Impact of Chemical Endocrine Disruptors and Hormone Modulators on the Endocrine System.

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function.

Nutritional Intervention in Cushing's Disease: The Ketogenic Diet's Effects on Metabolic Comorbidities and Adrenal Steroids.

BACKGROUND: a very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of a VLCKD in patients with Cushing's disease (CD) as adjunctive therapy to treatment for the primary disease. METHODS: we evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline after 1 week and 3 weeks of VLCKD and, further, after 2 weeks of a low-carbohydrate ketogenic diet (LCKD). RESULTS: after 5 weeks of diet, a significant decrease in BMI (p = 0.002), waist circumference (WC) (p = 0.024), systolic blood pressure (p = 0.015), diastolic blood pressure (p = 0.005), ACTH (p = 0.026), cortisone (p = 0.025), total cholesterol (p = 0.006), LDL cholesterol (p = 0.017), triglycerides (p = 0.016) and alkaline phosphatase (p = 0.008) and a significant increase in HDL cholesterol (p = 0.017), vitamin D (p = 0.015) and oral disposition index (oDI) (p = 0.004) was observed in the CD patients. A significant decrease in BMI (p = 0.003), WC (p = 0.002), systolic blood pressure (p = 0.025), diastolic (p = 0.007) blood pressure and total cholesterol (p = 0.026) and an increase in HDL cholesterol (p = 0.001) and oDI (p < 0.001) was observed in controls. CONCLUSIONS: the current study confirms that a ketogenic diet is effective in improving metabolic disorders in CD and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities.

Very Low-Calorie Ketogenic Diet: A Potential Application in the Treatment of Hypercortisolism Comorbidities.

A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcal/day), low carbohydrate intake (<50 g/day) and normoproteic (1−1.5 g of protein/kg of ideal body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushing's syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.

Metabolic comorbidities of adrenal insufficiency: Focus on steroid replacement therapy and chronopharmacology.

Adrenal insufficiency (AI) is characterized by higher mortality and morbidity compared with the general population. Conventional replacement steroid therapy, currently recommended for the treatment of AI, is associated with increased frequency of metabolic comorbidities due to daily overexposure. By contrast, dual-release hydrocortisone is associated with a decreased risk of metabolic comorbidities, providing an adequate release of hydrocortisone and mimicking the physiological profile of cortisol. These favorable effects are due to a reduced daily steroid exposure that does not affect the expression of the clock genes which are involved in metabolic pathways and are regulated by the normal physiological circadian rhythm of endogenous cortisol. This narrative review focuses on the possible metabolic comorbidities of AI due to steroid replacement therapy, which evaluates the effects of conventional and novel drugs with attention to chronopharmacology.