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Open access

Sanjeet Kumar Jaiswal, Vijaya Sarathi, Saba Samad Memon, Robin Garg, Gaurav Malhotra, Priyanka Verma, Ravikumar Shah, Manjeet Kaur Sehemby, Virendra A Patil, Swati Jadhav, Anurag Ranjan Lila, Nalini S Shah, and Tushar R Bandgar

Introduction:

177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL.

Methods:

This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy.

Results:

A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11–62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity.

Conclusion:

177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.

Open access

Lijuan Fu, Jinhuan Ma, Sumei Yan, and Qijun Si

Background:

Whether polymorphisms in VDR gene affect the risk of postmenopausal osteoporosis or not remain unclear. Thus, the authors performed a meta-analysis to more robustly assess associations between polymorphisms in VDR gene and the risk of postmenopausal osteoporosis by integrating the results of previous literature.

Methods:

Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible literature, and 67 genetic association studies were finally selected to be included in this meta-analysis.

Results:

We found that ApaI rs7975232 (dominant comparison: OR = 0.77, P = 0.007; allele comparison: OR = 0.81, P = 0.04), BsmI rs1544410 (dominant comparison: OR = 0.69, P = 0.002; allele comparison: OR = 0.78, P = 0.008) and TaqI rs731236 (recessive comparison: OR = 1.32 , P = 0.01) polymorphisms were significantly associated with the risk of postmenopausal osteoporosis in Caucasians, whereas FokI rs10735810 polymorphism was significantly associated with the risk of postmenopausal osteoporosis in Asians (dominant comparison: OR = 0.61, P = 0.0001; recessive comparison: OR = 2.02, P = 0.001; allele comparison: OR = 0.68, P = 0.002).

Conclusions:

This meta-analysis shows that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms may affect the risk of postmenopausal osteoporosis in Caucasians, while BsmI rs1544410 polymorphism may affect the risk of postmenopausal osteoporosis in Asians.

Open access

Jülide Durmuşoğlu, Henri J L M Timmers, Pepijn van Houten, Hans F Langenhuijsen, Ad R M M Hermus, and Annenienke C van de Ven

Background:

Adrenocortical carcinoma is a rare malignancy with a poor prognosis. We hypothesized that patients with adrenocortical carcinoma are at high risk for venous thromboembolism, given the numerous risk factors such as malignancy, abdominal surgery, immobility and hormonal excess. The aim of this study was to determine retrospectively the incidence of venous thromboembolisms after surgical treatment in patients with adrenocortical carcinoma.

Materials and methods:

A retrospective study was performed, collecting data from all patients diagnosed with adrenocortical carcinoma from 2003 to 2018 at the Radboud University Medical Centre, The Netherlands.

Results:

In 34 patients, eight postoperative venous thromboembolisms, all pulmonary embolisms, were diagnosed in the first 6 months after adrenalectomy (23.5%). In addition, one patient developed pulmonary embolism just prior to surgery and one patient 7 years after surgery. Five of the eight patients with postoperative venous thromboembolisms presented with symptomatic pulmonary embolism whereas the other three pulmonary embolisms were incidentally found on regular follow up CT scans. Seven of the eight venous thromboembolisms occurred within 10 weeks after surgery. Seven of the eight patients had advanced stage adrenocortical carcinoma and four patients already received low-molecular weight heparin during the development of the venous thromboembolism. There was one case of fatal pulmonary embolism in a patient with a cortisol producing tumor with pulmonary metastases, despite the use of a therapeutic dose thromboprophylaxis.

Conclusion:

Patients with adrenocortical carcinoma are at high risk of developing postoperative venous thromboembolisms. Prolonged postoperative thromboprophylaxis could be considered in these patients.

Open access

Barbara J Boucher

Our knowledge of vitamin D has come a long way since the 100 years it took for doctors to accept, between 1860 and 1890, that both sunlight and cod liver oil (a well-known folk remedy) cured and prevented rickets. Vitamins D2/D3 were discovered exactly a hundred years ago, and over the last 50 years vitamin D has been found to have many effects on virtually all human tissues and not just on bone health, while mechanisms affecting the actions of vitamin D at the cellular level are increasingly understood, but deficiency persists globally. Observational studies in humans have shown that better provision of vitamin D is strongly associated, dose-wise, with reductions in current and future health risks in line with the known actions of vitamin D. Randomised controlled trials, commonly accepted as providing a ‘gold standard’ for assessing the efficacy of new forms of treatment, have frequently failed to provide supportive evidence for the expected health benefits of supplementation. Such RCTs, however, have used designs evolved for testing drugs while vitamin D is a nutrient; the appreciation of this difference is critical to identifying health benefits from existing RCT data and for improving future RCT design. This report aims, therefore, to provide a brief overview of the evidence for a range of non-bony health benefits of vitamin D repletion; to discuss specific aspects of vitamin D biology that can confound RCT design and how to allow for them.

Open access

Hei Yi Vivian Pak, Andrew Lansdown, Peter Taylor, Aled Daffyd Rees, John Stephen Davies, and Caroline Hayhurst

Objective: Acromegaly is a rare condition and there is often a long path to diagnosis for many patients. We sought to explore patient’s perceptions and understanding of acromegaly, to examine the quality of communication and find gaps in the information provided at diagnosis.

Design: A prospective study using qualitative research methodology and grounded theory. A semi-structured interview was conducted with 18 patients treated for acromegaly in a single tertiary centre and verbatim transcripts were thematically analysed for overarching themes.

Results: 18 patients with acromegaly were interviewed. The mean age of participants was 52 (range 30–72). Four overarching themes emerged: (1) Patients rely on online resources to understand acromegaly in the time between diagnosis and tertiary care clinic; (2) There is not enough support available for patients; (3) Patients have a basic understanding of acromegaly and associated conditions, but the long term impact is underestimated; (4) Patients initially felt intimidated by the multidisciplinary team panel, but overall found it useful.

Conclusion: Acromegalic patients have a strong need for information at the point of initial diagnosis, in particular online resources and interaction with other experienced patients. Wider dissemination of patient educational resources into primary and secondary care settings may improve overall patient satisfaction, treatment adherence and subsequent health care provider-patient relationships.

Open access

Ling Hu, Ying Hu, and Ting Li

Objective: The purpose of this study was to explore the prevalence of thyroid nodules (TN) and metabolic syndrome (MS) and to analyze the correlation between TN and the components of MS.

Methods: A total of 1526 subjects were divided into two groups: a TN group and a non-thyroid nodules (NTN) group. The height, weight, blood pressure, fasting blood glucose level, fasting plasma insulin level, serum lipid profile, uric acid level, serum thyroid-stimulating hormone (TSH) level, free triiodothyronine (FT3) level, and free thyroxine (FT4) level of each patient were measured. Insulin resistance (IR) was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). Fatty liver and TN were detected by color Doppler ultrasonography.

Results: (1) The overall prevalence of TN was 39.5%; it was significantly higher in women than in men (P<0.01) and progressively increased with age in both sexes. (2) The overall prevalence of MS was 25.6%; it was significantly higher in men than in women (P<0.01) and progressively increased with age in both sexes. (3) FT3 was significantly lower in the TN group than in the NTN group (P<0.01). (4) Body mass index, triglycerides, and HOMA-IR were higher in the TN group than in the NTN group (P<0.05). (5) The existence of TN was significantly associated with overweight/obesity (OR = 1.03, 95% CI = 1.024 - 1.089), and with insulin resistance (IR) (OR = 1.98, 95% CI = 1.645 - 2.368), after adjusting for age and sex.

Conclusions: The prevalence of thyroid nodules and metabolic syndrome in the Nanchang area increases with age, and overweight/obesity and IR in patients are associated with thyroid nodules.

Open access

Ling Zhou, Ruixue Zhang, Shuangyan Yang, Yaguang Zhang, and Dandan Shi

Background: Our previous study revealed that astragaloside IV (AS-IV) effectively improved gestational diabetes mellitus (GDM) by reducing hepatic gluconeogenesis. Due to the importance of placental oxidative stress, we further explored the protective role of AS-IV on placental oxidative stress in GDM.

Methods: First, non-pregnant mice were orally administrated with AS-IV to evaluate its safety and effect. Then GDM mice were orally administered with AS-IV for 20 days and its effect on the symptoms of GDM, placental oxidative stress, secretions of inflammatory cytokines, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway, were evaluated.

Results: AS-IV had no adverse effect on non-pregnant mice. On the other hand, AS-IV significantly attenuated the GDM-induced hyperglycemia, glucose intolerance, insulin resistance, placental oxidative stress, productions of inflammatory cytokines and the activation of TLR4/NF-κB pathway.

Conclusion: AS-IV effectively protected against GDM by alleviating placental oxidative stress and inflammation, in which TLR4/NF-κB might be involved.

Open access

Pan Chen, Liqin Pan, Wensi Huang, Huijuan Feng, Wei Ouyang, Juqing Wu, Jing Wang, Yuying Deng, Jiaxin Luo, and Yanying Chen

Objective: To evaluate the relationship between the BRAF V600E mutation in lymph node metastasis (LNM) and its invasive characteristics in papillary thyroid cancer (PTC).

Material and Methods: A total of 373 PTC patients were enrolled in this study conducted at Zhujiang Hospital of Southern Medical University between January 2017 and December 2018. PTCs with cervical lymph node metastases were verified pathohistologically, and primary tumors and LNM were examined for the BRAF V600E mutation. Patients were excluded from the study if they the BRAF V600E mutation was examined only in primary tumors or only in LNM.

Results: Of the 373 patients examined, BRAF V600E mutation frequency in primary tumors was slightly higher than in LNM (81.5% vs. 78.0%, p = 0.000), the intra-class correlation coefficient (ICC) was 0.865 (95% CI 0.835−0.890). The BRAF V600E mutation in both primary tumor and LNM negatively correlated with the size of the largest metastatic focus of LNM (Odds ratio, OR = 0.297, 95% CI 0.143-0.616, p = 0.001; OR = 0.242, 95% CI 0.119-0.492, p = 0.000, respectively). There was no relationship between BRAF V600E mutation in LNM and the number, extranodal extension or stage of LNM (p < 0.05).

Conclusion: The BRAF V600E mutation in LNM may not be related to the invasive characteristics of LNM in PTC.

Open access

Grethe A. Ueland, Thea Grinde, Paal Methlie, Oskar Kelp, Kristian Løvås, and Eystein Husebye

Objective: Autonomous cortisol secretion (ACS) is a condition with ACTH-independent cortisol overproduction from adrenal incidentalomas (AI) or adrenal hyperplasia. The hypercortisolism is often mild, and most patients lack typical clinical features of overt Cushing’s syndrome (CS). ACS is not well defined and diagnostic tests lack validation.

Methods: Retrospective study of 165 patients with AI evaluated clinically and by assay of morning plasma ACTH, late-night saliva cortisol, serum dehydroepiandrosterone sulphate (DHEAS), 24-hour urine free cortisol, and cortisol after dexamethasone suppression.

Results: Patients with AI (n=165) were diagnosed as non-functioning incidentalomas (NFI) (n = 82) or ACS (n = 83) according to current European guidelines. Late-night saliva cortisol discriminated poorly between NFI and ACS showing a high rate of false positive (37 %) and false negative (54 %) results. The conventional low dose dexamethasone suppression test (LDDST) did not improve the diagnostic specificity, compared with the 1 mg overnight DST. Receiver operating characteristic curve analysis of DHEAS in the two cohorts demonstrated an area under the curve of 0.76 (p<0.01) with a sensitivity for ACS of 58% and a specificity of 80% using the recommended cutoff at 1.04 µmol/L (40 µg/dL).

Conclusion: We here demonstrate in a large retrospective cohort of incidentaloma patients, that neither DHEAS, late night saliva cortisol nor 24-hour urine free cortisol are useful to discriminate between non-functioning adrenal incidentalomas and ACS. The conventional LDDST do not add further information compared with the 1 mg overnight DST. Alternative biomarkers are needed to improve the diagnostic workup of ACS.

Open access

Lina Susana Silva-Bermudez, Freddy Jk Toloza, Maria Camila Perez-Matos, Russell J de Souza, Laura Banfield, Andrea Vargas-Villanueva, and Carlos O Mendivil

Objective: To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.

Patients and Methods: Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, body-mass index (BMI), insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random effects model. We performed subgroup analyses by study duration (<12 months versus ˃=12 months) and polycystic ovary syndrome status.

Results: Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (p<0.001) to 35.1 mg/dL for chlormadinone (p<0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, p<0.001) and drospirenone (+7.4 mg/dL, p<0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (p<0.001). Levonorgestrel (+6.8 mg/dL, p<0.001) and norgestimate (+11.5 mg/dL, p=0.003) increased LDLc, while dienogest decreased it (-7.7 mg/dL, p=0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.

Conclusion: Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.