Metformin Decreases Serum Thyroglobulin Concentration in Nonmedullary Thyroid Carcinoma.

Context: The conventional treatment of nonmedullary thyroid carcinoma (NMTC) includes surgical resection, thyrotropin (TSH) suppression, and 131-iodine. Some patients develop persistent/recurrent metastatic disease requiring expensive alternative therapies, such as external radiation and multikinase inhibitors, which may have clinically significant side effects. Recent in vitro studies, in vivo studies in animals, and association studies in humans suggest that metformin, an inexpensive medication with a modest side effect profile, may help prevent or treat NMTC.

Familial nonmedullary thyroid carcinoma.

Background: Nonmedullary thyroid carcinomas (NMTCs) originate from the thyroid epithelial cells and, until recently, were thought to arise sporadically without an inherited genetic predisposition. However, evidence of a familial predisposition to NMTC is accumulating.

Methods: This review addresses the strengths, weaknesses, and clinical implications of the observations indicating an inherited genetic predisposition to NMTC.

Familial papillary thyroid carcinoma.

Over the last decade, several lines of evidence have been accumulated that support the existence of fPTC susceptibility genes. Preliminary clinical characteristics of fPTC have been identified, and linkage studies have identified the chromosomal locations of putative fPTC susceptibility genes. A logical clinical approach to fPTC is emerging.

Glucocorticoid resistance and hypersensitivity.

This article emphasizes the disorders caused by mutations and polymorphisms of the alpha form of the glucocorticoid receptor. These disorders usually present with increased circulating cortisol concentrations and must be distinguished from Cushing's syndrome, because the therapies are markedly different. The other disorders present with clinical features limited to a specific organ system.

Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity.

A naturally occurring ACTH receptor [melanocortin 2 receptor (MC2R)] mutation (F278C) has been identified in a subject with ACTH-independent Cushing's syndrome. Functional characterization of this mutant receptor reveals that it is associated with elevated basal cAMP accumulation when compared with wild-type receptor-expressing cell lines. Dose responsiveness is similar between wild-type and mutant receptors in cell lines expressing similar numbers of binding sites.