Managing Common Estrogen Deprivation Side Effects in HR+ Breast Cancer: an Evidence-Based Review.

PURPOSE OF REVIEW: The article reviews the consequences of estrogen deprivation during endocrine therapy for breast cancer and provides an update on alternative therapies for the management of symptoms. RECENT FINDINGS: Endocrine therapy has progressed substantially in recent years, and its use is recommended for all breast cancer patients expressing hormone receptors. The main adverse events of this treatment can be controlled with medications and nonpharmacological measures. Antidepressants are effective in controlling vasomotor symptoms. Vaginal discomfort can be treated with local lubricants and pelvic floor physiotherapy, which may help in sexual dysfunction. Pathophysiological mechanisms of musculoskeletal symptoms during aromatase inhibitors treatment are not well understood, but some studies evaluating treatment with duloxetine, yoga, and acupuncture have shown some benefits. For prevention of bone loss, patients with risk factors should be offered bisphosphonates or denosumab. Individualization of treatment is crucial. Consideration should be given to therapy effects on quality of life, and strategies for controlling associated symptoms should be offered.

Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis.

PURPOSE OF REVIEW: The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. RECENT FINDINGS: As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. SUMMARY: Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

Oxytocin as a novel therapeutic option for type I diabetes and diabetic osteopathy.

OBJECTIVE: The aim of the present study was to highlight the newly discovered metabolic role of oxytocin (OT) in the type I diabetic rats. Previous studies have demonstrated that OT has a beneficial role on bone physiology and therefore, the OT effect on the diabetic osteopathy will be assessed as well. METHODS: Induction of the type I diabetes was carried out by an intraperitoneal injection of 60 mg/kg body weight of streptozotocin. The metabolic role of OT on diabetic rats after OT treatment with intramuscular injection of 40 µIU/kg body weight for 6 weeks was assessed. Histological and ultrastructural studies of rat pancreas samples, before and after the OT injection, were performed and compared with the obtained physiological results. RESULTS: Oxytocin treatment had positive metabolic effects in diabetic rats. This is based on the change in glucose metabolism, lipid profile, and insulin sensitivity in experimental animals. In addition, OT treatment showed histological regenerative changes of pancreatic islet cells of diabetic rats. Moreover, OT administration showed that it has an anabolic effect on the bone biology. CONCLUSIONS: The results suggest that activation of the oxytocin receptor (OTR) pathway by infusion of OT, OT analogs, or OT agonists may represent a promising approach for the treatment of diabetes and some of its complications, including diabetic osteopathy.

[Secondary osteoporosis or secondary contributors to bone loss in fracture. Endocrinological aspects of bone metabolism].

Bone works to play essential roles in mineral metabolism and hematopoiesis as well as to support our body and protect internal organs as a hard tissue. In order to accomplish these multiple functions, bone needs to communicate with other organs. Endocrine system functions as one of the communication pathways between bone and other organs. It has been known that bone is a target organ of many hormones. In addition, it has been established that bone itself produces hormones and works as an endocrine organ.

Performance of WHO growth standards on Indian children with growth related disorders.

OBJECTIVE: To assess performance of WHO 2006 standards on anthropometric measurements of children referred for growth related disorders to a speciality pediatric clinic in Pune, India, from June 2006 through June 2010. METHODS: Data presented in this study were collected retrospectively from case records of all children from birth to 60 mo (n=1840, mean age 2.7±1.3 y) who presented with growth related disorders; healthy age and sex matched children were recruited as controls (n=824, mean age 2.8±1.2 y). Children were divided as per their clinical diagnosis into eight different groups: growth hormone deficiency, bone disorders, syndromic short stature, familial short stature, hypothyroidism, nutritional and systemic disorder, other endocrinopathies and overgrowth disorders. Anthropometric parameters for all study subjects were converted to standard deviation scores (SD scores) using the WHO Anthro 2005. RESULTS: Mean height SD scores of children with growth related disorders were significantly lower than that of the controls, while that of the tall children were significantly higher (p<0.05). All children who were clinically very short were below the 1st percentile, while none of the children with overgrowth or normal children were classified as stunted. Weight for height SD scores of children with nutritional and systemic disorders were the lowest, while those for the obese children were the highest. CONCLUSIONS: The present results suggest that the WHO 2006 growth standards classify children with growth disorders appropriately and the classification is in concordance with the clinical assessment. They provide health practitioners in a clinical setting with an effective tool to assess growth of children.

Stem cells in skeletal physiology and endocrine diseases of bone.

Self-renewing, multipotent progenitors of skeletal tissues are found within skeletal segments (skeletal stem cells) and coincide with adventitial reticular cells of bone marrow vessels in situ and with explanted clonogenic stromal cells ex vivo. These cells, which can be identified and prospectively isolated based on a minimal surface phenotype noted for expression of CD146, CD105 and alkaline phosphatase, are established during bone development through interactions with developing sinusoids. They represent a crucial crossroad of skeletal and hematopoietic physiology, as well as of endocrine regulation of bone growth and remodeling. In addition, they are central to major endocrine functions of bone itself, such as regulation of renal phosphate handling. Skeletal stem cells represent a central model system for investigating skeletal diseases, as tools for in vitro and in vivo models, for cell therapy-based strategies, or as targets for drugs.

Polyostotic fibrous dysplasia with gigantism and huge pelvic tumor: a rare case of McCune-Albright syndrome.

We report a rare case of polyostotic fibrous dysplasia on endocrine hyperfunction with elevated human growth hormone and normal serum level of prolactin. There were some differential points of gender, gigantism, endocrine function, and GNAS gene from McCune-Albright syndrome. Malignant transformation was suspected in the pelvic tumor from imaging because rapid growth of the tumor by imaging was observed; however, no malignant change occurred in this case.

'Old' bones in young bodies: the tale of cystic fibrosis.

PURPOSE OF REVIEW: Cystic fibrosis (CF) is the most common genetic disease within the white population and leads to premature respiratory failure. Approximately, 60 000 individuals are currently living with CF in North America and Europe, almost half of whom are adults. RECENT FINDINGS: Dozens of studies across the globe indicate that CF adults have low bone density and increased rates of fractures. This genesis of the problem appears to be in late childhood to adolescence. SUMMARY: Prevention and treatment of CF-related bone disease must address the myriad risk factors (decreased absorption of fat-soluble vitamins due to pancreatic insufficiency, altered sex hormone production, chronic lung infection with increased serum levels of proinflammatory, bone-active cytokines, malnutrition and low body weight, physical inactivity and glucocorticoid therapy) for poor bone health. This review will address the pathogenesis, diagnosis and treatment of bone disease in CF. It will also discuss best practice guidelines for optimizing bone health in patients with CF.

[Effect of glucose and bone metabolism in endocrinal disorder].

It is well known that endocrine disorders; glucocorticoid excess including Cushing syndrome, high dose or long term steroid therapy and hyperthyroidism, induce secondary osteoporosis. These common endocrinal disorders affect not only bone metabolism but also glucose metabolism. Glucose metabolisms also play a important role in the progression of osteoporosis. To prevent secondary osteoporosis, multifocal intervention such as correction of insulin resistance or glucose metabolism, lifestyle, and drug therapy, need to be added to current management of endocrinal system.

Endocrine parameters of cystic fibrosis: back to basics.

Dramatic changes in the life expectancy of cystic fibrosis (CF) patients are occurring, creating a cohort of aging individuals experiencing long-term complications of this chronic disease. The two most common of these complications include CF-related diabetes and CF bone disease. The clinical implications of each have become better understood, as have potential therapies. However, data obtained from the basic science studies of both diseases have not been widely recognized. In this review, we focus on the known and hypothesized pathogenesis of these two disorders. Additionally, the molecular underpinnings of CF will be explained along with the potential interactions with endocrine disease phenotypes.

Devastating skeletal effects of delayed diagnosis of complicated primary hyperparathyroidism because of ectopic adenoma.

Primary hyperparathyroidism is a disease caused by exaggerated secretion of the parathyroid gland hormone, produced by an adenoma in 80% of cases. Ectopic adenomas occur in a small proportion of cases. Herein, the authors report a 72-year-old woman with a delayed diagnosis of primary hyperparathyroidism, produced by an intrathoracic adenoma, with a longstanding course, presenting with severe osteoporosis, multiple fractures, bone deformities, and neurologic impairments. Persistent hypercalcemia, high levels of alkaline phosphatase, and parathyroid hormone were documented and a paratracheal mass was found on a helicoidal tomography of the thorax. After surgical removal, the histopathological examination confirmed an ectopic adenoma of the parathyroid gland and the patient achieved some improvement in her clinical picture.

Vitamin D receptor activators can protect against vascular calcification.

An apparent conflict exists between observational studies that suggest that vitamin D receptor (VDR) activators provide a survival advantage for patients with ESRD and other studies that suggest that they cause vascular calcification. In an effort to explain this discrepancy, we studied the effects of the VDR activators calcitriol and paricalcitol on aortic calcification in a mouse model of chronic kidney disease (CKD)-stimulated atherosclerotic cardiovascular mineralization. At dosages sufficient to correct secondary hyperparathyroidism, calcitriol and paricalcitol were protective against aortic calcification, but higher dosages stimulated aortic calcification. At protective dosages, the VDR activators reduced osteoblastic gene expression in the aorta, which is normally increased in CKD, perhaps explaining this inhibition of aortic calcification. Interpreting the results obtained using this model, however, is complicated by the adynamic bone disorder; both calcitriol and paricalcitol stimulated osteoblast surfaces and rates of bone formation. Therefore, the skeletal actions of the VDR activators may have contributed to their protection against aortic calcification. We conclude that low, clinically relevant dosages of calcitriol and paricalcitol may protect against CKD-stimulated vascular calcification.

Posttransplant metabolic acidosis: a neglected factor in renal transplantation?

PURPOSE OF REVIEW: The occurrence and pathogenesis of metabolic acidosis after renal transplantation is reviewed. Posttransplant acidosis is shown to be a key mechanism for major metabolic complications in mineral and muscle metabolism, and for anemia, discussed in the context of both acidosis and renal transplantation. RECENT FINDINGS: Continuous improvement in kidney transplant survival has shifted attention to long-term outcomes, specifically to disorders linked to cardiovascular disease, physical capacity and quality of life. Metabolic acidosis is gaining growing acceptance as a clinical entity and has occasionally come into focus in the context of renal transplantation. The possible link to metabolic disturbances resulting in impairment of musculoskeletal disorders and physical limitations, however, has not been considered specifically. SUMMARY: Available evidence suggests a high prevalence of (compensated) metabolic acidosis after renal transplantation, presenting as low serum bicarbonate and impaired renal acid excretion. This condition is associated with relevant disorders in mineral metabolism and muscle function. Current knowledge about the effects of acidosis on renal electrolyte handling, mineral metabolism and protein synthesis suggests that acid/base derangements contribute to the muscle and bone pathology, as well as anemia, encountered after kidney transplantation. Consequently, posttransplant acidosis may be a relevant factor in the causal pathway of impaired physical capacity observed in this patient group.

The effect of energy balance on endocrine function and bone health in youth.

Female athletes are susceptible to both disordered eating and menstrual cycle disturbances (MCDs). Disordered eating in combination with high energy expenditure from exercise can lead to energy deprivation. Current theories suggest that MCDs are caused by energy deprivation rather than by exercise alone. A number of endocrine adaptations occur with energy deprivation and MCDs, which are concomitant with imbalanced bone turnover, reduced bone density and potentially increased fracture risk. This chapter reviews current evidence concerning the disruption of bone metabolism that accompanies disordered eating and MCDs in physically active girls and young women, including high-performance athletes. Initially, an overview of the aetiology of exercise-associated MCDs and their link with disordered eating is provided. Thereafter, studies reporting changes in areal bone mineral density (aBMD) in female athletes with MCDs are considered in conjunction with change in athletes' physical activity, nutritional status and menstrual histories. A comprehensive overview of the disruption of bone metabolism that accompanies nutritionally related MCDs is also provided. Emphasis is placed upon the role of energy deprivation and its endocrine effects, which, when sustained, result in imbalanced bone turnover and low aBMD. Based on current evidence, recommendations are made for the prevention and treatment of disturbed bone metabolism and low BMD in female athletes with MCDs. Finally, consideration is given to the effects of intense training and energy deprivation on endocrine function and skeletal health in men.

Calcific tendinitis: natural history and association with endocrine disorders.

A retrospective, observational cohort study of 102 consecutive patients (125 shoulders) with calcific tendinitis is presented. Of the patients, 73 (71.6%) were women and 29 (28.4%) were men. Compared with population prevalences, significant levels of endocrine disorders were found. We compared 66 patients (62 women [93.9%] and 4 men [6.1%]; mean age, 50.3 years) (81 shoulders) with associated endocrine disease with 36 patients (11 women [30.6%] and 25 men [69.4%]); mean age, 52.4 years) (44 shoulders) without endocrine disease. The endocrine cohort was significantly younger than the non-endocrine cohort when symptoms started (mean, 40.9 years and 46.9 years, respectively), had significantly longer natural histories (mean, 79.7 months compared with 47.1 months), and had a significantly higher proportion who underwent operative treatment (46.9% compared with 22.7%). Disorders of thyroid and estrogen metabolism may contribute to calcific tendinitis etiology. Classifying calcific tendinitis into type I (idiopathic) and type II (secondary or endocrine-related) aids prognosis and management.

P450 oxidoreductase deficiency: a new form of congenital adrenal hyperplasia.

PURPOSE OF REVIEW: P450 oxidoreductase deficiency--a newly described form of congenital adrenal hyperplasia--typically presents a steroid profile suggesting combined deficiencies of steroid 21-hydroxylase and 17alpha-hydroxylase/17,20-lyase activities. These and other enzymes require electron donation from P450 oxidoreductase. The clinical spectrum of P450 oxidoreductase deficiency ranges from severely affected children with ambiguous genitalia, adrenal insufficiency and the Antley-Bixler skeletal malformation syndrome to mildly affected individuals with polycystic ovary syndrome. We review current knowledge of P450 oxidoreductase deficiency and its broader implications. RECENT FINDINGS: Since the first report in 2004, at least 21 P450 oxidoreductase mutations have been reported in over 40 patients. The often subtle manifestations of P450 oxidoreductase deficiency suggest it may be relatively common. P450 oxidoreductase deficiency, with or without Antley-Bixler syndrome, is autosomal recessive, whereas Antley-Bixler syndrome without disordered steroidogenesis is caused by autosomal dominant fibroblast growth factor receptor 2 mutations. In-vitro assays of P450 oxidoreductase missense mutations based on P450 oxidoreductase-supported P450c17 activities provide excellent genotype/phenotype correlations. The causal connection between P450 oxidoreductase deficiency and disordered bone formation remains unclear. SUMMARY: P450 oxidoreductase mutations cause combined partial deficiency of 17alpha-hydroxylase and 21-hydroxylase. Individuals with an Antley-Bixler syndrome-like phenotype presenting with sexual ambiguity or other abnormalities in steroidogenesis should be analyzed for P450 oxidoreductase deficiency.