Metabolic syndrome (MetSyn) is a major health problem affecting approximately 25% of the worldwide population. Since the gut microbiota is highly connected to the host metabolism, several recent studies have emerged to characterize the role of the microbiome in MetSyn development and progression. To this end, our study aimed to identify the microbiome patterns which distinguish MetSyn from type 2 diabetes mellitus (T2DM). We performed 16S rRNA amplicon sequencing on a cohort of 70 individuals among which 40 were MetSyn patients. The microbiome of MetSyn patients was characterised by reduced diversity, loss of butyrate producers (Subdoligranulum, Butyricicoccus, Faecalibacterium prausnitzii) and enrichment in the relative abundance of fungal populations. We also show a link between the gut microbiome and lipid metabolism in MetSyn. Specifically, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) display a positive effect on gut microbial diversity. When interrogating the signature of gut microbiota in a subgroup of patients harbouring both MetSyn and T2DM conditions, we observed a significant increase in taxa such as Bacteroides, Clostridiales, and Erysipelotrichaceae. This preliminary study shows for the first time that T2DM brings unique signatures of gut microbiota in MetSyn patients. We also highlight the impact of metformin treatment on the gut microbiota. Metformin administration was linked to changes in Prevotellaceae, Rickenellaceae, and Clostridiales. Further research focusing on the microbiome-metabolome patterns is needed to clarify the exact association of various gut microbial communities with the progression of T2DM and the occurrence of various complications in MetSyn patients.

Metabolic syndrome (MetSyn) has a rapidly growing worldwide prevalence, affecting over 1 billion people. MetSyn is clustering many pathological conditions, which, untreated, could increase the risk and often lead to more severe metabolic defects such as type 2 diabetes and non-alcoholic fatty liver disease. Many data demonstrate the complex role of gut microbiota in the host metabolism, and hence, deciphering the microbiome patterns linked to MetSyn could enable us for novel diagnosis and monitoring markers and for better disease management. Moreover, interventions designed to alter patient microbiome composition may help prevent or decrease morbidity linked with MetSyn. However, the microbiome composition is largely different across geographically distinct populations. Our study investigated the microbiota and mycobiome patterns in Romanian metabolic syndrome patients. We also correlated the identified microbiome–mycobiome patterns with levels of metabolites important for host health such as short chain fatty acids, organic acids, and taurine. We found that MetSyn patients are harboring a microbiome enriched in Enterobacteriaceae, Turicibacter sp., Clostridium coccoides, and Clostridium leptum, while beneficial taxa such as Butyricicoccus sp., Akkermansia muciniphila, and Faecalibacterium prausnitzii were decreased. These microbiome changes were correlated with lower butyrate levels and increased succinate. In terms of mycobiome signatures, MetSyn was associated with a high abundance of Saccharomyces and Aspergillus species. Our data are the first reported on a Romanian population and confirming that the pathogenesis of MetSyn is closely related to gut microbiome and homeostasis.

Endogenous Cushing's syndrome is rare, with an incidence of 0.7-2.4 per a million people a year. Clinical presentation of Cushing syndrome can be pleomorphic, and establishing diagnosis can be difficult. Early recognition and rapid control of hypercortisolaemia are necessary to decrease morbidity and mortality in these patients. We report a series of 6 endogenous Cushing's syndromes of different etiologies (4 Cushing's disease and 2 adrenal Cushing's syndrome) assessed in our endocrine department over a decade (2009-2019). In order to highlight the diversity of clinical forms, diagnostic tools and specific management of this condition we labelled each case suggestively: the typical Cushing's disease, the Pseudo Cushing's, the elusive Cushing's disease, the mild autonomous cortisol hypersecretion, Cushing's syndrome in pregnancy and Cushing's disease with thromboembolism. We discussed their particularities which were revelatory for the diagnosis, such as dermatologic, cardiovascular, musculoskeletal, neuropsychiatric, or reproductive signs, reviewing literature for each manifestation. We also discuss the commonalities and differences in laboratory and imagistic findings. Therapeutic approach can also differ with respect to the particular condition of each patient and the multiple choices of therapy will be reviewed.

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm with distinctive clinical and immunophenotypic features, involving somatic mutations of BRAF and activation of MAPK pathway. Other BRAF mutated neoplasms such as papillary thyroid carcinoma (PTC), may also occur synchronous with EDC. There are several reports in the literature of concurrent Langerhans Cell Histiocytosis (LCH) and PTC which suggests that the association is not random, however ECD with systemic involvement and PTC has only been reported in one case only. We report a second case of EDC and concurrent PCT in a 30 years old young man, who first presented in our service with two years history of bilateral exophthalmos and progressive asthenia. Thyroid function was normal, excluding Graves disease. He had no polyuria and no other signs of hypopituitarism. The MRI of the orbit showed bilateral retroorbital pseudonodular masses of 3 cm. PET-CT scan was performed to reveal additional retroperitoneal pararenal masses with partial ureteral obstruction, bilateral and symmetric osteosclerosis of the meta – and diaphysis of femur and humerus, cardiac involvement with pericardial effusion and a right thyroid nodule with high metabolic activity. Bone scintigraphy unveiled typical lesions for ECD. Left retroorbital biopsy was performed and histiocytes with frothy cytoplasm were observed. Genetic and IHC testing of retroorbital tissue revealed BRAF V600E mutation. IHC of the histiocytes was positive for CD163 and for Phospho-ERK. EDC with central nervous system, bone, retroperitoneum and cardiac involvement was diagnosed and treatment with BRAF inhibitor vemurafenib was commenced, with rapid improvement of both exophthalmos and retroperitoneal masses at 3 and 6 months of treatment. FNAB for the thyroid nodule was performed that was suspicious of malignancy and followed by total thyroidectomy. Pathology report revealed a right papillary thyroid carcinoma T2N1b, with the presence of high cell component expressing BRAF V600E mutation. Radioiodine therapy was also performed and patient is currently under surveillance with levothyroxine substitution. This case outlines the systemic involvement of EDC and its association with BRAF-positive PTC with a view of considering an EDC diagnosis workup in a non-LCH histiocytic lesion with A BRAF(V600E) mutation.