- Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update. [Journal Article]
- ECExp Clin Endocrinol Diabetes 2017 Apr 25
- Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main endocrine complications after the surgical treatment for thyroid cancer. Postsurgical HypoPT can be transient, protra...
Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main endocrine complications after the surgical treatment for thyroid cancer. Postsurgical HypoPT can be transient, protracted or permanent. Its frequency varies according to the underlying cervical pathology, surgical technique, and mainly the experience of the surgeon. Risk factors for HypoPT include aggressiveness of the tumor, extent of surgery, the presence of parathyroid gland in the pathologic specimen, and surgeon experience. Clinical manifestations of postsurgical HypoPT can be acute or chronic. An adequate surgical technique that minimizes trauma and preserve the vascularization of the parathyroid glands is the better procedure to reduce the risk of postoperative HypoPT. Acute hypocalcemia may be managed with intravenous or oral calcium supplements, according to the level of serum calcium and the presence of signs and symptoms. Patients with permanent HypoPT require lifelong calcium and vitamin D supplementation. Calcitriol is the vitamin D metabolite of preference because of its high activity and short half-life. Both PTH (1-34) and intact PTH (1-84) have demonstrated to be attractive options in hypoparathyroid patients who cannot maintain stable serum and urinary calcium levels with calcium and vitamin D supplementation. However, the long-term safety of these preparations has not been established. Postsurgical HypoT is an unavoidable consequence of total or near-total thyroidectomy for thyroid cancer. Replacement and suppressive therapy are necessary in these patients. Thyroid hormone suppression therapy has shown to be accompanied by a decreased risk of disease progression and recurrence; however, it may also be associated with increased risk of dysrhythmia and loss of bone mass. Therefore, the intensity of TSH suppression must be established in a personalized way after balancing risk and benefits, according to the severity of the thyroid cancer, the response to therapy, and the individual risk factors for adverse events.
- Regulation of uridine diphosphate-glucuronosyltransferase 2B15 expression during ovulation in the rat. [Journal Article]
- EJEndocr J 2017 Apr 22
- Uridine diphosphate-glucuronosyltransferase 2B15 (UGT2B15) conjugates 5α-androstane-3α, 17β-diol (3α-diol) to 3α-diol glucuronide (3α-diol G) in steroid target tissues. The present study investigated...
Uridine diphosphate-glucuronosyltransferase 2B15 (UGT2B15) conjugates 5α-androstane-3α, 17β-diol (3α-diol) to 3α-diol glucuronide (3α-diol G) in steroid target tissues. The present study investigated the regulation of UGT2B15 expression during the ovulatory process in the rat. Real-time PCR analysis revealed that treatment of immature rats with equine chorionic gonadotropin followed by human chorionic gonadotropin transiently stimulated UGT2B15 gene expression in granulosa cells of preovulatory follicles within 6 h. The progesterone receptor antagonist RU486 suppressed the gonadotropin-induced UGT2B15 expression. The expression of UGT2B15 and the levels of 3α-diol G were transiently increased by luteinizing hormone (LH) treatment in cultured preovulatory follicles. The LH-stimulated UGT2B15 mRNA level in cultured preovulatory follicles was inhibited by inhibitors of adenylyl cyclase, phosphoinositide 3-kinase and mitogen-activated protein kinase. Furthermore, a vitamin D receptor agonist (calcitriol) suppressed the LH-stimulated UGT2B15 expression in a dose-dependent manner. Taken together, these results indicate that gonadotropins transiently stimulate UGT2B15 expression and activity in preovulatory follicles, and UGT2B15 mRNA levels are regulated by the progesterone receptor and vitamin D receptor.
- High phosphate induces a pro-inflammatory response by vascular smooth muscle cells. Modulation by vitamin D derivatives. [Journal Article]
- CSClin Sci (Lond) 2017 Apr 25
- In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently corre...
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3.3 mM) medium caused an increased expression of the pro-inflammatory mediators ICAM-1, IL-1β, IL-6, IL-8 and TNF-α (not corroborated at the protein levels for ICAM-1), as well as an increase in reactive oxygen/nitrogen species (ROS/RNS) production. This was accompanied by the activation of NF-kB signalling as demonstrated by the increase in the nuclear translocation of NF-kB -p65 assessed by western blotting and confocal microscopy. Since all these events were attenuated by an antioxidant pre-incubation with the radical scavenger MnTBAP, it is suggested that the inflammatory response is up-stream mediated by the ROS/RNS-induced activation of NF-kB. Addition of paricalcitol 3·10(-8)M to cells in HP prevented the phosphate-induced ROS/RNS increase, the activation of NF-kB and the cytokine up-regulation. A bimodal effect was observed, however, for different calcitriol concentrations, since 10(-10) and 10(-12)M attenuated but 10(-8)M stimulated this phosphate-induced pro-oxidative and pro-inflammatory response. Therefore, these findings provide novel mechanisms whereby high phosphate may directly favours vascular dysfunctions, and new insights on the protective effects exerted by vitamin D derivatives.
- Recommended vitamin D levels in the general population. [Journal Article]
- EDEndocrinol Diabetes Nutr 2017; 64 Suppl 1:7-14
- CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.
- Parathyroid hormone targets in chronic kidney disease and managing severe hyperparathyroidism. [Journal Article]
- NNephrology (Carlton) 2017; 22 Suppl 2:47-50
- Appropriate targets for parathyroid hormone (PTH) in patients with chronic kidney disease (CKD) stages 3-5D are controversial, as are the means by which these targets might be achieved. Secondary hyp...
Appropriate targets for parathyroid hormone (PTH) in patients with chronic kidney disease (CKD) stages 3-5D are controversial, as are the means by which these targets might be achieved. Secondary hyperparathyroidism is linked to symptoms like bone pain and itch, in addition to less clinically overt issues like bone fragility as well as vascular and soft tissue calcification which may lead to adverse hard endpoints, particularly fracture and death. Recognized therapies for managing a rising PTH include vitamin D analogues, with or without calcimimetic (where available), in addition to management of serum mineral concentrations with diet, binders and dialysis. Despite these interventions, many patients eventually develop refractory metabolic abnormalities of severe hyperparathyroidism (HPT). Treatment decisions in severe HPT in Australia previously centred around whether to perform parathyroidectomy or use calcimimetics in combination with calcitriol (or its analogues) with goals of symptom relief, fracture reduction and reducing vascular risk. The decision to remove Pharmaceutical Benefits Scheme reimbursement for the calcimimetic cinacalcet during 2015, means that parathyroidectomy has now become the only treatment likely to benefit most patients with severe HPT who are medically fit for operative intervention. Although improvements in care are apparent for patients with CKD, there remains an urgent need for basic science and large international trials to inform better ways to manage HPT.
- Do the benefits of using calcitriol and other vitamin D receptor activators in patients with chronic kidney disease outweigh the harms? [Journal Article]
- NNephrology (Carlton) 2017; 22 Suppl 2:51-56
- The primary indication for administration of calcitriol or other vitamin D receptor activators (VDRA) in chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Prevention and treatment...
The primary indication for administration of calcitriol or other vitamin D receptor activators (VDRA) in chronic kidney disease (CKD) is secondary hyperparathyroidism (SHPT). Prevention and treatment of SHPT appears important, as imbalances in mineral metabolism are associated with renal osteodystrophy, and higher parathyroid hormone (PTH) levels are associated with increased rates of mortality and morbidity in CKD patients. There is, however, a lack of controlled trial data that show lowering PTH with calcitriol/VDRA equates to improved clinical outcomes. Recent randomized controlled trials have concentrated on potential benefits of calcitriol/VDRA on cardiovascular outcomes and reduction of proteinuria and on possible differences between calcitriol and the various VDRA. Several systematic reviews and meta-analyses have also been published, evaluating the benefits and harms of calcitriol/VDRA. Concerns have been raised about the effectiveness of calcitriol/VDRA for suppression of SHPT in the CKD stages 3-5 population, as well as potential adverse outcomes such as hypercalcaemia and elevation in FGF23 levels, suggesting their routine use to treat SHPT in the pre-dialysis CKD population may not be favourable. Conversely, concerns still exist about the wide PTH range in advanced CKD, and that high values may negatively impact bone quality, result in the progression of parathyroid hyperplasia and decrease the effectiveness of treatments to reduce PTH. We discuss the current controversies relating to the challenges in the management of SHPT in patients with CKD stages 3-5 and the need for more evidence to determine the efficacy or harm of using calcitriol/VDRA in this population.
- Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats. [Journal Article]
- PMPlanta Med 2017 Apr 20
- Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced o...
Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In this study, we aimed to investigate whether tanshinol has potential therapeutic effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five groups: a control group, a model group, and three model groups treated with 25 or 50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards, all animals underwent a surgical procedure to induce bone defects at the right proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or calcitriol treatment was continued to the endpoint. At the experimental endpoint, compared to the model group, 25 mg/kg tanshinol could significantly reverse glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing mechanical bone strength, causing a significant 11 % increase in trabecular number, and reducing trabecular separation by 28 %. In addition, tanshinol improved the bone microarchitecture and prevented glucocorticoid-induced bone loss by promoting bone formation and inhibiting bone resorption. Moreover, results of bone defect repair and muscle weight measurements revealed that tanshinol accelerated the bone fracture healing process and attenuated muscle atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold increases in vascular endothelial growth factor mRNA expression in calluses from the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels from glucocorticoid-induced elevation. These findings demonstrate the potential benefits of tanshinol against glucocorticoid-induced osteoporosis and glucocorticoid-induced myopathy, which warrants further investigation in future studies.
- Effects of 1alpha, 25-dihydroxyvitamin D3 on programmed cell death of Ishikawa endometrial cancer cells through ezrin phosphorylation. [Journal Article]
- JOJ Obstet Gynaecol 2017; 37(4):503-509
- This study investigated the effects of 1α, 25-dihydroxyvitamin D3-induced cell death and its underlying molecular mechanisms in Ishikawa endometrial carcinoma cells. The effects of 1α, 25-dihydroxyvi...
This study investigated the effects of 1α, 25-dihydroxyvitamin D3-induced cell death and its underlying molecular mechanisms in Ishikawa endometrial carcinoma cells. The effects of 1α, 25-dihydroxyvitamin D3 on Ishikawa cells were examined by 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide, thiazolyl blue (MTT) assay. 1α, 25-dihydroxyvitamin D3 was shown to induce programmed cell death in Ishikawa endometrial carcinoma cells by activation of caspase-3 and caspase-9, along with elevation of Bcl-2 and Bcl-xL. Cell viability was reduced by 1α, 25-dihydroxyvitamin D3 in a concentration-dependent manner up to 2.5 μM. In addition, ezrin phosphorylation increased with the 1α, 25-dihydroxyvitamin D3 concentration (0-0.5 μM). The protein level of caspase-9 was increased by 1α, 25-dihydroxyvitamin D3 up to 0.5 μM. This is the first report regarding the efficacy and molecular mechanisms underlying the effects of 1α, 25-dihydroxyvitamin D3 in endometrial cancer cells. Our findings indicate that 1α, 25-dihydroxyvitamin D3 induces endometrial cancer cell death in a concentration-dependent manner. Impact statement Up to date, there is no report about the efficacy and molecular underlying mechanisms on the effect of vitamin D3 in endometrial cancer cells. Our findings indicate that 1α, 25-dihydroxyvitamin D3. which is an active metabolite of vitamin D3, induces Ishikawa endometrial cancer cell death in a concentration-dependent manner by activation of caspase-3 and -9, along with elevation of Bcl-2 and Bcl-xL. In addition, the same concentration of 1α, 25-dihydroxyvitamin D3 that provoked apoptotic signals caused phosphorylation of ezrin at threonine 567 in a VDR-dependent manner. This study suggests that 1α, 25-dihydroxyvitamin D3 within the optimal range (0.5 uM) would induce apoptosis through Fas-ezrin-caspase-3, -8, -9 signalling axis which may be a critical cell death regulator in Ishikawa endometrial cancer cell. Further study will be more interesting to address molecular connections or prove this critical optimal concentration range of vitamin D.
- Association of Preoperative Calcium and Calcitriol Therapy With Postoperative Hypocalcemia After Total Thyroidectomy. [Journal Article]
- JOJAMA Otolaryngol Head Neck Surg 2017 Apr 13
- CONCLUSIONS: Preoperative calcium and calcitriol supplementation, in addition to routine postoperative supplementation, was associated with a reduced incidence of symptomatic hypocalcemia, length of hospital stay, and overall charges following total thyroidectomy.
New Search Next
- GeneReviews(®) [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- The phenotypic spectrum of X-linked hypophosphatemia (XLH) ranges from isolated hypophosphatemia to severe lower-extremity bowing. XLH frequently manifests in the first two years of life when lower-e...
The phenotypic spectrum of X-linked hypophosphatemia (XLH) ranges from isolated hypophosphatemia to severe lower-extremity bowing. XLH frequently manifests in the first two years of life when lower-extremity bowing becomes evident with the onset of weight bearing; however, it sometimes is not manifest until adulthood, as previously unevaluated short stature. In adults, enthesopathy (calcification of the tendons, ligaments, and joint capsules) associated with joint pain and impaired mobility may be the initial presenting complaint. Persons with XLH are prone to spontaneous dental abscesses; sensorineural hearing loss has also been reported.