Thrombotic microangiopathy associated with lenvatinib therapy.

Summary: Systemic thrombotic microangiopathy (TMA) is a serious condition whose early treatment is essential to reduce morbidity and mortality. TMA with only renal involvement has been associated with tyrosine kinase inhibitors, including lenvatinib, a drug used for certain advanced neoplasms. To date, TMA with systemic involvement associated with this drug has not been described. We present the case of a patient with progressive metastatic thyroid cancer who developed this complication after starting treatment with lenvatinib. We describe the signs and symptoms that led to the diagnosis and the treatment required for her recovery. Learning points: Thrombotic microangiopathy (TMA) is a group of disorders characterized by thrombosis in capillaries and arterioles due to an endothelial injury. Both, localized and systemic forms have been described.TMA with systemic involvement is characterized by hemolytic anemia, low platelets, and organ damage.Vascular endothelial growth factor signaling inhibitors have been associated with TMA, either restricted to the kidney or with systemic involvement.Lenvatinib has been rarely associated with TMA. Although only forms with isolated or predominantly renal involvement had been described so far, a predominantly systemic form can occur.Lenvatinib-induced systemic TMA must be distinguished from primary forms by measuring ADAMTS-13. Treatment includes discontinuation of the drug and supportive measures.When anemia and thrombocytopenia coexist in a patient receiving treatment with lenvatinib, a peripheral blood smear to exclude TMA is recommended.

Ectopic Cushing syndrome: Report of 9 cases. / Síndrome de Cushing ectópico: descripción de 9 casos.

INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. METHODS: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840µg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended.

Síndrome de Cushing ectópico: descripción de 9 casos / Ectopic Cushing syndrome: Report of 9 cases

Introducción: El síndrome de Cushing ectópico (SCE) es una entidad rara debida a la secreción de ACTH por tumores extrahipofisarios. Su baja frecuencia dificulta la adquisición de experiencia en su manejo. El objetivo de este trabajo es describir a los pacientes con SCE atendidos en el servicio de Endocrinología en un hospital de tercer nivel en un periodo de 15 años. Métodos: Se trata de un estudio retrospectivo de los datos clínicos, bioquímicos y radiológicos, tratamiento recibido, y evolución de los pacientes con SCE atendidos entre los años 2000 y 2015. Resultados: Se incluyeron 9 pacientes (6 mujeres) con una edad media de 47 años. El síndrome clínico se desarrolló en un tiempo inferior a 3 meses en todos los casos excepto en uno, y la mayoría presentaba edemas, hiperpigmentación y/o hipopotasemia. La media del cortisol libre urinario y de la ACTH fue de 2.840μg/24h y 204pg/ml, respectivamente. El origen ectópico se confirmó por la combinación de pruebas dinámicas no invasivas y estudios radiológicos en la mayoría de los casos. El tumor responsable pudo identificarse en 8 casos y 7 presentaban diseminación metastásica. El tratamiento primario consistió en cirugía en un caso, cirugía más terapia sistémica en 3 y quimioterapia en otros 3. En 4 pacientes fue necesaria la suprarrenalectomía bilateral para controlar el hipercortisolismo. Tras un seguimiento medio de 40 meses, 3 habían fallecido, 5 permanecían vivos y en uno se había perdido el seguimiento. Conclusiones: Se confirma que el SCE abarca un amplio espectro de tumores de diferente agresividad y naturaleza. Habitualmente el origen ectópico del síndrome de Cushing puede sospecharse y confirmarse en la mayoría de los casos sin necesidad de pruebas invasivas. Tanto el control del hipercortisolismo como del tumor requieren múltiples modalidades terapéuticas, siendo recomendable el manejo multidisciplinar

Introduction: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. Methods: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. Results: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840μg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. Conclusions: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended