ORIGINAL ARTICLE
Serum selenium is low in newly diagnosed Graves’
disease: a population-based study
Inge B€ ulow Pedersen*, Nils Knudsen†, Allan Carl e*, Lutz Schomburg‡, Josef K€ ohrle‡, Torben Jørgensen§¶
,
**,
Lone Banke Rasmussen††, Lars Ovesen‡‡ and Peter Laurberg*
*Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, Aalborg, †Endocrine Unit, Medical
Clinic I, Bispebjerg Hospital, Copenhagen, Denmark, ‡Institute for Experimental Endocrinology, Charit e-Universit€ atsmedizin, Berlin,
Germany, §Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, ¶Faculty of Health and Medical Sciences,
University of Copenhagen, Copenhagen, **Faculty of Medicine, Aalborg University, Aalborg, ††Department of Nutrition, National
Food Institute, Technical University of Denmark, Søborg and ‡‡Department of Internal Medicine, Slagelse Hospital, Slagelse,
Denmark
Summary
Context Selenium deficiency may play an important role in the
initiation and progression of autoimmune thyroid disease.
Objective To compare serum selenium (s-Se) values in patients
with newly diagnosed autoimmune thyroid disease and controls
from the Danish population.
Design and settings S-Se was measured in triplicate by a fluo-
rimetric method.
Participants Patients with newly diagnosed Graves’ disease (GD)
(n = 97) or autoimmune overt hypothyroidism (AIH) (n = 96),
euthyroid subjects with high serum levels of thyroid peroxidase
antibody (TPO-Ab) (TPO-Ab > 1500 U/ml, n = 92) and random
controls (n = 830).
Main outcome measure Differences in s-Se values.
Results S-Se was lower in patients with GD than in controls
(mean (SD), GD: 899 lg/l (184); controls: 988 lg/l (197),
P < 001). This was confirmed in a multivariate logistic regres-
sion model adjusting for age, sex, mineral supplements, smoking,
geographical region and time of sampling (P < 001). In a linear
model, s-Se was similar in patients with AIH (mean (SD):
984 lg/l (249)) and in controls (P = 086). In the multivariate
model however, s-Se was marginally lower in patients with AIH
compared to controls (P = 004). There was no significant differ-
ence in s-Se between euthyroid participants with high TPO-Ab
and random controls (linear: P = 097; multivariate: P = 027).
Conclusion Patients with newly diagnosed GD and AIH had
significantly lower s-Se compared with random controls. Our
observation supports the postulated link between inadequate
selenium supply and overt autoimmune thyroid disease, espe-
cially GD.
(Received 26 November 2012; returned for revision 30 January
2013; finally revised 11 February 2013; accepted 13 February 2013)
Introduction
Autoimmune thyroid diseases (AITD) are the most common
autoimmune disorders in the population. Several studies includ-
ing twin studies and epidemiological studies have demonstrated
that genetic factors are crucial determinants in the susceptibility
to autoimmune disease. However, on a given genetic back-
ground, environmental and endogenous factors such as age and
previous parities play an important role in the development and
maintenance of AITD. Among the many environmental factors
that have been suggested to influence the development of thy-
roid autoimmunity, the iodine intake may be the most impor-
tant. Other suggested risk factors include smoking, oestrogens,
drugs, stressful life events, irradiation, infection, allergy, alcohol
consumption and selenium deficiency.
1
Selenium is an essential trace mineral and an essential nutri-
ent for synthesis of the amino acid selenocysteine which is
incorporated into a number of selenoproteins. Until now, 25
human genes encoding selenoproteins are known, of which most
are enzymes.
2
The thyroid gland is one of the organs with the
highest content of selenium per mass unit due to the presence
of several selenoproteins involved in thyroid hormone metabo-
lism. Selenium-containing glutathione peroxidases may play an
important role in the antioxidant defence of the thyroid gland
by protecting the thyrocytes from any excess hydrogen peroxide
(H
2
O
2
) produced during thyroid hormone synthesis. In cases of
severe iodine deficiency (ID), thyroidal iodine autoregulation
and the high serum TSH stimulate the production of H
2
O
2.
When the selenium availability is below a certain value, the
glutathione peroxidase activity may be insufficient to remove the
excess H
2
O
2
, which may be one of the mechanisms involved in
thyroid gland destruction as seen in areas with combined iodine
Correspondence: Inge B€ ulow Pedersen, Department of Endocrinology
and Medicine, Aalborg Hospital, Aarhus University Hospital, DK-9000
Aalborg, Denmark. Fax: + 45 99 32 61 61; Tel.: +45 996135;
E-mail: I.Bulow@rn.dk
© 2013 Blackwell Publishing Ltd 1
Clinical Endocrinology (2013) doi: 10.1111/cen.12185