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Open access

Ruxuan Zhao, Ting-Ting Shi, Sha Luo, Yun-Fu Liu, Zhong Xin, and Jin-Kui Yang

Background: Graves’ orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include: Clinical Activity Score (CAS), computed tomography (CT), and magnetic resonance imaging (MRI). These approaches are mainly associated with orbital muscles, however, there are not many studies that focus on the lacrimal gland inflammation of GO patients.

Objective: The aim of this study is to assess the usefulness of 99mTc-DTPA SPECT/CT in evaluating the lacrimal gland inflammation in Graves orbitopathy, as compared with other methods.

Methods: A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical-endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed.

Results: The lacrimal glands in patients with GO were significantly larger in all measured dimensions (p < 0.001) on CT scans relative to those in controls. Increased lacrimal gland DTPA uptake ratios (p < 0.001) were displayed in active GO patients compared to controls and were also correlated with TRAb levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients.

Conclusions: These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

Open access

Mateo Amaya-Montoya, Daniela Duarte-Montero, Luz D Nieves-Barreto, Angélica Montaño-Rodríguez, Eddy C Betancourt-Villamizar, María P Salazar-Ocampo, and Carlos O Mendivil

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowest vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.

Open access

Sahar Hossam El Hini, Yehia Zakaria Mahmoud, Ahmed Abdelfadel Saedii, Sayed Shehata Mahmoud, Mohamed Ahmed Amin, Shereen Riad Mahmoud, and Ragaa Abdelshaheed Matta

Objective

Angiopoietin-like proteins (ANGPTL) 3, 4 and 8 are upcoming cardiovascular biomarkers. Experimental studies showed that thyroid hormones altered their levels. We assessed ANGPTL3, 4 and 8 as predictors of cardiovascular functions among naïve subclinical and naïve overt hypothyroidism (SCH and OH) and altered ANGPTL levels with levothyroxine replacement (LT4) and their association with improved cardiovascular risk factors and cardiovascular function.

Design and methods

The study was a prospective follow-up study that assessed ANGPTL3, 4 and 8 levels, vascular status (flow-mediated dilation% of brachial artery (FMD%), carotid intima-media thickness (CIMT), aortic stiffness index (ASI)), left ventricle (LV) parameters (ejection fraction (EF), myocardial performance index (MPI), and LV mass), well-known cardiovascular risk factors and homeostatic model for the assessment of insulin resistance, at two time points, that is, among naïve SCH, naïve OH, and healthy subjects groups; and at 6 months after achieving the euthyroid state with LT4 by calculating their increased or decreased delta changes (∆↑ or ∆↓) in longitudinal arm among LT4-hypothyroid groups.

Results

Significantly elevated levels of ANGPTL3, 4 and 8 among hypothyroid groups than the healthy subjects were reduced with LT4. Multivariate analysis revealed ANGPTLs as independent predictors of cardiovascular functions and the contributors for ANGPTL level included ANGPTL3 and 4 for impaired FMD%, and ANGPTL8 for LV mass among naïve SCH; ANGPTL3 for EF% and ANGPTL8 for CIMT in naïve OH; ∆↓ANGPTL3 for ∆↓ASI meanwhile ∆↑freeT4 for ∆↓ANGPTL3, ∆↓fasting glucose, ∆↓triglyceride, and ∆↓thyroid peroxidase antibody for ∆↓ANGPTL4 among LT4-SCH. ∆↓ANGPTL4 for ∆↓MPI and ∆↓LV mass, meanwhile ∆↓TSH and ∆↓triglyceride for ∆↓ANGPTL3, ∆↑free T3 and ∆↓HOMA-IR for ∆↓ANGPTL4, and systolic blood pressure and waist circumference for ∆↓ANGPTL8 among LT4-OH.

Conclusion

Elevated ANGPTL3, 4 and 8 levels are differentially independent predictors of endothelial and cardiac function and are reduced with LT4 in SCH and OH.

Open access

Yanmei Lou, Yanyan Zhang, Ping Zhao, Pei Qin, Changyi Wang, Jianping Ma, Xiaolin Peng, Hongen Chen, Dan Zhao, Shan Xu, Li Wang, Ming Zhang, Dongsheng Hu, and Fulan Hu

To assess the association between fasting plasma glucose (FPG) change trajectory and incident hypertension among Chinese people, this cohort study included 11,791 adults aged 18 to 80 years without hypertension at first entry and who completed at least four follow-ups between 2009 and 2016. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between FPG change trajectory and probability of hypertension. During a median follow-up of 5.10 years (total person-years 61,887.76), hypertension developed in 2177 participants. After adjusting for baseline potential confounders, the probability of hypertension increased with the increasing FPG change trajectory (adjusted OR [aOR] 1.22, 95% CI 1.07-1.40), bell-shape trajectory (aOR 1.15, 95% CI 1.02-1.30) and other-shape trajectory (aOR 1.13, 95% CI 1.02-1.25) which showed a higher variability of FPG compared to the decreasing group. In addition, the increasing FPG change trajectory was associated with a higher probability of hypertension compared with the decreasing group regardless of age and body mass index (BMI) but was only significant in males and in those with normal FPG at baseline. Our study indicates that the increasing FPG change trajectory determines the highest risk of hypertension, demonstrating the importance of maintaining low and stable levels of FPG, especially in males and in those with normal FPG.

Open access

Mahmoud Al-Masri, Tawfiq Al-Shobaki, Hani Al-Najjar, Rafal Iskanderian, Enas Younis, Niveen Abdallah, Abdelghani Tbakhi, Hussam Haddad, Mohammad Al-Masri, Zeinab Obeid, and Awad Jarrar

Purpose

This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center.

Methods

Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected.

Results

A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0–168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3–142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0–228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3–157)) (P = 0.941, HR = 0.940).

Conclusion

BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

Open access

Alicia Romano, Juan Pablo Kaski, Jovanna Dahlgren, Nicky Kelepouris, Alberto Pietropoli, Tilman R Rohrer, and Michel Polak

Objective: To assess cardiovascular (CV) safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical practice.

Design: Two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating long-term effectiveness and safety of GH in >38,000 paediatric patients, of which 421 had NS.

Methods: Serious adverse events, serious adverse reactions (SARs), and non-serious adverse reactions (NSARs) were reported by the treating physicians. CV comorbidities at baseline and throughout the studies were also recorded.

Results: The safety analysis set comprised 412 children with NS (29.1% females), with a mean (standard deviation) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. CV comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve stenosis and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safety events. The most common were the NSARs: headache (eight events in seven patients) and arthralgia (five events in three patients). Two SARs occurred in one patient (brain neoplasm and metastases to spine). No CV safety events were recorded in patients with NS. Five CV comorbidities in five patients were reported after initiation of GH treatment: three cases of unspecified CV disease, one ruptured abdominal aortic aneurysm and one pulmonary valve stenosis.

Conclusions: GH treatment had a favourable safety profile in patients with NS, including those with CV comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with Noonan syndrome and CV disease.

Open access

Xiaoya Zheng, Shanshan Yu, Jian Long, Qiang Wei, Liping Liu, Chun Liu, and Wei Ren

Objective: Both primary thyroid lymphoma (PTL) and diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) are two rare malignant tumours with different therapies and prognoses. This study compared their clinical features.

Methods: From a retrospective review of the pathologic database at our institute between January 2015 and August 2020, 52 PTL patients and 40 DSVPTC patients were included. Demographic, clinical, laboratory and ultrasound data were extracted from electronic medical records. Statistical analyses were performed using GraphPad Prism 5.0.

Results: Both PTL and DSVPTC were more likely to occur in women (83.7% and 67.5%), but DSVPTC patients were younger (median age: 36 vs 64.5), had fewer compressive symptoms, and more frequently had neck lymph node metastasis than PTL patients. The prevalence of Hashimoto’s thyroiditis (HT) and hypothyroidism was significantly higher in PTL patients than in DSVPTC patients (31% vs 17.5%). Hyperthyroidism could only be found in DSVPTC patients, which accounted for 7.5%. Heterogeneous echogenicity and irregular edges were frequently observed in both PTL and DSVPTC. However, compared with PTL, DSVPTC exhibited smaller lesion sizes, higher frequencies of diffuse sonographic patterns and calcification, and lower frequencies of hypoechoic features and internal blood flow signal. The overall survival rate with PTL was 77.23%, which was lower than that with DSVPTC (90.91%), but this difference was not significant (p=0.096).

Conclusion: Clinical characteristics such as age, compression symptoms, and sonographic features such as a large mass with heterogeneous echogenicity, hypoechoic, irregular edges, and calcification are helpful for impression diagnosis of PTL and DSVPTC before surgery.

Open access

Xingyan Liu, Mei Xu, Min Qian, and Lindong Yang

The cytochrome P450 family 17 (CYP17) is associated with hyperandrogenism in women, and the association between CYP17 gene polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive. In order to determine whether the CYP17 T/C (rs74357) gene polymorphism is an exposure risk for PCOS, a comprehensive meta-analysis summarizing 19 studies was performed. The pooled odds ratio (OR) and the corresponding 95% CI were measured under five genetic models, and the stratified analyses by ethnicity, Hardy–Weinberg equilibrium, testosterone levels and BMI in controls were carried out to identify the causes of substantial heterogeneity. The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in four genetic models. Moreover, the outcomes of subgroup analysis by ethnicity indicated that the frequencies of the C allele of CYP17 T/C (rs74357) polymorphism were markedly higher in women from Asia than in Caucasians (T vs C: OR 0.85, 95% CI = 0.74–0.99, P < 0.05). Therefore, these findings suggested that the CYP17 T/C (rs74357) gene polymorphism played an indispensable part in increasing the susceptibility of PCOS when carrying the C allele, which proposed that the polymorphism of the CYP17 gene may be a predictive factor for the risk of PCOS or an important pathway in PCOS-associated metabolic and hormonal dysregulation.

Open access

Shatha Alharazy, M Denise Robertson, Susan Lanham-New, Muhammad Imran Naseer, Adeel G Chaudhary, and Eman Alissa

Background

Measurement of free 25-hydroyvitamin D (25(OH)D) status has been suggested as a more representative marker of vitamin D status than that of total 25(OH)D. Previously, free 25(OH)D could only be calculated indirectly; however, a newly developed direct assay for the measurement of free 25(OH)D is now available. The aim of this study therefore was to investigate directly measured total and free vitamin D levels association with metabolic health in postmenopausal healthy women living in Saudi Arabia.

Methods

A sample of 302 postmenopausal women aged ≥50 years (n  = 302) living in Saudi Arabia were recruited in a cross-sectional study design. Blood samples were collected from subjects for measurement of serum levels of total 25(OH)D, directly measured free 25(OH)D, metabolic bone parameters, lipid profile, and other biochemical tests.

Results

A positive correlation was found between directly measured free and total 25(OH)D (r = 0.64, P< 0.0001). Total but not free 25(OH)D showed significant association with serum intact parathyroid hormone (P = 0.004), whilst free 25(OH)D but not total 25(OH)D showed a significant association with total cholesterol and LDL-C (P = 0.032 and P = 0.045, respectively).

Conclusions

Free 25(OH)D and total 25(OH)D were found to be consistently correlated but with different associations to metabolic health parameters. Further research is needed to determine which marker of vitamin D status would be the most appropriate in population studies.

Open access

Debra M Gordon, Pablo Beckers, Emily Castermans, Sebastian Jcmm Neggers, Liliya Rostomyan, Vincent Bours, Patrick Petrossians, Vinciane Dideberg, Albert Beckers, and Adrian F. Daly

Objective: Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma-paraganglioma (PPGL). Founder effects play an important role in regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in South Africa have not been explored in PPGL.

Design: We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors.

Methods: Next-generation panel and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes.

Results: From a group of 13 patients we identified six with PPGL, four with sporadic or familial isolated pituitary adenomas (FIPA), and three with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently-unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHB exon 3 deletion were also identified. Other PPGL patients had variants in SDHB, SDHD and three MEN1 variants were identified among MEN1 and young-onset pituitary adenoma patients.

Conclusions: This is the first identification of a Dutch founder effect for PPGL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes.