Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

The Role of Artificial Intelligence in Endocrine Management: Assessing ChatGPT's Responses to Prolactinoma Queries.

This research investigates the utility of Chat Generative Pre-trained Transformer (ChatGPT) in addressing patient inquiries related to hyperprolactinemia and prolactinoma. A set of 46 commonly asked questions from patients with prolactinoma were presented to ChatGPT and responses were evaluated for accuracy with a 6-point Likert scale (1: completely inaccurate to 6: completely accurate) and adequacy with a 5-point Likert scale (1: completely inadequate to 5: completely adequate). Two independent endocrinologists assessed the responses, based on international guidelines. Questions were categorized into groups including general information, diagnostic process, treatment process, follow-up, and pregnancy period. The median accuracy score was 6.0 (IQR, 5.4-6.0), and the adequacy score was 4.5 (IQR, 3.5-5.0). The lowest accuracy and adequacy score assigned by both evaluators was two. Significant agreement was observed between the evaluators, demonstrated by a weighted κ of 0.68 (p = 0.08) for accuracy and a κ of 0.66 (p = 0.04) for adequacy. The Kruskal-Wallis tests revealed statistically significant differences among the groups for accuracy (p = 0.005) and adequacy (p = 0.023). The pregnancy period group had the lowest accuracy score and both pregnancy period and follow-up groups had the lowest adequacy score. In conclusion, ChatGPT demonstrated commendable responses in addressing prolactinoma queries; however, certain limitations were observed, particularly in providing accurate information related to the pregnancy period, emphasizing the need for refining its capabilities in medical contexts.

The acromegaly treatment satisfaction questionnaire (Acro-TSQ): turkish adaptation, validity, and reliability study.

PURPOSE: The patient-reported outcome becomes important to evaluate the situation perceived by the patients and to develop new strategies. This study aims to adapt the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ), which was specially developed for patients with acromegaly, into Turkish by conducting a validity and reliability study. METHODS: After the translation and back-translation process, Acro-TSQ was filled in by face-to-face interviews with 136 patients diagnosed with acromegaly and currently receiving somatostatin analogue injection therapy. Internal consistency, content validity, construct validity, and reliability of the scale were determined. RESULTS: Acro-TSQ had a six-factor structure and explained 77.2% of the total variance in the variable. The Cronbach alpha value calculated for internal reliability showed high internal consistency (Cronbach's alpha = 0.870). Factor loads of all items were found to be between 0.567 and 0.958. As a result of EFA analysis, one item fell into a different factor in the Turkish version of the Acro-TSQ, different from its original form. CFA analysis shows that acceptable fit values are obtained for fit indices. CONCLUSION: The Acro-TSQ, a patient-reported outcome tool, shows good internal consistency, and good reliability, suggesting it is an appropriate assessment tool for patients with acromegaly in the Turkish population.

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.

A National Multicenter Study of Leptin and Leptin Receptor Deficiency and Systematic Review.

CONTEXT: Homozygous leptin (LEP) and leptin receptor (LEPR) variants lead to childhood-onset obesity. OBJECTIVE: To present new cases with LEP and LEPR deficiency, report the long-term follow-up of previously described patients, and to define, based on all reported cases in literature, genotype-phenotype relationships. METHODS: Our cohort included 18 patients (LEP = 11, LEPR = 7), 8 of whom had been previously reported. A systematic literature review was conducted in July 2022. Forty-two of 47 studies on LEP/LEPR were selected. RESULTS: Of 10 new cases, 2 novel pathogenic variants were identified in LEP (c.16delC) and LEPR (c.40 + 5G > C). Eleven patients with LEP deficiency received metreleptin, 4 of whom had been treated for over 20 years. One patient developed loss of efficacy associated with neutralizing antibody development. Of 152 patients, including 134 cases from the literature review in addition to our cases, frameshift variants were the most common (48%) in LEP and missense variants (35%) in LEPR. Patients with LEP deficiency were diagnosed at a younger age [3 (9) vs 7 (13) years, P = .02] and had a higher median body mass index (BMI) SD score [3.1 (2) vs 2.8 (1) kg/m2, P = 0.02], which was more closely associated with frameshift variants (P = .02). Patients with LEP deficiency were more likely to have hyperinsulinemia (P = .02). CONCLUSION: Frameshift variants were more common in patients with LEP deficiency whereas missense variants were more common in LEPR deficiency. Patients with LEP deficiency were identified at younger ages, had higher BMI SD scores, and had higher rates of hyperinsulinemia than patients with LEPR deficiency. Eleven patients benefitted from long-term metreleptin, with 1 losing efficacy due to neutralizing antibodies.

Assessment of Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios in patients with acromegaly.

BACKGROUND: Cardiovascular complications, including ventricular arrhythmias associated with abnormalities of ventricular repolarization, are the leading cause of morbidity and mortality in patients with acromegaly. Herein, we aimed to investigate ventricular repolarization using Tp-e interval, Tp-e interval/QT, and Tp-e interval/QTc ratios in acromegalic patients compared to healthy subjects. METHODS: A total of 29 patients (aged 51.9 ± 11.2, 65.5% women) with acromegaly and 30 control subjects (aged 47.3 ± 14.4, 63.3% women) were enrolled in the study. Tp-e and QT interval, corrected QT (QTc), Tp-e/QT, and Tp-e/QTc ratios were calculated from the 12-lead electrocardiogram. RESULTS: Tp-e interval (89.28 ± 12.16 vs. 75.97 ± 9.92 ms; p < 0.001), Tp-e/QT ratio (0.237 ± 0.045 vs. 0.212 ± 0.029; p = 0.019), and Tp-e/ QTc ratio (0.218 ± 0.031 vs. 0.195 ± 0.026; p = 0.003) were significantly higher in patients with acromegaly compared to control group. A positive correlation was determined between left atrial volume index (LAVI) and Tp-e interval (r = 0.272, p = 0.039). DISCUSSION: The current study is the first to have shown significantly increased Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were increased in acromegalic patients. These results may be important for screening malignant arrhythmic events in acromegaly.

The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.

BACKGROUND: Increased bone turnover is a hallmark of hyperthyroidism. The underlying factors of how thyroid hormones affect bone cells are still under the spotlight. Previous studies indicated serum osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and interleukin-6 (IL-6) as mediators of the effect of thyroid hormones on bone metabolism. Ultimately, the present research aimed to examine the association of IL-6 with OPG and RANKL in patients with hyperthyroidism. METHODS: We carried out this study with 39 newly diagnosed and untreated Graves' patients and 43 healthy controls. In addition to routine tests, we measured serum OPG, RANKL, and IL-6 levels. RESULTS: Mean age and sex distribution were similar in both groups. The hyperthyroid group had significantly higher OPG (p = 0.002) and IL-6 (p < 0.001) levels, but RANKL levels were significantly lower in this group (p < 0.001). We found OPG not to correlate with free T4 and T3, while it had a moderate and negative correlation with thyrotropin (TSH) (r = -0.372, p = 0.001). IL-6 had no correlation with OPG but positively correlated with free T4 (r = 0.445, p < 0.001) and free T3 (r = 0.326, p = 0.035). It also negatively correlated with RANKL (r = -0.247, p = 0.033). DISCUSSION: Maintaining skeletal development and integrity is partially regulated by a normal balance of thyroid hormones. We concluded that increases in serum OPG and IL-6 levels accompanied hyperthyroidism. However, excessive levels of the hormones might cause drops in serum RANKL levels. Our results suggested that OPG, RANKL, and IL-6 might be involved in the cross-talking among immunity, thyroid function, and bone metabolism in the case of hyperthyroidism.

Renoprotective effects of dapagliflozin in an iron overload non-diabetic rat model.

PURPOSE: Sodium glucose co-transporter (SGLT) 2 inhibitors are oral anti-diabetic drugs with proven kidney protective effects. Renal protective effects in non-diabetic individuals have also been shown in recent studies. The aim of this study was to determine the renal protective effects of dapagliflozin by evaluating the oxidative stress markers in the kidney tissue and demonstrating it in renal histological sections in an iron-overloaded rat model. METHODS: A total of 24 Wistar Albino rats were separated into 3 groups of 8 rats. Iron sucrose (60 â€‹mg/kg/day) was administered intraperitoneally to the first group (Group Fe) (n â€‹= â€‹8), iron sucrose and dapagliflozin (0.1 â€‹mg/kg/day) to the second group (Group Fe â€‹+ â€‹D) (n â€‹= â€‹8) and intraperitoneal saline as placebo to the control group (Group C) (n â€‹= â€‹8) for 4 weeks. The glomerular changes were semi-quantitatively scored with Oxford Classification. Oxidative stress was analyzed from the tissue fluorescent oxidation product (FLOP), malondialdehyde (MDA) and total sulfhydryl (T-SH) levels. RESULTS: Dapagliflozin prevented glomerular and mesangial damage of iron overload in the non-diabetic rat model. MDA levels were significantly higher in Group Fe compared to the Group C, and there was no significant difference between the Fe â€‹+ â€‹D group and Group C. T-SH levels were preserved in the Fe â€‹+ â€‹D group and were significantly higher than in the Fe group. CONCLUSIONS: The results of this study showed that dapagliflozin helped preserve the glomerular and mesangial structure histologically and reduced oxidative stress markers in a non-diabetic iron overload rat model.

Pedabarography May Play a Role in Foot Plantar Scanning in Acromegaly.

Aims: Acromegaly is associated with symptoms in many organs, including the heart, colon, skin, bones, and many joints. Patients with long-term treatment or biochemical control still suffer from acromegaly arthropathy (AA). Primarily, the weight-bearing joints of the lower extremity are affected and at last deformation emerges. The aim of this study is to detect the changes in the feet with pedabarography in patients with acromegaly. Materials and Methods: Nineteen patients with acromegaly (4 males and 15 females) and 13 healthy controls (1 male and 12 females) were included in the study (p=0.31). There was no difference between acromegaly patients and controls in terms of gender, age, and BMI; median age and BMI were (54 (20-67) vs. 52 (30-58), p=0.85) and (32.5 (20.3-42.7) vs. 29.5 (22.4-38.6), p=0.93), respectively. Static plantar pressures of bilateral foot of all participants in the standing position were measured by pedabarography. Results: In pedabarographic analysis, there were only significant difference in rearfoot surface right and rearfoot surface left (p=0.04 and p=0.01), respectively. The mean of the right rearfoot surface (43.5 cm2 vs. 36.6 cm2) and the mean of the left rear foot surface were higher than the controls (47.4 cm2 vs. 40.2 cm2). Forefoot surface, forefoot load, forefoot weight ratio, rearfoot load, total foot surface, total load, total peak pressure, and total average pressure were higher in left foot in both groups, but there was no difference between the two groups. Conclusion: In our study, there was a significant difference between acromegaly patients and healthy controls, only on the right rarefoot surface and the left rarefoot surface, and was higher on the left in both groups. These patients often experience changes in the hindfoot and heel, and foot surface area and pressure distribution may vary. Early diagnosis and proper treatment of the disease can prevent the development of complications and improve the quality of life. Foot scanning using pedabarography in the management of AA is a useful tool that can be used to manufacture customized orthopedic insoles and ergonomic shoe designs to prevent irreversible damage and reduce overload and lower extremity pain.

Early-onset severe obesity due to homozygous p.R105W (c313C> T) mutation in leptin gene in Turkish siblings: Two cases reports.

Congenital leptin deficiency (CLD) is a rare cause of monogenic form obesity due to homozygous or compound heterozygous mutations in the LEP gene. To date, nine pathogenic mutations have been reported. In this study, we present are; an 18-year-old morbidly obese girl and a 14-year-old obese brother, both with homozygous mutation in the LEP gene [p.R105W (c313C> T)] and their data after three years of recombinant leptin treatment. To date, few cases of CLD have been reported in the literature. The cases reported here were siblings who were not diagnosed despite presentation at the clinic due to obesity in childhood, and diagnosis was delayed until adolescence. Clinicians need to consider CLD, a monogenic form of obesity in children with early severe obesity onset, especially if they are the child of a consanguineous marriage.

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

The effect of iatrogenic subclinical hyperthyroidism on anxiety, depression and quality of life in differentiated thyroid carcinoma

Background/aim: Overt thyroidism is known to cause neuropsychiatric disorders but studies on subclinical hyperthyroidism (SCH) are limited. Subclinical hyperthyroidism induction by administering L-Thyroxine (LT4) is the standard treatment method in differentiated thyroid carcinoma (DTC) follow-up. Our aim was to investigate whether anxiety, depression and quality of life are affected in DTC patients followed-up with exogenous SCH. Materials and methods: The patients were divided into exogenous SCH by LT4-DTC (n = 127), euthyroid-DTC (n = 66) and exogenous euthyroid-benign thyroid noduüle (BTN) who underwent thyroidectomy for benign thyroid pathology (n = 85) groups. Results: The rate of moderate/severe anxiety was significantly higher in SCH-DTC than euthyroid-BTN group (27.5%, n = 35 vs. 9.4%, n = 8) (P = 0.001). TSH levels and Beck anxiety inventory (BAI) scores were significantly negatively correlated(P = 0.009 r = ­0.16). Free T4 and BAI were significantly positively correlated (P = 0.04 r = 0.4). The groups were similar in terms of depression severity (P = 0.15). Subclinical hyperthyroid-DTC group scored significantly lowerthan euthyroid-BTN group in all scales of SF-36 quality of life survey. Conclusion: LT4-induced SCH, which is a part of traditional DTC treatment, can exacerbate the anxiety symptoms in patients and disrupt their quality of life, depending on the level of fT4.

Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-tolymphocyte ratio in different etiological causes of thyrotoxicosis

Background/aim: The most common causes of thyrotoxicosis include Graves' disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), and subacute granulomatous thyroiditis (SAT). In our study, we aimed to see whether neutrophil­to­lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet­to­lymphocyte ratio (PLR), and mean platelet volume (MPV) may be helpful in the differential diagnosis of these diseases. Materials and methods: We retrospectively analyzed the hospital records of the Endocrinology Clinic of our hospital between 2016 and 2019. We included data from 66 GD, 37 TA, and 35 SAT patients. We compared the data with those of 35 healthy subjects as controls. Results: NLR, MLR, and PLR were found to be higher in the SAT group when compared to other groups. The post hoc analysis of comparison of NLR, MLR, and PLR in each group showed that NLR and PLR were significantly different in the SAT group when compared to the GD, TA, and controls groups (P < 0.001, P = 0.003, and P < 0.001 for NLR respectively and P < 0.001 for PLR in all groups). MPV levels were different between groups (P = 0.007). However, the intergroup analysis (Tukey's test) failed to show a statistically significant difference for any of the groups. In patients with SAT, PLR and NLR were significantly higher than in the GD, TA, and control groups. MLR was also higher in SAT when compared to other groups, but the difference was not statistically significant. Conclusion: High PLR and NLR may be helpful to differentiate SAT from GD and TA, the other common causes of thyrotoxicosis.

Low frequency of HLA-B27 in ankylosing spondylitis and its relationship with clinical findings in patients from Turkey.

OBJECTIVE: Human leukocyte antigen B27 (HLA-B27) is strongly associated with ankylosing spondylitis (AS). However, the association between clinical findings and HLA-B27 vary in terms of geographic area. This study aimed to determine the frequency of HLA-B27 positivity and its relationship with clinical findings. MATERIAL AND METHODS: All subjects fulfilling the modified New York diagnosis criteria for AS enrolled in study. The demographic data and histories of the patients were collected retrospectively from patient files. Polymerase chain reaction-based HLA-B27 analysis of all cases was performed. RESULTS: The male to female ratio was 2.5, and mean age of disease onset was 28.3 years. HLA-B27 positivity was detected in 115 patients (70%). Although there was no significant connection between the clinical findings and HLA-B27 positivity, there was a positive relationship between the presence of syndesmophytes and HLA-B27 positivity (p=0.044). The number of patients treated with anti-tumor necrosis factor was higher in the HLA-B27-positive group; however, the difference was not significant (39.1% and 28.9%, respectively). More patients were treated with anti-tumor necrosis factor in the HLA-B27-positive group than in the HLA-B27-negative group; however, the difference was not significant (39.1% and 28.9%, respectively). CONCLUSION: Compared with northern Europe, HLA-B27-positive rate of patients with AS has been shown to be lower in Turkey. Except for the presence of syndesmophytes, there was not a statistically significant relationship between HLA-B27 positivity and clinical and radiologic findings.