Free hormone assays

The specific binding by serum proteins of circulating thyroid and steroid hormones is a phenomenon whose physiological significance is still not fully understood. Recent controversy on these proteins' role in hormone transport reveals that disagreement persists regarding the basic physicochemical implications of their presence within the microcirculation. Theoretical analysis of the effects of intracapillary protein binding reactions on target-tissue hormone uptake is of considerable complexity and has not, as yet, been successfully accomplished. A fuller analysis of the physicochemical consequences of hormone binding in body compartments under the 'dynamic' conditions which obtain in vivo is a necessary prerequisite to the demonstration of the validity (or otherwise) of the free hormone hypothesis, and the elucidation of the physiological role, if any, of serum binding proteins. Similar misunderstanding of physicochemical concepts has also emerged in the field of free hormone measurement. The advent of relatively simple immunoassay techniques and kits has made 'free hormone assay' more widely available than hitherto, resulting in a near exponential increase in the number of publications in this area. However, close examination of some of the modern technologies reveals that the ideas on which they are based contradict elementary physicochemical laws, and are demonstrably incorrect. Indeed many such kits--though claimed as conforming to legitimate physicochemical principles--comprise nothing more than increasingly complex reagent 'cocktails' (often of undisclosed chemical nature) empirically adjusted to yield clinically acceptable results in certain patient categories. Not only has the publication of numerous reports based on the use of such kits created considerable confusion in the endocrinological and physiological literature, but, in attempting to justify their claims, commercial kit manufacturers have introduced numerous false concepts into the free hormone measurement field.