Clinical

Clin Thyroidol 2015;27:183–184. THYROIDOLOGY ®

Selenium Supplementation Affects Normal Thyroid

Function, But The Impact Is Only Modest
Albert G. Burger
Winther KH, Bonnema SJ, Cold F, Debrabant B, Nybo M, Cold S, Hegedus L. Does selenium
supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a
Danish population. Eur J Endocrinol 2015;172:657-67. Epub March 4, 2015.

SUMMARY

Background during from November 1998 through June 1999. The

The first indication of a specific role for selenium
in thyroid physiology was obtained during studies
of endemic goiter in the Congo (1, 2). These studies
were mainly performed by Belgian researchers in
an area that was severely deficient in iodine and
selenium. The results indicated that neither thyroxine
nor iodine treatment alone would improve serum T3
levels despite increasing FT4 levels. Moreover, TSH
behaved paradoxically, remaining unchanged or
even increasing. Substitution with selenium rapidly
normalized thyroid hormone levels and decreased
serum TSH. In the following years it was established
that the deiodinases (DIO1 and DIO2) belong to the
family of rare selenoproteins, with approximately 70
species found in mammals (3). The high selenium
content of the thyroid suggests that this oligo element
is important in the proper functioning of the gland.
Selenium is present mainly in meat; in many Western
countries, serum levels of selenium are at the lower
limit of normal. It was therefore tempting to study the
effect of selenium treatment in patients with goiter,
Graves’ disease, and autoimmune thyroiditis (4, 5). An
intriguing observation was the inverse relationship of
serum selenium concentration and thyroid volume
in simple goiters. The selenium-specific effects on
the thyroid in areas without severe iodine deficiency
were not spectacular; detailed studies were needed
to justify the use or nonuse of selenium supplementa-
tion in patients with selected thyroid disorders.
Methods
This study from Denmark, which has an excellent
centralized medical chart system, was performed
age of the study population was limited to patients
from 60 to 74 years of age. The inclusion criteria
have been published (https://clinicaltrials.gov/ct2/
show/NCT01819649). Out of 2897 potential sub-
jects, 491 were included in this prospective study.
The subjects received a daily dose of either 100,
200 or 300 µg of a yeast selenium preparation on
an arbitrary basis. The placebo group received the
same tablets without selenium. Each group included
approximately 120 to 130 patients. The subjects
were treated for 5 years and were seen at the clinic
at baseline and then at 6, 12, 18, 24, and 60 months
of treatment.
Results
Of the initial 491participants, 361 could be assessed
after 5 years. Subjects who were on thyroxine
treatment or started on thyroxine during the study
were excluded from the statistical evaluation. A total
of 25 subjects withdrew from the study because
they thought they perceived some side effects (hair
loss, skin reactions, and grooved nails). They were
removed from the study even though these symptoms
were also noticed in the placebo group. With increas-
ing selenium dosage (100 to 300 µg/day) there was an
arithmetic increase in plasma concentrations (approx-
imately 60 ng/L for each 100-µg dose). Increasing
selenium doses were found to affect serum TSH. With
100 µg/day, serum TSH decreased by 0.066 mU/L.
The highest dose of selenium (300 µg/day) decreased
serum TSH on average by 0.2 mU/L. Serum FT3 con-
centrations were not affected by selenium, while FT4
levels decreased significantly, by 0.11 pmol/L, with

CLINICAL THYROIDOLOGY  l  JULY 2015 183 VOLUME 27  l  ISSUE 7  l  © 2015

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Selenium Supplementation Affects Normal Thyroid Function, Albert G. Burger
But The Impact Is Only Modest
no difference between 6 months and 5 years.
Conclusions
This is one of the few prospective studies on the pre-
sumptive impact of selenium on thyroid function.
The study subjects were recruited from a national
registry for thyroid function. From the 2897 regis-
ANALYSIS AND COMMENTARY
This study was well designed and well conducted.
There are, however, some minor critical issues, such
as the unanswered question of why the number of
participants decreased (to 73%) during the 5 years of
study. Moreover, the study was performed during the
time that salt iodination was introduced in Denmark.
Thus, the authors cannot completely exclude that
iodination affected some of their data. In this case,
however, TSH values should also have been affected
in the placebo group, but this was not found.
The effects on serum TSH and FT4 were minimal
but significant. The lowered FT4 and TSH values
References
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Huang SA, Simonides WS, Zeold A, Bianco AC.
CLINICAL THYROIDOLOGY  l  MAY 2015 184 VOLUME 27  l  ISSUE 5  l  © 2015
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tered subjects, 491 were retained for the study, and
361 completed the 5-year follow-up. Serum TSH and
FT4 decreased significantly with selenium treatment.
TSH values decreased by 0.2 mU/L. With the highest
dose of selenium, these effects were significant. No
specific side effects were reported.
with unchanged serum T3 would be consistent with
a higher conversion rate of T4 to T3 and, thus, could
reflect an activation of deiodinases. However, this
hypothesis would obtain some additional support
only if FT3 had been measured as well. The study has
one more important message—the absence of any
major side effect. This is reassuring, since at least
one other study reported that long-term treatment
with selenium tends to increase the risk for diabetes
(5). This provides reassurance that the selective use
of selenium in Graves” ophthalmopathy and autoim-
mune thyroiditis Is not associated with any harm.
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regulated thyroid hormone signaling. Endocr Rev
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