Does total tumour diameter, multifocality, number of tumour foci, or laterality predict lymph node metastasis or recurrence in differentiated thyroid cancer?

Introduction: Data regarding laterality, focality, or total tumour diameter (TTD) in papillary thyroid cancer (PTC) are limited. We aimed to investigate the impact of focality, TTD, number of tumour foci, or laterality on aggressive features in PTC. Material and methods: Patients were categorized based on maximum tumour diameter (MTD) (≤ 10 vs. > 10 mm), focality, laterality, or the number of tumour foci (1/2/ ≥ 3). We also categorized the patients as follows: Group 1, unifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 2, multifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 3, multifocal microcarcinoma (MTD ≤ 10/TTD > 10 mm); Group 4, unifocal macrocarcinoma (MTD > 10/TTD > 10 mm); Group 5, multifocal macrocarcinoma (MTD > 10/TTD > 10 mm). Results: The mean diagnosis age (n = 511) was 44.7 (± 12.7) years, the majority of the patients were < 55 years old (n = 310) and female (n = 416). An increasing number of tumour foci were associated with a higher MTD or TTD, a higher ratio of extrathyroidal extension (ETE), vascular or lymphatic invasion, lymph node metastasis (LNM) or distant metastasis, or the need for radioactive iodine (RAI). There was no difference in the parameters between Group 3 and Group 2, or Group 4. Vascular invasion, American Thyroid Association high risk, LNM at diagnosis, and RAI total dose were higher in Group 5 than in Group 3. Microscopic or macroscopic ETE, T1b, and T4a were positive predictors for recurrence. Male sex, multifocality, number of tumour foci (≥ 3), MTD (> 10 mm), TTD (> 10 mm), Group 5, microscopicor macroscopic ETE, lymphatic or vascular invasion, RAI need, T2, and T4b were positive predictors for LNM. Conclusion: MTD and TTD increase the risk of LNM but not the recurrence in PTC. TTD, multifocality, and bilaterality can be considered risk factors in PTC staging systems and risk calculators

Intensification of Insulin Treatment With Insulin Degludec/Aspart in Type 2 Diabetic Patients: A 2-Year Real-World Experience

AimTo evaluate the effects of insulin degludec/insulin aspart (IDegAsp) coformulation as an intensification of insulin treatment for glycemic control in patients with type 2 diabetes (T2D) in a long term real-world clinical setting.Materials and MethodsThis retrospective non-interventional study, included 210 patients with T2D who to IDegAsp coformulation from prior insulin treatment in a tertiary endocrinology center between September 2017 and December 2019. The baseline data was taken as the index date and defined as the first IDegAsp prescription claim. Previous insulin treatment modalities, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight were recorded, respectively at the 3rd, 6th, 12th, and 24th months of the IDegAsp treatment.ResultsOut of the total 210 patients, 166 patients under insulin treatment switched to twice-daily IDegAsp treatment, 35 patients switched to once daily IDegAsp and twice premeal short-acting insulin regimen as a modified basal-bolus (BB) treatment, and nine patients commenced with once-daily IDegAsp treatment. HbA1c decreased from 9.2% ± 1.9% to 8.2% ± 1.6% in 6 months, 8.2% ± 1.7% in the first year, and 8.1% ± 1.6% in the second year of the therapy (p< 0.001). FPG decreased from 209.0 ± 85.0 mg/dL to 147.0 ± 62.6 mg/dL in the second year (p< 0.001). The required total daily dose of insulin increased in the second year of IDegAsp treatment compared to baseline. However, there was a borderline significance increase in IDegAsp requirement for the whole group at the two-year follow-up (p = 0.05). Patients who were administered twice daily IDegAsp injections required more total insulin in the first and second years due to added premeal short-acting insulin injections (p < 0.05). The frequency of patients with HbA1c < 7% was 31.8% in first year and 35.8% in second year under IDegAsp treatment.Insulin dose was de-escalated in 28.5% of the patients under BB treatment, while 15% under twice-daily IDegAsp required increased BB treatment.ConclusionIntensification of insulin treatment with IDegAsp coformulation improved glycemic control in patients with T2D. The total daily insulin requirement increased but the IDegAsp requirement lightly increased at the two-year follow-up. Patients under BB treatment required de-escalation of insulin treatment

Effects of Aminoguanidine on Glomerular Basement Membrane Thickness and Anionic Charge in a Diabetic Rat Model

We investigated the effect of aminoguanidine (AG) administration on GBM thickness, glomerular heparan sulfate (HS) content, and urinary albumin and HS excretion in diabetic rats. After induction of diabetes, female Wistar rats were divided into 2 groups: Group AGDM (n=11) received 1g/L aminoguanidine bicarbonate in drinking water, group DC (n=12) was given only tap water. Control rats received AG (group AGH, n=8) or tap water (group HC, n=8). At the end of a period of 8 weeks, urinary albumin and glycosaminoglycan (GAG) excretion was detected. GBM heparan sulfate distribution and count was determined under the electron microscope. The AGDM group had lower urinary albumin and GAG excretion than diabetic controls. GBM thickness was increased in diabetic rats compared to groups of AGDM and HC. In AGDM group alcian blue stained particle distribution and count in the GBM was similar to healthy controls. In conclusion AG prevents the decrease of anionic charged molecules in the GBM and GBM thickening. This can be one of the mechanisms by which AG decreases albuminuria in diabetic rats

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. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

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

Summary Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and gener ally 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 defciency can ensure safe and efective treatment. Purpose We observed a tendency to use high doses of cholecalciferol for vitamin D defciency 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 fnal 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 cal cium levels. The serum 25(OH)D level was signifcantly 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 defciency/insufciency in a short time (1–3 months). The cut-of 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 hypercal cemia. 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 efective treatment of vitamin D defciency

Long-term efficacy and safety of subcutaneous pasireotide alone or in combination with cabergoline in Cushing’s disease

ObjectiveThis study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing’s disease (CD).Study designThis is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments.ResultsOf 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6–62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events.ConclusionAddition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303