Marek Ruchała’s research while affiliated with Poznan University of Medical Sciences and other places

Graves' disease (GD) and Graves' orbitopathy (GO) are multifactorial disorders with links to the gut microbiome and autoimmunity. It is observed that patients with GD exhibit altered gut microbiome diversity. However, little is known about the role of oral microbiota in GD and GO. This study aims to investigate the impact of oral health and oral sanitation on the clinical course of GO in patients disqualified from glucocorticoid treatment due to oral infections. We reviewed 188 admissions of 127 patients with GO, hospitalized in a tertiary university hospital. Clinical, biochemical, imaging, ophthalmological, and oral health assessment data from each admission were analyzed. Patients excluded from the glucocorticoids (GCs) therapy due to oral foci of infection had the clinical activity score (CAS) reassessed after three months, and they were divided into two groups: with and without improvement. Finishing dental treatment in the meantime was the only factor significantly correlated with improvement in these patients (p = 0.041). The secondary finding was that anti-thyroid peroxidase antibodies titer was significantly higher in the group with oral foci of infection considered as a contraindication for GCs (medians 28.50 vs 128.00; p = 0.026), and those patients were more likely to smoke than the group without oral issues (p = 0.024). The results of our study suggest that monitoring and treating oral diseases may be pertinent in patients with GO and might serve as a supportive treatment strategy for managing the condition. What is known: There is a recognized link between gut dysbiosis and the autoimmune processes in Graves' Disease (GD) and Graves' Orbitopathy (GO). What is new: Elevated levels of TPOAb have been observed in patients with GO who also have oral foci of infection. Dental treatment has been shown to lead to significant clinical improvements in patients with GO. Maintaining oral hygiene might serve as a supportive treatment strategy for managing GO.

Gaucher disease (GD), the most common ultra-rare metabolic disorder, results from lipid accumulation. Systemic inflammation, cellular stress, and metabolic dysfunction may influence endocrine function, including the thyroid. This study evaluated thyroid function and morphology in 60 GD patients, alongside carbohydrate and lipid metabolism. Anthropometric, biochemical, and hormonal tests were conducted, including thyroid ultrasound and shear-wave elastography (SWE). Clinical data, bone mineral density (BMD), and body composition (BOD POD) analyses were correlated. Healthy controls, matched for age, sex, and body mass index (BMI), were included. GD patients had higher thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels within normal limits. Hypothyroidism occurred in 7%, elevated anti-thyroid antibodies in 8%, and nodular goiter in 23%. Patients with nodular goiter showed lower platelet counts and higher chitotriosidase and glucosylsphingosine (lysoGb-1) levels. Patients with type 3 GD had larger thyroid volumes and greater stiffness on SWE than patients with type 1 GD. GD patients also exhibited increased metabolic risk, including central obesity and elevated glucose levels. GD patients, despite normal thyroid hormone levels, exhibit subtle alterations in thyroid function indicators. Their increased risk of central obesity and glucose metabolism disorders, alongside higher TSH and FT4 levels, underscores the need for closer monitoring and further investigation.

Although gene panels for complex phenotypes target genes contributing significantly to phenotypic variation, identifying causal mutations remains challenging. We aimed to define the process of analysing gene panel data to uncover genomic insights for traits with complex inheritance. The implemented procedure included the exploration of (i) the association between phenotypic variability and the variability of SNPs within genes, (ii) the association attributed to specific variants, (iii) causality potential by analysing the genomic context in the vicinity of the significantly associated SNPs (iii_a) either through clustering – to identify variants with genotypic patterns similar to the significant SNPs, or (iii_b) through smoothing the set of original P values to incorporate the information on the impact of the particular mutations, as expressed by the SNP-specific PhRED-CADD scores. This procedure was applied to the data from the obesity gene panel. No significant gene-level associations were found. However, the SNP-level results were promising in narrowing down the initially available set of variants to determine the true causal mutations. We introduced a procedure for analysing gene panel data to identify potentially causal mutations for phenotypes with complex inheritance patterns. The procedure allows for narrowing down the originally available set of variants offered by a gene panel, consisting of genes important for the phenotype under study, to SNPs that have a statistically and genomically validated potential to be causal in modifying protein structure.

Introduction and Objectives: Isolated hypogonadotropic hypogonadism (IHH) may be associated with pituitary gland and olfactory system disorders. We aimed to correlate findings of Magnetic Resonance Imaging (MRI) of the pituitary gland and olfactory system in IHH patients with the patients’ olfactory phenotype. Patients and methods: The present research was a single-center retrospective case-control study. MRI patterns of pituitary gland and olfactory system were studied in 46 patients, of whom 29 (63%) were classified on the basis of olfactometry as having Kallmann syndrome (KS) (16 patients with anosmia; 13 patients with hyposmia) and 17 (37%) as having normosmic IHH (nIHH). Results were compared with age- and sex-matched healthy controls. Genetic diagnosis was conducted in all IHH patients based on next-generation sequencing (NGS). Results: Almost 70% prevalence of pituitary hypoplasia was observed in IHH subjects. Olfactory Bulb (OB) abnormalities were identified in 80.4% of all patients, both the KS (82.8%) and the nIHH (76.5%) subjects. Incidence of unilaterally abnormal, hypoplastic Olfactory Sulcus (OS) was equally frequent in nIHH and KS. Statistically, piriform cortical thickness was significantly lower in all patient groups than in controls. Conclusions: MRI cannot exclusively differentiate between KS and nIHH, as both conditions may present with OB and OS abnormalities. A surprisingly high frequency of olfactory system abnormalities was observed in nIHH patients, while anterior pituitary hypoplasia was prevalent across all IHH patients. Notably, OB abnormalities were more predominant in KS patients than in those with nIHH.

Paragangliomas (PGLs) are a heterogeneous group of tumors of the nonepithelial neuroendocrine type with a significant percentage being genetically determined. They can develop from cells of the parasympathetic as well as the sympathetic nervous system. Tumors located in head and neck usually have a parasympathetic origin, whereas those in abdomen have a sympathetic origin. The aim of this study was to determine whether the development of PGLs at both locations is associated with specific variants of genes with proven relevance for the formation of these tumors. 31 patients with abdominal PGL and 16 with head and neck PGLs were analyzed at 12 genes whose defects are among the most common genetic determinants of PGLs. The impact of SNPs on differentiation between both tumor types was assessed by fitting a decision tree and quantifying genotype effects of SNPs by the Shapley Additive Explanation metric. The study demonstrated that SNPs rs3748576 within KIF1B gene and rs10060259 within SDHA gene increase the probability of abdominal tumour locations, while heterozygous GA genotypes of rs2435351 located within RET gene increase the probability of head and neck locations. The SNPs marked genes involved in the formation and functioning of the nervous system, but are located in introns, and thus themselves do not contribute to protein diversity. Still, intronic SNPs can indirectly affect the transcriptome by influencing alternative splicing, mRNA stability, or overlap with non-coding genes and other regulatory elements that affect transcription. Given this, it seems important to consider variants from non-coding regions in genetic analyses.

Background Saliva could be an attractive alternative to blood for assessing thyroid hormonal function. Objectives Our goal was to determine if the levels of thyroid hormones in saliva can accurately reflect a person’s thyroid status and if they consistently correlate with the levels of the same hormones in the blood. Design We conducted a cross-sectional study. Methods We enrolled a total of 109 participants with different thyroid conditions. We measured TSH (Thyroid-Stimulating Hormone), free T3 (fT3), and free T4 (fT4) in the blood using two different immunoassay methods: electrochemiluminescence immunoassay (ECLIA) and chemiluminescence immunoassay (CLIA). Saliva samples were collected using Salivette® tubes, and then we analyzed the levels of thyroid hormones in the saliva using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results Comparing salivary and serum levels of thyroid hormones, we observed significantly lower fT4 and higher fT3 levels in saliva (p < 0.001), regardless of the measurement method. We also found that salivary fT3 and fT4 levels were positively correlated in the entire group of participants (p < 0.001, R 0.575), as well as in those with TSH values within the normal reference range (p < 0.001, R 0.570). We further divided participants based on their TSH reference intervals and assessed the correlations between serum and salivary thyroid hormones within these groups. We also discovered that taking exogenous levothyroxine influenced the correlations between serum and salivary thyroid hormones. Thyroid antibodies did not have a significant impact on the levels of thyroid hormones in both serum and saliva. Conclusion This study demonstrates that salivary thyroid hormones can partially reflect the levels of these hormones in the blood. Saliva may be a useful tool in a clinical setting for patients with thyroid antibodies, but it may not be as effective for those who are taking levothyroxine as a treatment.

The thyroid hormone (TH) status is routinely assessed by thyrotropin (TSH) and thyroxine (T4). Both biomarkers are mainly regulated by TH receptor beta, whereas many peripheral organs employ the alpha receptor. Serum cluster of differentiation 5‐like molecule (CD5L) is a liver‐derived protein under control of both TH receptor isoforms. However, clinical data on its relation to TH status are sparse. An additional biomarker of TH status is needed in particular during pregnancy, where the routine biomarkers become dynamically disturbed. This study aimed to determine possible covariates regulating serum CD5L and to test its potential suitability as additional TH biomarker during pregnancy. A sandwich ELISA for serum CD5L was established using newly raised antibodies. Circadian effects and the impact of liver disease on serum CD5L concentrations were assessed. Serum samples from pregnant women with well‐characterized TH and trace element status were analyzed, and CD5L concentrations were correlated with other indicators of TH status including TSH, fT4, fT3, copper, and selenium concentrations. The new quantitative assay for CD5L showed high accuracy. Serum CD5L was stable in dilution and refreezing experiments and did not show strong circadian variance or dependency on liver disease. In serum of pregnant women, CD5L correlated positively to fT3, but not to fT4 or TSH. Significant positive correlations of CD5L were observed with serum levels of the TH‐responsive trace elements selenium and copper. The data support the potential suitability of serum CD5L as an additional marker of TH status, with potential value for pregnancy and thyroid disease.

Background: Acromegaly is a rare endocrine condition caused by excessive growth hormone (GH) production. Hypogonadotropic hypogonadism (HH) affects 30%–50% of acromegaly patients. Objectives: This study examined the frequency of HH in men with acromegaly and the effects of neurosurgical treatment during the follow-up period. Materials and Methods: A retrospective analysis of medical records from January 2015 to December 2022 was conducted. Data included clinical history, laboratory results, and pituitary MRI findings. Statistical analysis was performed using Statistica 13.3. Results: Patients were divided into two groups: a cross-sectional sample (preoperative n = 62; postoperative n = 60) and a longitudinal sample (n = 53). In the longitudinal sample, preoperative HH was diagnosed in 41 males (77.36%). Post-surgery, HH prevalence decreased to 58.49% (n = 31), with a significant increase in postoperative testosterone levels (9.1 vs. 12.1 nmol/L; p < 0.001), particularly in patients with preoperative HH (7.2 vs. 10.2 nmol/L; p < 0.001). Among 41 patients with HH, 12 (29.27%) showed recovery. Testosterone levels were lower in patients with macroadenomas (7.2 nmol/L vs. 11.05 nmol/L; p < 0.001). Patients with HH had higher baseline levels of GH and insulin-like growth factor 1 (IGF-1) (GH: 3.37 ng/mL; IGF-1: 551 ng/mL vs. GH: 1.36 ng/mL; IGF-1: 355 ng/mL). Luteinizing hormone (LH) levels above 3.3 mIU/mL and follicle-stimulating hormone (FSH) levels above 4.4 mIU/mL predicted hypogonadism remission (Area under the curve (AUC): 0.838 and 0.792, respectively). Conclusions: Younger patients with macroadenoma and hyperprolactinemia are more likely to have preoperative hypogonadism. Neurosurgical treatment can normalize LH, FSH, and total testosterone in approximately 30% of these patients.