Search Results

You are looking at 51 - 60 of 65 items for

  • Abstract: anti-androgenic x
  • Abstract: Bisphenol-A x
  • Abstract: Drugs x
  • Refine by Access: All content x
Clear All Modify Search
Open access

Anastasia P Athanasoulia-Kaspar, Matthias K Auer, Günter K Stalla, and Mira Jakovcevski

Objective

Patients with non-functioning pituitary adenomas exhibit high morbidity and mortality rates. Growth hormone deficiency and high doses of glucocorticoid substitution therapy have been identified as corresponding risk factors. Interestingly, high levels of endogenous cortisol in, e.g., patients with post-traumatic stress disorder or patients with Cushing’s disease have been linked to shorter telomere length. Telomeres are noncoding DNA regions located at the end of chromosomes consisting of repetitive DNA sequences which shorten with aging and hereby determine cell survival. Therefore, telomere length can serve as a predictor for the onset of disease and mortality in some endocrine disorders (e.g., Cushing’s disease).

Design/methods

Here, we examine telomere length from blood in patients (n = 115) with non-functioning pituitary adenomas (NFPA) in a cross-sectional case–control (n = 106, age-, gender-matched) study using qPCR. Linear regression models were used to identify independent predictors of telomere length.

Results

We show that patients with NFPA exhibited shorter telomeres than controls. No significant association of indices of growth hormone deficiency (IGF-1-level-SDS, years of unsubstituted growth hormone deficiency etc.) with telomere length was detected. Interestingly, linear regression analysis showed that hydrocortisone replacement dosage in patients with adrenal insufficiency (n = 52) was a significant predictor for shorter telomere length (β = 0.377; P = 0.018) independent of potential confounders (gender, age, BMI, arterial hypertension, systolic blood pressure, number of antihypertensive drugs, total leukocyte count, waist-to-hip ratio, waist circumference, diabetes mellitus type 2, HbA1c, current statin use). Median split analysis revealed that higher hydrocortisone intake (>20 mg) was associated with significantly shorter telomeres.

Conclusion

These observations strengthen the importance of adjusted glucocorticoid treatment in NFPA patients with respect to morbidity and mortality rates.

Open access

Eva Olga Melin, Magnus Hillman, and Mona Landin-Olsson

Objective

To explore associations between high midnight salivary cortisol (MSC) secretion and high blood pressure (BP) in type 1 diabetes (T1D).

Methods

Cross-sectional study of 196 adult patients with T1D (54% men). Associations between high MSC (≥9.3 nmol/L) and high systolic BP (>130 mmHg), and high diastolic BP (>80 mmHg) were explored for all patients, users and non-users of antihypertensive drugs (AHD). Adjustments were performed for age, sex, diabetes-related variables, p-creatinine, smoking, physical inactivity, depression and medication.

Results

The prevalence of high MSC differed between patients with high and low systolic BP in all 196 patients: 39 vs 13% (P = 0.001); in 60 users of AHD: 37 vs 12% (P = 0.039), and in 136 non-users of AHD: 43 vs 13% (P = 0.012). Significant associations with high systolic BP were for all patients: physical inactivity (adjusted odds ratio (AOR) 6.5), high MSC (AOR 3.9), abdominal obesity (AOR 3.7), AHD (AOR 2.9), age (per year) (AOR 1.07), and p-creatinine (per µmol/L) (AOR 1.03); for 60 users of AHD: high MSC (AOR 4.1) and age (per year) (AOR 1.11); for 136 non-users of AHD: abdominal obesity (AOR 27.4), physical inactivity (AOR 14.7), male sex (AOR 9.0), smoking (AOR 7.9), and age (per year) (AOR 1.08). High MSC was not associated with high DBP.

Conclusions

In adult patients with T1D, high systolic BP was associated with physical inactivity, high MSC secretion, abdominal obesity, p-creatinine, age, and AHD, the latter indicating treatment failure.

Open access

Riying Liang, Meijun Wang, Chang Fu, Hua Liang, Hongrong Deng, Ying Tan, Fen Xu, and Mengyin Cai

Background:

Obesity is associated with the development and progression of chronic kidney disease. Emerging evidence suggests that glucagon-like peptide-1 receptor agonist could reduce renal damage and albuminuria. Sirtuin 1 (SIRT1) was considered as a crucial regulator in metabolism-related kidney disease. Herein, the role of SIRT1 in liraglutide-ameliorated high-fat diet (HFD)-induced kidney injury was illustrated.

Methods:

Male C57BL/6 mice were fed HFD for 20 weeks to induce kidney injury that was then treated with liraglutide for 8 weeks to estimate its protective effect on the kidney. Also, the mechanism of the drug in SV40 MES 13 (SV40) mouse mesangial cells was elucidated.

Results:

Liraglutide treatment ameliorated HFD-induced metabolic disorders, including hyperglycemia, increasing body weight, and insulin resistance. In addition, kidney weight, urine albumin-to-creatinine, and kidney morphological changes such as vacuolated tubules, glomerulomegaly, thickened glomerular basement membrane, and tubulointerstitial fibrosis were also significantly ameliorated. Furthermore, apoptotic cells and apoptosis markers were downregulated in the kidney of liraglutide-treated mice. In addition, the expression of SIRT1 protein was upregulated, whereas thioredoxin-interacting protein (TXNIP), which serves as a mediator of oxidative stress and apoptosis in metabolism disease, was downregulated by liraglutide. In SV40 cells, the effect of liraglutide on reversing the upregulation of cleaved caspase-3 induced by high glucose (30 mM) was hampered when SIRT1 was knocked down; also, the downregulation of TXNIP by liraglutide was blocked.

Conclusions:

Liraglutide might have a beneficial effect on metabolism-related kidney damage by inhibiting apoptosis via activation of SIRT1 and suppression of TXNIP pathway.

Open access

Guido Zavatta and Bart L Clarke

The first adjunctive hormone therapy for chronic hypoparathyroidism, recombinant human parathyroid hormone (1–84) (rhPTH(1–84)) was approved by the FDA in January 2015. Since the approval of rhPTH(1–84), growing interest has developed in other agents to treat this disorder in both the scientific community and among pharmaceutical companies. For several reasons, conventional therapy with calcium and activated vitamin D supplementation, magnesium supplementation as needed, and occasionally thiazide-type diuretic therapy remains the mainstay of treatment, while endocrinologists and patients are constantly challenged by limitations of conventional treatment. Serum calcium fluctuations, increased urinary calcium, hyperphosphatemia, and a constellation of symptoms that limit mental and physical functioning are frequently associated with conventional therapy. Understanding how conventional treatment and hormone therapy work in terms of pharmacokinetics and pharmacodynamics is key to effectively managing chronic hypoparathyroidism. Multiple questions remain regarding the effectiveness of PTH adjunctive therapy in preventing or slowing the onset and progression of the classical complications of hypoparathyroidism, such as chronic kidney disease, calcium-containing kidney stones, cataracts, or basal ganglia calcification. Several studies point toward an improvement in the quality of life during replacement therapy. This review will discuss current clinical and research challenges posed by treatment of chronic hypoparathyroidism.

Key points:

  • Conventional therapy with calcium and activated forms of vitamin D are currently the mainstays of treatment for most patients with chronic hypoparathyroidism.

  • Hormone therapy can be administered through FDA-approved once-daily rhPTH(1–84), or off-label multiple-daily injections of teriparatide. The former is the only FDA-approved drug, with safety and efficacy supported by a randomized placebo-controlled trial and open-label long-term extension trial data.

  • Twice-daily teriparatide has been used in children safely for up to 10 years.

  • New pharmacological options that replace the deficient hormone wi ll likely be available within the next few years.

Open access

Soraya Puglisi, Paola Perotti, Mattia Barbot, Paolo Cosio, Carla Scaroni, Antonio Stigliano, Pina Lardo, Valentina Morelli, Elisa Polledri, Iacopo Chiodini, Giuseppe Reimondo, Anna Pia, and Massimo Terzolo

Objective

Metyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment.

Design and methods

Before adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82).

Results

In all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P < 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P < 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P < 0.01; diastolic pressure, −16 (−50; +2 mmHg), P < 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient.

Conclusions

This prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.

Open access

M L Gild, M Bullock, C K Pon, B G Robinson, and R J Clifton-Bligh

Metastatic differentiated thyroid cancers (DTC) are resistant to traditional chemotherapy. Kinase inhibitors have shown promise in patients with progressive DTC, but dose-limiting toxicity is commonplace. HSP90 regulates protein degradation of several growth-mediating kinases such as RET, and we hypothesized that HSP90 inhibitor (AUY922) could inhibit RET-mediated medullary thyroid cancer (MTC) as well as papillary thyroid cancer (PTC) cell growth and also radioactive iodine uptake by PTC cells. Studies utilized MTC cell lines TT (C634W) and MZ-CRC-1 (M918T) and the PTC cell line TPC-1 (RET/PTC1). Cell viability was assessed with MTS assays and apoptosis by flow cytometry. Signaling target expression was determined by western blot and radioiodine uptake measured with a gamma counter. Prolonged treatment of both MTC cell lines with AUY922 simultaneously inhibited both MAPK and mTOR pathways and significantly induced apoptosis (58.7 and 78.7% reduction in MZ-CRC-1 and TT live cells respectively, following 1 μM AUY922; P<0.02). Similarly in the PTC cell line, growth and signaling targets were inhibited, and also a 2.84-fold increase in radioiodine uptake was observed following AUY922 administration (P=0.015). AUY922 demonstrates in vitro activity against MTC and PTC cell lines. We observed a potent dose-dependent increase in apoptosis in MTC cell lines following drug administration confirming its anti-tumorigenic effects. Western blots confirm inhibition of pro-survival proteins including AKT suggesting this as the mechanism of cell death. In a functional study, we observed an increase in radioiodine uptake in the PTC cell line following AUY922 treatment. We believe HSP90 inhibition could be a viable alternative for treatment of RET-driven chemo-resistant thyroid cancers.

Open access

Jia Liu, Lin Zhang, Jing Fu, Qiu Wang, and Guang Wang

Objective

Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes.

Methods

A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured.

Results

In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: β = −0.263, P < 0.05; adipo-IR: β = −0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01).

Conclusion

The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.

Open access

Carina Ankarberg-Lindgren, Aneta Gawlik, Berit Kriström, Laura Mazzanti, Elisabeth J Ruijgrok, and Theo C J Sas

Objective

Transdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut estradiol patches. The aim of the study was to assess 1-month stability of cut estradiol patches from four different manufacturers in the laboratory at room temperature (+21°C) and at an elevated temperature (+35°C).

Design and methods

Estraderm MX 50 µg, Systen 50 µg and Oesclim 25 µg matrix patches were cut into eight pieces while Estradot 50 µg small patches were cut in half. The cut patches were stored in their respective pouches at +21°C or at +35°C for up to 1 month. The estradiol drug was extracted from the patch by ethyl acetate n-hexane and determined by radioimmunoassay.

Results

Storage at +21°C or +35°C up to 1 month did not reduce the estradiol concentration in Estraderm MX, Systen and Oesclim patches. However, although the estradiol in Estradot patches was not affected by storage at +21°C, at +35°C, estradiol decreased by 57% (±1%) in cut pieces.

Conclusions

Unused Estraderm MX, Systen and Oesclim patch pieces may be stored for at least 1 month at ≤+35°C. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures.

Open access

Melinda Kertész, Szilárd Kun, Eszter Sélley, Zsuzsanna Nagy, Tamás Kőszegi, and István Wittmann

Background

Type 2 diabetes is characterized, beyond the insulin resistance, by polyhormonal resistance. Thyroid hormonal resistance has not yet been described in this population of patients. Metformin is used to decrease insulin resistance, and at present, it is assumed to influence the effect of triiodothyronine, as well.

Methods

In this open-label, pilot, hypothesis-generating, follow-up study, 21 patients were included; all of them were euthyroid with drug naïve, newly diagnosed type 2 diabetes. Before and after 4 weeks of metformin therapy, fructosamine, homeostasis model assessment for insulin resistance (HOMA-IR), thyroid hormones, T3/T4 ratio, and TSH, as well as blood pressure and heart rate using ambulatory blood pressure monitor were measured. We also conducted an in vitro study to investigate the possible mechanisms of T3 resistance, assessing T3-induced Akt phosphorylation among normal (5 mM) and high (25 mM) glucose levels with or without metformin treatment in a human embryonal kidney cell line.

Results

Metformin decreased the level of T3 (P < 0.001), the ratio of T3/T4 (P = 0.038), fructosamine (P = 0.008) and HOMA-IR (P = 0.022). All these changes were accompanied by an unchanged TSH, T4, triglyceride, plasma glucose, bodyweight, blood pressure, and heart rate. In our in vitro study, T3-induced Akt phosphorylation decreased in cells grown in 25 mM glucose medium compared to those in 5 mM. Metformin could not reverse this effect.

Conclusion

Metformin seems to improve T3 sensitivity in the cardiovascular system in euthyroid, type 2 diabetic patients, the mechanism of which may be supracellular.

Open access

Satoshi Higuchi, Hideki Ota, Yuta Tezuka, Kazumasa Seiji, Hidenobu Takagi, Jongmin Lee, Yi-Wei Lee, Kei Omata, Yoshikiyo Ono, Ryo Morimoto, Masataka Kudo, Fumitoshi Satoh, and Kei Takase

Objectives

This study compared cardiac function, morphology, and tissue characteristics between two common subtypes of primary aldosteronism (PA) using a 3T MR scanner.

Design

A retrospective, single-center, observational study.

Methods

We retrospectively reviewed 143 consecutive patients with PA, who underwent both adrenal venous sampling and cardiac magnetic resonance. We acquired cine, late gadolinium enhancement, and pre- and postcontrast myocardial T1-mapping images.

Results

PA was diagnosed as unilateral aldosterone-producing adenoma (APA) in 70 patients and bilateral hyperaldosteronism (BHA) in 73. The APA group showed significantly higher plasma aldosterone concentration (PAC) and aldosterone to renin rate (ARR) than the BHA group. After controlling for age, sex, antihypertensive drugs, systolic and diastolic blood pressure, and disease duration, the parameters independently associated with APA were: left ventricular end-diastolic volume index (EDVI: adjusted odds ratio (aOR) = 1.06 (95% CI: 1.030–1.096), P < 0.01), end-systolic volume index (ESVI: 1.06 (1.017–1.113), P < 0.01), stroke index (SI: 1.07 (1.020–1.121), P < 0.01), cardiac index (CI: 1.001 (1.000–1.001), P < 0.01), and native T1 (1.01 (1.000–1.019), P = 0.038). Weak positive correlations were found between PAC and EDVI (R = 0.28, P < 0.01), ESVI (0.26, P < 0.01), and SI (0.18, P = 0.03); and between ARR and EDVI (0.25, P < 0.01), ESVI (0.24, P < 0.01), and native T1 (0.17, P = 0.047).

Conclusions

APA is associated with greater LV volumetric parameters and higher native T1 values, suggesting a higher risk of volume overload and myocardial damage.