maandag 30 januari 2012

Intrinsic imperfections of endocrine replacement therapy

In 2003 verscheen het artikel Intrinsic imperfections of endocrine replacement therapy van J.A. Romijn, J.W.A Smit en S.W.J. Lamberts. Voor veel mensen betekende het artikel een erkenning voor hun ervaringen met een hormoontherapie met z’n tekortkomingen. Ook zorgde het artikel voor begrip.

Intrinsic imperfections of endocrine replacement therapy [pdf]
JA Romijn, JWA Smit and SWJ Lamberts

Overvloed en onbehagen - Uitdagingen voor de moderne endocrinologie
JWA Smit

Hormonal substitution therapy has been extremely successful, with respect to morbidity and mortality, in the treatment of the major syndromes of endocrine insufficiency. However, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased quality of life.

It is likely that these complaints are, at least in part, caused by intrinsic imperfections of hormone replacement strategies in mimicking normal hormone secretion. Unfortunately, these complaints are often difficult to assess by clinicometric or biochemical tests, because the effects of hormones in general, and thus of hormone replacement strategies in particular, are difficult to quantify at the tissue level. Therefore, in clinical practice we rely mostly on plasma variables – ‘plasma endocrinology’ – which are a poor reflection of hormone action at the tissue level.

Appreciation of these intrinsic shortcomings of endocrine therapy is of utmost importance to prevent incorrect labelling of the complaints of many endocrine patients and to achieve further improvement in endocrine replacement strategies.

Thyroxine

The thyroid secretes tri-iodothyronine (T3) (~ 20%) in addition to thyroxine (T4) (~ 80%). In the absence of thyroid function, exogenous thyroxine is not able to normalise the concentrations of T4 and T3 in all tissues in rodents, even in the presence of normal TSH concentrations. Despite this knowledge, currently available preparations of T3 have unfavourable pharmacological profiles and adequate markers of biological effect are lacking. Additional evidence is required before combination therapy can be advised.

Tri-iodothyronine

There are no slow-release preparations of T3, which would provide stable plasma concentrations in view of the half-life of T3 (~ 1 day). The optimal dose is uncertain. The relationship between plasma concentrations of T3 and tissue-specific concentrations of T3 in humans is unknown during T3 therapy in hypothyroidism.

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