Diffusion-sink sampling for minimally invasive measurement of tissue available hormones

The interpretation of hormone concentrations measured in blood plasma is made difficult by some features of hormone physiology that are common to many endocrine systems: 1) secretion occurs in episodes; and 2) specific binding proteins profoundly influence the availability of hormone to tissue. Frequently repeated sampling and specific measurement of the freely diffusing hormone concentration are thus desirable. Traditional methods to this end are invasive, laborious, and frequently impractical. Diffusion-sink (DS) devices that are able to continuously sample the freely-diffusing concentration of a hormone in a biological fluid over a period of time have been built; these devices can be used for minimally invasive sampling. For some steroid hormones, DS devices can be worn orally to estimate tissue-available hormone in saliva; direct installation of DS devices in interstitial fluid is also possible. Experience to date in using these devices to measure corticosteroids and progesterone suggests several practical advantages, including: 1) similar time-averaging capability as with invasive area-under-the-curve methods; 2) specificity for the freely-diffusing concentration even in the presence of varying concentrations of protein-bound forms; and 3) ability to sample under conditions where traditional methods are prohibitively invasive, such as normal work and sleep. The diffusion-sink sampling approach can probably be combined with appropriate immunoassay methodologies to yield measurements that are simple and quick enough for routine clinical use.