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Amiodarone-induced thyrotoxicosis (AIT) are not uncommon endocrinopathies. Clinicians are sometimes faced with difficult diagnostic and therapeutic situations. The disease pathophysiology is partially understood, explaining the lack of predictive factors for occurrence. Different international recommendations for their management have been published: the most recent in 2018 by the European Thyroid Association (ETA) (Ross et al., 2016; Bartalena et al., 2018). The purpose of this paper is to present the essential concepts for their management and to review the literature since 2018.

Background Sudden cardiac deaths are twice more frequent in diabetic patients with cardiac autonomic neuropathy. Sudden cardiac death etiologies remain unclear and no recommendations are made to identify factors associated with cardiorespiratory arrest in diabetic patients. We hypothesized, from two clinical cases, that impaired hypoxic ventilatory drive, induced by diabetic autonomic neuropathy, is a cause of misdiagnosed severe cardiac events. Case presentation We describe the cases of two patients with isolated low blood saturation on pulse oximeter during the systematic nurse check-up (77% and 85% respectively) contrasting with the absence of any complaint such as dyspnea, polypnea or other respiratory insufficiency signs observed during the clinical examination. Arterial blood gas measurements subsequently confirmed that blood oxygen saturation was low and both patients were indeed hypoxemic. Patient 1 suffered from vascular overload complicated by cardiac arrest caused by hypoxemia in light of the quick recovery observed after ventilation. Pulmonary edema was diagnosed in patient 2. The common denominator of these 2 cases described in this brief report is the absence of respiratory failure clinical signs contrasting with the presence of confirmed hypoxemia. Also, in both cases, such absence of precursory signs seems to be induced by an impaired ventilatory drive to hypoxemia. This appears to be related to the autonomic diabetic neuropathy encountered in those 2 patients. Conclusions Therefore, we describe, in this brief report, cardiac autonomic neuropathy as a cause of impaired hypoxic ventilatory drive involved in severe acute cardiorespiratory events in two type 1 diabetic patients. We assume that altered response to hypoxemia due to cardiac autonomic neuropathy and non-functional central neurological breathing command could play a key role in sudden deaths among diabetic patients. An important point is that hypoxemia can be easily missed since no clinical signs of respiratory failure are reported in these two clinical cases. Systematic screening of cardiac autonomic neuropathy in diabetic patients and proactive detection of impaired hypoxic ventilatory drive for early management (e.g. treatment of hypoxemia) should be systematically undertaken in diabetic patients to prevent its dramatic consequences such as cardiorespiratory arrest and death.

Resumen: La ocurrencia de muerte súbita cardiaca es dos veces más frecuente en pacientes diabéticos con neuropatía autonómica. La etiología de la muerte súbita cardiaca aún no está clara, y no existen recomendaciones para identificar factores asociados con el paro cardiorrespiratorio en pacientes diabéticos. Proponemos la hipótesis, con base en dos casos clínicos, de que un deterioro en la actividad respiratoria hipóxica, inducido por la neuropatía autonómica diabética, es una causa del diagnóstico erróneo de eventos cardiacos graves. Presentación de casos: Describimos los casos de dos pacientes con baja saturación sanguínea aislada, medida con oxímetro de pulso durante la revisión rutinaria (77% y 85%, respectivamente), que contrasta con la ausencia de molestias como disnea, polipnea u otros signos de insuficiencia respiratoria durante el examen clínico. La gasometría arterial confirmó subsecuentemente la baja saturación de oxígeno en la sangre, y que ambas pacientes se hallaban hipoxémicas. La paciente 1 sufría una sobrecarga vascular complicada con paro cardiaco causado por hipoxemia, en vista de la rápida recuperación observada después de la ventilación. En la paciente 2 se diagnosticó edema pulmonar. El denominador común en los dos casos descritos en este breve reporte es la ausencia de signos clínicos de insuficiencia respiratoria y su contraste con la presencia confirmada de hipoxemia. Asimismo, en ambos casos, la ausencia de dichos signos precursores parece deberse a un deterioro en la actividad ventilatoria hipóxica, que resultó en hipoxemia. Ésta parece estar relacionada con la neuropatía autonómica diabética encontrada en estas dos pacientes. Conclusiones: Por tanto, en este breve reporte señalamos a la neuropatía autonómica cardiaca como una causa de deterioro en la actividad respiratoria hipóxica, vinculado con eventos cardiorrespiratorios agudos y severos en dos pacientes con diabetes tipo 1. Asumimos que una respuesta alterada a la hipoxemia debida a la neuropatía autonómica cardiaca y un comando respiratorio neurológico central no-funcional podría tener un papel clave en la muerte súbita entre pacientes diabéticos. Un punto importante es que es fácil pasar por alto la hipoxemia, puesto que no se reportan signos de insuficiencia respiratoria en estos dos casos clínicos. Es necesario aplicar una búsqueda sistemática de neuropatía autonómica cardiaca y detectar de manera proactiva el deterioro en la actividad respiratoria hipóxica en pacientes diabéticos, para garantizar un manejo temprano de la condición (p. ej., dando tratamiento a la hipoxia) y prevenir consecuencias dramáticas, como el paro cardiorrespiratorio y la muerte.

Thyroid cancer is the most common endocrine cancer, with a good prognosis in most cases. However, some cancers of follicular origin are metastatic or recurrent and eventually become radioiodine refractory thyroid cancers (RAIR-TC). These more aggressive cancers are a clinical concern for which the therapeutic arsenal remains limited. Molecular biology of these tumors has highlighted a hyper-activation of the Mitogen-Activated Protein Kinases (MAPK) pathway (RAS-RAF-MEK-ERK), mostly secondary to the BRAFV600E hotspot mutation occurring in about 60% of papillary cancers and 45% of anaplastic cancers. Therapies targeting the different protagonists of this signaling pathway have been tested in preclinical and clinical models: first and second generation RAF inhibitors and MEK inhibitors. In clinical practice, dual therapies with a BRAF inhibitor and a MEK inhibitor are being recommended in anaplastic cancers with the BRAFV600E mutation. Concerning RAIR-TC, these inhibitors can be used as anti-proliferative drugs, but their efficacy is inconsistent due to primary or secondary resistance. A specific therapeutic approach in thyroid cancers consists of performing a short-term treatment with these MAPK pathway inhibitors to evaluate their capacity to redifferentiate a refractory tumor, with the aim of retreating the patients by radioactive iodine therapy in case of re-expression of the sodium–iodide symporter (NIS). In this work, we report data from recent preclinical and clinical studies on the efficacy of MAPK pathway inhibitors and their resistance mechanisms. We will also report the different preclinical and clinical studies that have investigated the redifferentiation with these therapies.