Inappropriate secretion of thyrotropin by the pituitary.

Inappropriate secretion of thyrotropin (IST) is characterized by elevated serum free thyroid hormone and unsuppressed thyrotropin (TSH) levels, and results from either a TSH-secreting pituitary tumor (nIST) or a selective resistance to thyroid hormone action (nnIST). Although in most patients TSH levels are definitely high, in a quarter of the cases they are within the 'normal range'. In some of these cases, TSH had an elevated biologic activity and an apparent molecular weight smaller than in normals. The current availability of ultrasensitive TSH immunoradiometric assay, able to distinguish suppressed from unsuppressed TSH levels enables the recognition of the disease. The distinction between nnIST and nIST rests on clinical, neuroradiological, and biochemical criteria, the most useful of which are the alpha-subunit:TSH molar ratio (increased in nIST), and the evaluation of the TSH responses to thyrotropin-releasing hormone and high doses of 3,5,3'-triiodothyronine, both qualitatively normal in nnIST, while absent in nIST. The therapy of choice for patients with nIST is pituitary surgery, followed by irradiation in case of surgical failure. Chronic administration of bromocriptine is effective in a minority of cases. The long-acting somatostatin analogue SMS 201-995 has given promising results in 2 patients. In nnIST, bromocriptine is frequently uneffective, while small doses of 3,5,3'-triiodothyronine or 3,5,3'-triiodothyroacetic acid, a thyroid hormone derivative with a strong inhibitory effect on TSH secretion but poor thyromimetic activity on peripheral tissues, are effective in controlling TSH hypersecretion.