A Randomized Clinical Trial of Intravenous Methylprednisolone With 2 Protocols in Patients With Graves Orbitopathy.

CONTEXT: Intravenous glucocorticoid (IVGC) is an accessible and affordable treatment for Graves orbitopathy (GO); the 4.5-g protocol is well studied, but many details of treatment protocols need to be clarified. OBJECTIVE: To compare the efficacy and safety of weekly and monthly protocol of IVGC in GO. METHODS: A prospective, randomized, observer-masked, single-center clinical trial, followed up to week 24, at the third affiliated hospital of Southern Medical University; 58 patients with active and moderate to severe GO, aged 18-60 years old, who had not received relevant treatment were included. The intervention was weekly protocol or monthly protocol of IVGC; both received a cumulative dose of methylprednisolone 4.5 g and had a duration of 12 weeks. The overall effective rate, improvement of quality of life (QOL) and signal intensity ratio (SIR) were measured. RESULTS: There was no significant difference in the effective rate between the 2 groups at week 12 and week 24 (86.21% vs 72.41%, P = .195; 86.21% vs 82.61%, P = .441), there was no significant difference in the improvement of clinical activity score, exophthalmos, soft tissue involvement, diplopia, and QOL. At week 24, the mean SIR and maximum SIR of the 2 groups were lower than those before treatment, and there were no statistically significant difference between the 2 groups. There was no significant difference in the incidence of adverse events between the 2 groups (31.03% vs 27.59%, P = .773). CONCLUSION: The efficacy and safety of the 2 protocols are comparable; the monthly protocol could be used as an alternative to the weekly protocol.

Excess dietary zinc drives a Cushing's-like syndrome in ovariectomized mice - Implications for postmenopausal obesity.

Postmenopausal women have an increased risk of obesity, but the underlying cause is not clear. We unexpectedly found that excess dietary zinc induced severe obesity and a Cushing's-like syndrome without increased food intake in ovariectomized (Ovx) but not in sham-operated mice. Zinc accumulated in the adrenal glands and inhibited adrenal 17,20-lyase activity and steroid synthesis. As adrenal steroids are the only source of estrogen in Ovx mice, estrogen deficiency induced adrenal hyperplasia, glucocorticoid overproduction, and consequent development of a Cushing's-like syndrome. Adrenal steroid supplementation prevented the effects of zinc. Plasma zinc was positively correlated with cortisol level and negatively correlated with the levels of adrenal steroids and estrogen in obese postmenopausal women. The finding of a link between dietary zinc, estrogen deficiency, and postmenopausal obesity, implies that postmenopausal obesity might be prevented by supplementation with a adrenal steroid and avoiding excess dietary zinc.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.