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Open access

Natércia Neves Marques de Queiroz, Franciane Trindade Cunha de Melo, Fabrício de Souza Resende, Luísa Corrêa Janaú, Norberto Jorge Kzan de Souza Neto, Manuela Nascimento de Lemos, Ana Carolina Lobato Virgolino, Maria Clara Neres Iunes de Oliveira, Angélica Leite de Alcântara, Lorena Vilhena de Moraes, Tiago Franco David, Wanderson Maia da Silva, Scarlatt Souza Reis, Márcia Costa dos Santos, Ana Carolina Contente Braga de Souza, Pedro Paulo Freire Piani, Neyla Arroyo Lara Mourão, Karem Mileo Felício, João Felício Abrahão Neto and João Soares Felício

Objective:

Investigate the prevalence of vitamin D deficiency in an equatorial population through a large-sample study.

Methods:

Cross-sectional study with 30,224 healthy individuals from the North Region, in Brazil (Amazônia – state of Pará), who had 25-hydroxy-vitamin D (25(OH)D) and intact parathyroid hormone (PTH) serum levels measured by immunoassay method. Those with history of acute or chronic diseases were excluded. Abnormal levels of calcium, creatinine, glycemia and albumin were also exclusion criteria.

Results:

25(OH)D levels were 29.1 ± 8.2 ng/mL and values <12.7 ng/mL were equal to < −2 s.d. below average. Hypovitaminosis D was present in 10% of subjects according to the Institute of Medicine (values <20 ng/mL) and in 59%, in consonance with Endocrine Society (values 20–30 ng/mL as insufficiency and <20 ng/mL as deficiency) criteria. Individuals were divided according to four age brackets: children, adolescents, adults and elderly, and their 25(OH)D levels were: 33 ± 9; 28.5 ± 7.4; 28.3 ± 7.7; 29.3 ± 8.5 ng/mL, respectively. All groups differed in 25(OH)D, except adolescents vs adults. Regression model showed BMI, sex, living zone (urban or rural) and age as independent variables to 25(OH)D levels. Comparing subjects with vitamin D deficiency (<20 ng/mL) to those with vitamin D insufficiency (20–30 ng/mL), a difference between PTH levels in these two groups was observed (95.9 ± 24.7 pg/mL vs 44.2 ± 64.5 pg/mL; P < 0.01). Additionally, the most accurate predictive vitamin D level for subclinical hyperparathyroidism in ROC curve was 26 ng/mL.

Conclusion:

Our equatorial population showed low prevalence of vitamin D hypovitaminosis ranging with age bracket. The insufficient category by Endocrine Society was corroborated by our PTH data.

Open access

Tomás P Griffin, Caroline M Joyce, Sumaya Alkanderi, Liam M Blake, Derek T O’Keeffe, Delia Bogdanet, Md Nahidul Islam, Michael C Dennedy, John E Gillan, John J Morrison, Timothy O’Brien, John A Sayer, Marcia Bell and Paula M O’Shea

Introduction

Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants.

Methods

The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine.

Results

The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted calcium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband’s brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband’s daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up.

Conclusions

W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.

Open access

Jung Soo Lim, Seung-Eun Lee, Jung Hee Kim, Jae Hyeon Kim and The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korean Endocrine Society

Purpose

To evaluate the clinical characteristics and prognostic factors in patients with adrenocortical carcinoma (ACC) in South Korea.

Methods

A nationwide, registry-based survey was conducted to identify pathologically proven ACC at 25 tertiary care centers in South Korea between 2000 and 2014. Cox proportional hazard model and log-rank test were adopted for survival analysis.

Results

Two hundred four patients with ACC were identified, with a median follow-up duration of 20 months (IQR 5–52 months). The median age at diagnosis was 51.5 years (IQR 40–65.8 years), and ACC was prevalent in women (n = 110, 53.9%). Abdominal pain was the most common clinical symptom (n = 70, 40.2%), and ENSAT stage 2 was most common (n = 62, 30.4%) at the time of diagnosis. One hundred sixty-nine patients underwent operation, while 17 were treated with other modalities. The remission rate was 48%, and median recurrence-free survival time was 46 months. Estimated 5-year recurrence-free rate was 44.7%. There were more women, large tumor, atypical mitosis, venous invasion, and higher mitotic count in cancer recurrence group. Estimated 5-year overall survival and disease-specific survival rates were 64.5 and 70.6%, respectively. Higher ENSAT stage and advanced pathologic characteristics were risk factors for all-cause mortality of ACC. Large tumor size and cortisol-secreting tumor were additional risk factors for ACC-specific death.

Conclusions

We report the first epidemiologic study regarding ACC in an Asian population. ENSAT stage 4; lymph node involvement; non-operative group; and invasion of vein, sinusoid, or capsule were associated with an increased risk for all-cause mortality.

Open access

Zeeshan Javed, Maria Papageorgiou, Leigh A Madden, Alan S Rigby, Eric S Kilpatrick, Stephen L Atkin and Thozhukat Sathyapalan

Context

Endothelial microparticles (EMPs) are novel, surrogate biomarkers of endothelial function and have been shown to be elevated in women with polycystic ovary syndrome (PCOS). It remains poorly understood how pharmacological options for managing PCOS affect EMP levels.

Objective

To characterise and compare the effects of empagliflozin vs metformin on the circulating levels of EMPs in overweight/obese women with PCOS.

Methods

This was a randomised, comparative, 12-week single-centre trial conducted at the Academic Diabetes, Endocrinology and Metabolism Research Centre, Hull, UK. This analysis includes data from 39 overweight/obese women with PCOS who completed the study and were randomised to empagliflozin (15 mg/day) (n = 19) or metformin (1500 mg/day) (n = 20). Blood samples were collected at baseline and 12 weeks after treatment and analysed for specific surface proteins (ICAM-1, VCAM-1, PECAM-1, E-selectin and endoglin) expressed by circulating EMPs using flow cytometry.

Results

In the empagliflozin group, ICAM-1 (P = 0.006), E-selectin (P = 0.016) and VCAM-1 (P = 0.001) EMPs increased significantly following 12 weeks of treatment, but no changes were seen in PECAM-1 (P = 0.93) or endoglin (P = 0.13) EMPs. In the metformin group, VCAM-1 EMPs (P < 0.001) increased significantly after 12 weeks of treatment, whereas all other EMPs remained unchanged. When data were expressed as percentage change from baseline in each group, no significant differences were seen between groups for any biomarker (P-values from 0.22 to 0.80).

Conclusions

Short-term administration of empagliflozin and metformin in overweight/obese women with PCOS appear to increase EMPs expressed by endothelial cells during their activation.

Open access

Rosalie Cabry, Philippe Merviel, Aicha Madkour, Elodie Lefranc, Florence Scheffler, Rachel Desailloud, Véronique Bach and Moncef Benkhalifa

The negative impact of endocrine-disrupting pesticides on human fertility is now a key issue in reproductive health. There are much fewer literature data about the impact of pesticide exposure on women than on men and very few studies of women participating in an in vitro fertilization (IVF) programme. In the present review, we found that (1) various pesticides with an endocrine-disrupting action are associated with poor oocyte maturation and competency, embryonic defects and poor IVF outcomes, and (2) some pesticide compounds are linked to specific causes of female infertility, such as premature ovarian insufficiency, polycystic ovarian syndrome, and endometriosis. IVF participants living in agricultural regions should be informed about the fertility decline, low ongoing pregnancy rates, and elevated risk of miscarriage associated with exposure to high doses of pesticides.

Open access

Hichem Bouguerra, Gorrab Amal, Stephan Clavel, Hamouda Boussen, Jean-François Louet and Asma Gati

Large prospective studies established a link between obesity and breast cancer (BC) development. Yet, the mechanisms underlying this association are not fully understood. Among the diverse adipocytokine secreted by hypertrophic adipose tissue, leptin is emerging as a key candidate molecule linking obesity and cancer, since it promotes proliferation and invasiveness of tumors. However, the potential implication of leptin on tumor escape mechanisms remains unknown. This study aims to explore the effect of leptin on tumor resistance to NK lysis and the underlying mechanism. We found that leptin promotes both BC resistance to NK92-mediated lysis and β oxidation on MCF-7, by the up-regulation of a master regulator of mitochondrial biogenesis, the peroxisome proliferator activated receptor coactivator-1 α (PGC1A). Using adenoviral approaches, we show that acute elevation of PGC1A enhances the fatty acid oxidation pathway and decreases the susceptibility of BC cells to NK92-mediated lysis. Importantly, we identified the involvement of PGC1A and leptin in the regulation of hypoxia inducible factor-1 alpha (HIF1A) expression by tumor cells. We further demonstrate that basal BC cells MDA-MB-231 and BT-20 exhibit an increased PGC1A mRNA level and an enhanced oxidative phosphorylation activity; in comparison with luminal BC cells MCF7 and MDA-361, which are associated with more resistance NK92 lysis. Altogether, our results demonstrate for the first time how leptin could promote tumor resistance to immune attacks. Reagents blocking leptin or PGC1A activity might aid in developing new therapeutic strategies to limit tumor development in obese BC patients.

Open access

Matilde Calanchini, Michael Tadman, Jesper Krogh, Andrea Fabbri, Ashley Grossman and Brian Shine

Open access

Virginie Grouthier, Zeina Chakhtoura, Isabelle Tejedor, Yasmina Badachi, Vincent Goffin and Philippe Touraine

Objective

Multiple fibroadenomas (MFA) of the breast is a rare benign disease, thus its natural history is poorly understood. The aim of our study was to describe the radiological evolution of MFA and to evaluate the influence of different factors on this evolution.

Methods

This was a longitudinal cohort study. All patients included had two clinical and radiological assessments (breast ultrasound (US) and/or MRI) at least 5 years apart.

Results

Seventy-two women were followed for 7.6 ± 2.1 years. The radiological evolution showed a decrease or stability in the number of fibroadenomas (FA) in 26/44 cases on the MRI and in 38/64 cases on the US. There was a decrease of size in 35/44 cases on the MRI and in 53/64 cases on the US. An increase in the number of FAs was found in 18/44 cases in the MRI and 26/64 cases in the US with, for the majority, a decrease of size (19/26 by MRI and 16/18 by MRI). Older age at the first FA (P < 0.0001) and at the diagnosis of MFA (P < 0.0001), pregnancy (P = 0.003) and progestin use (P < 0.001), particularly lynestrenol (P < 0.0001), had a beneficial effect on the evolution of MFA.

Conclusion

This is the first longitudinal study describing women with MFA. The radiological evolution of MFA seamed favorable and similar to that expected for a single FA. We identified factors influencing the evolution of the disease, including progestin treatments such as lynestrenol, which could have a beneficial effect. Our cohort should be followed further in order to expand our knowledge of MFA, especially concerning the risk of breast cancer.

Open access

Thomas Couronne, Paul Girot, Julien Hadoux, Thierry Lecomte, Alice Durand, Caroline Fine, Katia Vandevoorde, Catherine Lombard-Bohas and Thomas Walter

Objective

First-line chemotherapy in metastatic neuroendocrine carcinomas (NECs) is based on etoposide and platinum. However, there is no standard concerning second-line treatment. The objective of this study was to evaluate efficacy and tolerance of dacarbazine or temozolomide in metastatic digestive NEC as post first-line treatment.

Material and methods

This study included patients with a metastatic NEC of digestive or unknown primary site. All patients received platinum-etoposide as first-line chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were clinical/morphological responses, toxicity, and overall survival (OS).

Results

Twenty-seven patients were included: 17 received dacarbazine and 10 temozolomide as post-first line treatments. Median PFS was 3.0 (95%CI (2.2;3.7)) months. There was no significant difference between dacarbazine and temozolomide on PFS. Clinical and morphological responses were found in 12 and 9 patients, respectively. Median OS was 7.2 (95%CI (2.2;12.2)) months. The toxicity profile was that expected with such treatments.

Conclusion

LV5FU2-dacarbazine or temozolomide-capecitabine chemotherapies allow a temporary clinical response for almost half of patients and/or a morphological response for a third of patients.

Open access

E M Winter, A Ireland, N C Butterfield, M Haffner-Luntzer, M-N Horcajada, A G Veldhuis-Vlug, L Oei, G Colaianni and N Bonnet

In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.