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Ghrelin is produced mostly in the stomach and hypothalamus and has important roles in the release of growth hormone and in control of appetite. This article outlines the many potential clinical applications for ghrelin, which reflect its physiological activities.
The conditions enabling spermatogonial stem cells to be grownin vitro and transplanted in vivo, where they can restore fertility, are now well-established in murine systems. This review describes the features of these cells and their potential use in human cancer treatment, diseases affecting fertility, and potentially in gene therapy.
Strategies that preserve or perhaps increase the β-cell mass in the pancreas could prevent diabetes. There are promising immunomodulatory approaches that include giving at-risk subjects insulin across mucosal barriers, and treating affected patients with monoclonal antibodies that alter immune regulation.
Neuroendocrine responses differ markedly in chronic critical illness compared with acute illness, and the chronic response may be harmful. Hyperglycemia is a major risk factor, and control of blood glucose is important. Because hypothalamic–pituitary axes interact during chronic illness, validating new therapies aimed at correcting multiple endocrine pathways seems warranted.
Administration of testosterone to men markedly reduces sperm counts and is a very efficient and well tolerated method of contraception. Combinations with progestogens or with gonadotropin-releasing hormone antagonists are even more effective and suggest that hormonal contraception in men is feasible and may be as effective as the currently used methods.
Thyroid cancer is the commonest endocrine malignancy, and drugs that target protein kinases offer a new approach in combating this and other malignancies. This review describes the various kinase targets in thyroid cancers, and details the inhibitors of the kinases RET and BRAF that are now in clinical trials.
Isoenzymes of 11[beta]-hydroxysteroid dehydrogenase affect the tissue-specific interconversion of cortisone and cortisol. In rodents, selective inhibitors of these enzymes improve insulin sensitivity, and we await clinical trials to test whether such drugs can be “magic bullets” to treat type 2 diabetes and the metabolic syndrome.
Radiation is still used to treat childhood malignancies, and many individuals have in the past been exposed to external radiation. The various risk factors, incidence rates and characteristics of thyroid cancer and other neoplasms after exposure to low-dose radiation are becoming clearer, as are screening and treatment strategies.
Diabetes and obesity are associated with pathway-selective insulin resistance in the phosphatidylinositol 3-kinase and CBL E3 ubiquitin protein ligase–(CBL)/CBL E3 ubiquitin protein ligase associated protein (CAP) signaling pathways, while insulin signaling via extracellular signal-regulated kinase (ERK) is comparatively unaffected, tipping the balance of insulin's actions so that they favor abnormal vasoreactivity, angiogenesis, and other pathways implicated in the development and progression of microvascular disease.
Thyroid-cell proliferation depends on TSH; suppression of TSH with levothyroxine decreases progression and recurrence rates for thyroid cancer. Long-term TSH suppression benefits patients at high risk of cancer recurrence but not low-risk patients, so TSH levels should be targeted accordingly.
Turner syndrome is a common genetic disorder that leads to a wide range of endocrine and other abnormalities, but no firm diagnostic guidelines exist. Growth hormone and hormone-replacement therapy can correct the major features, but the long-term consequences of such treatments are unknown.
Proglucagon-derived peptides from the pancreas and gut regulate various aspects of energy homeostasis, with many potential therapeutic applications—glucagon is used to treat hypoglycemia, and researchers are testing glucagon antagonists and glucagon-derived peptide 1 receptor (GLP-1R) agonists to treat type 2 diabetes, and a GLP-2 analogue to treat short-bowel syndrome.