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Screening for mutations in theRETproto-oncogene has revolutionized management of multiple endocrine neoplasia type 2 (MEN2), although controversy still exists regarding the timing and extent of surgical intervention. This Viewpoint discusses the relationship between genotype and phenotype in MEN2 and describes strategies to determine the appropriate age for patients to undergo thyroidectomy.
At present, patients with hypoadrenalism are treated with hydrocortisone replacement regimens which aim to mimic the natural circadian rhythms of glucocorticoid secretion. As current knowledge regarding glucocorticoid biology increases, however, it is becoming clear that replacement therapies are nonphysiologic and could affect patients' quality of life.
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.
Hypertension and heart failure can be treated with mineralocorticoid-receptor antagonists, although therapy is associated with an increased incidence of hyperkalemia. Data from three influential clinical trials—RALES, EPHESUS and 4E—are described and the findings discussed within the context of mineralocorticoid-receptor biology.
Gamma Knife® radiosurgery is widely used to treat patients with pituitary adenoma. Although this procedure has a high success rate, it is also associated with potential complications, including visual dysfunction. This Viewpoint considers whether the benefits of Gamma Knife®surgery outweigh the risks.
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.
