Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report.

BACKGROUND: Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical. CASE PRESENTATION: We present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. CONCLUSION: The purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Risk factors for hypocalcemia after total thyroidectomy.

BACKGROUND: Hypocalcemia is a common complication of total thyroidectomy; transient hypocalcemia has been reported in up to 68% of the patients. MATERIALS AND METHODS: Chart review of all patients undergoing total thyroidectomy from 2016 to 2020. Clinical, biochemical, and pathological information was registered. We sought correlations between the different variables and the occurrence of post-operative hypocalcemia. This is a retrospective study carried out at a tertiary care teaching hospital. OBJECTIVES: The aim of the study was to ascertain the incidence of hypocalcemia after thyroidectomy and to establish potential clinical and pathological risk factors for its development. RESULTS: Three hundred and thirty-seven patients were included in this study (78% female), with a median age of 47 years. The majority (75%) harbored thyroid neoplasms. Post-operative hypocalcemia developed in 43 patients (12.7%). On bivariate analysis, the most significant risk factor was an intraoperative injury of the parathyroid glands (OR = 2.49, 95% CI = 1.11-5.59), followed by a surgical time > 2.5 h (OR = 2.0, 95% CI = 1.03-4.19), concomitant lymph node dissection (OR = 2.45, 95% CI = 1.2-4.9), and placement of drains (OR = 2.40, 95% CI = 1.19-4.87). Only parathyroid injury remained statistically significant on multivariable analysis. CONCLUSIONS: The most significant risk factor for the development of post-operative hypocalcemia after thyroidectomy is injury of the parathyroid glands, which is usually noticed by the surgeon.

INTRODUCCIÓN: La hipocalcemia es una complicación común después de una tiroidectomía; la hipocalcemia transitoria ha sido reportada hasta en el 68% de los pacientes posoperados. MATERIALS Y MÉTODOS: Revisión de expedientes de pacientes a los cuales se les realizo una tiroidectomía total entre el 2016 y 2020. La información clínica, bioquímica y patológica fue recopilada. Se busco una correlación entre las variables y el desarrollo de hipocalcemia. Es un estudio retrospectivo en un hospital escuela de atención terciaria. OBJETIVOS: Determinar la incidencia de hipocalcemia pos-tiroidectomía y establecer posibles factores de riesgo clínicos y patológicos para desarrollarlo. RESULTADOS: Se incluyeron 337 pacientes en este estudio (78% mujeres), con edad media de 47 años. La mayoría (75%) presentaron neoplasias tiroideas. Cuarenta y tres pacientes desarrollaron hipocalcemia (12.7%). En el análisis bivariado el factor de riesgo mas importante fue la lesión de paratiroides (RM = 2.49, IC95% = 1.11-5.59), seguido por un tiempo quirúrgico > 2.5 horas (RM = 2.0, IC 95% = 1.03­4.19), disección linfática (RM = 2.45, IC95% = 1.2-4.9) y la colocación de drenajes (RM = 2.40, IC95% = 1.19-4.87). Únicamente la lesión de paratiroides mantuvo significancia en el análisis multivariado. CONCLUSIONES: La lesión de paratiroides es el factor de riesgo mas grande para desarrollar hipocalcemia y generalmente es identificado por el cirujano.

[Proinflammatory cytokines in polycystic ovarian syndrome]. / Citocinas proinflamatorias en el síndrome de ovario poliquístico.

During folliculogenesis, different proinflammatory cytokines have a physiological role in the weakening of the follicle wall and an eventual rupture at ovulation. Chronic inflammation is closely related to endothelial dysfunction, cardiovascular disease, coronary artery disease, and polycystic ovary syndrome. Polycystic ovary syndrome is characterized by androgen excess and ovarian dysfunction. Emerging evidence suggests that the long-term metabolic effects and cardiovascular complications observed in this syndrome may be related to the presence of a mild chronic inflammatory state. It is unclear whether androgen excess promotes an inflammatory state or, conversely, whether inflammatory molecules stimulate androgen production. Early detection of risk factors will help in the prevention and control of cardiovascular diseases, since the metabolic alterations associated with this syndrome can predispose to worse cardiovascular health outcomes.

Diferentes citocinas proinflamatorias producidas durante la foliculogénesis tienen un rol fisiológico en el debilitamiento de la pared del folículo y la eventual ruptura en la ovulación. La inflamación crónica está relacionada de forma muy cercana con disfunción endotelial, enfermedad cardiovascular, enfermedad arterial coronaria y con el síndrome de ovario poliquístico. El síndrome de ovario poliquístico se caracteriza por un exceso de andrógenos y disfunción ovárica. Evidencia emergente sugiere que los efectos metabólicos a largo plazo y las complicaciones cardiovasculares observadas en este síndrome pueden estar relacionadas con la presencia de un estado inflamatorio crónico leve. Es poco claro si el exceso de andrógenos promueve un estado inflamatorio o, contrariamente, si las moléculas inflamatorias estimulan la producción de andrógenos. La detección temprana de los factores de riesgo ayudará en la prevención y el control de las enfermedades cardiovasculares, dado que las alteraciones metabólicas asociadas con este síndrome pueden predisponer a peores resultados de salud cardiovascular.

Insulinoma after sleeve gastrectomy: A case report.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, and its prevalence has increased from 5% to 37% since 2008. One common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic state. While rare, insulinomas can cause this state, where symptoms are more common in the fasting state; thus, evaluation of insulin secretion is needed. Until now, there have been no reports of insulinoma after LSG. CASE SUMMARY: We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/dL, which are compatible with Whipple's triad. Initially, dumping syndrome was suspected, but after a second low fasting plasma glucose was documented, a 72-h fasting test was performed that tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. After laparoscopic enucleation of the insulinoma, the symptoms and hypoglycemia disappeared. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. CONCLUSION: Insulinoma after LSG is a rare condition, and clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Metformin in Differentiated Thyroid Cancer: Molecular Pathways and Its Clinical Implications.

Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis. Aside being the first-line therapy for Type 2 Diabetes (T2D), many pleiotropic effects have been discovered in recent years, such as its capacity to reduce cancer risk and tumorigenesis. Although widely studied, the effect of metformin on thyroid cancer remains controversial. Potential mechanisms for its growth inhibitory effects have been elucidated in various preclinical studies that involved pathways related to adenosine mono-phosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), mitochondrial glycerophosphate dehydrogenase (mGPDH), and the nuclear factor κB (NF-κB). Hyperinsulinemia increases cell glucose uptake and oxidative stress, and promotes thyroid cell growth, leading to hyperproliferation, carcinogenesis, and the development of malignant tumors. Furthermore, it has also been related to thyroid nodules size in nodular disease, as well as tumoral size in patients with thyroid cancer. Several clinical studies concluded that metformin might have an important role as an adjuvant therapy to reduce the growth of benign and malignant thyroid neoplasms. This suggests that metformin might be useful for patients with differentiated or poorly differentiated thyroid cancer and metabolic diseases such as insulin resistance or diabetes.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Are overweight and obesity risk factors for invasive mechanical ventilation in severe coronavirus disease 2019 pneumonia?

ABSTRACT Objective: Describe the demographic, clinical, and biochemical characteristics of overweight or obese people with severe COVID-19 pneumonia and evaluate its association with mechanical ventilation requirements in a Mexican cohort. Subjects and methods: Data were obtained from medical electronic records. Patients were divided in three groups according to the World Health Organization (WHO) classification of body mass index (BMI): lean, overweight and obese. Baseline characteristics and clinical course were compared among these 3 groups. Results: The study included a total of 355 patients with confirmed COVID-19 diagnoses. Patients with obesity and overweigh, according to the WHO classification, had no significantly increased risk of requiring intubation and invasive mechanical ventilation (IMV) compared to lean subjects, with an odds ratio (OR) of 1.82 (95% CI, 0.94-3.53). A post hoc and multivariate analysis using a BMI > 35 kg/m2 to define obesity revealed that subjects above this cut off had as significantly increased risk of requiring IMV after with an OR of 2.86 (95% CI, 1.09-7.05). Conclusion: We found no higher risk of requiring IMV in patients with overweight or obesity while using conventional BMI cutoffs. According to our sensitivity analyses, the risk of IMV increases in patients with a BMI over 35 kg/m2.

Shear-wave elastography as a tool in the assessment of thyroid nodules.

INTRODUCTION: Shear-wave elastography (SWE) has been shown to be predictive of malignancy in thyroid nodules. OBJECTIVE: To determine, by SWE, the stiffness cutoff point with the highest specificity and sensitivity to detect thyroid nodules that require surgery. METHODS: Cross-sectional study of ultrasonographically-evaluated patients for thyroid nodules over a period of three years; the TI-RADS classification system was used, and nodule stiffness was determined by SWE. Histopathological specimens were classified using the Bethesda system, and the stiffness cutoff point with the highest specificity and sensitivity was obtained using ROC curves. RESULTS: Forty-one percent of the nodules were classified as TI-RADS 5, and 59 %, as TI-RADS 1-4. In TI-RADS 5 nodules, median stiffness of those in Bethesda system IV-VI categories was 35.9 kPa; in nodules with TI-RADS 1-4, 21.6 kPa. In TI-RADS 5 nodules, a cutoff point > 32.5 kPa had a specificity of 75 % and sensitivity of 57 % to detect those requiring surgery; in TI-RADS 1 to 4 nodules, a cutoff point of 21.5 kPa had a specificity of 63 % and sensitivity of 51 %. CONCLUSION: SWE-determined stiffness is useful to detect nodules that require surgical evaluation.

INTRODUCCIÓN: La elastografía por ondas de corte (SWE) ha demostrado ser predictiva de malignidad en nódulos tiroideos. OBJETIVO: Determinar mediante SWE, el punto de corte de la rigidez con mayor especificidad y sensibilidad para detectar nódulos tiroideos que requieren cirugía. MÉTODOS: Estudio transversal de pacientes con nódulos tiroideos evaluados ultrasonográficamente en un periodo de tres años; se empleó la clasificación TI-RADS y mediante SWE se determinó la rigidez de los nódulos. Con el sistema Bethesda se clasificaron las muestras histopatológicas y mediante curva ROC se obtuvo el punto de corte de la rigidez con mayor especificidad y sensibilidad. RESULTADOS: 41 % de los nódulos fue TI-RADS 5 y 59 %, TI-RADS 1-4. En los TI-RADS 5, la mediana de rigidez de los nódulos con categoría IV-VI del sistema Bethesda fue de 35.9 kPa y en los nódulos con TI-RADS 1-4, 21.6 kPa. En los nódulos TI-RADS 5, la rigidez > 32.5 kPa tuvo especificidad de 75 % y sensibilidad de 57 % para detectar los que requieren cirugía; en los TI-RADS 1-4, el valor de corte de 21.5 kPa tuvo especificidad de 63 % y sensibilidad de 51 %. CONCLUSIÓN: La rigidez determinada por SWE es útil para detectar nódulos que requerirán exploración quirúrgica.

Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery.

INTRODUCTION: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). OBJECTIVE: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. METHODS: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. RESULTS: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. CONCLUSION: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS.

INTRODUCCIÓN: En México no se han utilizado los instrumentos Shorth Form 36 Items (SF-36) ni Baryatric Assesment Reporting Outcomes System (BAROS) para evaluar la calidad de vida (CV) antes y después de la cirugía bariátrica (CB). OBJETIVO: Describir los cambios en la CV con los cuestionarios SF-36 y BAROS, en pacientes con obesidad severa antes y después de la CB. MÉTODOS: Se recolectaron los datos clínicos y antropométricos de pacientes sometidos a cirugía baríatrica entre 2015 y 2016. Se consideró con significación estadística una p < 0.05. RESULTADOS: Se analizaron 230 pacientes, 98 y 132 antes y después de la CB; la mayoría fue del sexo femenino (81 %). El índice de masa corporal inicial fue de 48 kg/m2 (44-53). La CV medida con el SF-36 demostró un incremento en la puntuación del componente físico de 43 a 54.2 (p < 0.001) y en el componente mental, de 53.3 a 56.6 después de la CB. Con BAROS, en 98.5 % se registraron resultados buenos a excelentes en la CV en los primeros tres meses. CONCLUSIÓN: Al ser medida con los cuestionarios SF-36 y BAROS se definió que la CV de los pacientes mexicanos con obesidad severa mejora después de la CB.

Evaluación de la calidad de vida en pacientes mexicanos con obesidad severa antes y después de cirugía bariátrica / Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery

Resumen Introducción: En México no se han utilizado los instrumentos Shorth Form 36 Items (SF-36) ni Baryatric Assesment Reporting Outcomes System (BAROS) para evaluar la calidad de vida (CV) antes y después de la cirugía bariátrica (CB). Objetivo: Describir los cambios en la CV con los cuestionarios SF-36 y BAROS, en pacientes con obesidad severa antes y después de la CB. Métodos: Se recolectaron los datos clínicos y antropométricos de pacientes sometidos a cirugía baríatrica entre 2015 y 2016. Se consideró con significación estadística una p < 0.05. Resultados: Se analizaron 230 pacientes, 98 y 132 antes y después de la CB; la mayoría fue del sexo femenino (81 %). El índice de masa corporal inicial fue de 48 kg/m2 (44-53). La CV medida con el SF-36 demostró un incremento en la puntuación del componente físico de 43 a 54.2 (p < 0.001) y en el componente mental, de 53.3 a 56.6 después de la CB. Con BAROS, en 98.5 % se registraron resultados buenos a excelentes en la CV en los primeros tres meses. Conclusión: Al ser medida con los cuestionarios SF-36 y BAROS se definió que la CV de los pacientes mexicanos con obesidad severa mejora después de la CB.

Abstract Introduction: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). Objective: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. Methods: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. Results: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. Conclusion: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS.

Elastografía por ondas de corte como herramienta en la evaluación de los nódulos tiroideos / Shear-wave elastography as a tool in the assessment of thyroid nodules

Resumen Introducción: La elastografía por ondas de corte (SWE) ha demostrado ser predictiva de malignidad en nódulos tiroideos. Objetivo: Determinar mediante SWE, el punto de corte de la rigidez con mayor especificidad y sensibilidad para detectar nódulos tiroideos que requieren cirugía. Métodos: Estudio transversal de pacientes con nódulos tiroideos evaluados ultrasonográficamente en un periodo de tres años; se empleó la clasificación TI-RADS y mediante SWE se determinó la rigidez de los nódulos. Con el sistema Bethesda se clasificaron las muestras histopatológicas y mediante curva ROC se obtuvo el punto de corte de la rigidez con mayor especificidad y sensibilidad. Resultados: 41 % de los nódulos fue TI-RADS 5 y 59 %, TI-RADS 1-4. En los TI-RADS 5, la mediana de rigidez de los nódulos con categoría IV-VI del sistema Bethesda fue de 35.9 kPa y en los nódulos con TI-RADS 1-4, 21.6 kPa. En los nódulos TI-RADS 5, la rigidez > 32.5 kPa tuvo especificidad de 75 % y sensibilidad de 57 % para detectar los que requieren cirugía; en los TI-RADS 1-4, el valor de corte de 21.5 kPa tuvo especificidad de 63 % y sensibilidad de 51 %. Conclusión: La rigidez determinada por SWE es útil para detectar nódulos que requerirán exploración quirúrgica.

Abstract Introduction: Shear-wave elastography (SWE) has been shown to be predictive of malignancy in thyroid nodules. Objective: To determine, by SWE, the stiffness cutoff point with the highest specificity and sensitivity to detect thyroid nodules that require surgery. Methods: Cross-sectional study of ultrasonographically-evaluated patients for thyroid nodules over a period of three years; the TI-RADS classification system was used, and nodule stiffness was determined by SWE. Histopathological specimens were classified using the Bethesda system, and the stiffness cutoff point with the highest specificity and sensitivity was obtained using ROC curves. Results: Forty-one percent of the nodules were classified as TI-RADS 5, and 59 %, as TI-RADS 1-4. In TI-RADS 5 nodules, median stiffness of those in Bethesda system IV-VI categories was 35.9 kPa; in nodules with TI-RADS 1-4, 21.6 kPa. In TI-RADS 5 nodules, a cutoff point > 32.5 kPa had a specificity of 75 % and sensitivity of 57 % to detect those requiring surgery; in TI-RADS 1 to 4 nodules, a cutoff point of 21.5 kPa had a specificity of 63 % and sensitivity of 51 %. Conclusion: SWE-determined stiffness is useful to detect nodules that require surgical evaluation.

Familial hypercholesterolemia in Mexico: Initial insights from the national registry.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

Utility of the STOP-Bang and Epworth scales and the neck-to-height ratio to detect severe obstructive apnea-hypopnea syndrome in severe obesity.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is present in 80% of patients evaluated for bariatric surgery (BS). Extensive evaluation is not widely available, but treatment is mandatory for severe cases. The Snore, Tiredness, Observed apneas and Pressure - Body mass index, Age, Neck circumference and Gender (STOP-Bang) and Epworth questionnaires and neck-to-height ratio (NHtR) are accessible clinical tools to screen for sleep and metabolic disturbances, but their utility to detect severe OSAHS in patients with severe obesity has not been determined. OBJECTIVES: To evaluate the cutoff point of those clinical tools that may predict severe OSAHS, confirmed by polysomnography in patients referred for BS. SETTING: Tertiary referral center in Mexico City. METHODS: We applied the STOP-Bang and Epworth questionnaires, evaluated anthropometric characteristics, and collected samples for arterial gasometry and metabolic parameters from 68 patients with severe obesity, who were then referred for polysomnography before their evaluation for BS. RESULTS: Of the 68 patients participating in the study, 67.7% were female, with a median age of 43 years (35-49 years) and a body mass index (BMI) of 45.5 kg/m2 (42.4-50.9 kg/m2; 28.3% had a BMI ≥ 50 kg/m2). A STOP-Bang cutoff >5 points had a sensitivity of 60% and specificity of 90% for detecting severe OSAHS (area under the curve [AUC] = .962); meanwhile, an NHtR >.25 had a sensitivity of 90% and specificity of 52.5% (AUC = .759). The Epworth scale score >11 points had a sensitivity of 57.1% and specificity of 83.3% (AUC = .802). CONCLUSION: Clinical data may be useful to detect severe sleep apnea in high-risk populations, allowing for rapid referral and better use of resources.

Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.

Transcriptome and methylome analysis reveals three cellular origins of pituitary tumors.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

An Update on Gastroenteropancreatic Neuroendocrine Neoplasms: From Mysteries to Paradigm Shifts.

Although neuroendocrine neoplasms (NEN) were once thought to be rare and mostly "benign" diseases, they are now being redefined in light of recently discovered molecular information. NENs constitute a spectrum of variably differentiated neoplasms, ranging from well-differentiated tumors with a protracted course over many years to very aggressive neuroendocrine carcinomas. Although the majority of NEN are non-functional lesions, some of these tumors, do produce a hormonal hypersecretion syndrome. Their reappraisal has led scientist to unveil previously unknown oncogenic pathways and connections that resulted in a new category in the International Classification of Diseases (ICD-11) and a revised version of the World Health Organization Classification (WHO 2018). Complex diseases like NEN require a multidisciplinary approach that includes the perspectives of endocrinologists, medical and surgical oncologists, radiation oncologists, imaging specialists and pathologists. There are currently virtually thousands of ongoing trials evaluating the efficacy and safety of several molecular targeted therapies. The purpose of this review was to critically evaluate recent information regarding the pathogenesis, diagnosis and treatment of NEN.

Molecular alterations in non-functioning pituitary adenomas.

BACKGROUND: Clinically non-functioning Pituitary Adenomas (NFPA) are among the most common neoplasms of the sellar region. They usually present with compressive symptoms such as headache and visual field defects and not infrequently, are found incidentally. NFPA are classified as gonadotropinomas, null cell adenomas, according to their immunohistochemical phenotype. The molecular alterations responsible for the development of these lesions are incompletely understood, and there is scarce information regarding the molecular alterations and markers. OBJECTIVE: We carried out an in-silico analysis aimed at identifying the molecular alterations in NFPA and to discover new molecular markers. METHODS: Twenty-three microarray libraries were analyzed. Fourteen correspond to NFPA and 9 to control tissue gland. They were analyzed using Partek Genomic Suite to identify differentially expressed genes and WebGestalt and Metascape to understand the meaning behind the gene lists. RESULTS: Pituitary adenomas showed a markedly different transcriptome compared to the non-tumoral gland, regardless of their putative immunophenotype. Genes related to calcium metabolism such as CACNA2D4, immune-related CXCR4, and stem cell-related KLF8 and PITX2 were altered. CONCLUSIONS: Differentially expressed calcium metabolism and immune-related genes in NFPA represent attractive molecular markers and potential therapeutic targets.