RESUMEN

Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis. Aside being the first-line therapy for Type 2 Diabetes (T2D), many pleiotropic effects have been discovered in recent years, such as its capacity to reduce cancer risk and tumorigenesis. Although widely studied, the effect of metformin on thyroid cancer remains controversial. Potential mechanisms for its growth inhibitory effects have been elucidated in various preclinical studies that involved pathways related to adenosine mono-phosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), mitochondrial glycerophosphate dehydrogenase (mGPDH), and the nuclear factor κB (NF-κB). Hyperinsulinemia increases cell glucose uptake and oxidative stress, and promotes thyroid cell growth, leading to hyperproliferation, carcinogenesis, and the development of malignant tumors. Furthermore, it has also been related to thyroid nodules size in nodular disease, as well as tumoral size in patients with thyroid cancer. Several clinical studies concluded that metformin might have an important role as an adjuvant therapy to reduce the growth of benign and malignant thyroid neoplasms. This suggests that metformin might be useful for patients with differentiated or poorly differentiated thyroid cancer and metabolic diseases such as insulin resistance or diabetes.

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RESUMEN

A hipertensão resistente (HAR) ocorre quando a pressão arterial (PA) permanece acima da meta recomendada após o uso de três fármacos anti-hipertensivos com ação sinérgica em suas doses máximas toleradas recomendadas, preferencialmente incluindo um diurético. A identificação da contribuição do volume intravascular e da renina sérica na manutenção dos níveis elevados da PA permite um tratamento mais eficaz da hipertensão, ao atuar sobre o controle do volume intravascular, equilíbrio de sódio e sobre os efeitos do sistema renina-angiotensina-aldosterona (SRAA) no rim. Bloqueio sequencial do néfron (BSN) consiste em um aumento progressivo na depleção de sódio usando um diurético tiazídico, um bloqueador do receptor mineralocorticoide (espironolactona), furosemida e, finalmente, amilorida. Os mecanismos de ação, as indicações e os efeitos adversos são discutidos na presente revisão.

Resistant hypertension (HAR) occurs when blood pressure (BP) remains above the recommended target after the use of three antihypertensive drugs with synergistic action at their maximum recommended tolerated doses, preferably including a diuretic. The identification of the contribution of intravascular volume and serum renin in maintaining high BP levels allows a more effective treatment of hypertension, by acting on the control of intravascular volume, sodium balance and on the effects of the renin-angiotensin-aldosterone system (RAS) in the kidney. Sequential nephron block (BSN) consists of a progressive increase in sodium depletion using a thiazide diuretic, a mineralocorticoid receptor blocker (spironolactone), furosemide and, finally, amiloride. Mechanisms of action, indications and adverse effects are discussed in the present review

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