Genetic diagnosis in acromegaly and gigantism: From research to clinical practice.

It is usually considered that only 5% of all pituitary neuroendocrine tumours are due to inheritable causes. Since this estimate was reported, however, multiple genetic defects driving syndromic and nonsyndromic somatotrophinomas have been unveiled. This heterogeneous genetic background results in overlapping phenotypes of GH excess. Genetic tests should be part of the approach to patients with acromegaly and gigantism because they can refine the clinical diagnoses, opening the possibility to tailor the clinical conduct to each patient. Even more, genetic testing and clinical screening of at-risk individuals have a positive impact on disease outcomes, by allowing for the timely detection and treatment of somatotrophinomas at early stages. Future research should focus on determining the actual frequency of novel genetic drivers of somatotrophinomas in the general population, developing up-to-date disease-specific multi-gene panels for clinical use, and finding strategies to improve access to modern genetic testing worldwide.

Ectopic Hormonal Syndromes: Cushing's Syndrome and Acromegaly.

Ectopic hormone production may be present in neuroendocrine and non-endocrine neoplasms. Ectopic sources of growth hormone, adrenocorticotropin (ACTH), or their releasing factors are uncommon but clinically relevant. Ectopic ACTH tumors have been studied more than the rest, but there are still no comprehensive multidisciplinary guidelines that include all the pitfalls in the diagnosis and management of ectopic hormonal syndromes and the neoplasms associated with ectopic Cushing or acromegaly. The frequency of neuroendocrine neoplasms and other neoplasms with neuroendocrine differentiation has been increasing in recent decades. The review of the available data on these tumors, their classification, and improvements in diagnostic and therapeutic procedures is important to understand the relevance of ectopic Cushing's syndrome and acromegaly in clinical practice.

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.

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.

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.

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.

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.

Asociación de los índices neutrófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19 / Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality

Resumen Introducción: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. Objetivo: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. Método: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. Resultados: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. Conclusión: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Abstract Introduction: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. Objective: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. Method: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. Results: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002] with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. Conclusion: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19.

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.

Erratum to "From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells".

[This corrects the article DOI: 10.1155/2020/4768281.].

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.

High biochemical recurrence rate after withdrawal of cabergoline in prolactinomas: is it necessary to restart treatment?

PURPOSE: Treatment with dopamine agonists (DA) is highly effective in patients with prolactinomas. In selected patients, discontinuation of DA after several years of successful treatment is possible, however, hyperprolactinemia recurs in 60-80% of them. It is unclear what is the clinical significance of these recurrences and hence, whether or not reinitiation of therapy is necessary. OBJECTIVES: To evaluate the recurrence rate in prolactinoma patients after DA withdrawal and the necessity to restart treatment. METHODS: Patients with >2 years of treatment with cabergoline (CBG) who achieved normoprolactinemia and a > 50% reduction in tumor size were included. DA dose was down titrated until withdrawal. Basal tumor size, as well as PRL and gonadal steroid levels were recorded at diagnosis, at withdrawal of DA and every 3-6 months for 1-3 years. RESULTS: Fifty patients were included (38 women, 34 macroprolactinomas). After withdrawal, 34 (68%) presented recurrence of hyperprolactinemia. PRL levels <5 ng/mL at the time of withdrawal predicted remission (sensitivity 76%, specificity of 63%). CBG was restarted in eight patients (23%) because of the presence of hypogonadism. CBG was withheld in the remaining 26, based on the following arguments: (1) premenopausal women without biochemical hypogonadism, (54%); (2) asymptomatic men under 65 without biochemical hypogonadism (19%); (3) asymptomatic postmenopausal women (19%); (4) asymptomatic men over 65 (8%). After a median follow-up of 30 months, no increase in PRL levels or tumor growth was documented. CONCLUSIONS: Biochemical recurrence in prolactinomas is very frequent, however, in only a few of these patients reinitiation of DA is necessary.

From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells.

OBJECTIVE: To report the immunohistochemical and molecular evaluation of a patient with ectopic ACTH syndrome (EAS) from a MCAT which has single cells with features of both 96 medullary and cortical differentiation. Case Description and Methods. A 16-year-old woman presented with severe EAS and a large right MCAT composed of ACTH-secreting cells resembling pheochromocytoma and another lineage similar to adrenal carcinoma. Immunohistochemistry (IHC) showed positivity for medullary (ACTH, chromogranin A, synaptophysin, and PS-100) and epithelial components (inhibin, melan-A, and calretinin). Embryonic stem cell markers were evaluated using RT/PCR and immunofluorescence. After initial surgery, the tumor recurred shifting to rapidly progressive ACTH-independent liver metastasis. RESULTS: Histopathology and IHC revealed two distinct and intermingled cellular patterns, while some cells immunostained for both medullary and cortical markers. Demonstration of all stem cell biomarkers by RT/PCR and immunofluorescence was predominantly localized to the nucleus, whereas SOX2 immunoreactivity was evident in the cytoplasm as well. CONCLUSION: The expression of cancer stem cell biomarkers points towards the involvement of primitive embryonic cells as the origin of this neoplasm and maybe to the clinically aggressive and biochemically changing behavior.

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.

Current Approach of Functioning Head and Neck Paragangliomas: Case Report of a Young Patient with Multiple Asynchronous Tumors.

Introduction. Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla and from the extra-adrenal autonomic paraganglia, respectively. Only 1-3% of head and neck PGL (HNPGL) show elevated catecholamines, and at least 30% of Pheo and PGL (PCPG) are associated with genetic syndromes caused by germline mutations in tumor suppressor genes and proto-oncogenes. Clinical Case. A 33-year-old man with a past medical history of resection of an abdominal PGL at the age of eleven underwent a CT scan after a mild traumatic brain injury revealing an incidental brain tumor. The diagnosis of a functioning PGL was made, and further testing was undertaken with a PET-CT with 68Ga-DOTATATE, SPECT-CT 131-MIBG, and genetic testing. Discussion and Conclusion. The usual clinical presentation of functioning PCPG includes paroxistic hypertension, headache, and diaphoresis, sometimes with a suggestive family history in 30-40% of cases. Only 20% of PGL are located in head and neck, of which only 1-3% will show elevated catecholamines. Metastatic disease is present in up to 50% of cases, usually associated with a hereditary germline mutation. However, different phenotypes can be observed depending on such germline mutations. Genetic testing is important in patients with PCPG since 31% will present a germline mutation. In this particular patient, an SDHB gene mutation was revealed, which can drastically influence the follow-up plan and the genetic counsel offered. A multidisciplinary approach is mandatory for every patient presenting with PCPG.SDHB gene mutation was revealed, which can drastically influence the follow-up plan and the genetic counsel offered. A multidisciplinary approach is mandatory for every patient presenting with PCPG.

Efficacy of the treatment with dapagliflozin and metformin compared to metformin monotherapy for weight loss in patients with class III obesity: a randomized controlled trial.

BACKGROUND: Mexico has one of the highest prevalence rates of obesity worldwide. New pharmacological strategies that focus on people with class III obesity are required. Metformin and dapagliflozin are two drugs approved for the treatment of diabetes. Beyond its effects on glucose, metformin has been suggested by some studies to result in weight loss. Therapy with dapagliflozin is associated with a mild but sustained weight loss in patients with diabetes. The primary outcome of the study is to determine if the combined treatment with dapagliflozin and metformin is more effective than monotherapy with metformin for weight loss in patients with class III obesity and prediabetes or diabetes who are awaiting bariatric surgery (including those patients who do have surgery). We also aimed to assess the effect of this combined treatment on waist circumference, triglycerides, blood pressure, and inflammatory cytokines. METHODS: This randomized phase IV clinical trial will include patients with diabetes or prediabetes who are between the ages of 18 and 60 years and exhibit grade III obesity (defined as body mass index ≥ 40 kg/m2). Patients using insulin will be excluded. Subjects will be randomized to one of two groups as follows: 1) metformin tablets 850 mg PO bid or 2) metformin tablets 850 mg PO bid plus dapagliflozin tablets 10 mg PO qd. The sample size required is 108 patients, which allows for a 20% dropout rate: 54 patients in the metformin group and 54 in the metformin/dapagliflozin group. All participants will receive personalized nutritional advice during the study. A run-in period of one month will be used to assess tolerance and adherence to treatment regimens. Anthropometric and biochemical variables will be recorded at baseline and at 1, 3, 6, and 12 months. A serum sample to determine glucagon, ghrelin, adiponectin, resistin, interleukin 6, and interleukin 10 will be collected at baseline and before surgery, or at 12 months (whatever happens first). Adherence to treatment and adverse and secondary events will be recorded throughout the study. An intention-to-treat analysis will be used. DISCUSSION: Forty-six percent of the patients in our Obesity Clinic have been diagnosed with prediabetes (32%) or diabetes (14%). The use of dapagliflozin in this population could improve weight loss and other cardiovascular factors. This effect could be translated into less time before undergoing bariatric surgery and better control of associated comorbidities. TRIAL REGISTRATION: Clinicaltrials.gov, ID: NCT03968224. Retrospectively registered on May 29, 2019.

Are there really any predictive factors for a successful weight loss after bariatric surgery?

BACKGROUND: Currently, bariatric surgery is the most effective treatment for severe obesity and its metabolic complications; however, 15-35% of the patients that undergo bariatric surgery do not reach their goal for weight loss. The aim of this study was to determine the proportion of patients that didn't reach the goal of an excess weight loss of 50% or more during the first 12 months and determine the factors associated to this failure. METHODS: We obtained the demographic, anthropometric and biochemical information from 130 patients with severe obesity who underwent bariatric surgery in our institution between 2012 and 2017. We used self-reports of physical activity, caloric intake and diet composition. An unsuccessful weight loss was considered when the patient lost < 50% or more of the excess weight 12 months after surgery. We compared the characteristics between the successful and unsuccessful groups in order to find the factors associated with success. RESULTS: We included 130 patients (mean age 48 ± 9 years, 81.5% were women). One year after surgery, 26 (20%) had loss < 50% EBW. Unsuccessful surgery was associated with an older age, previous history of hypertension, abdominal surgery or depression/anxiety, also the number of comorbidities and unemployment affected the results. These patients loss enough weight to improve some of their comorbidities, but they are more prone to regain weight 2 years after surgery. CONCLUSIONS: A fifth of the patients undergoing bariatric surgery may not lose enough weight to be considered successful by current standards. Some patients may benefit from the surgery in the short term, but they are more likely to regain weight after 2 years. The factors influencing this result are still controversial but may be population-specific. Early detection of the patients that are more likely to fail is imperative to establish additional therapeutic strategies, without denying them the opportunity of surgery or waiting for weight re-gain to occur.