Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male.

21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand, mutations within the CYP17A1 gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone. In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the CYP21A2 and CYP17A1 genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C > G (p.Thr390Arg) in CYP17A1, which is the second documented case in literature, stands out due to its unique set of accompanying features. Mutations occurring in CYP21A2 and CYP17A1 result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.

A Novel Variant in AKAP9 Gene, a Controversial Gene, in Long QT Syndrome.

Introduction: Long QT syndrome (LQTS) is a common congenital cause of fatal cardiac arrhythmia. Characteristic clinical findings are prolonged QT interval and ventricular arrhythmia on electrocardiogram (ECG), syncope, seizure, and sudden death. It is a genetically heterogeneous disease. To date, disease-causing variant have been reported in seventeen genes. The AKAP9 is still considered controversial among those genes. Case Report: We report the case of a 10-year-old female who was born from a non-consanguineous Turkish couple. She visited pediatrics cardiology clinic presenting with dyspnea and tachycardia. Prolongation of the QT interval was detected in her ECG. Panel test associated with LQTS genes was performed. She was diagnosed with long QTS type 11 due to a heterozygous variant in AKAP9:c.11487_11489 delTACinsCGTA, p.(Thr3830ValfsTer12), that was revealed through next-generation sequencing test. The variant was also found in her mother and brother. Discussion and Conclusion: Novel heterozygous frameshift variant in the AKAP9 gene was considered as "Uncertain Significance (VUS)" in the ACMG classification. The novel variant is absent from population databases (PM2); it is a null variant (PVS1_moderate). AKAP9 gene has the lowest known rate among the causes of LQTS. Information is limited on genotype-phenotype correlation. Yet it is still among the candidate genes. Although the relationship of the AKAP9 gene with LQTS has not yet been fully indicated, individuals with a pathogenic variant in AKAP9 gene and silent carriers may be at risk for fatal cardiac events. Improvements of the genetic tests in the near future may contribute to the literature and clinical research about AKAP9 gene.

Cancer rates and characteristics of thyroid nodules with macrocalcification.

AIMS: The aim of this study was to determine the malignant potential of thyroid nodules with macrocalcifications and to evaluate the role of other sonographic findings in the diagnosis of malignancy in thyroid nodules besides macrocalcifications. METHODS: The findings of 8250 patients who applied to our outpatient clinic and underwent thyroid ultrasonography(US) between 2008 and 2021 were retrospectively reviewed. We included a total of 296 patients with 296 macrocalcified nodules (macrocalcification group) and an age- and sex matched group of 300 patients (control group) with the cytopathologic and/or histopathologic data of fine-needle aspiration biopsy (FNAB) of thyroid nodules without calcification. Demographic characteristics of these patients, US characteristics of the nodules, and thyroid function tests were recorded. Cytopathological data of FNAB were classified according to BETHESDA. RESULTS: The malignancy rate was 14.2% (42/296) in the macrocalcification group and 5.3% (16/300) in the control group (p < 0.001). There was no significant relationship between interrupted peripheral calcification and malignancy. Hypoechoic or markedly hypoechoic appearance, irregular border, solid structure, presence of accompanying pathological lymphadenopathy on sonographic examination and upper and middle zone localization were other sonographic features that increased the risk of malignancy of a nodule. The presence of autoimmunity was not found to be associated with the risk of malignancy. TSH and calcitonin levels of malignant nodules were higher than benign nodules. There was no significant difference between gender and malignancy. In the univariate analysis, it was found that the presence of macrocalcification increased the risk of malignancy 2.935 times. (OR:2.935, p < 0.001.95% CI for OR 1.611-5.349) In addition, being younger, being in the high TIRADS category, and being in the upper and middle zones were factors that increased the risk of malignancy. Gender, TSH level, nodule volume and structure were not associated with malignancy. However, after multivariate analysis, factors that significantly increased the risk of malignancy were younger age, higher TIRADS category, and nodule localization. CONCLUSION: In our study, the malignancy rate was higher in the macrocalcification group than in the control group. However, no correlation was found after multivariate analysis. In the multivariate analysis, younger age, higher TIRADS category, and nodules located in the upper and middle zone were other factors associated with malignancy. There was no association between peripheral interrupted calcification and malignancy risk.

Should we reconsider high-risk features in thyroid ultrasonography?

OBJECTIVE: Round shape is generally considered to reduce the risk of malignancy according to recent guidelines. On the contrary, according to some reports, spherically shaped thyroid nodules are associated with a higher risk of malignancy. Thus, we aimed to evaluate the malignancy risk of solid round isoechoic nodules detected at thyroid ultrasonography and compare it with that of solid ovoid isoechoic nodules. METHODS: Between 2017 and 2022, solitary solid round isoechoic nodules with diameters ³10 and £25 mm at thyroid ultrasonography were retrospectively selected and enrolled in the study. Age, size, nodule volume, serum thyrotropin levels, thyroid antibody levels, and cytopathological and histopathological results were recorded. RESULTS: A total of 457 solitary solid isoechoechoic nodules from 457 patients (262 females and 195 males; median age, 59 [31-70] years) were selected, of which 203 were solid round isoechoic nodules, and 254 were solid ovoid isoechoic nodules. A total of 54 surgical operations were performed on 457 nodules, and 31 of them resulted in malignancy. From the 31 malignant results, 25 originated from solid round isoechoic nodules and the remaining 6 originated from solid ovoid isoechoic nodules (p<0.025). CONCLUSION: We found that round nodules have higher malignancy rates than ovoid nodules. We think that ultrasonographic risk stratification systems used to target the most suitable nodules for the necessary biopsies can be dynamically updated, and sphericity can be added as a parameter in patient-based decision-making.

The sonographer's and pathologist's perspective of echogenic microfoci in papillary thyroid carcinoma.

Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF. Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists. Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001). Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

The prevalence of smoking among soldiers of the gendarmerie in a provincial center and affecting factors: A cross-sectional study from Turkey.

Determining the smoking rates and nicotine dependency levels of soldiers can be a guide in smoking cessation interventions and developing a policy for smoking prevention for soldiers serving in military units. The cross-sectional study was conducted with a total of 313 soldiers stationed in gendarmerie units in a city center in the Central Anatolian Region of Turkey. Data were collected between 01.06.2021 and 31.07.2021 by face-to-face interview technique using Personal Information Form and Fagerström Nicotine Addiction Test. It was determined that 54.6% of the participants smoked, 87.1% had low-moderate nicotine addictions, and 94.9% were smokers in their friends' circle. It was revealed that the prevalence of smoking among the participants was high, and the nicotine addiction levels of the participants working in the "Prison" unit were higher.

Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.

CONTEXT: The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS: This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS: Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION: Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.

Long-term effects of radioiodine treatment on thyroid functions and ultrasonographic features in patients with toxic adenoma and toxic multinodular goitre.

OBJECTIVE: This study aimed to investigate the long-term effect of radioiodine (RAI) treatment on thyroid functions and ultrasonographic changes in the thyroid gland and toxic nodules. METHODS: Thyroid function tests and ultrasonography reports of patients diagnosed with toxic adenoma (TA) or toxic multinodular goitre (TMNG) between 2000 and 2021 were retrospectively analysed. RESULTS: We included 100 patients whom thyroid function and ultrasonography results were obtained from our outpatient clinic before and at least 36 months post-RAI. At the end of the follow-up period, the mean thyroid volume reduction in patients with TA and TMNG was 56.6% ± 3.1% and 51.1% ± 6.7%, respectively; the mean volume decrease of all toxic nodules was 80.5% ± 1.9%. The volume of the thyroid and toxic nodules was significantly reduced up to 12 years (p < 0.01). Between 3 and 10 years after RAI therapy, the annual incidence of hypothyroidism was 2.0% and 1.5% in the TA and TMNG groups, respectively. Toxic nodules were more frequently solid and hypoechoic in post-RAI ultrasounds (p < 0.01). CONCLUSIONS: The volume of thyroid gland and toxic nodules continuously decreases, as the risk of hypothyroidism increases up to 10 years after RAI treatment. After RAI treatment, patients should be followed up to check their thyroid functions. In post-RAI examinations, toxic nodules may show ultrasonographic features suspicious for malignancy. History taking should include previous RAI therapies and old scintigraphy scans should be evaluated to avoid unnecessary procedures and non-diagnostic biopsy results.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia.

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.

Secondary metabolites from the underground parts of Valeriana sisymbriifolia Vahl. and their in vitro cytotoxic activities.

Cytotoxic activity-guided isolation studies on the underground parts of Valeriana sisymbriifolia Vahl. led to the isolation of 12 secondary metabolites including two undescribed iridoids, sisymbriifolivaltrate and sisymbriifolioside, and two unreported sesquiterpene lactones, sisymbriifolins A and B. Chemical structures of the isolates were established by extensive 1D and 2D NMR analyses as well as HR-ESI-MS. The in vitro cytotoxic activities of the extract, sub-fractions and isolates on lung (A549), breast (MCF7), gastric (HGC27) and prostate (PC3) cancer cell lines were evaluated by MTS assay. Sisymbriifolivaltrate, didrovaltrate, valtrate, 7-homovaltrate and 1-α-acevaltrate exhibited promising cytotoxic activity on MCF7 cell line with IC50 values ranging from 2.5 to 12.3 µM, while valtrate demonstrated the best cytotoxicity against A549 cells with the IC50 value of 7.5 µM. Valtrate and 7-homovaltrate were found to exert noteworthy cytotoxicity towards HGC27 cell line (IC50 values: 2.3 and 3.7 µM, respectively), whereas valtrate, 7-homovaltrate and 1-α-acevaltrate (IC50 values: 2.3-9.7 µM) were found to be potent cytotoxic against PC3 cells. Among the tested compounds, particularly valepotriate-type iridoids were found to be the main cytotoxic principles of V. sisymbriifolia.

Evaluation of chronic pruritus and associated skin findings in patients with diabetes mellitus.

Background/aim: To explore the dermatological lesions associated with chronic pruritus in patients who were followed up at our clinic for type 1 and type 2 diabetes mellitus (DM). Materials and methods: The study population consisted of 249 patients with DM, who presented to the endocrinology clinic at Ankara University Faculty of Medicine between January 2022, and March 2022, regardless of whether they had reported experiencing pruritus symptoms. The visual analog scale and 5-D itch scale were used to determine the severity of itching in patients. Dermatological examination findings were also evaluated. Results: Of the 249 patients with DM, mean duration since diabetes was diagnosed was 12 ± 9.2 [median 10 (0.3-46)] years, and the mean HbA1c levels were 8.1% ± 2.1%. Pruritus was detected in 77 (30.9%) patients and the mean duration of diabetes diagnosis was 13.4 ± 9.7 years. Examination of the microvascular and macrovascular complications showed that the incidence of retinopathy, nephropathy, neuropathy and peripheral arterial disease was 31.2% (p = 0.003), 31.2% (p = 0.005), 66.2% (p < 0.001) and 10.4% (p = 0.038), respectively, in the group with pruritus. These incidences were significantly higher in the group with pruritus than in those without pruritus. Dermatological examination showed that the most common condition was xerosis (64%), followed by fungal skin infection (16%) and bullous pemphigoid (8%). No skin findings were noted in 7% of patients who complained of itching. Conclusion: Chronic pruritus may be associated with several factors such as poor glycemic control, high BMI and microvascular and macrovascular complications in patients with DM. Especially in patients with severe generalized pruritus who do not respond to standard antipruritic treatments, the use of DPP-4 inhibitors, a class of oral antidiabetic agents, should be questioned and all medications being used by the patient should be reviewed.

Primary hyperparathyroidism and sarcoma: A case report and literature review.

ABSTRACT: The relationship between primary hyperparathyroidism (PHPT) and bone sarcoma is debatable, especially after wider use of teriparatide treatment, concerns have intensified on the issue. Extensive search in English literature revealed 10 cases reported having PHPT and sarcomas. Besides, three cases of bone sarcoma occurring after teriparatide treatment had been reported. Hereby, we report a 51-year-old woman with a prolonged history of PHPT. She was diagnosed with chondrosarcoma 9 years after refusal and lack of treatment for PHPT. She was cured surgically for both chondrosarcoma and parathyroid adenoma at 1-year interval. So far, large cohorts did not show an increase in the incidence of bone sarcomas in PHPT. Several case observations, including the current one, as well as data from in vitro and rat studies, pointed out prolonged parathormone exposure, may be a risk for bone sarcomas. Under these circumstances, a safer attitude on individual basis would be the prevention of prolonged parathormone exposures.

Is lifelong follow-up necessary for low-risk papillary thyroid carcinoma? Case series and a review of the literature.

ABSTRACT: Late recurrences of papillary thyroid carcinoma (PTC) are seen rarely, especially for low-risk PTC. However, there are cases of late metastasis described in the literature, even four decades after the first treatment. We presented three low-risk PTC cases with late recurrences. In the first case, recurrence with distant organ metastasis without locoregional disease occurred 36 years after the first treatment. Recurrences in second and third cases were seen with lateral neck metastasis without central (skip metastasis), 17 and 10 years after the primary treatment. Initial treatment was ideal, and all three were followed with a complete response for years, after recurrences were diagnosed and appropriate treatments were administered. Increasing frequency of low-risk PTC increases medical costs of these patients. Thus, some suggest shortening the follow-up period not only because the increasing health burden but also because of the rarity of late recurrences as well. Some authors suggest that dynamically risk-stratified (DRS) low-risk thyroid cancer patients having excellent response to treatment after 5 years of follow-up can be discharged to primary care. Primary care facilities may follow patients with unmeasurable Thyroglobulin (Tg) levels; however, our cases suggest continuing thyroglobulin measurements (annual or at least every few years) for the exceptional but possible late recurrences.

Congenital Myasthenic Syndromes in Turkey: Clinical and Molecular Characterization of 16 Cases With Three Novel Mutations.

BACKGROUND: Congenital myasthenic syndromes (CMS) are composed of numerous hereditary disorders involving genetic mutations in proteins essential to the integrity of neuromuscular transmission. The symptoms of CMS vary according to the age at onset of symptoms, and the type and severity of muscle weakness. Effective treatment and genetic counseling depend upon the underlying pathogenic molecular mechanism and subtype of CMS. METHODS: A retrospective and cross-sectional study was performed with 16 patients with a genetically confirmed diagnosis of CMS to share our experience with clinical symptoms, demographic data, genetic variants, and treatments applied. RESULTS: Sixteen patients with a specific CMS genetic diagnosis (three novel mutations) were identified, including CHRNE (n = 7), DOK7 (n = 2), AGRN (n = 2), RAPSN (n = 1), CHRNA1 (n = 1), CHRNB1 (n = 1), CHAT (n = 1), and SCN4A (n = 1). Age at onset of symptoms ranged from the neonatal period to 12 years. Genetic diagnosis was confirmed between the ages of three months and 17 years. A significant delay was determined between the onset of symptoms and genetic diagnosis of the disease. CONCLUSIONS: This study highlights the importance of genetic testing in CMS. Due to the rarity of CMS, more cases will be recognized and reported as the use of laboratory and genetic testing accelerates. We hope that our experience will grow and contribute further to the literature as clinical follow-up and treatment increase.

Activity-Guided Isolation of Cytotoxic Non-Glycosidic Ester Iridoids from Valeriana alliariifolia Adams and Unravelling Their Cell Death Mechanisms.

The aim of this study was to isolate the cytotoxic compounds from V. alliariifolia via activity-guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1-11) most of which belong to non-glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7-deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4-6 and 8 were found to be the potent cytotoxic compounds (IC50 <10 µM) against at least one of the tested cancer cell lines. Thus, 2, 4-6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4-6 and 8 could be potential anticancer drug leads that deserve further in vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.

Can Serum Thyroglobulin Levels Help to Identify the Involved Neck Compartment of Differentiated Thyroid Carcinoma?

We aimed to evaluate the predictive ability of serum thyroglobulin (Tg) levels on the localization of the metastatic lymph node compartments in locoregional metastases of papillary thyroid cancer (PTC). This retrospective study included 143 patients who underwent neck dissections for a total of 172 for persistent/recurrent locoregional PTC. They were grouped according to the localization of lymph node metastasis (LNM): Central (C-LNM), Lateral (L-LNM), both central and lateral LNM (C+L LNM). To confirm that the Tg cutoff discriminated LNM localizations, the sample was categorized as suppressed (<0.1 mU/l) or non-suppressed (>0.1 mU/l) according to TSH and ROC analysis. Mixed-effects models were used to investigate the effect of LNM localization on Tg levels and to eliminate the confounding effects of TSH, tumor burden (defined as the number and the largest diameter of LNM), and RAI. Mean Tg levels were 1.43 µg/l for C-LNM (n=47), 3.7 µg/l for L-LNM (n=99), and 8.60 µg/l for C+L LNM (n=26). Independent of TSH, tumor burden and RAI, the mean Tg levels of L-LNM and C+L LNM groups were not significantly different, while that of C-LNM was significantly lower than those of L-LNM and C+L LNM. To discriminate C-LNM from L-LNM and C+L LNM in patients with TSH>0.1 mU/l, the optimal cutoff for Tg was 1.05 µg/l (sensitivity=74.7%, specificity=70.4%, PPV=87.7%). L-LNM increases serum Tg levels more than C-LNM in persistent/recurrent locoregional nodal disease of PTC. Tg above 1.05 µg/l may indicate lateral LNM. Tg may be an important marker for the localization of LNM in the neck.

Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS-CoV-2 from 946 whole-exome sequencing data in the Turkish population.

Heterogeneity in symptoms associated with COVID-19 in infected patients remains unclear. ACE2 and TMPRSS2 gene variants are considered possible risk factors for COVID-19. In this study, a retrospective comparative genome analysis of the ACE2 and TMPRSS2 variants from 946 whole-exome sequencing data was conducted. Allele frequencies of all variants were calculated and filtered to remove variants with allele frequencies lower than 0.003 and to prioritize functional coding variants. The majority of detected variants were intronic, only two ACE2 and three TMPRSS2 nonsynonymous variants were detected in the analyzed cohort. The main ACE2 variants that putatively have a protective or susceptibility effect on SARS-CoV-2 have not yet been determined in the Turkish population. The Turkish genetic makeup likely lacks any ACE2 variant that increases susceptibility to SARS-CoV-2 infection. TMPRSS2 rs75603675 and rs12329760 variants that were previously defined as common variants that have different allele frequencies among populations and may have a role in SARS-CoV-2 attachment to host cells were determined in the population. Overall, these data will contribute to the formation of a national variation database and may also contribute to further studies of ACE2 and TMPRSS2 in the Turkish population and differences in SARS-CoV-2 infection among other populations.

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

Prognostic value of the lactate/albumin ratio for predicting mortality in patients with pneumosepsis in intensive care units.

ABSTRACT: The lactate/albumin (L/A) ratio correlates with Acute Physiology and Chronic Health Evaluation 2 (APACHE-2) and Sequential Organ Failure Assessment (SOFA) scores. This study examined whether the L/A ratio has prognostic value in a larger group of critically ill (adult) patients admitted to an intensive care unit (ICU) due to pneumosepsis.This retrospective study analyzed the data of 273 patients with pneumosepsis admitted to the Internal Medicine ICU of Adana City Training and Research Hospital between 2018 and 2020. Patients diagnosed with pneumosepsis were included in the study. The data were obtained from the hospital system. Patients who had cancer, who were pregnant, and patients whose necessary data could not obtain for the study were excluded from the study.The L/A ratio was superior to lactate or albumin alone as a predictor of mortality. Furthermore, this result was valid for patients with kidney and hepatic dysfunction. A correlation occurred between the L/A ratio and APACHE-2 and SOFA scores in patients with pneumosepsis.The L/A ratio can be an independent predictor of mortality in patients with pneumosepsis and patients with pneumosepsis with renal and hepatic dysfunction. The L/A ratio correlated positively with lactate levels and APACHE-2 and SOFA scores but negatively with albumin levels.