Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador.

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.

IGF-I deficiency and enhanced insulin sensitivity due to a mutated growth hormone receptor gene in humans.

Human size is achieved by the coordinated expression of many genes. From conception to adulthood, a given genomic endowment is modified by highly variable environmental circumstances. During each stage of a person's life, distinct nutritional and hormonal influences continuously shape growing physical features until mature characteristics are attained. Underlying processes depend on precise provision of substrates and energy extracted by insulin action from nutrients, which allows cell proliferation, differentiation, and survival, under the concerted actions of growth hormone and insulin-like growth factor-I (IGF-I). It should be noted that growth and metabolic signaling pathways are interdependent and superimposed at multiple levels. Attainment of a fully developed human phenotype should be considered as a harmonious increment in body size rather than a simple increase in height. From this perspective we herein analyze adult features of individuals with an inactive growth hormone receptor, who consequently have severely diminished concentrations of serum insulin and endocrine IGF-I.

Fístula aorto-duodenal secundaria, una rara oportunidad para realizar un procedimiento de Whipple / Secondary aorto-duodenal fistula, a rare opportunity to perform a Whipple procedure

La fístula aortoentérica (FAE) es la solución de continuidad entre la arteria aorta y una porción del sistema digestivo; su incidencia va del 0.04 al 0.07% y su mortalidad alcanza hasta 79%, lo que la convierte en un verdadero reto a la hora de establecer su manejo por la efectividad con la cual se debe efectuar su manejo. Existen diversas manifestaciones de la enfermedad que pueden distraer su diagnóstico, sin embargo es común el dolor abdominal y el sangrado digestivo acompañado o no de signos de inestabilidad hemodinámica. Actualmente, no existe un consenso para el manejo de las FAE; sin embargo, los pilares fundamentales son: control de la infección, reparación vascular y reconstrucción entérica; para esto es indispensable un equipo multidisciplinario de gran experiencia. Se presenta el caso de una paciente de 76 años con varias comorbilidades, portadora de bypass aorto-bi-femoral por enfermedad aterosclerótica de la aorta. Acudió por dolor abdominal, sangrado digestivo alto e inestabilidad hemodinámica. Luego de la valoración inicial fue diagnosticada de FAE y sepsis. Tomando en cuenta las recomendaciones mundiales, se realizó un procedimiento en 2 tiempos que incluían: a) reparo vascular: bypass extra-anatómico, exéresis de prótesis y cierre del muñón aórtico y, b) reparo entérico (por la magnitud anatómica de la lesión intestinal y luego de haber descartado la factibilidad de una rafia o derivación intestinal): como último recurso un procedimiento de Whipple

Aortoenteric fistulas are defined as a communication between the aorta and a portion of the digestive system. This pathology has a 0.04-0.07% incidence with a mortality rate of up to 79% making it's management a true challenge. Clinical manifestations vary thus common symptoms include abdominal pain and digestive bleeding and may or may not include signs of hemodynamic instability. Until now there is no consensus regarding the management of FAE hence the pillars of treatment include: infection control, vascular reparation and enteric reconstruction. A multidisciplinary team is imperative. We are presenting the case of a 76-year-old female with various comorbidities and a history of an aortic bifemoral bypass reconstruction due to aortic sclerosis disease; that presented with abdominal pain, upper digestive bleeding and hemodynamic instability. She was diagnosed with a FAE and sepsis. Taking into consideration international recommendations she was treated with a single procedure in two times. For the vascular correction: an extra-anatomical bypass; removal of previous prosthetic aortic implant and closure of the aortic stump. Due to the magnitude of the intestinal damage simple closure and intestinal derivation were discarded as options for enteric repair and a Whipple procedure was used as a last resource.