Evening versus Morning Administration of Levothyroxine: a randomised controlled double-blind trial

Primary hypothyroidism is a common disease, especially frequent among women,
and usually has a large impact on quality of life. Untreated hypothyroidism can
lead to serious symptoms, and needs to be treated with levothyroxine
(synthetised T4). Subclinical hypothyroidism ( elevated TSH with a normal T4)
can also give symptoms of hypothyroidism, and there are contradictory trial
results concerning the elevated risks of cardiovasculair incidents in
sublinical hypothyroidism. This is why consensus concerning the need for
treatment of subclinical hypothyroidism with levothyroxine still lacks.
Especially a clear improvement of quality of life could be a reason to start
treatment with levothyroxine.
Hypothyroid patients worldwide are advised to take levothyroxine tablets in the
morning half an hour before breakfast. This is because a fiber-enriched diet
and ingestion of certain drugs have been shown to have an adverse effect on the
intestinal absorption of L-thyroxine.
In a recent study we showed that TSH significantly decreased and T4 an T3
significantly increased after changing the administration time of levothyroxine
from morning to the evening, at bedtime.

To study in a large randomised double-blind trial, if the administration of
levothyroxine at bedtime significantly changes TSH and thyroid hormone levels
compared to morning administration. Furthermore we want to evaluate the change
of quality of life in patients with significant thyroid hormone changes. In
some patients the change in administration time of levothyroxine will cause
them to become subclinical hypo- or hyperthyroid. Through quality of life
questionairres we will evaluate if their quality of life changes because of
this.

A randomised controlled double-blind cross-over studyamong patients with
primary hypothyroidism. Patients will be asked to take a tablet in the morning
as well as in the evening, with one of these tablets containing levothyroxine
and the other tablet will be a placebo. The patient and his/her doctor will not
know which tablet contains the actual levothyroxine. After 2 months the tablets
will be switch, so that the tablet containing levothyroxine is taken at a
different moment of the day. Every 4 weeks patients will return to the
outpatient department for a check-up and bloodtests. At the start of the study
and at 8 and 16 weeks Bij aanvang van de studie, en na 8 en 16 weken zal een
uitgebreide QOL-vragenlijst worden afgenomen.

During the study, patients will have to take 2 tablets a day (one in the
morning and one at bedtime), instead of 1 tablet. During these 16 weeks they
will return to the outpatient department five times for a check-up, and
bloodsamples will be taken.

For the period of 16 weeks patients will need to take two tablets instead of
one tablet. During this period they will visit the outpatient department 5
times, where blood samples will be taken.