Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort.

BACKGROUND & AIMS: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with obesity, severe malabsorptive diarrhea, and certain endocrine abnormalities. Common variants in PCSK1 also have been associated with obesity in heterozygotes in several population-based studies. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells. We investigated clinical and molecular features of PC1/3 deficiency. METHODS: We studied the clinical features of 13 children with PC1/3 deficiency and performed sequence analysis of PCSK1. We measured enzymatic activity of recombinant PC1/3 proteins. RESULTS: We identified a pattern of endocrinopathies that develop in an age-dependent manner. Eight of the mutations had severe biochemical consequences in vitro. Neonates had severe malabsorptive diarrhea and failure to thrive, required prolonged parenteral nutrition support, and had high mortality. Additional endocrine abnormalities developed as the disease progressed, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, and hypothyroidism. We identified growth hormone deficiency, central diabetes insipidus, and male hypogonadism as new features of PCSK1 insufficiency. Interestingly, despite early growth abnormalities, moderate obesity, associated with severe polyphagia, generally appears. CONCLUSIONS: In a study of 13 children with PC1/3 deficiency caused by disruption of PCSK1, failure of enteroendocrine cells to produce functional hormones resulted in generalized malabsorption. These findings indicate that PC1/3 is involved in the processing of one or more enteric hormones that are required for nutrient absorption.

Evaluation of the isokinetic muscle strength, balance and anaerobic performance in patients with young male hypogonadism.

Hypogonadism is a clinical condition that occurs due to infrequent abnormalities in the hypothalamic-pituitary-gonadal (HPG) axis in adolescence. Symptoms include weakening of muscle and bone strength. 30 young male patients with congenital hypogonadotropic hypogonadism (CHH) and 20 healthy young males were included in the present study. Quadriceps and hamstring muscle strength, balance and anaerobic performance capacities of the study group were measured both before and six months after Testosterone replacement therapy (TRT). The strength of the extensor and flexor muscles of both legs showed a statistically significant increase in the isokinetic test values at 60(0)/sec and 180(0)/sec angular velocity (p < 0.05). When the parameters related to balance were investigated, a statistically significant difference was found for stability indices of left and right between pre-TRT and post-TRT (p = 0.001 for both comparisons). According to the patients' anaerobic performance measurement results, a statistically significant improvement (p < 0.001) was also found between pre-TRT and post-TRT values for each parameter. It was shown that TRT significantly increases muscle strength, balance, and anaerobic performance of patients with male CHH. As a result, we absolutely recommend the use of TRT in patients with male CHH.

Prediction of testosterone response to human chorionic gonadotrophin in idiopathic hypogonadotropic hypogonadism patients.

In clinical practice, the human chorionic gonadotrophin (hCG) stimulation test is widely used to evaluate testicular function. Inhibin B, a gonadal peptide regulating follice-stimulating hormone (FSH) secretion, is an established marker of Sertoli cell function and spermatogenesis in adults. The aim of this study was to determine whether basal inhibin B levels are able to predict testosterone response to hCG in idiopathic hypogonadotropic hypogonadism (IHH) patients and to evaluate the correlation between inhibin B and gonadotropins in these patients and controls. Inhibin B (n=15) and other hormones (n=29) were measured in 29 patients with IHH and 32 controls. Inhibin B (n=8) and testosterone levels (n=25) before and after hCG stimulation were measured in 25 male patients with IHH by an immunoassay specific for inhibin B. Basal inhibin B was compared to the testosterone increase after hCG. There was a significant increase in inhibin B (22.6 +/- 9.8 vs 45.07 +/- 13 pg/mL; p=.005), free testosterone (2.92 +/- 0.55 vs. 7.9 +/- 1.5 pg/mL; p=.002), and total testosterone (69.0 +/- 15.9 vs. 184.9 +/- 44.1 ng/mL; p = .013) levels 72 hours after hCG injection. Inhibin B and the hCG-induced free testosterone and total testosterone increment correlated strongly (r=0.802, P<.001; r=0.793, P<.001, respectively). We conclude that basal inhibin B predicts the testosterone response to hCG in IHH patients and therefore gives reliable information about Leydig cell reserve. Furthermore, inhibin B levels show negative correlation with luteinizing hormone (LH) in control patients and positive correlation with FSH and LH in IHH patients. LH may effect inhibin B secretion. Further studies are necessary to define the physiology of inhibin B in human males.

Projection of new thresholds for hypertension to outpatient clinic patients and impact of risk factors: a cross-sectional study.

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on hypertension management recommend new stage 1 hypertension thresholds (130-139/80-89 mmHg) for starting antihypertensive treatment. OBJECTIVE: To analyze the impact of the 2017 ACC/AHA guidelines on patients' diagnoses within daily practice, in comparison with management using the 2018 European hypertension guidelines, regarding the new thresholds. DESIGN AND SETTING: Cross-sectional study conducted in a hypertension outpatient clinic at a tertiary-level public hospital. METHODS: The diagnosis of hypertension was defined separately using each guideline. The participants were patients who were attending the hypertension clinic, who were evaluated using the thresholds of two guidelines, based on cardiovascular risk factors, including age, gender, smoking status, diabetes mellitus, dyslipidemia, obesity, osteoporosis, chronic renal failure and family history of hypertension. RESULTS: After adapting the guidelines to the blood pressure values of our sample, 74.5% (n = 277) of the patients were diagnosed as hypertensive according to the blood pressure classification of the European Society of Cardiology (ESC) guidelines published in 2018, while 91.1% (n = 339) of the patients were hypertensive according to the new 2017 ACC/AHA guidelines. Multivariate regression analysis revealed that the significant demographic and cardiovascular risk factors associated with hypertension, based on the 2018 European Society of Hypertension (ESH)/ESC guidelines, were age (odds ratio, OR: 1.027; 95% confidence interval, CI: 1.001-1.054; P = 0.042), obesity (OR: 4.534; 95% CI: 1.830-11.237; P = 0.001) and family history of hypertension (OR: 2.199; 95% CI: 1.252-3.862; P = 0.006). CONCLUSIONS: The factors associated with the definition of hypertension may vary through changing the threshold values.

The relationship between anxiety, coping strategies and characteristics of patients with diabetes.

BACKGROUND: This study provided essential information, about Turkish patients with type I and type II diabetes, concerning: levels of anxiety, coping strategies used, and relationships that exist among anxiety, coping strategies, sociodemographic and medical characteristics. METHODS: A sample comprising 161 Turkish adults with both types of diabetes participated in the study. The trait anxiety scale, the brief COPE, sociodemographic and medical questionnaire were administered to patients with diabetes. RESULTS: The mean age was 49.01 (SD = 9.74), with a range from 20 to 60 years. The majority of the participants were female (60.9%) and type II diabetes (75.8%). 79% of the participants experienced anxiety. A clear majority of the participants reported to integrate their diabetes. Acceptance, religion, planning, positive reframing, instrumental support, emotional support, self-distraction and venting were the most frequently used coping strategies. The most frequently used problem-focused and the emotion-focused coping strategies were found to be similar in both type I and type II diabetes. However, participants with type II diabetes had relatively higher scores on the problem-focused strategies than those with type I. Participants with type I diabetes used humour, venting and self-blame more than those with type II diabetes. Other findings indicated that only a small minority responded to diabetes-related problems by denial, behavioural disengagement and substance use. Significant correlations were found among anxiety, coping strategies and sociodemographic characteristics of the participants. Moreover, Self-blame was found to be correlated significantly with both the problem-focused and emotion-focused coping strategies. Self-blame was also significantly correlated with both instrumental support and emotional support indicated that higher self-blame caused more frequent use of instrumental and emotional support by patients with diabetes. CONCLUSION: The findings of this study indicate that care for patients with diabetes should address their physical, psychological, social and economic wellbeing and the findings point to the importance of taking individual coping strategies into account when evaluating the impact of diabetes on psychosocial wellbeing. Because of the mean of anxiety were not in normal range, for this study, health professionals need to pay attention to patient's psychological state. This is especially true for patients who are likely to use self-blame and behavioural disengagement as a coping strategy. Through psychosocial interventions, professionals need to assist patients in establishing positive self evaluations. Delineation of coping strategies might be useful for identifying patients in need of particular counselling and support.

Projection of new thresholds for hypertension to outpatient clinic patients and impact of risk factors: a cross-sectional study

ABSTRACT BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on hypertension management recommend new stage 1 hypertension thresholds (130-139/80-89 mmHg) for starting antihypertensive treatment. OBJECTIVE: To analyze the impact of the 2017 ACC/AHA guidelines on patients' diagnoses within daily practice, in comparison with management using the 2018 European hypertension guidelines, regarding the new thresholds. DESIGN AND SETTING: Cross-sectional study conducted in a hypertension outpatient clinic at a tertiary-level public hospital. METHODS: The diagnosis of hypertension was defined separately using each guideline. The participants were patients who were attending the hypertension clinic, who were evaluated using the thresholds of two guidelines, based on cardiovascular risk factors, including age, gender, smoking status, diabetes mellitus, dyslipidemia, obesity, osteoporosis, chronic renal failure and family history of hypertension. RESULTS: After adapting the guidelines to the blood pressure values of our sample, 74.5% (n = 277) of the patients were diagnosed as hypertensive according to the blood pressure classification of the European Society of Cardiology (ESC) guidelines published in 2018, while 91.1% (n = 339) of the patients were hypertensive according to the new 2017 ACC/AHA guidelines. Multivariate regression analysis revealed that the significant demographic and cardiovascular risk factors associated with hypertension, based on the 2018 European Society of Hypertension (ESH)/ESC guidelines, were age (odds ratio, OR: 1.027; 95% confidence interval, CI: 1.001-1.054; P = 0.042), obesity (OR: 4.534; 95% CI: 1.830-11.237; P = 0.001) and family history of hypertension (OR: 2.199; 95% CI: 1.252-3.862; P = 0.006). CONCLUSIONS: The factors associated with the definition of hypertension may vary through changing the threshold values.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist increases plasma adiponectin levels in type 2 diabetic patients with proteinuria.

Adiponectin appears to be an important modulator for metabolic and vascular diseases. A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2 diabetic patients with proteinuria. Sixty-four patients (mean age, 46.1+/-4.6 yr; 30 male, 34 female) and 26 healthy volunteers (mean age, 45.3+/-4.8 yr; 14 male, 12 female) were included. Patients with proteinuria were treated with 4-mg/d rosiglitazone (n=21, 10 males, 11 females) for 4 wk. Adiponectin levels in patients were significantly lower than those of controls (p<0.001). There were significant negative correlations between adiponectin concentrations and insulin levels as well as homeostasis model assessment (HOMA) index in patient's group (r=-0.538, p<0.001; r=-0.393, p=0.001, respectively). There was also a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r=-0.526, p=0.002). Plasma adiponectin levels in patients with proteinuria (n=31; 3.91+/-2.57 microg/mL) were significantly lower than those without proteinuria (n=33; 10.15+/-1.97 microg/mL) (p<0.001). After the treatment period, adiponectin levels significantly increased (p<0.001) and proteinuria, plasma insulin, and HOMA indexes significantly decreased in treatment group (p<0.001, p<0.001, p<0.001, respectively). The results suggest that adiponectin is inversely correlated with proteinuria and treatment with peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist rosiglitazone both corrects proteinuria and increases the low adiponectin levels in diabetic patients.