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.

Primary hypophysitis is a rare inflammatory condition which is mostly encountered in women. It represents 0.2–0.8% of pituitary pathologies and its annual incidence is estimated at 1 case per 9 million inhabitants. We present the case of a 28-year-old male, smoker, with sudden onset decreased libido, polyuria and polydipsia. At presentation he had an epicranial lipoma with and no other suggestive clinical signs. Biochemistry revealed hypernatremia 146 nmol/L, low testosterone level 0.5 ng/mL, low normal FSH and LH, normal prolactin level, normal adrenal and thyroid function. The dehydration test was positive for central diabetes insipidus (test stopped after 4 hours due to high plasma osmolality- 307 mOsm/l while urinary osmolality was lower than 300 mOsm/l and increased to 756 mOsm/l after Desmopressin). Diagnosis of central diabetes insipidus and hypogonadotropic hypogonadism has been made. Pituitary MRI showed thickening of the pituitary stalk close to the chiasm, a homogenous enlarged pituitary gland with loss of posterior bright spot. Serum alpha-fetoprotein and β-HCG were negative both in blood and CSF and scrotal ultrasound was normal excluding germinoma; normal blood angiotensin-converting enzyme, negative tuberculin purified protein derivative test and normal chest CT excluded sarcoidosis, tuberculosis and lung cancer. Also CSFflow cytometry, serum IGG4, c-ANCA, HIV serology were normal. The patient was treated with Desmopressin and Testosterone undecanoate and reevaluated at 3 and 6 months - pituitary IRM showed regression of the pituitary stalk mass, with persistence of DI and hypogonadism. The etiological spectrum of pituitary stalk (PS) lesions is broad, presenting a diagnostic challenge. We will discuss the differential diagnosis and management of this unusual case of primary infundibulohypophysitis. Pituitary stalk biopsy in this case was considered deleterious and not absolutely necessary as repeated MRI at 3 months showed a reduction of the stalk lesion. In cases of suspected lymphocytic hypophysitis, it is reasonable to try a course of high-dose glucocorticoids before proceeding to PS biopsy. However a positive response to glucocorticoids is not specific for hypophysitis, as a temporary relief can be observed also in lymphoma and germinomas. Similarly, in the absence of mass effect symptoms, like in our case it is reasonable to observe a PS lesion ensuring close hormonal and radiological follow-up as spontaneous resolution of PS has been observed. Conclusion: Primary hypophysitis occurring in a young man is a rare condition with poorly understood pathogenesis and lack of specific markers, thus represents a diagnostic challenge.

Glucocorticoids (GC) play major role in the physiologic stress response. However chronic exposure to glucocorticoids as seen in Cushing’s disease (CD) has detrimental effects on multiple systems: cardiovascular, metabolic, immune, psychological. Papillary thyroid carcinoma is the most common type of thyroid cancer and the most common endocrine malignancy and its incidence has been increasing lately. However concomitant thyroid cancer with CD is uncommon. We report a case of papillary thyroid microcarcinoma (PTMC) in a woman with metabolic syndrome and multinodular goiter, diagnosed with CD due to a corticotroph pituitary microadenoma. Both CD and thyroid cancer were cured after surgery. A review of literature shown association between papillary thyroid carcinoma and Cushing’s disease is very rare and so far there is no known genetic mutation to link the two neoplastic conditions. While this may be a random association, possible implications of chronic GC exposure in cancer progression are discussed.

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.

Case presentation: Mrs. S presented in an endocrine clinic for fatigue, weight loss, restlessness and goiter. She was obese with a BMI of 51 kg/mp, hypertensive and had a medium size, nontender goiter. Lab test revealed hyperglycaemia, suppressed TSH (<0.03mUI/L), on two separate occasions, mid-normal fT4 and T3. Thyroid ultrasound revealed multinodular goiter. A diagnosis of polynodular goiter with subclinical hyperthyroidism was made and patient was commenced on thiamazole 30 mg/day. She was also scheduled for a RAIU. Three weeks later she was admitted in the endocrine unit with a BMI of 47kg/mp. At presentation she had plethora, purpura on her breasts and bruised easily at venipuncture sites. FBC revealed neutrophilia with lymphocytopenia, normal platelets. Thyroid function tests revealed suppressed TSH (0.0164 mUI/L) with low fT4. Thiamazole was stopped. RAIU revealed low radioiodine uptake in the thyroid. Midnight plasma and salivary cortisol were high, morning plasma cortisol was borderline high, with increased ACTH. Urine cortisol was 10 fold upper limit of normal, low dexamethasone suppression test was negative. MRI of the pituitary revealed left sided pituitary microadenoma of 7,5/7 mm. Diagnosis of Cushing’s disease has been made and transsphenoidal adenomectomy was perfomed. At 3 weeks postoperatively patient has returned to clinic with symptoms of cortisol withdrawal while on 30 mg of cortisone daily. She had a BMI of 42 kg/mp, no plethora and no purpura. Cortisol day curve was within the therapeutic range. Off therapy, morning plasma cortisol was 8.89 mcg/dL, normal ACTH, midnight plasma cortisol of 1.44 mcg/dL and lower normal range of urinary free cortisol. Thyroid function tests were normal. Conclusion: Hypercortisolism is known to alter pituitary hormones, however it is not usual that mild Cushing’s disease to suppress TSH to ‘thyrotoxic’ level. In this case of unsuspected Cushing’s disease, thyroid function test alteration led to diagnosis.