- Skeletal Consequences of Nephropathic Cystinosis. [Journal Article]
- JBJ Bone Miner Res 2018 Jun 15
- Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite ...
Nephropathic cystinosis is a rare lysosomal storage disorder. Patients present in the first year of life with renal Fanconi syndrome that evolves to progressive chronic kidney disease (CKD). Despite the multiple risk factors for bone disease, the frequency and severity of skeletal disorders in nephropathic cystinosis have not been described. We performed systematic bone and mineral evaluations of subjects with cystinosis seen at the NIH (N = 30), including history and physical examination, serum and urine biochemistries, DXA, vertebral fracture assessment, skeletal radiographs, and renal ultrasound. Additionally, histomorphometric analyses are reported on six subjects seen at the UCLA-Bone and Mineral Metabolism Clinic. In NIH subjects, mean age (range) was 20 years (5-44), 60% were CKD G1 to G4, and 40% had a renal transplant. Mean bone mineral density (BMD) Z-scores were decreased in the femoral neck, total hip and 1/3 radius (p < 0.05). Low bone mass at ≥1 site was present in 46% of subjects. Twenty-seven percent of subjects reported ≥ 1 long bone fracture. Thirty-two percent of subjects had incidental vertebral fractures, which were unrelated to transplant status. Long bone deformity/bowing was present in 64%; 50% had scoliosis. Diffuse osteosclerosis was present in 22% of evaluated subjects. Risk factors included CKD, phosphate wasting, hypercalciuria, secondary hyperparathyroidism, hypovitaminosis D, male hypogonadism, metabolic acidosis and glucocorticoid/immunosuppressive therapy. Over half of the non-transplanted subjects had ultrasonographic evidence of nephrocalcinosis or nephrolithiasis. Histomorphometric analyses showed impaired mineralization in 4 of 6 studied subjects. We conclude that skeletal deformities, decreased bone mass, and vertebral fractures are common and relevant complications of nephropathic cystinosis, even before renal transplantation. Efforts to minimize risk factors for skeletal disease include optimizing mineral metabolism and hormonal status, combined with monitoring for nephrocalcinosis/nephrolithiasis. This article is protected by copyright. All rights reserved.
- Androgens induce growth of the limb skeletal muscles in a rapamycin-insensitive manner. [Journal Article]
- AJAm J Physiol Regul Integr Comp Physiol 2018 Jun 13
- Signaling through the mechanistic target of rapamycin complex 1 (mTORC1) has been well-defined as an androgen-sensitive transducer mediating skeletal muscle growth in vitro, however, this has yet to ...
Signaling through the mechanistic target of rapamycin complex 1 (mTORC1) has been well-defined as an androgen-sensitive transducer mediating skeletal muscle growth in vitro, however, this has yet to be tested in vivo. As such, male mice were subjected to either sham or castration surgery and allowed to recover for 7 weeks to induce atrophy of skeletal muscle. Then, castrated mice were implanted with either a control pellet or pellet that administered rapamycin (~2.5 mg/kg/day). Seven days post implant, a subset of castrated mice with control pellets and all castrated mice with rapamycin pellets were given once weekly injections of nandrolone decanoate (ND) to induce muscle growth over a 6-week period. Effective blockade of mTORC1 by rapamycin was noted in the skeletal muscle by the inability of insulin to induce phosphorylation of ribosomal S6 kinase 1 70 kD (Thr389) and uncoordinated like kinase 1 (Ser757). While castration reduced TA mass, muscle fiber cross sectional area, and total protein content, ND administration restored these measures to sham levels in a rapamycin-insensitive manner. Similar findings were also observed in the plantaris and soleus, suggesting this rapamycin-insensitive effect was not specific to the TA or fiber type. Androgen-mediated growth was not due to changes in translational capacity. Despite these findings in the limb skeletal muscle, rapamycin completely prevented the ND-mediated growth of the heart. In all, these data indicate that mTORC1 has a limited role in the androgen-mediated growth of the limb skeletal muscle, however, mTORC1 was necessary for androgen-mediated growth of heart muscle.
- Metabolic Syndrome in Male Hypogonadism. [Journal Article]
- FHFront Horm Res 2018; 49:131-155
- Metabolic syndrome (MetS) and hypogonadism (HG) are frequently comorbid. In this review, we summarize interconnections between the construct of MetS and the presence of HG, as well as the effect of s...
Metabolic syndrome (MetS) and hypogonadism (HG) are frequently comorbid. In this review, we summarize interconnections between the construct of MetS and the presence of HG, as well as the effect of specific treatments for each condition on this association. Data from meta-analytic studies suggest a bidirectional pathogenic relationship. In fact, reduced T (-2.21 [-2.43 to -1.98] nmol/L) at baseline predicts incident MetS. On the other hand, MetS at study entry increases the risk of developing HG (OR 2.46 [1.77-3.42]). The bidirectional pathogenic link between MetS and HG is further confirmed by the fact that treating MetS with insulin sensitizer is associated with an increase in T. In addition, a huge effect on increasing T is found in obese men undergoing procedures for losing weight, with more dramatic results obtained after bariatric surgery than after low calorie diet (increase in T 8.73 [6.51-10.95] nmol/L and 2.87 [1.68-4.07] nmol/L, respectively, according to a recent meta-analysis). On the other hand, there is evidence of an improvement in several metabolic derangements characterizing MetS in subjects treated with T. However, the latter results are still not conclusive and need further evidence from randomized clinical trials.
- Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study. [Journal Article]
- AHAnn Hepatol 2018 July - August ,; 17(4):615-623
- CONCLUSIONS: Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.
- Di-(2-Ethylhexyl) Phthalate Increases Obesity-Induced Damage to the Male Reproductive System in Mice. [Journal Article]
- OMOxid Med Cell Longev 2018; 2018:1861984
- CONCLUSIONS: DEHP and obesity jointly caused damage to male productive function. Oxidative stress in testicular tissue, and a high level of leptin, may provide some evidence to clarify the mechanisms of male SH with DEHP and obesity.
- [Diagnosis and management of adult-onset idiopathic hypogonadotropic hypogonadism]. [Journal Article]
- ZYZhonghua Yi Xue Za Zhi 2018 May 29; 98(20):1597-1600
- Objective: To investigate the clinical features and management of male patients with adult-onset idiopathic hypogonadotropic hypogonadism (AIHH). Methods: Clinical features and treatment of six pat...
Objective: To investigate the clinical features and management of male patients with adult-onset idiopathic hypogonadotropic hypogonadism (AIHH). Methods: Clinical features and treatment of six patients with AIHH between January 2010 and June 2017 were retrospectively reviewed. Results: The patients were all male, with an age of 26 (20-35) years old and they experienced complete pubertal development. The main complaints were decreased libido, erectile dysfunction and gynecomastia. Physical examination found that the testicular size was 15 (12-20) ml and they were fully virilized. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone was 0.1 (0.1-0.8) U/L, 0.4 (0.1-0.9) U/L and 0.62 (0.10-0.90) nmol/L, respectively. Pituitary MRI and other pituitary hormones were all normal. Testosterone was administrated to three patients and the libido and erectile function returned to normal. Sperm was successfully induced in two patients after combined gonadotropin therapy for 4-6 months. One patient had a reversed hypothalamus-pituitary-testis axis function. Conclusions: The mechanism of male AIHH is unknown. Compared to those with congenital hypogonadotropic hypogonadism, patients with AIHH may achieve better spermatogenesis after gonadotropin therapy. Small portion of patients may have a reversal of hypothalamus-pituitary-testis axis function.
- Novel Therapy for Male Hypogonadism. [Review]
- CUCurr Urol Rep 2018 Jun 09; 19(8):63
- Hypogonadism and the treatment of low testosterone is increasingly a subject of medical inquiry and controversy. The few treatments that are FDA-approved such as testosterone topicals, injections, an...
Hypogonadism and the treatment of low testosterone is increasingly a subject of medical inquiry and controversy. The few treatments that are FDA-approved such as testosterone topicals, injections, and pellets create significant demand from patients for treatments with more convenient means of administration, fewer adverse effects, and the ability to maintain male fertility. Off-label drugs are in abundant use for low testosterone, including selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors.
- C11-oxy C19 and C11-oxy C21 steroids in neonates: UPC2-MS/MS quantification of plasma 11β-hydroxyandrostenedione, 11-ketotestosterone and 11-ketoprogesterone. [Journal Article]
- SSteroids 2018 Jun 06; 138:1-5
- The purpose of this study was to identify the C11-oxy C19 and C11-oxy C21 steroids in male and female neonate plasma. At birth, the most abundant C11-oxy steroids detected in neonatal plasma were 11β...
The purpose of this study was to identify the C11-oxy C19 and C11-oxy C21 steroids in male and female neonate plasma. At birth, the most abundant C11-oxy steroids detected in neonatal plasma were 11β-hydroxyandrostenedione, ∼13 nM, and 11-ketoprogesterone, ∼23 nM. C11-oxy C19 steroids were higher than C19 steroids in neonatal plasma, 22.2 nM vs 5.4 nM. The inclusion of C11-oxy C19 and C21 steroid reference ranges in routine steroid analyses will assist the characterization of disorders associated with impaired steroidogenic enzyme expression and the identification of potential biomarkers.
- Metabolic patterns in insulin-resistant male hypogonadism. [Journal Article]
- CDCell Death Dis 2018 Apr 22; 9(6):671
- Male hypogonadism associated with insulin resistance (IR) very often leads to metabolic syndrome, at variance with hypogonadism in its first stadium of insulin sensitivity (IS). A plasma metabolomic ...
Male hypogonadism associated with insulin resistance (IR) very often leads to metabolic syndrome, at variance with hypogonadism in its first stadium of insulin sensitivity (IS). A plasma metabolomic investigation of these patients can provide useful information in comparison with the values of IS patients. To this aim plasma from insulin-resistant males with hypogonadism were analysed by using ultra high-performance liquid chromatography (UHPLC) and high-resolution mass spectrometry (HRMS). Thus, metabolites were compared to the controls through multivariate statistical analysis and grouped by metabolic pathways. Metabolite database searches and pathway analyses identified imbalances in 18-20 metabolic pathways. Glucose metabolism (e.g., glycolysis and the Krebs cycle) is fuelled by amino acids degradation, in particular of branched amino acids, in individuals with lean body mass. Gluconeogenesis is strongly activated. Some crucial pathways such as glycerol are skewed. Mitochondrial electron transport is affected with a reduction in ATP production. Beta-oxidation of short and medium chain fatty acids did not represent an energy source in hypogonadism, at variance with long and branched fatty acids, justifying the increase in fat mass. Carnosine and β-alanine are strongly reduced resulting in increased fatigue and mental confusion. A comparison of IR with IS male hypogonadism will contribute to a better understanding of how these two hormones work in synergy or antagonise each other in humans. It could also help to select patients who will respond to hormone treatment, and provide accurate biomarkers to measure the response to treatment eventually leading to better strategies in preventing systemic complications in patients not fit for hormone replacement therapy.
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- Premature ovarian insufficiency and early depletion of the ovarian reserve in the monogenic Mulibrey nanism disorder. [Journal Article]
- HRHum Reprod 2018 Jun 01
- What is the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gen...
What is the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gene?