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Open access

Caroline Y Hayashi, Danilo T A Jaune, Cristiano C Oliveira, Bárbara P Coelho, Hélio A Miot, Mariângela E A Marques, José Vicente Tagliarini, Emanuel C Castilho, Carlos S P Soares, Flávia R K Oliveira, Paula Soares, and Gláucia M F S Mazeto

Background

Thyroid nodules diagnosed as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/suspected follicular neoplasm' (FN/SFN), according to Bethesda’s classification, represent a challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy.

Methods

We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility.

Results

In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61–0.93) in 10 of the 12 nuclear parameters evaluated.

Conclusion

CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.

Open access

Iulia Soare, Anca Sirbu, Mircea Mihai Diculescu, Bogdan Radu Mateescu, Cristian Tieranu, Sorina Martin, Carmen Gabriela Barbu, Mirela Ionescu, and Simona Fica

Background and aims: Low bone mineral density (BMD) is a common complication in patients with inflammatory bowel disease (IBD). However, debates are ongoing with regard to the other involved factors, especially in younger patients. This study aimed to evaluate the parameters that contribute to decreased BMD, focusing on premenopausal women and men aged <50 years.

Methods: This study has evaluated 81 patients with IBD and 81 age-, sex- and body mass index (BMI)-matched controls. Blood tests were conducted on IBD patients, and dual-energy X-ray absorptiometry (DXA) scan was performed on both groups.

Results: Low BMD and fragility fracture were found to be more prevalent in IBD patients than in healthy subjects (49.3% vs 23.4%, p = 0.001 and 9.8% vs 1.2%, p = 0.01, respectively). Patients with low BMD were older, with a longer disease duration, higher faecal calprotectin (FC) level and lower magnesium and lean mass (appreciated as appendicular skeletal muscle index (ASMI)). Multiple regression analysis revealed that ASMI, age and use of glucocorticoids were independent parameters for decreased BMD. Although 91.3% of the patients had a 25-hydroxy vitamin D level of <30 ng/mL, it was not a statistically significant factor for decreased BMD.

Conclusion: In our study, the levels of vitamin D did not seem to have an important impact on BMD. Conversely, FC, magnesium and lean mass are important factors, suggesting that good control of disease, adequate magnesium intake and increased lean mass can have a good impact on bone metabolism in patients with IBD.

Open access

Laszlo Samson, Ildiko Hircsu, Monika Katko, Miklos Bodor, Annamaria Gazdag, Andrea Anett Gazso, Bela Kovacs, Janos Posta, Eszter Balogh, Peter Mocsary, Harjit Pal Bhattoa, and Endre V Nagy

Objective

To investigate factors affecting conscious iodine intake among pregnant and lactating women in a rural area in Hungary.

Methods

Pregnant women were studied and followed during lactation. Urinary and breast milk iodine concentration (UIC and MIC) were measured by inductively coupled plasma mass spectrometry. Potential interfering factors, including age, educational status and smoking were assessed.

Results

During pregnancy and lactation, mild iodine deficiency was observed; median UIC were 66 and 49 µg/L, respectively. Educational status was found to be a strong determinant of both iodine nutrition and smoking status during pregnancy (P < 0.01 and P < 0.001) and lactation (P < 0.001 and P < 0.01). While smoking and non-smoking lactating mothers had similar concentrations of urinary iodine (median UIC: 47 and 51 µg/L, P = 0.95), the breast milk of smoking mothers contained less iodine (median MIC: 150 and 203 µg/L, P = 0.03).

Conclusions

Both low iodine intake and smoking contribute to the higher risk of iodine deficiency in women with lower educational status. In smokers, MIC is often low in spite of normal UIC, presumably due to the iodine transport blocking effect of the cigarette smoke towards breast milk; normal UIC may be misinterpreted as sufficient iodine supply towards the child. Antenatal health promotion strategies should focus on young women with lower educational status, even in regions where sufficient iodine intake has been achieved in non-pregnant adults.

Open access

Małgorzata Kałużna, Malgorzata Kaluzna, Agnieszka Nomejko, Aleksandra Słowińska, Katarzyna Wachowiak-Ochmańska, Katarzyna Pikosz, Katarzyna Ziemnicka, and Marek Ruchala

Background: Polycystic ovary syndrome (PCOS) is a multi-symptom disorder linked with a range of metabolic and hormonal disturbances. Psychological and sexual aspects of PCOS also need to be considered.

Objective of the study: This study aimed to assess sexual satisfaction(SS) in PCOS patients and eumenorrheic controls (CON). The relationships between SS, depressive symptoms, health-related quality of life (HRQoL), and hormonal and metabolic profiles were evaluated.

Methods: 190 patients with PCOS (mean age:26.34±5.47 years) and 197 age-matched CON (mean age:27.12±4.97 years) were enrolled in the study. All subjects completed: Polish version of the Sexual Satisfaction Questionnaire(SSQ), WHO Quality of Life-BREF (WHOQOL-BREF) and Center for Epidemiologic Studies Depression Scale-Revised (CESD-R) questionnaire. Fasting blood samples were collected to assess hormonal, lipid, and glucose profiles. Anthropometric measures were collected. Metabolic syndrome (MS) was evaluated according to the IDF-AHA/NHLBI criteria.

Results: Patients with PCOS and MS had lower SS vs. non-MS PCOS. There were no significant differences in the level of SS, presence of depressive symptoms, or HRQoL between PCOS and CON (p>0.05). Negative correlations were found between the SS level and BMI, waist circumference, and waist-to-height ratio in PCOS women. However, overweight or obese PCOS women did not differ in SS levels vs. normal-weight PCOS patients. The social dimension of WHOQOL-BREF was the only significant predictor of SS in PCOS patients.

Conclusions: SS in PCOS women appears to be undisturbed. However, MS in PCOS patients could negatively influence SS. The level of SS should be assess in PCOS women, especially if MS is present.

Open access

Mirjana Doknic, Marko Stojanovic, Ivan Soldatovic, Tanjana Milenkovic, Vera Zdravkovic, Maja Jesic, Sladjana Todorovic, Katarina Mitrovic, Rade Vukovic, Dragana Miljic, Dragan Savic, Mihajlo Milicevic, Aleksandar Stanimirovic, Vojislav Bogosavljevic, Sandra Pekic, Emilija Manojlovic-Gacic, Aleksandar Djukic, Danica Grujicic, and Milan Petakov

Objective: To analyze metabolic parameters, body composition (BC) and bone mineral density (BMD) in childhood onset GH deficiency (COGHD) patients during transition period (TP).

Design: Single center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2±2.0 years, range 16-25) transferred after growth completion from two pediatric clinics to adult endocrine unit. Two separate analyses were performed: 1) cross-sectional analysis of hormonal status, metabolic parameters, BC and BMD at first evaluation after transfer from pediatrics to adult department; 2) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP.

Results: COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor related (TUMC) in 23.5% and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (p<0.01) and lower Z score at L-spine (p<0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to rhGH-untreated group (p<0.01). Three years of rhGH after growth completion resulted in significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with decrease in FM (5.2%).

Conclusion: The effect of rhGH in childhood is invaluable for metabolic status, BC and BMD in transition to adulthood. Tumor related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BD and BMD in patients with persistent COGHD.

Open access

XuTing Song, Jia-Nan Zhang, Duo-Wei Zhao, Yu-Fei Zhai, Qi Lu, Mei-Yu Qi, Ming-Hai Lu, Shou-Long Deng, Hong-Bing Han, Xiu-Qin Yang, and Yu-Chang Yao

Insulin-like growth factor 1 (IGF1),also known as somatomedin C, is essential for the regulation of animal growth and development. In many species, the IGF1 gene can be alternatively spliced into multiple transcripts, encoding different pre-pro-IGF1 proteins. However, the exact alternative splicing patterns of IGF1 and the sequence information of different splice variants in sheep are still unclear. In this study, four splice variants (class 1-Ea, class 1-Eb, class 2-Ea, and class 2-Eb) were obtained, but no IGF1 Ec, similar to that found in other species, was discovered. Bioinformatics analysis showed that the four splice variants shared the same mature peptide (70 amino acids) and possessed distinct signal peptides and E peptides. Tissue expression analysis indicated that the four splice variants were broadly expressed in all tested tissues and were most abundantly expressed in the liver. In most tissues and stages, the expression of class 1-Ea was highest, and the expression of other splice variants was low. Overall, levels of the four IGF1 splice variants at the fetal and lamb stages were higher than those at the adult stage. Overexpression of the four splice variants significantly increased fibroblast proliferation and inhibited apoptosis (P < 0.05). In contrast, silencing IGF1 Ea or IGF1 Eb with siRNA significantly inhibited proliferation and promoted apoptosis (P < 0.05). Among the four splice variants, class 1-Ea had a more evident effect on cell proliferation and apoptosis. In summary, the four ovine IGF1 splice variants have different structures and expression patterns and might have different biological functions.

Open access

Nandini Shankara Narayana, Lam P Ly, Veena Jayadev, Carolyn Fennell, Sasha Savkovic, Ann J Conway, and David J Handelsman

Objective

To define the optimized inter-injection interval of injectable testosterone undecanoate (TU) treatment for hypogonadal and transmen based on individual dose titration in routine clinical practice.

Design and methods

A prolective observational study of consecutive TU injections in men undergoing testosterone replacement therapy for pathological hypogonadism or masculinization of female-to-male transgender (transmen) subject to individual dosing titration to achieve a stable replacement regimen.

Results

From 2006 to 2019, 6899 injections were given to 325 consecutive patients. After excluding the 6-week loading dose, 6300 injections were given to 297 patients who had at least three and a median of 14 injections. The optimal injection interval (mean of last three injection intervals) had a median of 12.0 weeks (interquartile range 10.4–12.7 weeks). The interval was significantly influenced by age and body size (body surface area, BSA) but not by diagnosis or trough serum LH, FSH, and SHBG. Longer (≥14 weeks; 68/297, 23%), but not shorter (≤10 weeks; 22/297, 7.4%), intervals were weakly correlated with age but not diagnosis or other covariables. Low blood hemoglobin increased with trough serum testosterone to reach plateau once testosterone was about 10 nmol/L or higher.

Conclusion

Optimal intervals between TU injection after individual titration resulted in the approved 12-week interval in 70% of patients with only minor influence for clinical application of BSA and not of trough serum LH, FSH, and SHBG. Individually optimized inter-injection interval did not differ between men with primary or secondary hypogonadism or transmen.

Open access

Ping Gu, Yuege Lin, Qi Wan, Dongming Su, and Qun Shu

Background

Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation. However, the underlying mechanism of β-cell adaptation during gestation or gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physiological hormone in gestation and delivery, and it also contributes to the maintenance of β-cell function. The aim of this study was to investigate the role of oxytocin in β-cell adaptation during pregnancy.

Methods

The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigated. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells.

Results

The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A 3-week oxytocin treatment promoted the proliferation of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion and induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose-stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells.

Conclusions

These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and the lack of oxytocin could be associated with the risk of GDM.

Open access

Sakina H Bharmal, Wandia Kimita, Juyeon Ko, and Maxim S Petrov

Objective

Early identification of individuals at high risk for metabolic derangements after an attack of acute pancreatitis (AP) is critical with a view to tertiary preventing of this disease. The aim was to investigate whether fasting pancreatic and gut hormones at baseline were predictive of future risk of new-onset prediabetes after acute pancreatitis (NOPAP) in individuals with non-necrotising AP.

Methods

This was a prospective longitudinal cohort study that included 69 consecutive non-diabetic participants with AP, of whom 55% (n = 38) had normoglycaemia both at baseline and during follow-up, 25% (n = 17) had prediabetes both at baseline and during follow-up, and 20% (n = 14) were normoglycaemic at baseline but developed NOPAP during follow-up. The associations between the study groups and circulating fasting levels of pancreatic and gut hormones (insulin, glucagon, C-peptide, amylin, glucose-dependent insulinotropic peptide, glucagon-like peptide-1, pancreatic polypeptide, and peptide YY) were studied using multinomial regression in both unadjusted and adjusted analyses.

Results

Elevated plasma insulin and glucagon at baseline were significantly associated with NOPAP (adjusted odds ratio 1.99, 95% CI 1.01 to 3.92 and adjusted odds ratio 3.44, 95% CI 1.06 to 11.19, respectively). The same hormones had no significant association with antecedent prediabetes in AP. The other studied hormones were not significantly associated with the study groups.

Conclusions

Normoglycaemic AP individuals with elevated fasting levels of insulin and glucagon at baseline constitute a high-risk group for future NOPAP.

Open access

Ida Staby, Jesper Krogh, Marianne Klose, Jonas Baekdal, Ulla Feldt-Rasmussen, Lars Poulsgaard, Jacob Bertram Springborg, and Mikkel Andreassen

Introduction

Patients with pituitary adenomas undergoing transsphenoidal surgery require pre- and post-surgery examination of pituitary hormones. There is currently no consensus on how to evaluate the adrenal axis post-surgery. The aims of this study were to investigate factors that may predict postoperative adrenal insufficiency (AI) and to investigate the overall effect of transsphenoidal surgery on pituitary function.

Methods

One hundred and forty-three consecutive patients who had undergone transsphenoidal surgery for pituitary adenomas were included. Data on tumour size, pituitary function pre-surgery, plasma basal cortisol measured within 48 h post-surgery and pituitary function 6 months post-surgery were collected. Patients with AI prior to surgery, perioperative glucocorticoid treatment, Cushing’s disease and no re-evaluation after 1 month were excluded (n = 93) in the basal cortisol analysis.

Results

Low plasma basal cortisol post-surgery, tumour size and previous pituitary surgery were predictors of AI (all P < 0.05). A basal cortisol cut-off concentration of 300 nmol/L predicted AI 6 months post-surgery with sensitivity and negative predictive value of 100%, specificity of 81% and positive predictive value of 25%. New gonadal, thyroid and adrenal axis insufficiencies accounted for 2, 10 and 10%, respectively. The corresponding recovery rates were 17, 7 and 24%, respectively

Conclusion

Transsphenoidal surgery had an overall beneficial effect on pituitary endocrine function. Low basal plasma cortisol measured within 48 h after surgery, tumour size and previous surgery were identified as risk factors for AI. Measurement of basal cortisol post-surgery may help to identify patients at risk of developing AI.