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Open access

Kaisu Luiro, Kristiina Aittomäki, Pekka Jousilahti, and Juha S Tapanainen

Objective

To study the use of hormone therapy (HT), morbidity and reproductive outcomes of women with primary ovarian insufficiency (POI) due to FSH-resistant ovaries (FSHRO).

Design

A prospective follow-up study in a university-based tertiary clinic setting.

Methods

Twenty-six women with an inactivating A189V FSH receptor mutation were investigated by means of a health questionnaire and clinical examination. Twenty-two returned the health questionnaire and 14 were clinically examined. Main outcome measures in the health questionnaire were reported as HT, morbidity, medication and infertility treatment outcomes. In the clinical study, risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS) were compared to age-matched controls from a national population survey (FINRISK). Average number of controls was 326 per FSHRO subject (range 178–430). Bone mineral density and whole-body composition were analyzed with DXA. Psychological and sexual well-being was assessed with Beck Depression Inventory (BDI21), Generalized Anxiety Disorder 7 (GAD-7) and Female Sexual Function Index (FSFI) questionnaires.

Results

HT was initiated late (median 18 years of age) compared with normal puberty and the median time of use was shorter (20–22 years) than the normal fertile period. Osteopenia was detected in 9/14 of the FSHRO women despite HT. No major risk factors for CVD or diabetes were found.

Conclusions

HT of 20 years seems to be associated with a similar cardiovascular and metabolic risk factor profile as in the population control group. However, optimal bone health may require an early-onset and longer period of HT, which would better correspond to the natural fertile period.

Open access

M von Wolff, C T Nakas, M Tobler, T M Merz, M P Hilty, J D Veldhuis, A R Huber, and J Pichler Hefti

Humans cannot live at very high altitude for reasons, which are not completely understood. Since these reasons are not restricted to cardiorespiratory changes alone, changes in the endocrine system might also be involved. Therefore, hormonal changes during prolonged hypobaric hypoxia were comprehensively assessed to determine effects of altitude and hypoxia on stress, thyroid and gonadal hypothalamus–pituitary hormone axes. Twenty-one male and 19 female participants were examined repetitively during a high-altitude expedition. Cortisol, prolactin, thyroid-stimulating hormone (TSH), fT4 and fT3 and in males follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone were analysed as well as parameters of hypoxemia, such as SaO2 and paO2 at 550 m (baseline) (n = 40), during ascent at 4844 m (n = 38), 6022 m (n = 31) and 7050 m (n = 13), at 4844 m (n = 29) after acclimatization and after the expedition (n = 38). Correlation analysis of hormone concentrations with oxygen parameters and with altitude revealed statistical association in most cases only with altitude. Adrenal, thyroid and gonadal axes were affected by increasing altitude. Adrenal axis and prolactin were first supressed at 4844 m and then activated with increasing altitude; thyroid and gonadal axes were directly activated or suppressed respectively with increasing altitude. Acclimatisation at 4844 m led to normalization of adrenal and gonadal but not of thyroid axes. In conclusion, acclimatization partly leads to a normalization of the adrenal, thyroid and gonadal axes at around 5000 m. However, at higher altitude, endocrine dysregulation is pronounced and might contribute to the physical degradation found at high altitude.

Open access

Nese Cinar and Alper Gurlek

Adipose tissue secretes a variety of active biological substances, called adipocytokines, that act in an autocrine, paracrine, and endocrine manner. They have roles in appetite control, thermogenesis, and thyroid and reproductive functions. All these molecules may lead to local and generalized inflammation, mediating obesity-associated vascular disorders including hypertension, diabetes, atherosclerosis, and insulin resistance. Thyroid dysfunction is associated with changes in body weight, thermogenesis, and energy expenditure. The connections between cardiovascular risk factors such as dyslipidemia, impaired glucose tolerance, insulin resistance, atherosclerosis, and thyroid dysfunction have been reported in several studies. The adipocytokines serve as causative or protective factors in the development of these disorders in the states of thyroid dysfunction. Abnormal levels of adipocytokines (adiponectin (ADP), leptin, resistin, vaspin, and visfatin) in hypo- and hyperthyroidism have been reported with controversial results. This review aims to update the implication of novel adipokines ADP, vaspin, and visfatin in thyroid dysfunction.

Open access

Eva Olga Melin, Jonatan Dereke, Maria Thunander, and Magnus Hillman

Objective

Neuroinflammatory responses are implicated in depression. The aim was to explore whether depression in patients with type 1 diabetes (T1D) was associated with high circulating galectin-3, controlling for metabolic variables, s-creatinine, life style factors, medication and cardiovascular complications.

Design

Cross-sectional.

Methods

Participants were T1D patients (n = 283, 56% men, age 18–59 years, diabetes duration ≥1 year). Depression was assessed by Hospital Anxiety and Depression Scale-depression subscale. Blood samples, anthropometrics and blood pressure were collected, and supplemented with data from medical records and the Swedish National Diabetes Registry. Galectin-3 ≥2.562 µg/l, corresponding to the 85th percentile, was defined as high galectin-3.

Results

Median (quartile1, quartile3) galectin-3 (µg/l) was 1.3 (0.8, 2.9) for the 30 depressed patients, and 0.9 (0.5, 1.6) for the 253 non-depressed, P = 0.009. Depression was associated with high galectin-3 in all the 283 patients (adjusted odds ratio (AOR) 3.5), in the 161 men (AOR 3.4), and in the 122 women (AOR 3.9). HbA1c, s-lipids, s-creatinine, blood pressure, obesity, smoking, physical inactivity, cardiovascular complications and drugs (antihypertensive, lipid lowering, oral antidiabetic drugs and antidepressants) were not associated with high galectin-3.

Conclusions

This is the first study to show an association between depression and galectin-3. Depression was the only explored parameter associated with high circulating galectin-3 levels in 283 T1D patients. High galectin-3 levels might contribute to the increased risk for Alzheimer’s disease, cardiovascular and all-cause mortality observed in persons with depression. Potentially, in the future, treatment targeting galactin-3 might improve the prognosis for patients with high galectin-3 levels.

Open access

Andrea V Haas, Paul N Hopkins, Nancy J Brown, Luminita H Pojoga, Jonathan S Williams, Gail K Adler, and Gordon H Williams

There are conflicting data on whether variations of physiologic cortisol levels associated with cardiovascular risk. We hypothesize that prior discordant findings are related to problems associated with varying sample size, techniques for assessing cardiovascular risk and failure to adequately account for environmental factors. To address these issues, we utilized a large sample size, selected the Framingham risk score to compute cardiovascular risk and performed the study in a highly controlled setting. We had two main objectives: determine whether higher, yet physiologic, cortisol levels associated with increased cardiovascular risk and determine whether caveolin-1 (rs926198) risk allele carriers associated with increased cardiovascular risk. This was a cross-sectional study of 574 non-diabetic individuals who completed a common protocol. Data collection included fasting blood samples, blood pressure measurements and a 24-h urine-free cortisol collection. Five hundred seventeen of these participants also completed caveolin-1 genotyping. Subjects were classified as belonging to either the low-mode or high-mode urine-free cortisol groups, based on the bimodal distribution of urine-free cortisol. In multivariate analysis, Framingham risk score was statistically higher in the high-mode cortisol group (10.22 (mean) ± 0.43 (s.e.m.)) compared to the low-mode cortisol group (7.73 ± 0.34), P < 0.001. Framingham risk score was also statistically higher in the caveolin-1 risk allele carriers (8.91 ± 0.37) compared to caveolin-1 non-risk allele carriers (7.59 ± 0.48), P = 0.034. Overall, the estimated effect on Framingham risk score of carrying the caveolin-1 risk allele was 1.33 ± 0.61, P = 0.029. Both urinary cortisol and caveolin-1 risk allele status are independent predictors of Framingham risk score.

Open access

Sebastião Freitas de Medeiros, Cinthia Marenza Ormond, Matheus Antônio Souto de Medeiros, Nayara de Souza Santos, Camila Regis Banhara, and Márcia Marly Winck Yamamoto

Objective

To examine the anthropometric, and metabolic connections of 17-hydroxypregnenolone in the normo- and hyperandrogenemic polycystic ovary syndrome phenotypes.

Materials and methods

This cohort study was conducted at the Julio Muller University Hospital, Cuiabá, Brazil, between January 2014 and July 2016, and 91 normal cycling healthy women, 46 normoandrogenemic and 147 hyperandrogenemic, patients with polycystic ovary syndrome (PCOS) were enrolled according to the Rotterdam criteria. Several anthropometric, biochemical and hormonal parameters were properly verified and correlated with 17-hydroxypregnenolone (17-OHPE) concentrations.

Results

17-OHPE was higher in hyperandrogenemic PCOS than in normoandrogenemic PCOS and in control groups (P = 0.032 and P < 0.001, respectively). In healthy controls, 17-OHPE was positively associated with glucose, free estrogen index, DHEAS and negatively associated with compounds S. In normoandrogenemic PCOS patients, 17-OHPE presented positive correlations with VAI, LAP, cortisol, insulin and HOMA-IR. In the hyperandrogenemic group, 17-OHPE presented significant negative correlations with most anthropometric parameters, HOMA-IR, HOMA %B, estradiol, free estrogen index (FEI), C-peptide, and TG levels and positive correlations with HOMA-S and high-density lipoprotein cholesterol (HDL-C), sex-hormone binding globulin (SHBG), androstenedione (A4) and dehydroepiandrosterone (DHEA). Regarding hyperandrogenemic PCOS, and using a stepwise multiple regression, only HOMA-S and WHR were retained in the model (R 2 = 0.294, P < 0.001).

Conclusion

17-OHPE exhibited different relationships with anthropometric, and biochemical parameters in PCOS patients, depending on the androgen levels. In PCOS subjects with high androgen concentrations, 17-OHPE was negatively associated with most anthropometric parameters, particularly with those used as markers of adipose tissue dysfunction and frequently employed as predictors of cardiovascular disease risk; otherwise, 17-OHPE was positively associated with HDL-C and HOMA-S in this patients. Future studies are required to evaluate the clinical implications of these novel findings.

Open access

Sarah Byberg, Jesper Futtrup, Mikkel Andreassen, and Jesper Krogh

Objectives

Recent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to systematically assess the effect of reducing prolactin with dopamine agonist on established cardiovascular risk factors in patients with prolactinomas.

Design

Bibliographical search was done until February 2019 searching the following databases: PubMed, EMBASE, WHO and LILAC. Eligible studies had to include participants with verified prolactinomas where metabolic variables were assessed before and after at least 2 weeks treatment with dopamine agonists.

Methods

Baseline data and outcomes were independently collected by two investigators. The study was registered with PROSPERO (registration number CRD42016046525).

Results

Fourteen observational studies enrolling 387 participants were included. The pooled standardized mean difference of the primary outcome revealed a reduction of BMI and weight of −0.21 (95% CI −0.37 to −0.05; P = 0.01; I 2 = 71%), after treatment. Subgroup analysis suggested that the reduction of weight was primarily driven by studies with high prolactin levels at baseline (P = 0.04). Secondary outcomes suggested a small decrease in waist circumference, a small-to-moderate decrease in triglycerides, fasting glucose levels, HOMA-IR, HbA1c and hsCRP, and a moderate decrease in LDL, total cholesterol and insulin.

Conclusion

This systematic review suggests a reduction of weight as well as an improved lipid profile and glucose tolerance after treatment with dopamine agonist in patients with prolactinomas. These data are based on low-quality evidence.

Open access

David J F Smith, Hemanth Prabhudev, Sirazum Choudhury, and Karim Meeran

Introduction

Patients who need glucocorticoid replacement in both primary and secondary adrenal insufficiency (AI) have the choice of either once-daily prednisolone or thrice-daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers including glucose, weight, body mass index, systolic and diastolic blood pressure and waist circumference, although an increase in cholesterol and low-density lipoprotein (LDL) was suggested in a subgroup of these patients. The aim of this study was to expand the evidence base for the use of these agents as replacement therapy.

Methods

Data from 82 patients on hydrocortisone and 64 patients on prednisolone for AI at Imperial College Healthcare NHS Trust were analysed.

Results

There was no significant difference in total cholesterol, LDL levels or any other risk factors between hydrocortisone and prednisolone patients. Prednisolone was subjectively significantly more convenient than hydrocortisone (P = 0.048).

Conclusions

Prednisolone once daily is more convenient than hydrocortisone thrice daily, and there is no difference in the markers of cardiovascular risk measured. Because prednisolone mimics the circadian rhythm better than other glucocorticoids, it should be considered as an alternative to hydrocortisone for AI.

Open access

Anna Eremkina, Julia Krupinova, Ekaterina Dobreva, Anna Gorbacheva, Ekaterina Bibik, Margarita Samsonova, Alina Ajnetdinova, and Natalya Mokrysheva

Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (P = 0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (P = 0.012). After that, seven patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.

Open access

Valeria Hirschler, Claudia Molinari, Silvia Lapertosa, Gustavo Maccallini, and Claudio D Gonzalez

Background

The association between central obesity and cardiometabolic complications justifies exploring its association in normal-weight and overweight/obese (OW/OB) schoolchildren.

Objective

To describe cardiometabolic markers in four groups according to BMI/WC categories: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB, in a sample of Argentinean schoolchildren.

Methods

A cross-sectional study of 1264 Argentinean schoolchildren (624 F), aged 9.5 ± 2.2 years was performed between November 2013 and 2015. Children’s anthropometric measures, blood pressure (BP), glucose, lipids, and insulin were measured. Children were divided into four groups: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB.

Results

The prevalence of normal-weight children without central OB was 64.3% (796), normal weight with central OB 5% (66), OW/OB without central OB 11% (137), and OW/OB with central OB 21% (265). Normal weight with central OB had significantly higher triglycerides than normal-weight children without central OB (86 vs 70 mg/dL, respectively) and OW/OB children without central OB (81 vs 77 mg/dL). Multiple linear regression analyses showed that age, systolic BP, HDL-C, triglycerides, and maternal WC were significantly associated with children’s WC; R2 = 0.50 as well as children’s BMI; R2 = 0.37.

Conclusion

This study found that children with central OB might be at future higher cardiometabolic risk than those without central OB independently of the presence of OW/OB. However, future longitudinal studies should be performed to confirm these findings.