in children is on the rise, which has become one of the urgent public health problems to date. Recent clinical data and research show that the susceptibility of allergic diseases in offspring is inextricably associated with intergenerational transmission factors. Some unfavorable factors suffered by mothers before or during pregnancy may increase the allergic disease susceptibility in offspring. Therefore, it is of great significance to identify early risk factors (mother's generation) for the prevention of allergic diseases in children. At present, under the background of intergenerational transmission, some progress has been made in the research on the susceptibility of allergic diseases in offspring, and some researches have elucidated the potential molecular biological mechanisms. The current review summarizes the effects of maternal pregestational and prenatal unfavorable factors on the susceptibility of allergic diseases in offspring.