Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from patients with severe COVID-19.

Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of proinflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Proinflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of patients with severe COVID-19 might affect gestational health, particularly concerning umbilical cord function. This study tested the hypothesis that IL-6 present in the circulation of women with severe COVID-19 causes umbilical cord artery dysfunction by increasing ROS generation and activating redox-sensitive proteins. Umbilical cord arteries were incubated with serum from healthy women and women with severe COVID-19. Vascular function was assessed using concentration-effect curves to serotonin in the presence or absence of pharmacological agents, such as tocilizumab (antibody against the IL-6 receptor), tiron (ROS scavenger), ML171 (Nox1 inhibitor), and Y27632 (Rho kinase inhibitor). ROS generation was assessed by the dihydroethidine probe and Rho kinase activity by an enzymatic assay. Umbilical arteries exposed to serum from women with severe COVID-19 were hyperreactive to serotonin. This effect was abolished in the presence of tocilizumab, tiron, ML171, and Y27632. In addition, serum from women with severe COVID-19 increased Nox1-dependent ROS generation and Rho kinase activity. Increased Rho kinase activity was abolished by tocilizumab and tiron. Serum cytokines in women with severe COVID-19 promote umbilical artery dysfunction. IL-6 is key to Nox-linked vascular oxidative stress and activation of the Rho kinase pathway.

Health-related Quality of Life in Acromegaly Patients: Results from Generic and Disease-specific Questionnaires.

INTRODUCTION: Acromegaly is associated with high morbidity, but still controversial impact on the overall quality of life (QoL). MATERIAL AND METHODS: We evaluated QoL using a generic (SF-36) and a disease-specific questionnaire (AcroQoL) in an acromegalic cohort. RESULTS: Sixty-nine patients answered the questionnaires and had their records reviewed. In the SF-36 questionnaire, except for the Social Aspects domain, all others revealed a reduction in scores from 9.7 to 38.9%, when compared to the non-acromegalics. The cure was positively correlated with mental health (P = 0.023) and drug control was correlated with mental health (P = 0.023) and functional capacity (P = 0.013). In the AcroQoL questionnaire, the mean scores ranged from 54.7% to 72.8%. The use of antidepressants correlated with lower scores on the total AcroQoL (P = 0.039) and physical complaints (P = 0.003). The growth hormone value at diagnosis showed an inverse correlation with the total AcroQoL score (P = 0.014), Appearance Issues subscale (P = 0.081), and Personal Relations (P = 0.002). IGF-1 values at diagnosis and at the last visit showed no statistical correlation with any of the questionnaires. CONCLUSION: The finding of a reduction in QoL scores with both SF-36 and AcroQoL allows us to suggest this evaluation as part of the initial assessment and follow-up in acromegaly, to act globally on the individual's health condition.

Assessment of Anthropometric and Physical Health Indicators before and after Pituitary Surgery in Patients with Nonfunctioning Pituitary Adenomas, Acromegaly, and Cushing Disease.

INTRODUCTION: Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. METHODS: Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2 max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. RESULTS: The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2 max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. CONCLUSIONS: These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.

Precocious puberty due to human chorionic gonadotropin secreting germinoma.

This study aims to report a rare case of precocious puberty (PP) due to a human chorionic gonadotropin (hCG)-producing germinoma located in the suprasellar region. A 10-year-old male patient presented with sexual precocity, headache, drowsiness, loss of appetite, and papilledema. Significant acceleration of bone age in relation to chronological age, high serum total testosterone levels, and hypopituitarism (unresponsiveness to stimulation test) were observed. Magnetic resonance imaging (MRI) of the brain showed a large suprasellar tumor and triventricular dilatation. High hCG levels were found in both blood and cerebrospinal fluid. Hormone replacement therapy and transcranial surgery associated with radiotherapy were performed, with complete regression of sexual characteristics and normal laboratory tests post-operatively. Clinical and laboratory findings, in addition to MRI scans, led to the diagnosis of an hCG-producing tumor and PP, which represents a rare report in the literature.

Acquired factor VIII and von Willebrand factor (aFVIII/VWF) deficiency and hypothyroidism in a case with hypopituitarism.

This article reports a female who presented with bleeding, acquired factor VIII and von Willebrand factor (aFVIII-VWF) deficiency, and central deficiency in the thyroid and adrenal axis (Sheehan's syndrome). After starting hormone replacement therapy, relief of bleeding manifestations was associated with correction of both FVIII and VWF to normal. This report draws attention to a rare association between the acquired form of von Willebrand disease and hypothyroidism of central origin.

Diastolic function study with conventional and pulsed tissue Doppler echocardiography imaging in acromegalic patients.

UNLABELLED: Acromegaly is associated with myocardial hypertrophy and it can progress to diastolic and systolic dysfunction. PURPOSE: To evaluate diastolic function in acromegalic patients through conventional echocardiography (CD) and tissue Doppler imaging (TDI). METHODS: Seventeen acromegalic patients were submitted to CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in mitral, septal, and tricuspid regions. RESULTS: In comparison with controls the means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in 41% and 49% of acromegalics by DC and TDI, respectively, with no statistical difference among the two methods. An inverse linear correlation was shown between mitral E/A ratio and acromegalic age (r =-0.7). CONCLUSION: In this study, DC and TDI were equally effective in demonstrating diastolic dysfunction, a common finding in acromegalic patients.

Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker.

Angiogenesis, a fundamental process for the development and growth of a tumor, is less expressive in adenomas than in the normal pituitary tissue. There is controversy about the behavior of angiogenesis as a function of hormonal secretion or other characteristics of pituitary tumors. Endoglin (CD105) is a proliferation-associated antigen on endothelial cells, as well as an endothelial progenitor cell marker. We used the anti-endoglin antibody, a glycoprotein expressed in endothelial cells and conjunctive tissue, as a new marker particularly associated with neovascularization, in order to determine microvascular density (MVD) in pituitary adenomas. There were 77 samples, 31 males and 46 females, carriers of micro- (n = 24) or macroadenomas (n = 53). No significant difference was found in MVD concerning the variables of age, clinical presentation, and immunohistochemical phenotype or tumor size. MVD in males (median 5.4) was significantly higher (P = 0.001) than in females (median 3.0). Cell proliferation, as evaluated by the MIB-1 antibody (a cellular proliferation index [Ki-67 antigen], which is present in all stages of the cellular cycle except for the resting cells), ranged from 0% to 19.58%. No correlation was found between MIB-1 and MVD. It is possible to infer that the lower MVD found in pituitary adenomas in females reflects an inhibitory estrogen action on TGF-beta1, a protein involved in vascular remodeling. Because of its role as a TGF receptor ligand, endoglin proved to be sensitive in detecting this gender difference in pituitary tumor angiogenesis.

Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication.

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.

Immunohistochemical detection of estrogen receptor alpha in pituitary adenomas and its correlation with cellular replication.

With the aim of evaluating the relationship between pituitary tumorigenesis and the presence of estrogen receptor-alpha (ERalpha) by immunohistochemistry (IH) and their relevance to patients' clinical presentation, hormonal phenotypes of adenomas, preoperative neuroimaging findings, and the index of cellular replication MIB-1, a study was conducted with material from 91 women and 67 men with pituitary adenomas. The patients had acromegaly (29.7%), Cushing's disease (14.6%), hyperprolactinemic syndrome (20.9%), and clinically nonfunctioning tumors (34.8%). Of the patients, 14.6% had microadenomas, 52.5% had macroadenomas with or without suprasellar growth, 28.5% had invasive macroadenomas and in 4.4% the adenoma was not visualized. IH showed that 43 were positive for growth hormone (GH), 16 for corticotropin (ACTH), 18 for prolactin (PRL), 18 for PRL+GH, 6 for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), 15 had a plurihormonal reaction, and 42 had nonfunctioning adenomas. The presence of ERalpha was positive in 9/158 adenomas with a median value for the percentage of labeled cells of 42.89%, and in 6/16 controls (autopsy samples) with a median value for the percentage of labeled cells of 0.024%. ERalpha was significantly more prevalent in controls than in patients with adenomas (37.5 versus 5.7%; p = 0.001); however, the mean ERalpha concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERalpha was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERalpha-positive adenomas, ERalpha values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERalpha-positive and -negative adenomas, nor did the correlation between ERalpha values and the MIB-1 index attain significance in the total sample, even when only ERalpha-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERalpha exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.

O papel da ecografia pelvica no diagnostico diferencial das precocidades sexuais / The role of pelvic ultrasonography in the diagnosis of sexual precocities

Neste estudo foram avaliadas prospectivamente 21 meninas com caracteristicas sexuais secundarias manifestadas antes dos 8 anos de idade. A investigacao clinica, hormonal, radiologica e ecografica permitiu diagnosticar 7 casos de puberdade precoce verdadeira, 9 de telarca precoce, 4 de pubarca precoce e 1 de precocidade sexual transitoria. A avaliacao ultra-sonografica do utero e ovarios foi compativel com os demais achados nas formas completa e incompleta de puberdade precoce; sugeriu a presenca de uma variante de telarca precoce ("telarca variante") em 2 casos; e confirmou, atraves do acompanhamento, o diagnostico de puberdade transitoria, em uma paciente com cisto ovariano autonomo. Esses achados corroboram os da literatura, em relacao a importancia da ecografia pelvica no manejo de criancas com precocidade sexual

Acantosis nigricans: estudo retrospectivo em pacientes endocrinológicos / Acanthosis nigricans: retrospective study in endocrinologic patients

A Acalantosis Nigricans, uma lesäo cutânea que pode ser um marcador de outras patologias, foi avaliada numa populaçäo de 1245 pacientes endocrinológicos na qual mostoru uma prevalência de 4,5 por cento. Dos casos diagnosticados, 66,6 por cento das mulheres, 57,1 por cento dos homens e a totalidade das crianças, eram obseos. Dentre as manifestaçöes de hiperandrogenismo, a acne esteve presente em 61,2 por cento e o hirsutismo em 48,8 por cento das mulheres. O andrógeno mais frequentemente elevado foi a testosterona, seguido pelo sulfato de dehidroepiandrosterona. A expressäo clínica da Acantosis Nigricans foi, na maior parte das vezes, discreta ou moderada. Näo foi observada correlaçäo entre a intensidade de apresentaçäo clínica e histológica da lesäo. Neste trabalho discute-se a importância da detecçäo desta lesäo e o acompanhamento de seus portadores