Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis.

The kynurenine pathway (KP) of tryptophan degradation includes several compounds that reveal immunomodulatory properties. The present study aimed to investigate the alteration in KP metabolites in young women with autoimmune thyroiditis (AIT) and their associations with thyroid function. The thyroid function tests, antithyroid antibodies measurement and ultrasonography of the thyroid gland have been performed in 57 young women with AIT and 38 age-matched healthy controls. The serum levels of tryptophan, kynurenine (KYN) and its metabolites were determined, and the activity of KP enzymes was calculated indirectly as product-to-substrate ratios. KP was activated and dysregulated in AIT, along with significantly elevated levels of KYN and anthranilic acid (AA), at the expense of the reduction of kynurenic acid (KYNA), which was reflected by the increase in the AA/KYNA ratio (p < 0.001). In univariate and multiple regression analyses, peripheral deiodinase (SPINA-GD) activity in AIT was positively associated with KYNA, AA, and quinolinic acid (QA). The merger of AA, AA/KYNA ratio, QA and SPINA-GD exhibited the highest sensitivity and specificity to predict AIT (p < 0.001) in receiver operating characteristic (ROC) analysis. In conclusion, the serum KYN metabolite profile is dysregulated in young women with AIT and could serve as a new predictor of AIT risk.

Cushing's disease presenting with recurrent abscesses followed by post-remission hyperthyroidism.

Summary: We report a case of a 59-year-old woman with Cushing's disease who developed hyperthyroidism following treatment of hypercortisolaemia. The patient with a history of recurrent hospitalisations caused by multi-sited soft tissue abscesses was admitted with sepsis. Both her medical history and physical examination suggested Cushing's syndrome. The initial hormonal diagnostic process, conducted after sepsis treatment, brought forth conflicting results. However, hormonal assessment repeated 3 months later indicated pituitary hypercortisolaemia, which was confirmed through bilateral inferior petrosal sinus sampling and was successfully treated with transsphenoidal pituitary surgery. Three months after the surgery, the patient was readmitted to our epartment with symptoms of hyperthyroidism, which was confirmed by laboratory tests. Thyroid scintiscans indicated Graves' disease. However, the absence of anti-thyroid stimulating hormone antibodies suggested other etiologies of hyperthyroidism. Eventually, the patient underwent radioiodine therapy. Currently, her condition is improving and she has had no recurrence of abscesses, severe infections, or hyperthyroidism. In conclusion, while clinical manifestation of hypercortisolaemia might be non-specific, its treatment may trigger the development of autoimmune diseases. Learning points: The presence of recurrent severe infections should prompt physicians to consider the possibility of hypercortisolaemia. Chronic hypercortisolism is debilitating and can lead to significant disability. Dexamethasone suppression testing in patients with active or recent severe inflammatory or infectious illnesses may produce misleading or confusing results. Clinicians should be aware of the potential development of autoimmune diseases following successful treatment of hypercortisolaemia.

Serum expression levels of selected microRNAs and their association with glucose metabolism in young women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances, such as insulin resistance and prediabetes, and the risk for their occurrence is especially increased in hyperandrogenic (HA) phenotypes of PCOS. Circulating microRNAs (miRNAs) may be involved in PCOS pathogenesis and regulation of metabolic processes. OBJECTIVES: The aim of the study was to assess expression levels of selected circulating miRNAs in women with PCOS and to investigate the relationship of these miRNAs with glucose metabolism. PATIENTS AND METHODS: The study included 95 patients with HA­PCOS and 76 healthy women similar to the study group in age and body mass index. Measurements of sex hormone concentrations, oral glucose tolerance test (OGTT), and transvaginal ultrasonography were performed. Serum levels of selected miRNAs (miR­27a, miR­34a, miR­106b, miR­193b, miR­181a, miR­181b, and miR­320) were assessed with real­time polymerase chain reaction, and their association with PCOS and glucose metabolism parameters was studied. RESULTS: Serum levels of all studied miRNAs, except for miR­34a, differed between the patients with HA­PCOS and healthy women (all P <0.05). In HA­PCOS, miR­27a and miR­320 levels correlated with fasting glucose (R = 0.33; P = 0.001 and R = -0.35; P <0.001, respectively) and insulin concentrations (R = 0.26; P = 0.01 and R = -0.23; P = 0.03, respectively). Additionally, the level of miR­27a correlated with mean glucose concentration during OGTT (R = 0.26; P = 0.01). No such correlations were observed in the healthy women. In linear regression analyses, both miR­27a and miR­320 were associated with fasting glucose concentrations after adjustment for potentially confounding factors in the HA­PCOS group only. CONCLUSIONS: The expression profile of circulating miRNAs is altered in patients with HA­PCOS. Circulating miR­27a and miR­320 could serve as potential biomarkers of glucose metabolism disturbances in PCOS.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.