The relationship between thyroid and human-associated microbiota: A systematic review of reviews.

In recent years, a growing number of studies have examined the relationship between thyroid pathophysiology and intestinal microbiota composition. The reciprocal influence between these two entities has been proven so extensive that some authors coined the term "gut-thyroid axis". However, since some papers reported conflicting results, several aspects of this correlation need to be clarified. This systematic review was conceived to achieve more robust information about: 1)the characteristics of gut microbiota composition in patients with the more common morphological, functional and autoimmune disorders of the thyroid; 2)the influence of gut microbial composition on micronutrients that are essential for the maintenance of thyroid homeostasis; 3)the effect of probiotics, prebiotics and synbiotics, some of the most popular over-the-counter products, on thyroid balance; 4)the opportunity to use specific dietary advice. The literature evaluation was made by three authors independently. A five steps strategy was a priori adopted. After duplicates removal, 1106 records were initially found and 38 reviews were finally included in the analysis. The systematic reviews of reviews found that: 1) some significant variations characterize the gut microbiota composition in patients with thyroid disorders. However, geographical clustering of most of the studies prevents drawing definitive conclusions on this topic; 2) the available knowledge about the effect of probiotics and synbiotics are not strong enough to suggest the routine use of these compounds in patients with thyroid disorders; 3) specific elimination nutrition should not be routine suggested to patients, which, instead have to be checked for possible micronutrients and vitamins deficiency, often owed to gastrointestinal autoimmune comorbidities.

Therapeutic targeting of the pituitary tumor microenvironment.

The tumor microenvironment (TME), the complex environment in which tumors develop, has been increasingly targeted for cancer treatment in recent years. Aggressive pituitary tumors and pituitary carcinomas have been so far targeted with immune-checkpoint inhibitors (28 cases, including a large cohort), and anti-angiogenic drugs (34 cases), specifically bevacizumab (30 cases), sunitinib (three cases), and apatinib (one case). Here, we reviewed all these cases, reporting tumor response, potential predictors of response, as well as adverse events. Given that the histological type could potentially influence treatment response, we present the existing data separately for each type. Briefly, under ICIs, complete response was noted in one case, partial response in a third of cases, stable disease in 10% of cases, while 54% of tumors progressed. Under BVZ monotherapy, most cases (57%) showed stable disease, while 36% of tumors progressed; partial response was reported in only one case. The three cases treated with sunitinib monotherapy progressed. Regarding predictive factors of response, the tumor type (aggressive pituitary tumor versus pituitary carcinoma) appears as the strongest predictor of response to ICIs. To date, no predictor of response to anti-angiogenic drugs in the treatment of pituitary carcinomas and aggressive pituitary tumors has been identified. The interest of BZV add-on to first- or second-line chemotherapy warrants further investigation. In addition, we discuss perspectives regarding the TME-targeting in aggressive pituitary tumors and pituitary carcinomas, including perspectives on immunotherapy, anti-angiogenic drugs, as well as on other TME components, namely stromal cells, extracellular matrix, and secreted molecules.