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.

Hyperphosphatemia during nutrition recovery in patients with severe anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a disorder associated with many medical complications. Regarding phosphorus metabolism, the only recognized alteration is hypophosphatemia associated with refeeding syndrome. However, in our clinical practice, we have observed a high frequency of hyperphosphatemia in late phases of nutrition therapy in severely undernourished AN patients, which has barely been described. MATERIALS AND METHODS: We carried out a retrospective study of patients with AN hospitalized for severe decompensation of the disease. RESULTS: Eleven patients were included, all women, with a median age of 23 years [20-46] and a body mass index at admission of 12.2 kg/m2 [11.7-13.1]. Hyperphosphatemia was noted in 9 of the 11 cases (81.8%) with a median time to onset of 53 days [30-75]. The median peak serum phosphorus (P) level was 5.1 mg/dl [4.9-5.4]. An inverse relationship was found between the increase in P levels and phosphorus supplementation at the onset of admission. The magnitude of the P increase was associated with the body weight gain achieved during nutrition therapy. CONCLUSION: Late hyperphosphatemia during nutrition therapy in severely undernourished AN patients affects more than 80% of cases. Body weight gain throughout nutrition therapy is a predictor of increased P levels.

Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target.

Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.

Phenotype and resistance patterns of 10 resistant prolactinomas.

BACKGROUND: Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established. METHODS: We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2mg/week (or 3mg/week in cases where lower doses were not tested) for at least 3 months. RESULTS: Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78cm (80% macroadenomas). The mean maximal dose of CAB was 3.8mg/week. Five patients showed isolated MR, four combined MR+BR and only one isolated BR. MR patients were more often males and older than MR+BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor. CONCLUSIONS: Isolated MR and combined MR+BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance.

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.

Adrenal insufficiency in critical patients: New ethiopathogenic concepts and therapeutic implications. / Insuficiencia suprarrenal en el enfermo crítico: nuevos conceptos etiopatogénicos e implicaciones terapéuticas.

Recently, there have been advances in understanding of the changes that occur in the hypothalamic-pituitary-adrenal axis during the different stages of critical disease. Such advances have led to a paradigm change, so that the aforementioned adaptations are no longer considered the result of adrenal axis activation, but a consequence of decreased cortisol metabolism illness. Knowledge of this new pathophysiological bases should lead to reconsider the diagnosis and treatment of adrenal insufficiency in critically ill patients, a condition poorly understood to date.

SIADH secundario a adenocarcinoma seroso de ovario tratado con tolvaptán / SIADH secondary to serous ovarian adenocarcinoma treated with tolvaptan

La hiponatremia es la alteración electrolítica más frecuente en el medio hospitalario, y en un 30% de los casos se debe a un síndrome de secreción inapropiada de vasopresina (SIADH). El SIADH está descrito como cuadro paraneoplásico endocrinológico en múltiples tumores, entre los que excepcionalmente se encuentra el de ovario y las neoplasias ginecológicas en general. Presentamos un caso de SIADH paraneoplásico por un citoadenocarcinoma seroso de ovario de alto grado, estadio IV. Se trata del primer caso de SIADH crónico por cáncer de ovario tratado con Tolvaptán. En el presente caso el objetivo de eunatremia se alcanzó con una dosis baja de acuarético, lo que apoya la elevada sensibilidad, ya previamente documentada, de los SIADH tumorales al tratamiento con Tolvaptán.

Hyponatremia is the most common electrolyte disturbance in hospitals, and 30% of cases are due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). SIADH is described as an endocrine paraneoplastic syndrome in multiple tumors including, ovary and gynecological malignancies in general, although these are exceptional. We report a case of paraneoplastic SIADH for high-grade serous ovarian cystoadenocarcinoma stage IV. This is the first case of chronic SIADH for ovarian cancer treated with Tolvaptan. In this case the target of eunatremia was reached with a low dose of aquaretic, which supports the high sensitivity, as previously documented, of paraneoplasic SIADH to Tolvaptan.