ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in “aspect ratio” were 95.6%, 96.2%, and 95.4%, in “margin irregularity” were 90.7%, 90.5%, and 90.9%, in “margin smoothness” were 85.8%, 88.5%, and 83.0%, in “calcification” were 83.6%, 81.7%, and 82.0%, in “homogeneity” were 88.9%, 90.6%, and 82.2%, in “major echo” were 85.3%, 88.0%, and 85.4%, and in “contains very hypoechoic echo” were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis. Objective SW_TH01/II SWTH01II SWTHII SW TH01 II TH (SW_TH01/II computeraided computer aided (CAD TIRADS TI RADS (TI-RADS methods 201 2021 ratio irregularity smoothness calcification Results 22 sensitivity 956 95 6 95.6% 962 96 2 96.2% 954 4 95.4% 907 90 7 90.7% 905 5 90.5% 909 9 90.9% 858 85 8 85.8% 885 88 88.5% 830 83 0 83.0% “calcification 836 83.6% 817 81 81.7% 820 82 82.0% homogeneity “homogeneity 889 88.9% 906 90.6% 822 82.2% major echo 853 3 85.3% 880 88.0% 854 85.4% contains 920 92 92.0% 900 90.0% 924 92.4% 2.7 27 (2. 16 1 1. vs 297 29 29. 127 12 12. s 0.001. 0001 0.001 . 001 0.001) Conclusion SWTH TH0 20 202 95.6 96.2 95.4 90.7 90.5 90.9 85.8 88.5 83.0 83.6 81.7 82.0 88.9 90.6 82.2 85.3 88.0 85.4 92.0 90.0 92.4 2. (2 000 0.00 00 95. 96. 90. 85. 88. 83. 81. 82. 92. ( 0.0 0.

ABSTRACT FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation of blood lipid levels. Due to these actions, several laboratories have developed FGF21 analogs to treat patients with metabolic disorders such as obesity and diabetes. Here, we performed a systematic review and meta-analysis of randomized controlled trials that used FGF21 analogs and analyzed metabolic outcomes. Our search yielded 236 articles, and we included eight randomized clinical trials in the meta-analysis. The use of FGF21 analogs exhibited no effect on fasting blood glucose, glycated hemoglobin, HOMA index, blood free fatty acids or systolic blood pressure. However, the treatment significantly reduced fasting insulinemia, body weight and total cholesterolemia. None of the included studies were at high risk of bias. The quality of the evidence ranged from moderate to very low, especially due to imprecision and indirection issues. These results indicate that FGF21 analogs can potentially treat metabolic syndrome. However, more clinical trials are needed to increase the quality of evidence and confirm the effects seen thus far. FGF FGF2 functions production homeostasis levels actions diabetes Here metaanalysis meta analysis outcomes 23 articles metaanalysis. analysis. hemoglobin index pressure However insulinemia cholesterolemia bias low issues syndrome far 2

ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases. Objective ACE I/D, ID I/D , I D I/D) ACTN (ACTN RX R X PON (PON T107C TC T 107 C diabetes hypertension methods 7 5 screening Brazil consumption applied Results Additionally expected diabeteshypertense hypertense weight p 0.02, 002 0.02 0 02 0.02) 0.01, 001 0.01 01 0.01) percentage group Conclusion obesityrelated obesity related 10 00 0.0 0.

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events. (BPs fractures decades crystals time longterm term Longterm Long YearlyPivotal Yearly Pivotal up 1 (BMD reduction severe events is medicationrelated medication related morbimortality life

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo–pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months. Objective COVID19 COVID 19 COVID-1 disorder hypothalamo–pituitaryadrenal hypothalamopituitaryadrenal hypothalamo–pituitary adrenal hypothalamo pituitary (HPA SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- COVID19, 19, sparse Hence postCOVID19 postCOVID post post-COVID-1 methods 1860 18 18-6 lowdose low dose 1 ( mcg Results 3166 31 66 31.66 5 however 5833 58 33 58.33 Conclusion onethird one third severity COVID1 COVID- pituitaryadrenal hypothalamopituitary SARS-CoV postCOVID1 post-COVID- 186 18- 316 31.6 583 58.3 31. 58.

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH. Objective (CH gland date 1 methods 4 21 [2 44.6% 446 44 6 (44.6% 2 55.4% 554 55 (55.4%) families nextgeneration next generation relatives performed Results GHRHR GH1 GH GLI2 GLI PROP1, PROP1 PROP 1, POU1F1 POUF POU F LHX 23.4%, 234 , 23 (23.4%) PROP- Conclusion 23.4 63 7/11 711 7 (7/11 genetics factors [ 44.6 (44.6 55.4 5 (55.4% POU1F (23.4% 23. 7/1 71 (7/1 44. (44. 55. (55.4 (23.4 7/ (7/ (44 (55. (23. (7 (4 (55 (23 ( (5 (2

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1. Objective , (NAFLD) (NASH methods Epidemiological 57 examined Results 43 included 398 39 8 39.8 95 2 (HOMA 25 5 2. 0001 0 001 0.00 0016 016 0.016 respectively. respectively . respectively) group 26 ASTALT AST ALT (AST/ALT 1 highdensity density HDLc HDL c (HDL-c 4 mgdL mg dL mg/dL TC (TC 20 gammaglutamyl gamma glutamyl GGT (GGT 3 UL U L (TG 15 HDLc, c, HDL-c Conclusion (NAFLD 39. 9 000 00 0.0 01 0.01 0.

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The “GT+TT” genotype of the IGFBP3 rs2854744 polymorphism, compared with the “GG” genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 “T” allele, in comparison with the “G” allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 “GT+TT” genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations. Objective (NAFLD epidemic 5 consumption resistance rs rs285474 −202 202 (−20 G>T GT G T insulinlike like IGFBP (IGFBP3 study methods casecontrol case control 31 individuals 15 biopsyproven biopsy proven reactionrestriction reaction restriction analyses Results GT+TT GTTT TT “GT+TT GG “GG 2.7fold 27fold fold 2.7 2 7 P 0.009 0009 0 009 [OR 2.71 271 71 95 CI [CI 1.193.18. 119318 1.19 3.18 . 1 19 18 1.19-3.18) Additionally “T allele “G 0.008 0008 008 1.85 185 85 95CI 1.232.94. 123294 1.23 2.94 23 94 1.23-2.94) Conclusion susceptibility however populations rs28547 −20 20 (−2 (IGFBP 7fold 27 2. 0.00 000 00 9 193 1.193.18 11931 119 1.1 318 3.1 1.19-3.18 1.8 8 232 1.232.94 12329 123 1.2 294 2.9 1.23-2.94 rs2854 −2 (− 0.0 1.193.1 1193 11 1. 3. 1.19-3.1 1.232.9 1232 12 29 1.23-2.9 rs285 − ( 0. 1.193. 1.19-3. 1.232. 1.23-2. rs28 1.193 1.19-3 1.232 1.23-2 rs2 1.19- 1.23-

ABSTRACT Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL. Parameters of QoL along with clinical indices were compared among sub-groups divided according to Puget classification. Correlation analyses and regression analyses were performed to detect influential determinants to self-reported wellness. Results: Patients presented impaired QoL compared with general population ( p < 0.001), as assessed by SF-36. Correlation analyses indicated the detrimental influence resulting from central diabetes insipidus (CDI). Multivariate linear regression unveiled the adverse effect of CDI on Mental Component Summary (coefficient = −13.869, p = 0.007), GAD7 total score (coefficient = 2.072, p = 0.049) as well as PHQ9 total score (coefficient = 3.721, p = 0.001). Multivariate logistic regression verified CDI as a risk factor of developing depressive symptoms (OR = 6.160, p = 0.001). Conclusion: QoL of patients with craniopharyngioma was remarkably compromised before operation. CDI exerted detrimental influences on patients’ QoL and it might serve as a marker for early identification of patients at risk of depression. Objective (QoL oncology preoperative pre operative methods 10 3 SF36, SF36 SF , (SF-36) List90, List90 List 90, 90 List-90 GAD7, GAD (GAD7) PHQ (PHQ9 subgroups sub groups classification selfreported self reported wellness Results 0.001, 0001 0.001 0 001 0.001) SF36. 36. SF-36 CDI. . (CDI) coefficient 13869 13 869 −13.869 0.007, 0007 0.007 007 0.007) 2072 2 072 2.072 0.049 0049 049 3721 721 3.721 0.001. OR 6160 6 160 6.160 Conclusion operation depression 1 SF3 (SF-36 List9 9 List-9 (GAD7 (PHQ 000 0.00 00 SF-3 (CDI 1386 86 −13.86 207 07 2.07 0.04 004 04 372 72 3.72 616 16 6.16 (SF-3 List- (GAD 0.0 SF- 138 8 −13.8 20 2.0 37 7 3.7 61 6.1 (SF- 0. −13. 2. 3. 6. (SF −13 −1 −

ABSTRACT Objective: Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. Subjects and methods: The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. Results: R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. Conclusion: The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization. Objective . (CAD) ABCA transport (SNPs RC R C C17G, C17G CG 17G, 17G G C69T CT 69T T methods 7 6 replacement probes RTqPCR. RTqPCR RT qPCR. qPCR RT-qPCR Results 70.4% 704 70 4 (70.4% 57.8% 578 57 8 (57.8% OR 034 0 34 0.34 95 0.140.82 014082 0.14 0.82 14 82 (0.14-0.82 0.014. 0014 0.014 014 0.014] Similarly rs2740483 rs (rs2740483 63.3% 633 63 3 (63.3% 28.1% 281 28 1 (28.1% 442 42 4.42 2.139.16, 213916 2.13 9.16 , 2 13 9 16 (2.13-9.16) 0.001. 0001 0.001 001 0.001] 11.01 1101 11 01 [11.0 4.3115.24 4311524 4.31 15.24 31 15 24 (4.31-15.24 vs 386 86 3.8 2.4712.50, 2471250 2.47 12.50 47 12 50 (2.47-12.50) 0.015. 0015 0.015 015 0.015] Conclusion addition underexpression under revascularization (CAD 70.4 (70.4 57.8 5 (57.8 03 0.3 140 0.140.8 01408 0.1 082 0.8 (0.14-0.8 0.01 rs274048 (rs274048 63.3 (63.3 28.1 (28.1 44 4.4 139 2.139.16 21391 213 2.1 916 9.1 (2.13-9.16 000 0.00 00 11.0 110 [11. 3115 4.3115.2 431152 431 4.3 1524 15.2 (4.31-15.2 38 3. 4712 2.4712.50 247125 247 2.4 1250 12.5 (2.47-12.50 70. (70. 57. (57. 0. 0.140. 0140 08 (0.14-0. 0.0 rs27404 (rs27404 63. (63. 28. (28. 4. 2.139.1 2139 21 2. 91 9. (2.13-9.1 11. [11 311 4.3115. 43115 43 152 15. (4.31-15. 471 2.4712.5 24712 125 12. (2.47-12.5 (70 (57 0.140 (0.14-0 rs2740 (rs2740 (63 (28 2.139. (2.13-9. [1 4.3115 4311 (4.31-15 2.4712. 2471 (2.47-12. (7 (5 (0.14- rs274 (rs274 (6 (2 2.139 (2.13-9 [ 4.311 (4.31-1 2.4712 (2.47-12 ( (0.14 rs27 (rs27 (2.13- (4.31- 2.471 (2.47-1 (0.1 rs2 (rs2 (2.13 (4.31 (2.47- (0. (rs (2.1 (4.3 (2.47 (0 (2. (4. (2.4 (4

SUMMARY Calcitonin (CT) is a diagnostic and follow-up marker of medullary thyroid carcinoma. Heterophile antibodies (HAbs) may interfere during immunometric assay measurements and result in falsely high CT levels and different markers. A 50-year-old female patient was referred to our institution for elevated CT levels (3,199 pg/mL [0-11,5]). Physical examination and thyroid ultrasonography show no thyroid nodules. Because of the discrepancy between the clinical picture and the laboratory results, various markers and hormones were examined to determine whether there was any interference in the immunometric assay. Thyroglobulin (Tg) and Adrenocorticotropic hormone (ACTH) levels were also found inaccurately elevated. After precipitation with polyethylene glycol, CT, Tg, and ACTH levels markedly decreased, showing macro-aggregates. Also, serial dilutions showed non-linearity in plasma concentrations. Additionally, CT samples were pretreated with a heterophilic blocking tube before measuring, and the CT level decreased to < 0.1 pg/mL, suggesting a HAb presence. Immunoassay interference should be considered when conflicting laboratory data are observed. This may help reduce the amount of unnecessary laboratory and imaging studies and prevent patients from complex diagnostic procedures. (CT followup follow up carcinoma HAbs (HAbs 50yearold yearold 50 year old 3,199 3199 3 199 (3,19 pgmL pg mL 011,5. 0115 0 11,5 . 11 5 [0-11,5]) nodules results Tg (Tg (ACTH glycol macroaggregates. macroaggregates macro aggregates. aggregates macro-aggregates Also nonlinearity non linearity concentrations Additionally measuring 01 1 0. presence observed procedures 3,19 319 19 (3,1 011 011,5 115 11, [0-11,5] 3,1 31 (3, 011, [0-11,5 3, (3 [0-11, ( [0-11 [0-1 [0- [0 [

ABSTRACT Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India. Materials and methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical (inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas. Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33–60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13–60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas). Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger and had low surgical cure rates. Objective India setting methods 201 2022 inappropriately FSH/LH FSHLH FSH LH positive normalelevated normal Results 1 435 43 43. years men mm 3360 33 60 33–6 345 34 34. women GH 425 42 42. 1360 13 13–6 mm. . GH/TSH GHTSH (GH/TSH GHFSH firstline line 3 ( TSHomas) Conclusion respectively study rates 20 202 336 33– 136 13– 2

ABSTRACT Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Subjects and methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. Results: There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Conclusion: Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity. Objective leptinadiponectin (LAR children methods GOCS (GOCS 96 immunoassays calculated HOMAIR, HOMAIR HOMA IR , (HOMA-IR) triglycerideHDL triglyceride HDL triglycerideglucose glucose (TyG (BMI TyGBMI TyG-BMI WC (WC TyGWC. TyGWC . TyG-WC) analysis Results zscore z score adiposity age th point, point point) odds OR [OR 244 2 44 2.44 95 [CI 2.052.9. 20529 2.05 2.9 05 9 2.05-2.9) zscore, score, 164 1 64 1.64 1.272.12. 127212 1.27 2.12 27 12 1.27-2.12) Conclusion (HOMA-IR 24 4 2.4 052 2.052.9 2052 205 2.0 29 2. 0 2.05-2.9 16 6 1.6 272 1.272.12 12721 127 1.2 212 2.1 1.27-2.12 2.052. 20 2.05-2. 1. 1.272.1 1272 21 1.27-2.1 2.052 2.05-2 1.272. 1.27-2. 2.05- 1.272 1.27-2 1.27-

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases. (PPNAD ACTHindependent independent Cushings Cushing s CS. CS . (CS) 19 stones stature obesity diabetes hypertension mass level hypercortisolemia lowdose dose highdose high cortisol increased adrenalectomy blood tissue duplicationcontaining duplication containing 19p1313p1312 pp 19p13 13p13 12 p 19p13.13p13.12 CNC. (CNC) considered cases (CS 1 19p1313p131 19p1 13p1 19p13.13p13.1 (CNC 19p1313p13 19p 13p 19p13.13p13. 19p1313p1 19p13.13p13 19p1313p 19p13.13p1 19p13.13p

ABSTRACT Objective: The aim of this study is to investigate the molecular genetic causes of non-syndromic primary ovarian insufficiency (POI) cases with the gene panel based on next generation sequencing analysis and to establish the relationship between genotype and phenotype. Subjects and methods: Twenty three cases aged 14-40 years followed up with POI were included. Patients with a karyotype of 46, XX, primary or secondary amenorrhea before the age of 40, with elevated FSH (>40 IU/mL) and low AMH levels (<0.03 ng/mL) were included in the study. Molecular genetic analyzes were performed by the next generation sequencing analysis method targeted with the TruSightTM Exome panel. Results: Median age of the cases was 17.8 (14.0-24.3) years, and 12 (52%) cases admitted before the age of 18. Fifteen (65%) patients had consanguineous parents. In 2 (8.6%) cases, variants detected were in genes that have been previously proven to cause POI. One was homozygous variant in FIGLA gene and the other was homozygous variant in PSMC3IP gene. Heterozygous variants were detected in PROK2, WDR11 and CHD7 associated with hypogonadotropic hypogonadism, but these variants are insufficient to contribute to the POI phenotype. Conclusion: Genetic panels based on next generation sequencing analysis technologies can be used to determine the molecular genetic diagnosis of POI, which has a highly heterogeneous genetic basis. Objective nonsyndromic non syndromic (POI phenotype methods 1440 14 40 14-4 46 XX >40 (>4 IU/mL IUmL IU mL <0.03 003 0 03 (<0.0 ng/mL ngmL ng Results 178 17 8 17. 14.024.3 140243 14.0 24.3 24 3 (14.0-24.3 1 52% 52 (52% 18 65% 65 (65% parents 8.6% 86 6 (8.6% PSMCIP PSMC IP PROK2 PROK WDR WDR1 CHD hypogonadism Conclusion basis 144 4 14- >4 (> <0.0 00 (<0. 024 14.024. 14024 140 14. 243 24. (14.0-24. 5 (52 (65 8.6 (8.6 > ( <0. (<0 02 14.024 1402 (14.0-24 (5 (6 8. (8. <0 (< 14.02 (14.0-2 (8 < (14.0- (14.0 (14. (14 (1