Novel mechanisms involved in leptin sensitization in obesity.

Leptin is a hormone that is secreted by adipocytes in proportion to adipose tissue size, and that informs the brain about the energy status of the body. Leptin acts through its receptor LepRb, expressed mainly in the hypothalamus, and induces a negative energy balance by potent inhibition of feeding and activation of energy expenditure. These actions have led to huge expectations for the development of therapeutic targets for metabolic complications based on leptin-derived compounds. However, the majority of patients with obesity presents elevated leptin production, suggesting that in this setting leptin is ineffective in the regulation of energy balance. This resistance to the action of leptin in obesity has led to the development of "leptin sensitizers," which have been tested in preclinical studies. Much research has focused on generating combined treatments that act on multiple levels of the gastrointestinal-brain axis. The gastrointestinal-brain axis secretes a variety of different anorexigenic signals, such as uroguanylin, glucagon-like peptide-1, amylin, or cholecystokinin, which can alleviate the resistance to leptin action. Moreover, alternative mechanism such as pharmacokinetics, proteostasis, the role of specific kinases, chaperones, ER stress and neonatal feeding modifications are also implicated in leptin resistance. This review will cover the current knowledge regarding the interaction of leptin with different endocrine factors from the gastrointestinal-brain axis and other novel mechanisms that improve leptin sensitivity in obesity.

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.

Papillary Thyroid Carcinoma in Ectopic Thyroid Tissue Within a Suspected Cervical Paraganglioma.

ABSTRACT: Ectopic differentiated thyroid carcinoma represents less than 1% of all thyroid carcinoma cases, which usually arises along the cervical midline, and (delving into literature) there are scarce reports of such entity in nuclear medicine imaging studies. We present a rare case of a confirmed synchronous, orthotopic, and heterotopic (in lateral ectopic thyroid tissue) differentiated thyroid carcinoma in a patient who was previously misdiagnosed as having a cervical paraganglioma, based on compatible clinical, analytical, and imagenological (both structural and functional) findings.

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.

A review of systemic infiltrative diseases and associated endocrine diseases.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.

A review of systemic infiltrative diseases and associated endocrine diseases. / Revisión sobre enfermedades infiltrativas sistémicas y patología endocrinológica asociada.

Systemic infiltrative diseases are relatively rare conditions consisting of cell infiltration or substance deposition in multiple organs and systems, including endocrine glands. This article reviews endocrine changes in the main four diseases at epidemiological level: sarcoidosis, Langerhans cell histiocytosis, hereditary hemochromatosis, and systemic amyloidosis. Recommendations to endocrinologists for hormone work-up and management of patients with each of these conditions are provided.