The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Apr 2012
Randomized Controlled TrialEstimation of maximal cortisol secretion rate in healthy humans.
Cortisol secretion is related to ACTH concentration by a sigmoidal dose-response curve, in which high ACTH concentrations drive maximal cortisol secretion rates (CSR(max)). ⋯ Application of a mass-action model under conditions of cosyntropin stimulation provides a relatively simple method for estimation CSR(max) that accurately predicts measured cortisol concentrations. DEX administration did not significantly affect estimates of CSR(max) or free cortisol half-life.
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J. Clin. Endocrinol. Metab. · Mar 2012
ReviewClinical review: Current scientific rationale for the use of somatostatin analogs and mTOR inhibitors in neuroendocrine tumor therapy.
Among the innovative molecules used to manage neuroendocrine tumors, there is growing interest in combining the somatostatin analogs octreotide or pasireotide (SOM230) and everolimus (RAD001), an inhibitor that targets the protein kinase mammalian target of rapamycin (mTOR). ⋯ The combination of somatostatin analogs and everolimus in therapeutic trials offers a promising treatment option for neuroendocrine tumors.
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J. Clin. Endocrinol. Metab. · Mar 2012
Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk.
Subclinical thyroid dysfunction is common in older people. However, its clinical importance is uncertain. ⋯ Older people at high cardiovascular risk with low or very high TSH along with normal free T4 appear at increased risk of incident heart failure.
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J. Clin. Endocrinol. Metab. · Feb 2012
Review Case Reports Historical ArticleAndrogen deprivation therapy as primary treatment for prostate cancer.
Hormonal therapy has been the mainstay of treatment for advanced prostate cancer for over 70 yr. The timing and extent of androgen ablative therapy for earlier stage disease remains controversial. In addition, recent studies demonstrate that so-called "castration-resistant" tumors are still dependent on androgen receptor signaling. ⋯ Androgen deprivation therapy remains the treatment of choice for metastatic prostate cancer; however, it is not without its adverse effects, and most men with advanced disease eventually develop castration resistance. Newer compounds that more specifically and effectively target androgen and androgen receptor signaling in prostate cancer cells may provide more long-lasting remissions in advanced disease.
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J. Clin. Endocrinol. Metab. · Feb 2012
Clinical TrialClinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer.
Abiraterone acetate is a small-molecule cytochrome P450 17A1 (CYP17A1) inhibitor that is active in castration-resistant prostate cancer. ⋯ CYP17A1 inhibition with abiraterone acetate is characterized by significant suppression of androgen and cortisol synthesis. The latter is associated with a rise in ACTH that causes raised mineralocorticoids, leading to side effects and incomplete 17α-hydroxylase inhibition. Concomitant inhibition of 17,20-lyase results in diversion of 17-hydroxyprogesterone metabolites toward androgen synthesis via the backdoor pathway. Addition of dexamethasone reverses toxicity and could further suppress androgens by preventing a rise in substrates of backdoor androgen synthesis.