Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience.

OBJECTIVE: We aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter. METHODS: We retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi. RESULTS: The median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005). CONCLUSION: Overall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.

Risk of hypercalcemia in patients with very high serum 25-OH vitamin D levels.

OBJECTIVE: We aimed to evaluate the risk of hypercalcemia in patients with very high levels of 25-hydroxy vitamin D (25(OH)D). METHODS: The distribution of patients who were screened for 25(OH)D in our hospital between January 2014 and December 2018 was evaluated and patients with serum concentrations of 25(OH)D >88 ng/mL were selected. Then, biochemical parameters of the cases with 25(OH)D >88 ng/mL were compared according to calcium status, vitamin D level (group 1, 88-100 ng/mL; group 2, 100-150 ng/mL, and group 3, >150 ng/mL), and gender. RESULTS: A total of 282 932 patients who underwent 25(OH)D tests in our hospital were evaluated. A total of 1311 (0.5%) patients had very high 25(OH)D levels (>88 ng/mL). Four hundred and ninety-five patients who met our inclusion criteria and had complete data participated in the study. The median age was 58 years (interquartile range [IQR] = 41-71 years) and the median level of 25(OH)D was 104.6 mg/mL (IQR = 94.9-124.9 ng/mL). Most of the subjects (83.7%) with very high 25(OH)D levels were normocalcemic. A weak inverse correlation was observed between 25(OH)D level and intact parathyroid hormone (iPTH) level (r = -0.118, P = .01), but no correlation between 25(OH)D and calcium levels was observed. Alkaline phosphatase (ALP) levels were significantly higher in males (P = .032), and age and iPTH levels were higher in females (P < .001 and P = .004). ALP, phosphorus levels, and iPTH suppression rates were higher in hypercalcemic patients (P < .001, P < .001, and P < .001, respectively), while the iPTH level was significantly lower in hypercalcemic patients (P < .001) than in normocalcemic patients. Amongst the three groups with different 25(OH)D levels, no difference was found in levels of iPTH, calcium, phosphorus, ALP, or age. CONCLUSION: Most patients with very high vitamin D levels were normocalcemic, but severe hypercalcemia was also observed. Vitamin D replacement therapy and follow-up should be performed according to clinical guideline recommendations.

Presentation and management of patients with adrenal masses: a large tertiary centre experience.

BACKGROUND: Adrenal masses are found in up to 5%-7% of adults. The 2016 European guidelines on the management of adrenal incidentalomas have standardised the workup of these patients, but evidence of their impact on clinical practice is lacking. METHODS: Retrospective review of clinical presentation, radiological characteristics, and final diagnosis of a large cohort of patients with adrenal masses referred to a tertiary care centre 1998-2022. Sub-analysis compares outcomes before and after implementing the 2016 guidelines. RESULTS: A total of 1397 patients (55.7% women; median age 60 years [interquartile range {IQR}, 49-70]) were included. Incidental discovery was the most frequent mode of presentation (63.7%) and 30.6% of patients had masses ≥ 4 cm (median 2.9 cm [IQR, 1.9-4.7]). Unenhanced computed tomography Hounsfield units (HU) were available for 763 patients; of these, 32.9% had heterogeneous masses or >20 HU. The most common diagnoses were adrenocortical adenoma (56.0%), phaeochromocytoma (12.7%), adrenocortical carcinoma (10.6%), and metastases (5.7%). At multivariable analysis, significant predictors of malignancy included >20 HU or heterogeneous density (odds ratio [OR] 28.40), androgen excess (OR 27.67), detection during cancer surveillance (OR 11.34), size ≥ 4 cm (OR 6.11), and male sex (OR 3.06). After implementing the 2016 guidelines, the number of adrenalectomies decreased (6.1% pre-2016 vs 4.5% post-2016) and the number of patients discharged increased (4.4% pre-2016 vs 25.3% post-2016) for benign non-functioning adrenal masses. CONCLUSION: Implementing the 2016 guidelines positively impacted clinical practice, reducing unnecessary surgeries and increasing the discharge rate for benign adrenal masses, thereby preserving healthcare resources and patient burden.

Choroidal Thickness in Mild Autonomous Cortisol Secretion.

Objectives: To evaluate the patients with mild autonomous cortisol secretion (MACS) by means of choroidal thickness (CT) and also investigate whether CT may be a diagnostic tool in the management of MACS or not. Methods: Twenty-seven patients with MACS and 25 age-sex-matched healthy controls were enrolled in this cross-sectional comparative study. All the participants underwent CT measurement by using Spectralis optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany) with enhanced deep imaging mode at the subfoveal, 500-1000-1500 µm nasal and 500-1000-1500 µm temporal to the foveola. Results: The groups were similar in terms of spherical equivalence, age and axial lengths. The mean CT was significantly thicker in patients with MACS than controls in all measurement quadrants (p<0.001). There was no significant correlation between CT, size of the adenoma, basal cortisol, 1mg dexamethasone suppression test, salivary cortisol, 24-hour total urine-free cortisol, ACTH and DHEAS levels. However, 2 mg dexamethasone suppression test results were found to be significantly correlated with CT in temporal 500-1000 and 1500 µm quadrants (r=0.436, p=0.023, r=0.443, p=0.021 and r=0.488, p=0.010, respectively). Five (18.5%) eyes had pachychoroid pigment epitheliopathy in the MACS group. Conclusion: CT increases in patients with MACS and those tend to have pachychoroid pigment epitheliopathy more frequent than healthy individuals. A thicker choroid in the patients with MACS may be a novel biomarker both as a diagnostic tool for the degree of hypercortisolemia and cortisol-related comorbidity.

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.

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.

Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period.

BACKGROUND: The effect of preadmission metformin usage (PMU) on the mortality of coronavirus disease-2019 (COVID-19) patients with diabetes is conflicting. Most studies have focused on in-hospital mortality; however, mortality after discharge also increases in COVID-19 patients. AIMS: Examining the effect of PMU on all-cause mortality, including the post-discharge period. METHODS: Patients with diabetes who were hospitalised in 2020 due to COVID-19 were included in the study. They were divided into two groups: those with a history of metformin use (MF( +)) and those without such history (MF( -)). Propensity score matching (PSM) was performed at a ratio of 1:1 for age and sex. COX regression analyses were used to demonstrate risk factors for mortality. RESULTS: We investigated 4103 patients hospitalised for COVID-19. After excluding those without diabetes or with chronic liver/kidney disease, we included the remaining 586 patients, constituting 293 women (50%) with an overall mean age of 66 ± 11.9 years. After PSM analysis, the in-hospital and post-discharge mortality rates were higher in the MF( -) group though not significantly different. However, overall mortality was higher in the MF( -) group (51 (42.5%) vs. 35 (29.2%), p = 0.031). For overall mortality, the adjusted HR was 0.585 (95% CI: 0.371 - 0.920, p = 0.020) in the MF( +) group. CONCLUSION: PMU is associated with reducing all-cause mortality. This effect starts from the in-hospital period and becomes more significant with the post-discharge period. The main limitations were the inability to evaluate the compliance with metformin and the effects of other medications due to retrospective nature.

Subacute thyroiditis after inactive SARS-CoV-2 vaccine.

Viral infections have often been associated with subacute (De Quervain) thyroiditis. Rare cases of subacute thyroiditis have been reported after vaccines. Various vaccines have been developed with different techniques against SARS-CoV-2. This case report presents a rare case of subacute thyroiditis after the inactive SARS-CoV-2 virus vaccine, CoronaVac.

Publication outcome of research presented at the European Congress of Endocrinology: a web scraping-based analysis and critical appraisal.

PURPOSE: The current study aimed to determine the publication outcome of abstracts presented at the 16th European Congress of Endocrinology (ECE 2014). METHODS: All presentations were collected with the web scraping - Python coding from the official website and converted into Google Scholar and PubMed search links with coding. A particular interface was coded to evaluate the results. An online survey was sent to the authors to assess the impact of congress on their publication. RESULTS: A total of 1205 abstracts from 71 countries were featured at the congress of which, 1145 (95%) were poster presentations (PP), and 60 (5%) were oral presentations. Subsequently, 341 abstracts (28.3%) were published as a full paper. There was no major change from the abstract in 73.3% of full articles whereas 68.9% had at least one minor change. OP had higher conversion rates to publication than PP (65% vs 26.4; p = 0.01) and a higher median number of citations than PP (12 vs 6; p = 0.01). The median time to publication was 12 months (IQR: 2-24 months). OP was published in journals with a higher median impact factor (IF) than PP (5 vs 2.94; p = 0.01). Multi-country collaborative studies turned into more publications than single-country studies (OR: 3.91 95% CI: 2.52-6.06; p < 0.01). The congress's potential IF was calculated as 3.18. Among the authors responded to survey, 95% indicated that presenting at the congress was valuable for preparation of their publication. CONCLUSIONS: This first study evaluating the publication outcome of an international endocrinology congress suggests a 28.3% publication ratio with low discrepancy and 3.18 IF for ECE 2014.

Evaluation of diabetes self-management education in geriatrics with type 2 diabetes in Turkey.

BACKGROUND: This study was conducted to evaluate the diabetes education efficiency of individuals over 65 years old in Turkey, which has the highest prevalence of diabetes in Europe. METHODS: We retrospectively evaluated 320 patients who attended Turkey diabetes self-management group education program (TDSMEP) between 2016 and 2020 in a secondary hospital. Participants who have been followed up for a maximum of 9 months are grouped as over 65 years old and under. RESULTS: Of the 320 patients, 114 formed the geriatric group and 206 the non-geriatric group. After the training, the number of patients who had HbA1c≤7% increased significantly in both the geriatric (28.1-45.6%) and non-geriatric (19.9-42.2%) (P=0.001) groups. After the training, similar HbA1c goals were achieved in the geriatric and non-geriatric groups. The most significant HbA1c decrease was observed at the 3rd month of follow-up and remained stable until the 9th month. In logistic regression analysis, the factors affecting HbA1c failure (HbA1c>7%) after training in the geriatric group were long diabetes duration (OR=1.07, 95% CI: 1.02-1.13, P=0.01), high basal HbA1c levels (OR=1.31, 95% CI: 1.03-1.67, P=0.03), and low education level (OR=3.88, 95% CI: 1.54-9.76, P=0.001). CONCLUSIONS: This is the first study to evaluate the effectiveness of TDSMEP for geriatric individuals whose HbA1c≤7% increased from 28% to 45.6% during follow-up after the training. TDSMEP is recommended for all adult age groups, regardless of age range.

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.

Is only Thyroid Peroxidase Antibody Sufficient for Diagnosing Chronic Lymphocytic Thyroiditis?

OBJECTIVES: Recently, only anti-thyroid peroxidase (anti-TPO) has been suggested as an autoantibody in the diagnosis of chronic lymphocytic thyroiditis (CLT). In contrast, anti-thyroglobulin (anti-Tg) positivity has also been reported to be important. To evaluate this relationship more clearly, we planned to retrospectively investigate the autoantibody levels of the patients who underwent thyroid surgery for various reasons and those with CLT in postoperative pathology. METHODS: We evaluated 670 patients who underwent thyroid surgery (total/subtotal thyroidectomy) for various reasons at our hospital between January 2015 and March 2017. Patients with indications of Graves' disease, toxic multinodular goiter, and all malignancies except for thyroid papillary carcinoma (TPC) were excluded. Eighty-nine patients whose pathology findings were compatible with CLT and preoperative thyroid autoantibodies were identified enrolled in to the study. Patients with absence and presence of thyroid antibodies were included in the seronegative CLT group and seropositive CLT group, respectively. In addition, patients were divided into thyroid papillary carcinoma (TPC) and benign groups. RESULTS: According to the study criteria, 89 (83 females, six males) (mean age, 46.08±11.19 years) patients who had preoperatively identified autoantibodies were detected. Anti-TPO positivity was found in 47 (52.8%) cases, whereas anti-Tg positivity was found in 49 (55.1%). Only anti-TPO positivity was found in 18 (20.2%) cases, whereas only anti-Tg positivity was detected in 20 (22.5%). Twenty-two (24.7%) of the patients were seronegative. On comparing the seronegative and seropositive groups, seronegativity was more frequent in male patients (p=0.03). Thyroid-stimulating hormone was found to be significantly higher in the seropositive group (p=0.01). TPC was detected in 36 (40.4%) of all cases. No difference regarding age, thyroid function tests, and antibody levels was found between the benign and TPC groups. CONCLUSION: Although all of our cases were histopathologically diagnosed with CLT, serologically, 75.3% of thyroid autoimmunities could be shown when both antibodies were evaluated together. When only anti-TPO was considered, this rate decreased to 52.8%. Therefore, anti-Tg appears to be still important in showing autoimmunity. Prospective studies are needed to evaluate this relationship more clearly.