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Open access

Xiaomin Nie, Yiting Xu, Xiaojing Ma, Yun Shen, Yufei Wang and Yuqian Bao

Background

A high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear.

Objective

We aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women.

Methods

A total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay.

Results

FT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05).

Conclusions

In euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.

Open access

Ravikumar Shah, Anurag R Lila, Ramteke-Swati Jadhav, Virendra Patil, Abhishek Mahajan, Sushil Sonawane, Puja Thadani, Anil Dcruz, Prathamesh Pai, Munita Bal, Subhada Kane, Nalini Shah and Tushar Bandgar

Tumor-induced osteomalacia in the head and neck region remains a challenging diagnosis to manage. Literature pertaining to management and outcome details remains sparse. We describe two cohorts: cohort 1 included seven patients from a single center in Western India with tumors located in paranasal sinuses (n = 3), intracranial (n = 2) and maxilla (n = 2). The unique features from our series is the management of persistent disease with radiation therapy (n = 2) and peptide receptor radionuclide therapy (PRRT) (n = 1). Cohort two has 163 patients identified from 109 publications for systematic review. Paranasal sinuses, mandible, intracranial disease, maxilla and oral cavity, in descending order, are reportedly common tumor sites. Within this cohort, mean age was 46 ± 14 years at presentation with 44.1% having local symptoms. Duration of symptoms varied from 1 to 240 months. Pre-surgery mean serum phosphorus was 1.4 ± 0.4 mg/dL and median FGF-23 levels were 3.6 (IQR:1.8–6.8) times of normal upper limit of normal. Majority (97.5%) were managed primarily with surgical excision; however, primary radiotherapy (n = 2) and surgery combined with radiotherapy (n = 2) were also reported. Twenty patients had persistent disease while nine patients had recurrence, more commonly noted with intracranial and oral cavity tumors. Surgery was the most common second mode of treatment employed succeeded by radiotherapy. Four patients had metastatic disease. The most common histopathological diagnosis reported is PMT mixed connective tissue, while the newer terminology ‘PMT mixed epithelial and connective tissue type’ has been described in 15 patients.

Open access

Mauricio Alvarez, Oswaldo Rincón Sierra, Ginna Saavedra and Sergio Moreno

Objective

Vitamin B12 deficiency resulting from metformin use has been demonstrated in multiple studies. In this study, we aimed to evaluate the prevalence of vitamin B12 deficiency in patients with chronic metformin use and the relationship between vitamin B12 deficiency and diabetic neuropathy.

Methods

A cross-sectional study was conducted with 162 patients. Vitamin B12 levels were measured by chemiluminescence immunoassay. Diabetic neuropathy was evaluated by patient record, nerve conduction and Michigan test for the diagnosis of diabetic neuropathy. Additional data, including demographic characteristics were collected. A linear regression model was used to evaluate variables that correlated with vitamin B12 levels and diabetic neuropathy.

Results

Low vitamin B12 levels were found in 7.3% (95% CI: 4.0–12%) of patients. In those with diabetic neuropathy, altered (low and borderline) vitamin B12 level was 64% (95% CI: 47–78%) compared to 17% (95% CI: 10–26%) in patients without diabetic neuropathy (coefficient: −110.8; CI 95%: −165.8, −59.7). Those taking a higher metformin dose had lower levels of vitamin B12 (coefficient: −0.061; CI 95%: −0.09, −0.024). In addition, female patients had higher levels of vitamin B12 compared to men (coefficient: 49.1; CI 95%: 2.3–95).

Conclusions

Vitamin B12 deficiency is highly prevalent, especially in patients with diabetic neuropathy. In this study an inverse correlation was found between diabetic neuropathy and the plasma level of vitamin B12. Higher doses of metformin and male sex were factors related to lower levels of vitamin B12.

Open access

María Dolores Rodríguez Arnao, Amparo Rodríguez Sánchez, Ignacio Díez López, Joaquín Ramírez Fernández, Jose Antonio Bermúdez de la Vega, Diego Yeste Fernández, María Chueca Guindulain, Raquel Corripio Collado, Jacobo Pérez Sánchez, Ana Fernández González and ECOS Spain Study Collaborative Investigator Group

Background

Non-adherence to r-hGH treatments occurs in a variable percentage of subjects. One problem found when evaluating adherence is the great variability in methods of detection and definitions utilized in studies. This study assessed the level of adherence in subjects receiving r-hGH with the easypod™ electronic device.

Methods

National, multicenter, prospective and observational study involving 238 subjects (144 with GH deficiency (GHD), and 86 with small for gestational age (SGA), 8 with Turner Syndrome), who received r-hGH with easypod™ for at least 3 months before inclusion. The follow-up period was 4 years.

Results

Overall adherence was 94.5%; 97.5% after 6 months, 95.3% after 1 year, 93.7% after 2, 94.4% after 3 and 95.5% after 4 years of treatment. No differences in adherence were observed between prepubertal and pubertal groups and GHD and SGA groups. Change in height after 1 and 2 years, change in height SDS after 1 and 2 years, HV after 1 year, HV SDS after at 1 and 4 years, change in BMI after 1 year and change in BMI SDS at 1 and 2 years showed significant correlation with adherence. No significant differences in adherence according to IGF-I levels were found in follow-up visits or between groups.

Conclusions

The easypod™ electronic device, apart from being a precise and objective measure of adherence to r-hGH treatment, allows high compliance rates to be achieved over long periods of time. Adherence significantly impacts growth outcomes associated with r-hGH treatment.

Open access

Ana P Estrada-Flórez, Mabel E Bohórquez, Alejandro Vélez, Carlos S Duque, Jorge H Donado, Gilbert Mateus, Cesar Panqueba-Tarazona, Guadalupe Polanco-Echeverry, Ruta Sahasrabudhe, Magdalena Echeverry and Luis G Carvajal-Carmona

Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan–Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 × 10−5). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between genotypes. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population.

Open access

Dong Cen, Hui Liu, Zhe Wan, Zhongjie Lin, Yanting Wang, Junjie Xu and Yuelong Liang

Purpose

Gallbladder neuroendocrine neoplasm (GB-NEN) is a relatively rare neoplasm, accounting for 0.5% of all neuroendocrine neoplasm cases and 2.1% of gallbladder cancers. Because of the limited understanding of GB-NEN, the aim of this study was to explore the clinicopathology and survival of GB-NEN patients selected from the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

A total of 248 GB-NEN patients from the SEER database diagnosed between 2004 and 2015 were included. Kaplan–Meier curves were used to examine the survival time. Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals to analyze the impact of factors on overall survival and cancer-specific survival.

Results

The majority of the GB-NEN patients were women (67.3%), white (77%), and married (61.7%). Most tumors were <2 cm in size (31.0%), G3 stage (25.8%), and distant SEER stage (41.1%). 62.9% and 64.5% of cases showed an absence of lymph node metastasis and tumor metastasis, respectively. Patients who received gallbladder surgery had significantly better survival outcomes (P < 0.001). However, patients who received both gallbladder surgery and lymph node resection did not have better survival outcome compared with patients who received only gallbladder surgery. Multivariate Cox proportional hazard models indicated that older age, unmarried status, large tumor size (>5 cm), and distant SEER stage were significant independent predictors for decreased overall survival time and cancer-specific survival time (P < 0.05).

Conclusion

Age, marital status, tumor size, and SEER stage were predictors for the survival of GB-NEN patients. Gallbladder surgery was associated with better survival, but the combination of gallbladder surgery and lymphadenectomy had no effect on survival outcomes.

Open access

Maryam Iravani, Marie K Lagerquist, Elham Karimian, Andrei S Chagin, Claes Ohlsson and Lars Sävendahl

Estrogens may affect bone growth locally or systemically via the known estrogen receptors ESR1, ESR2 and G protein-coupled estrogen receptor 1 (GPER1). Mouse and human growth plate chondrocytes have been demonstrated to express GPER1 and ablation of this receptor increased bone length in mice. Therefore, GPER1 is an attractive target for therapeutic modulation of bone growth, which has never been explored. To investigate the effects of activated GPER1 on the growth plate, we locally exposed mouse metatarsal bones to different concentrations of the selective GPER1 agonist G1 for 14 days ex vivo. The results showed that none of the concentrations of G1 had any direct effect on metatarsal bone growth when compared to control. To evaluate if GPER1 stimulation may systemically modulate bone growth, ovariectomized C57BL/6 mice were treated with G1 or β-estradiol (E2). Similarly, G1 did not influence tibia and femur growth in treated mice. As expected, E2 treatment suppressed bone growth in vivo. We conclude that ligand stimulation of GPER1 does not influence bone growth in mice.

Open access

Frederique Van de Velde, Marlies Bekaert, Anja Geerts, Anne Hoorens, Arsène-Hélène Batens, Samyah Shadid, Margriet Ouwens, Yves Van Nieuwenhove and Bruno Lapauw

Purpose

Obese subjects with nonalcoholic fatty liver disease (NAFLD) are more prone to develop additional metabolic disturbances such as systemic insulin resistance (IR) and type 2 diabetes. NAFLD is defined by hepatic steatosis, lobular inflammation, ballooning and stage of fibrosis, but it is unclear if and which components could contribute to IR.

Objective

To assess which histological components of NAFLD associate with IR in subjects with obesity, and if so, to what extent.

Methods

This cross-sectional study included 78 obese subjects (mean age 46 ± 11 years; BMI 42.2 ± 4.7 kg/m2). Glucose levels were analysed by hexokinase method and insulin levels with electrochemiluminescence. Homeostasis model assessment-estimated insulin resistance (HOMA-IR) was calculated. Liver biopsies were evaluated for histological components of NAFLD.

Results

A positive association between overall NAFLD Activity Score and HOMA-IR was found (r s = 0.259, P = 0.022). As per individual components, lobular inflammation and fibrosis stage were positively associated with HOMA-IR, glucose and insulin levels (P < 0.05), and HOMA-IR was higher in patients with more inflammatory foci or higher stage of fibrosis. These findings were independent of age, BMI, triglyceride levels, diabetes status and sex (all P < 0.043). In a combined model, lobular inflammation, but not fibrosis, remained associated with HOMA-IR.

Conclusion

In this group of obese subjects, a major contributing histological component of NAFLD to the relation between NAFLD severity and IR seems to be the grade of hepatic lobular inflammation. Although no causal relationship was assessed, preventing or mitigating this inflammatory response in obesity might be of importance in controlling obesity-related metabolic disturbances.

Open access

Clara Odilia Sailer, Sophia Julia Wiedemann, Konrad Strauss, Ingeborg Schnyder, Wiebke Kristin Fenske and Mirjam Christ-Crain

Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium ≥150 mmol/L) by hypertonic saline infusion. Copeptin – a marker indicating vasopressin activity – serum sodium and osmolality, plasma IL-8 and TNF-α were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-α levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.12, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.

Open access

Jiashu Li, Aihua Liu, Haixia Liu, Chenyan Li, Weiwei Wang, Cheng Han, Xinyi Wang, Yuanyuan Zhang, Weiping Teng and Zhongyan Shan

Thyroid dysfunction is a frequently found endocrine disorder among reproductively aged women. Subclinical hypothyroidism is the most common condition of thyroid disorders during pregnancy and is defined as manifesting a thyroid-stimulating hormone concentration exceeding the trimester-specific reference value, with a normal free thyroxine concentration. Here, we evaluated the prospective association between spontaneous miscarriage and first-trimester thyroid function. We conducted a case–control study (421 cases and 1684 controls) that was nested. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) status were measured. We found that higher TSH was related to spontaneous miscarriage (OR 1.21; 95% CI, 1.13–1.30, P < 0.001). Compared with women with TSH levels of 0.4–<2.5 mIU/L, the risk of miscarriage was increased in women with TSH levels of 2.5–<4.87 mIU/L (OR 1.47; 95% CI, 1.16–1.87) and TSH greater than 4.87 mIU/L (OR 1.97; 95% CI, 1.22–3.18). After controlling for the confounding factor, TPOAb positivity status and FT4, the results were similar. The present study showed that higher TSH was associated with miscarriage in early pregnancy. In fact, TSH levels between 2.5 and 4.87 mIU/L increased the risk for miscarriage, with TSH greater than 4.87 mIU/L increasing the risk even further.