Endocrine Adverse Events Related To Immune Checkpoint Inhibitor Treatment: Relationship Between Antibodies and Severity of Thyroid Dysfunction.

OBJECTIVE: The purpose of this study was to identify predictive and risk factors for the development of immune-related endocrinopathies and to analyze the incidence and characteristics of immune-related endocrinopathies in our population Design: A retrospective, single-centre cohort carried out at Gregorio Marañón Hospital between January 2018 -December 2019. METHODS: A total of 163 patients were enrolled. In January 2018 and December 2019, we treated patients who underwent ICI treatment in the Medical Oncology Department of General University Hospital Gregorio Marañón, a tertiary care public hospital in Madrid, as part of an observational, retrospective, single-center cohort study. RESULTS: Endocrinopathies were diagnosed in 19.5% of the patients (n=32). The tumours with the highest incidence of endocrinopathies were non-small cell lung cancer (25,9%), kidney cell cancer (25%) and hepatocarcinoma (20%). Among the 32 patients who developed endocrinopathy, 18,8%, 19,13%, and 21,28% received anti-CTLA-4, anti-PD-1 and anti-PDL-1, respectively. Thyroid dysfunction was the most frequent endocrinopathy (12,8%). A higher percentage of patients with negative antiTPO and antiTG antibodies developed G1 hypothyroidism compared to patients with positive antibodies who developed a higher proportion of G2 hypothyroidism. The presence of an initial phase of thyrotoxicity was not related to greater severity. We observed longer progression-free survival in patients who developed thyroid dysfunction. CONCLUSION: Pre-existing antibodies were independently associated with endocrinopathies. Moreover, our study let us conclude that the presence of thyroid autoantibodies may be related to its severity. It is important to determine anti-thyroid antibodies prior to the start of immunotherapy as a risk factor for thyroid dysfunction, which in turn is a prognostic marker.

Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review.

INTRODUCTION: Combined methylmalonic acidemia and homocystinuria, cblC type is an inborn error of intracellular cobalamin metabolism and the most common one. The age of onset ranges from prenatal to adult. The disease is characterised by an elevation of methylmalonic acid (MMA) and homocysteine and a decreased production of methionine. The aim is to review existing scientific literature of all late onset cblC patients in terms of clinical symptoms, diagnosis, and outcome. METHODS: A bibliographic database search was undertaken in PubMed (MEDLINE) complemented by a reference list search. We combined search terms regarding cblC disease and late onset. Two review authors performed the study selection, data extraction and quality assessment. RESULTS: Of the sixty-five articles included in this systematic review, we collected a total of 199 patients. The most frequent clinical symptoms were neuropathy/myelopathy, encephalopathy, psychiatric symptoms, thrombotic microangiopathy, seizures, kidney disease, mild to severe pulmonary hypertension with heart failure and thrombotic phenomena. There were different forms of supplementation used in the different studies collected and, within these studies, some patients received several treatments sequentially and/or concomitantly. The general outcome was: 64 patients recovered, 78 patients improved, 4 patients did not improve, or the disease progressed, and 12 patients died. CONCLUSIONS: Most scientific literature regarding the late onset cblC disease comes from case reports and case series. In most cases treatment initiation led to an improvement and even recovery of some patients. The lack of complete recovery underlines the necessity for increased vigilance in unclear clinical symptoms for cblC disease.

Prevalence and incidence of type 2 diabetes mellitus in patients with adrenal incidentalomas: a study of 709 cases.

AIM: To evaluate the prevalence and incidence of type 2 diabetes in patients with nonfunctioning adrenal incidentalomas (NFAI) or adrenal incidentalomas (AI) with autonomous cortisol secretion (ACS). METHODS: In this single-center retrospective study, all patients with adrenal incidentalomas ≥1 cm and ACS or NFAI studied between 2013 and 2020 were included. ACS was defined by a post-dexamethasone suppression test (DST) serum cortisol concentration ≥1.8 µg/dl, in the absence of signs of hypercortisolism, and NFAI was defined as a DST < 1.8 µg/dl without biochemical evidence of hypersecretion of other hormones. RESULTS: Inclusion criteria were met by 231 patients with ACS and 478 with NFAI. At diagnosis, type 2 diabetes was present in 24.3% of patients. No differences were found in the prevalence of type 2 diabetes (27.7 vs. 22.6%, P = 0.137) between patients with ACS and NFAI. However, fasting plasma glucose values and glycated hemoglobin levels were significantly higher in patients with ACS than with NFAI (112 ± 35.6 vs. 105 ± 29 mg/dl, P = 0.004; and 6.5 ± 1.4 vs. 6.1 ± 0.9%, P = 0.005, respectively). Furthermore, patients with type 2 diabetes had higher urinary free cortisol (P = 0.039) and late-night salivary cortisol levels (P = 0.010) than those without type 2 diabetes. After a median follow-up of 28 months, no differences were found in the incidence of type 2 diabetes between the groups (HR 1.17, 95% 0.52-2.64). CONCLUSION: Type 2 diabetes was present in one fourth of our cohort. We found no differences in its prevalence or incidence between the groups. However, glycemic control might be worse among diabetic patients with ACS. Higher concentrations of urinary and salivary cortisol were found in patients with than without type 2 diabetes.

Diets for inflammatory bowel disease: What do we know so far?

In recent years, the role of diet in the pathogenesis of inflammatory bowel disease (IBD) has gained great interest within the scientific community. Eating habits from industrialised countries (the so-called western diet or WD) have been associated with a higher incidence of IBD in observational studies, although the dietary factors responsible for the development of the disease are still to be elucidated. Some components of the diet with proinflammatory potential may cause changes in immunity and intestinal microbiota, leading to the inflammatory reaction that causes IBD-related lesions. The quality of available evidence is low, due to methodological issues, such as the lack of intervention studies, small sample size and heterogeneity of studies. For this reason, scientific societies have offered their recommendations using clinical practice guidelines and consensus documents, in order to establish a common criterion in the nutritional treatment of patients with IBD. The objective of this review was to summarise the data published regarding diet in IBD and review the recommendations given by scientific societies.

Inferior petrosal sinus sampling and stimulation with CRH: 15 years of experience in a tertiary hospital.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is indicated in the diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS), especially when the results of the initial diagnostic tests are discordant. OBJECTIVE: To describe the patients who underwent this invasive functional test in a tertiary hospital. METHODS: This was an observational study of a retrospective cohort of patients with ACTH-dependent CS and IPSS between 2004 and 2019. We determined their epidemiological, hormonal, radiological and functional characteristics, and evaluated their diagnostic capacity and optimal cut-off points to differentiate between Cushing's disease (CD) and ectopic Cushing's syndrome (ECS). RESULTS: 23 patients were evaluated, of which 65.2% were women with the average age of 42 (36-62) years. ACTH secretion of pituitary origin was evident in 82.6% of the patients and of ectopic origin in 17.4%. Plasma cortisol, urinary free cortisol, and ACTH levels were higher in patients with ECS. Regarding IPSS, the baseline central/peripheral ACTH gradient detected 89.5% of patients with CD and after stimulation with CRH, 100%. The optimal cut-off points in the diagnosis of CD were 2.06 at baseline and 2.49 after CRH stimulation. CONCLUSION: IPSS with CRH stimulation is a test with a high diagnostic accuracy for correctly classifying patients with CD and ECS. The cut-off points of the gradients may be different from the classic ones. Therefore, we recommend that each center perform its own evaluation.

Late-onset methylmalonic acidemia and homocysteinemia / Acidemia metilmalónica y homocisteinemia de inicio tardío

Introduction: cobalamin C (Cbl C) deficiency is the most common defect in intracellular cobalamin metabolism, associated with methylmalonic acidemia and homocystinuria. Its late clinical presentation is heterogeneous and may lead to a diagnostic delay. Case report: we report the case of a 45-year-old man with a 20-year history of chronic kidney disease and recently diagnosed spastic paraparesis, both of unknown origin. Metabolic studies revealed elevated levels of homocysteine and methylmalonic acid in the blood and urine. A genetic study confirmed cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, carnitine, and folic acid was started. The patient eventually received a kidney transplant. Discussion: early diagnosis and appropriate treatment improve the clinical evolution of patients with Cbl C deficiency. Determination of homocysteine, organic acids, and other amino acids should be included in the differential diagnosis of patients with nephrological-neurological symptoms without a clear etiology. (AU)

Introducción: la deficiencia de cobalamina C (Cbl C) es el defecto más común en el metabolismo intracelular de la cobalamina, asociado a acidemia metilmalónica y homocistinuria. Su presentación clínica tardía es heterogénea y puede llevar a un retraso en el diagnóstico. Caso clínico: presentamos el caso de un varón de 45 años con 20 años de evolución de enfermedad renal crónica y paraparesia espástica de reciente diagnóstico, ambos de origen desconocido. Los estudios metabólicos revelaron niveles elevados de homocisteína y ácido metilmalónico en sangre y orina. El estudio genético confirmó el déficit de cobalamina C. Se inició tratamiento con hidroxocobalamina, betaína, carnitina y ácido fólico. El paciente pudo recibir un trasplante renal. Discusión: el establecimiento de un diagnóstico precoz y un tratamiento adecuado mejora la evolución clínica de los pacientes con déficit de Cbl C. La determinación de homocisteína, ácidos orgánicos y otros aminoácidos debe incluirse en el diagnóstico diferencial de los pacientes con síntomas nefrológico-neurológicos sin una etiología clara. (AU)

Late-onset methylmalonic acidemia and homocysteinemia.

INTRODUCTION: Introduction: cobalamin C (Cbl C) deficiency is the most common defect in intracellular cobalamin metabolism, associated with methylmalonic acidemia and homocystinuria. Its late clinical presentation is heterogeneous and may lead to a diagnostic delay. Case report: we report the case of a 45-year-old man with a 20-year history of chronic kidney disease and recently diagnosed spastic paraparesis, both of unknown origin. Metabolic studies revealed elevated levels of homocysteine and methylmalonic acid in the blood and urine. A genetic study confirmed cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, carnitine, and folic acid was started. The patient eventually received a kidney transplant. Discussion: early diagnosis and appropriate treatment improve the clinical evolution of patients with Cbl C deficiency. Determination of homocysteine, organic acids, and other amino acids should be included in the differential diagnosis of patients with nephrological-neurological symptoms without a clear etiology.

INTRODUCCIÓN: Introducción: la deficiencia de cobalamina C (Cbl C) es el defecto más común en el metabolismo intracelular de la cobalamina, asociado a acidemia metilmalónica y homocistinuria. Su presentación clínica tardía es heterogénea y puede llevar a un retraso en el diagnóstico. Caso clínico: presentamos el caso de un varón de 45 años con 20 años de evolución de enfermedad renal crónica y paraparesia espástica de reciente diagnóstico, ambos de origen desconocido. Los estudios metabólicos revelaron niveles elevados de homocisteína y ácido metilmalónico en sangre y orina. El estudio genético confirmó el déficit de cobalamina C. Se inició tratamiento con hidroxocobalamina, betaína, carnitina y ácido fólico. El paciente pudo recibir un trasplante renal. Discusión: el establecimiento de un diagnóstico precoz y un tratamiento adecuado mejora la evolución clínica de los pacientes con déficit de Cbl C. La determinación de homocisteína, ácidos orgánicos y otros aminoácidos debe incluirse en el diagnóstico diferencial de los pacientes con síntomas nefrológico-neurológicos sin una etiología clara.