Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hip fractures in men account for one third of all hip fractures and have a higher mortality than in women. The public health burden will increase as the increase in the numbers of elderly men in the community increases. In addition, the age-specific incidence of hip fractures may be increasing in some, but not all, countries. Vertebral fractures may be a public health problem as recent studies suggest that the prevalence in the community is 20-30%, similar to that reported in women. Forearm fractures should probably not be regarded as a public health problem. Peak bone mass is higher in men than women because men have bigger bones. Peak bone mineral density is the same. The amount of trabecular bone lost at the spine and iliac crest during ageing is similar in men and women. Cortical bone loss is less in men because endocortical resorption is less and periosteal formation is greater. Bone loss accelerates in elderly men because endocortical resorption and increasing cortical porosity increase the surface available for resorption. Bone fragility is less in men than women because: (a) the cross-sectional surface of the bone is larger; (b) trabecular bone loss is less as a percentage of the higher peak bone mass; (c) trabecular bone loss occurs by thinning rather than perforation; and (d) periosteal appositional growth compensates for endocortical resorption by maintaining the bending strength of bone. Reduced BMD in men with fractures may be due to reduced peak bone size and mass, and bone loss. Bone loss occurs by reduced bone formation. Whether men with fractures have increased bone fragility due to reduced periosteal appositional growth during ageing is unknown. The age-related decline in testosterone, adrenal androgens, growth hormone, and insulin-like growth factor 1 may contribute to reduced bone formation and bone loss. Men with vertebral fractures often have hypogonadism or illnesses with few clinical features that should be considered with a high index of suspicion (alcoholism, myeloma, malabsorption, primary hyperparathyroidism, haemochromatosis, Cushing's disease). Secondary hyperparathyroidism may contribute to bone loss by activating bone turnover and so increasing the number of bone remodelling units with impaired bone formation in each. There is no proven treatment for osteoporosis in men because there have been no trials using anti-fracture efficacy as an end point. Testosterone replacement should be considered in men with proven hypogonadism and vitamin D deficiency should be corrected if present. Calcium supplements and bisphosphonates are reasonable options given the lack of information.
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PMID:Osteoporosis in men. 936 40

The majority of pituitary tumors that cause Cushing's disease are small (<1 cm diameter), and most disease morbidity is due to the effects of elevated, non-suppressible, ACTH levels that these tumors secrete. Tumor-derived ACTH leads to adrenal-derived steroid hypersecretion and results in many disabling and sometimes life-threatening symptoms including abnormal fat deposition, skin thinning, psychological disturbances, hypertension, diabetes, osteoporosis and muscle weakness. Cushing's disease is associated with high morbidity and ultimately mortality. In experienced specialized centers, 70% of corticotroph microadenomas can be successfully resected by transsphenoidal pituitary surgery. However, surgical "cure" rates for larger ACTH-secreting pituitary tumors are achieved in only 30% of cases, and recent reports highlight a significant recurrence rate after longer term follow-up even in smaller tumors. Post-surgical persistence of ACTH hypersecretion may require pituitary-directed radiation, but this treatment may take some time to be effective, and like extensive surgical pituitary tumor resection, ultimately leads to partial- or total hypopituitarism in approximately 80% of cases. Although hypercortisolism may be completely resolved by adrenalectomy, this procedure does not suppress, and may act as a stimulus to pituitary tumor growth, and is associated with other co-morbidity. Although some currently available drug-based treatments for Cushing's disease effectively control hypercortisolism, their drawback has been that they do not impact on pituitary tumor growth. Recent studies have identified the potential utility of peroxisome-proliferator activating receptor-gamma (PPAR-gamma) novel ligands in in vitro, and in vivo Cushing's disease models, and have paved the way for early clinical studies to develop novel therapeutic approaches in Cushing's disease.
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PMID:PPAR-gamma in Cushing's disease. 1641 39

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)(+) mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg(+) mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg(+) mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg(+) mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg(+) mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg(+) mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue.
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PMID:Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling. 2321 15

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by a local untrained practitioner for more than 3 years without any significant improvement, and he developed weight gain, thinning of skin, muscle weakness and growth retardation. He was evaluated in 2015 and found to have iatrogenic Cushing's disease with severe skeletal complications and pituitary-adrenal-gonadal suppression, which persisted despite gradual withdrawal of steroids.
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PMID:Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management. 2855 84

Long-term remitted Cushing's disease (LTRCD) patients commonly continue to present persistent psychological and cognitive deficits, and alterations in brain function and structure. Although previous studies have conducted gray matter volume analyses, assessing cortical thickness and surface area of LTRCD patients may offer further insight into the neuroanatomical substrates of Cushing's disease. Structural 3T magnetic resonance images were obtained from 25 LTRCD patients, and 25 age-, gender-, and education-matched healthy controls (HCs). T1-weighted images were segmented using FreeSurfer software to extract mean cortical thickness and surface area values of 68 cortical gray matter regions and two whole hemispheres. Paired sample t tests explored differences between the anterior cingulate cortex (ACC; region of interest), and the whole brain. Validated scales assessed psychiatric symptomatology, self-reported cognitive functioning, and disease severity. After correction for multiple comparisons, ROI analyses indicated that LTRCD-patients showed reduced cortical thickness of the left caudal ACC and the right rostral ACC compared to HCs. Whole-brain analyses indicated thinner cortices of the left caudal ACC, left cuneus, left posterior cingulate cortex, right rostral ACC, and bilateral precuneus compared to HCs. No cortical surface area differences were identified. Cortical thickness of the left caudal ACC and left cuneus were inversely associated with anxiety symptoms, depressive symptoms, and disease duration, although certain associations did not persist after correction for multiple testing. In six of 68 regions examined, LTRCD patients had reduced cortical thickness in comparison to HCs. Cortical thickness of the left caudal ACC was inversely associated with disease duration. This suggests that prolonged and excessive exposure to glucocorticoids may be related to cortical thinning of brain structures involved in emotional and cognitive processing.
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PMID:Cortical thickness abnormalities in long-term remitted Cushing's disease. 3282 51