Función tiroidea en el paciente críticamente enfermo con traumatismo craneoencefálico y con muerte cerebral.

Introducción.- Ya que la muerte cerebral progresa a la muerte somática en 10 a 20% de los casos, el tratamiento del potencial donador es crítico, por lo que se han utilizado algoritmos y guías para mantener su estabilidad. A pesar de que existen estudios que evalúan los niveles de hormonas tiroideas en pacientes con muerte cerebral, estos se han hecho en pacientes con muerte cerebral secundaria a múltiples diagnósticos, y ninguno de éstos ha realizado una clasificación sindromática de los mismos. Material y Métodos.- Se estudiaron 28 pacientes con traumatismo craneoencefálico severo sin antecedentes de uso de hormonas tiroideas. Se midió T3 reversa, tiro globulina y perfil tiroides al ingreso y se siguió al paciente durante toda la hospitalización. En caso de progresión a muerte cerebral, se repetían los laboratorios. Se compararon los niveles basales de los sujetos sin muerte cerebral contra los que progresaron a muerte cerebral y, de los que progresaron, los niveles basales contra los niveles posterior a la muerte cerebral. Resultados.- No se encontró diferencia significativa en ninguno de los parámetros hormonales entre los grupos. No hubo diferencia significativa entre los niveles previos contra los posteriores a la muerte cerebral de los que progresaron. En todos los sujetos, la T3 reversa se encontró francamente elevada Discusión.- Los resultados confirman al síndrome del eutiroideo enfermo como causa de las modificaciones de las hormonas tiroides en el traumatismo craneoencefálico severo y en los que progresaron a muerte cerebral. Conclusiones.- El patrón de alteraciones hormonales tiroideas mas frecuente en los sujetos con traumatismo craneoencefálico severo es el del síndrome del eutiroideo enfermo. Se encontró un patrón similar en los pacientes con TCE severo que progresaron a muerte cerebral

Recent Understanding and Future Directions of Recurrent Corticotroph Tumors

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing’s disease (CD), which has high morbidity and mortality due to hypercortisolemia. “Non-functioning” or silent CTs (SCT) and the Crooke’s cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Both tend toward more aggressive behavior, recurrence, and a higher rate of malignant transformation to pituitary carcinoma. Tumorigenesis involves genetic, epigenetic, and post-transcriptional disruption of cell-cycle regulators, which increase cell proliferation, POMC overexpression, ACTH transcription, and/or hypersecretion. Furthermore, functioning CTs develop resistance to glucocorticoid-mediated negative feedback on ACTH secretion, through increased expression of testicular orphan nuclear receptor 4 (TR4), heat-shock protein 90 (HSP90), and loss-of-function mutation of CDK5 and ABL enzyme substrate 1 (CABLES1) gene. Overt autonomous hypercortisolemia is difficult to control, and multiple diagnostic studies and therapeutic modalities are commonly required. Cell-cycle regulation depends mainly on p27, cyclin E, cyclin-dependent kinases (CDKs), and the retinoblastoma protein (Rb)/E2F1 transcription factor complex. Gain-of-function mutations of ubiquitin-specific protease (USP) 8, USP48, and BRAF genes may subsequently cause overexpression of epithelial growth factor receptor (EGFR), and enhance POMC transcription, cell proliferation, and tumor growth. Epigenetic changes through micro RNAs and decreased DNA deacetylation by histone deacetylase type 2 (HDAC2), may also affect tumor growth. All the former mechanisms may become interesting therapeutic targets for CTs, aside from temozolomide, currently used for aggressive tumors. Potential therapeutic agents are EGFR inhibitors such as gefitinib and lapatinib, the purine analog R-roscovitine by dissociation of CDK2/Cyclin E complex, the HSP90 inhibitor silibinin (novobiocin), to reduce resistance to glucocorticoid-mediated negative feedback, and BRAF inhibitors vemurafenib and dabrafenib in BRAF V600E positive tumors. This review summarizes the molecular mechanisms related to CTs tumorigenesis, their diagnostic approach, and provides an update of the potential novel therapies, from the lab bench to the clinical translation

A Morphometric Study of the Extraocular Muscles

Extraocular muscles are important references in strabismus surgery and in placement of intraorbital devices. We analyzed extraocular muscles morphometry and possible anatomical variances of 20 orbits. We report the length, width, and points of insertion of the extraocular muscles. No anatomical variations in length, width and points of insertion were found. With regard to the rectus muscles, it was found that the superior rectus and lateral rectus are the longest muscles and that the width difference between the superior and inferior rectus is greater than that between the medial and lateral rectus and that the point of insertion of the rectus muscles has a variable morphology. The superior oblique muscle was smaller in caliber than the inferior oblique, as consistent with previous anatomical studies. Knowledge of the detailed morphology of extraocular muscles is fundamental in strabismus surgery and represents a key factor for the innovation of surgical techniques and orbital procedures

Estudio morfométrico de la arteria radial y su implicación en la cirugía de revascularización miocárdica = Morphometric study of the radial artery and its involvement in bypass surgery grafting

La arteria radial (AR) es utilizada en la práctica médica para la realización de diversos procedimientos quirúrgicos, entre los que destaca la cirugía de revascularización miocárdica. En la literatura actual hay poca información acerca de la compatibilidad de esta arteria con otros conductos vasculares. El objetivo fue determinar las características anatómicas, morfométricas y distribución de la arteria radial en el antebrazo. Se disecó la arteria radial de 10 antebrazos de cadáveres embalsamados; se identificaron y registraron los ramos musculares y vasa nervorum emitidos por la arteria, se midió la longitud total y obtuvieron tres muestras (proximal, media y distal) de cada una para ser procesadas mediante técnicas histológicas y se determinaron los grosores de la túnica media y los diámetros. Se observaron modas de 8 ramos arteriales para el músculo braquiorradial, 4 para los músculos flexor superficial de los dedos y flexor radial del carpo, un ramo arterial único para el músculo pronador cuadrado y una moda de 1 vasa nervorum para el ramo superficial del nervio radial. La longitud total de la arteria fue de 21,94 cm (±3,34). Los grosores encontrados fueron de 196,16 µm (±72,35), 148,25 µm (±40,40) y 158,96 µm (±45,74) en los segmentos proximal, medio y distal respectivamente. Los diámetros luminales mostraron una media de 1,48 mm (±0,70) en la región proximal, 1,01mm (±0,35) en la media y 1,43 mm (±0,47) en la distal. Considerando las características morfométricas, la arteria radial es una opción que satisface los criterios de longitud, diámetro luminal y grosor para ser utilizada como injerto

Conduits for myocardial revascularization grafts: the importance of morphology and imaging

The therapeutic options for patients with multivessel coronary artery disease, consist of pharmacological treatment, percutaneous coronary intervention and coronary artery bypass graft surgery. The ultimate goal of this surgery is to achieve complete revascularization with conduits that remain permeable for the remainder of the life of the patient. Some of the conduits used in this type of surgery, are the great saphenous vein, the internal thoracic artery, the radial artery and the ulnar artery. For a vascular conduit to be selected as a coronary revascularization graft, it must exhibit the following characteristics: sufficient length, lumen diameter and thickness of the vessel wall. It must also have minimal in situ ischemic consequences and an acceptable permeability over time of the conduit. Recent literatures of these conduits, as well as the importance of morphological and imaging studies are reviewed in this article

Supplementary Material: Diagnostic Tests for Differentiation between Cushing´s Syndrome and Non-Neoplastic Hypercortisolism: A Systematic Review and Meta-analysis

Context: Differential diagnosis between Cushing’s syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing’s syndrome) is crucial. Due to worldwide corticotropin-releasing hormone test CRH shortage, accuracy of alternative tests to Dexamethasone (Dex)-CRH is clearly needed. Objective: Asses the diagnostic accuracy of Dex-CRH, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. Methods: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. Data Synthesis: A total of 26 articles (2059 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 87% (81-91%; I2 34%) and 91% (85-94%; I2 15%), MSC 91% (85-94%; I2 65%) and 80% (70-88%; I2 70%), and LNSC 78% (66-86%; I2 54%) and 88% (83-92%; I2 36%), respectively. SROC areas under the curve were Dex-CRH 0.949, desmopressin test 0.941, MSC 0.939, and LNSC 0.940 without visual or statistical significance. The overall risk of studies bias was moderate. Conclusion: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. Our results should increase clinicians’ confidence when deciding which test to perform when facing this challenging differential diagnosis. Key Words: Cushing’s syndrome, neoplastic endogenous hypercortisolism, non-neoplastic hypercortisolism, pseudoCushing’s, dexamethasone CRH test, desmopressin test, salivary cortisol, midnight serum cortiso

High Molecular Weight ACTH-Precursor Presence in a Metastatic Pancreatic Neuroendocrine Tumor Causing Severe Ectopic Cushing's Syndrome: A Case Report

Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism