Endocrine Abstracts

L-T4 monotherapy remains the standard treatment of hypothyroidism, as RCTs comparing T4 and T4+T3 did not indicate superiority of the combination therapy. However, the issue is far from settled, as these RCTs can be criticized and 5–10% of patients on T4 have persistent complaints.

i) Has T4+T3 therapy a true effect on serum thyroid hormones? Under T4 monotherapy serum FT4 is higher and serum FT3 is lower than in healthy subjects, giving rise to abnormal T3/T4 ratio’s in 29% of patients. T4+T3 therapy produces lower FT4 and higher FT3 values, and thereby T3/T4 ratio’s are closer to normal values. There is conflicting data whether T3/T4 ratio’s are related to SNPs (e.g. in DIO2) and to persistent complaints.

ii) Has T4+T3 therapy a true effect on thyroid-hormone dependent actions? There is emerging but weak evidence that markers of thyroid hormone action (such as LDL-cholesterol, SHBG, bone alkaline phosphatase) are closer to normal under T4+T3 therapy than under T4 monotherapy.

iii) Has T4+T3 therapy a true effect on the clinical condition? Patients were asked for their preference in 4 RCTs. Preference for T4 was 25% and for T4+T3 48%; no preference was expressed by 27%. Preference has been related to loss of body weight and to combined SNPs in MCT10 and DIO2.

iv) Has T4+T3 therapy a true effect on clinical practice? Yes, absolutely. Many patients demand T4+T3 therapy, sometimes in a aggressive manner. Prescription of T3 tablets have increased, and pharmacy has discovered the potentially big market for T3, among others resulting in a steep price increase of T3 tablets but also in availability of 5 microgram T3 tablets. Only the ETA published detailed guidelines how to start the still experimental T4+T3 regimen (Eur Thyroid J 2012;1:55). The many unresolved issues call for many more clinical trials.of different designs.