Management of Advanced Medullary Thyroid Carcinoma: Current Systemic Therapy Options.

The current rapid development of more selective and effective drugs for the treatment of thyroid cancer has open a new era in the treatment of patients with this condition, in the past limited to the possibility of only radioactive iodine for well differentiated tumor and surgery for medullary thyroid carcinoma (MTC). The treatment of advanced medullary thyroid carcinoma has evolved in the last few years and options for patients with advanced disease are now available. Multikinase inhibitors (MKIs) with nonselective RET inhibition like Vandetanib and Cabozantinib were approved for the treatment of MTC, although the efficacy is limited due to the lack of specificity resulting in a higher rate of drug-related adverse events, leading to subsequent dose reductions, or discontinuation, and the development of a resistance mechanism like seen on the RET Val804 gatekeeper mutations. MTC is associated with mutations in the RET protooncogene, and new highly selective RET inhibitors have been developed including Selpercatinib and Pralsetinib, drugs that have demonstrate excellent results in clinical trials, and efficacy even in the presence of gatekeeper mutations. However, despite their efficacy and great tolerability, mechanisms of resistance have been described, such as the RET solvent front mutations. Due to this, the need of constant evolution and drug research is necessary to overcome the emergence of resistance mechanisms.

Adverse events associated with bone-directed therapies in patients with cancer.

Bone metastatic disease may lead to serious adverse events in patients with cancer. Bone-directed therapies, including bisphosphonates such as pamidronate and zoledronic acid and the human monoclonal antibody denosumab, are currently approved for the prevention of bone-related adverse events. However, despite the benefits of these drugs, they may cause side effects that are mostly associated with dosages and treatment durations. These side effects range from more frequent, mostly mild, and generally self-limited side effects-such as fever, myalgias, arthralgias, and electrolyte imbalances-to less frequent and more severe side effects such as medication-related osteonecrosis of the jaw and atypical femoral fractures. The purpose of this review is to familiarize clinicians with the literature regarding adverse events associated with bone-directed therapies in patients with cancer. It is important to be aware of these possible adverse events and to educate patients about the predisposing factors associated with side effects from bone-directed therapies and the preventive measures necessary to decrease the risk of occurrence.

Diabetes gestacional, hipotiroidismo y concentración urinaria de yodo en embarazadas. Yodurias en escolares en Paraguay: Exceso de yodo en la sal y riesgo de hiper e hipotiroidismo / Gestational diabetes, hypothyroidism and iodine urinary concentration in pregnant women. Urinary iodine in schoolage children in Paraguay: Iodine excess in salt and hyper and hypothyroidism risk

The main inclicator of iodine nutritional status of salt for human con-sumption is the urinary concentration of iodine, which is useful in monitoring universal levels in salt. Paraguay has suffered deficiency in salt with highprevalence of goiter in thepopulation reaching48.6%. In 2000, results of the ThyroidMobileproject in Latin America showed a goiter prevalence of 17% but 79.6% of the consumed iodized salt was adequate in paraguayan households (more than 15 ppm of iodine). The average values of iodine urinary concentration in 4487 scholars was 437 µg/L, 30% of the average value was between the ideal of 100 to 199 µg/L and 46.1% were above 300 mg/L, with risk of excess iodine. Urinary concentration of iodine during pregnancy was measure for the first time in Paraguay in 200 women; the average was 484 µg/L but diabetes and hypothyroidism during pregnancy was observe in 50% of them. Objective: Determine iodine concentration in urine of the school population in 17 departments of the country and measure the levels of iodine in urine in 200 pregnant women from 15-37 years of age and their levels of glycaemia, and thyroid TSH. Methods: During the years, 2006 and 2007 were evaluated 4487 school randomized, in a probabilistic sample, 3198 in rural areas and 1,289 in urban areas; casual urine samples was collected to determine iodine content. The urinary concentration of iodine in two hundredpregnant women, concentration of iodine in salt, and levels of glycaemia and TSH were also included in the present study All candidates agreed with the informed consent under the ethics rules. Results: These data showed by comparing the levels of iodine in urine concentration in more than adequate and excessive level but this last was markedly elevated (93.8%). The median level greater than 300 µg/L was observed in 100% of the 4,487 urine samples, while the median urinary iodine levels of300-500 µg/L was 91.3% and above 500 was 9.7%. These levels showed the risk of developing thyroid autoimmune diseases. In 200 pregnancy women the average of urine concentration of iodine was 498 pcg/L, subclinical and clinical hypothyroidism and gestational diabetes was 50% of both. Conclu-sion: To obtain normal median urinary iodine levels is necessary to decrease the amount of iodine in salt. The main recommendation is to insist on adequate monitoring of iodized salt consumption. Also continue surveillance and monitoring in sentinel sites reporting the importance of adequate iodine intake of the population especially in pregnant women that also need to be warm about the diabetes during pregnancy but also a regimen is necessary to keep them within the normal levels of glycemia. The subclinical hypothyroidism has been also studied in the same patients.

El principal indicador del impacto de la yodación de la sal de consumo humano es la concentración urinaria de yodo la cual es útil en el monitoreo de la sal. En la encuesta del año 1988 realizada en el Paraguay, se alcanzó una prevalencia de bocio de 48,6% en la población escolar con un déficit de yodo en la sal, pero el año 2000 en el estudio del proyecto de Tiroides Móvil, se redujo por el método ecográfico a 17%. Ese mismo año la mediana de los niveles urinarios en niños escolares de 6-12 años fue 258 µg/L, considerando que 30% se encontraba entre el valor ideal de 100 a 199 µg/L y 46,1% sobre 300 µg/L, implicando un riesgo de exceso de yodo en dicha población con las posibles consecuencias de aparición tanto de hipo como de hipertiroidismo. El 93% presentó exceso de yodo en la sal y la mediana urinaria fue 437 ug/ mL. Un grupo de embarazadas han sido estudiadas en el Hospital San Pablo por primera vez en el Paraguay para la determinación de la yoduria, yodo en sal, diabetes gestacional, hipotiroidismo en el embarazo y sus valores antropométricos resultando un hipotiroidismo subclínico del 50% y diabetes gestacional del 50%. Objetivo: Determinar las yodurias en la población escolar de 6-12 años pre púber de ambos sexos en 17 departamentos del país y en una submuestra en embarazadas y también niveles de glicemia en el embarazo en un hospital de Asunción. Sujetos y Métodos: En el periodo del 2006-2007 fueron evaluados 4.487 escolares randomizados, en una muestra probabilística, 3.198 en el área rural y 1.289 en el área urbana con muestras en orina casual. El año 2015, doscientas embarazadas fueron estudiadas con muestras de glicemia en ayunas y 2 horas post prandial, dosaje de TSH, yodo en sal de 100 gramos de la sal de consumo en sus hogares y de orina para ver la concentración de yodo en sal y urinaria de yodo. Todos los candidatos fueron estudiados bajo consentimiento autorizado y de acuerdo a normas éticas. Resultados: Al comparar los niveles de yodo en orina en el nivel más que adecuado y el excesivo de la yoduria se vió que éste último nivel estaba marcadamente elevado (93.8%), que la mediana de los niveles mayores a 300 ug/L era del 100% del total de las 4.487 muestras de orina, mientras que la mediana de los niveles de yoduria entre 300-500 µg/L fue de 91,3% y por encima de 500 fue 9.7% lo cual implicó el riesgo de desarrollar enfermedades tiroideas autoinmunes. Las embarazadas presentaron una mediana urinaria de yodo 484 µg/L, diabetes gestacional e hipotiroidismo subclínico en 50%. Conclusión: Para normalizar los niveles de yoduria, es necesario disminuir la cantidad de yodo en la sal. La recomendación es insistir en el monitoreo de la adecuada yodación de las sales de consumo familiar y continuar con la vigilancia y el monitoreo constante en sitios centinelas divulgando la importancia de la adecuada ingesta de yodo a la población. Un régimen dietético a las embarazadas es necesario implementar en el primer trimestre del embarazo.