Endocrine (2018) 61:308–316
Is serum TSH a biomarker of thyroid carcinoma in patients residing
in a mildly iodine-deﬁcient area?
Kristine Zøylner Swan
Viveque Egsgaard Nielsen
Jens Faunø Thrane
Marie Riis Mortensen
Henrik Baymler Pedersen
Steen Joop Bonnema
Received: 21 February 2018 / Accepted: 14 May 2018 / Published online: 31 May 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Purpose To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid
carcinoma (DTC) in a mildly iodine-deﬁcient area.
Methods Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical
departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals
with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish
background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortiﬁcation program
Results Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years]
were included. S-TSH was signiﬁcantly higher in the DTC group [median (IQR): 1.3 (0.9–1.9 mIU/L)] compared with the
benign TND group [0.9 (0.6–1.5 mIU/L)] (p < 0.0001). The median s-TSH in the background population was similar to that
found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p < 0.0001).
There was no association between s-TSH and DTC disease stage (p = 0.08–0.87).
Conclusions s-TSH was signiﬁcantly higher in patients with DTC than in those with benign TND. However, this difference
can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional
autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant
TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.
Thyroid stimulating hormone (TSH) controls thyroid
growth as well as thyroid hormone production and secre-
tion, mediated through the TSH-receptor on the thyrocyte.
TSH is very sensitive to even minor disturbances of the
thyroid function controlled by negative feedback mechan-
isms, and serum TSH (s-TSH) is, therefore, used as the ﬁrst
line screening test for thyroid function abnormalities .
Differentiated thyroid carcinoma (DTC), comprising
papillary thyroid carcinoma (PTC) and follicular thyroid
carcinoma (FTC), accounts for approximately 94% of all
thyroid cancers, and has a good prognosis in most patients
[2, 3]. The TSH-receptor is present on cells of human DTC
, and high levels of circulating TSH in mice stimulate
thyroid hyperplasia and subsequently cause metastasizing
thyroid carcinoma . Along this line, levothyroxine sup-
pressive therapy, achieving a low s-TSH level, is
* Kristine Zøylner Swan
Department of Oto-rhino-laryngology (ORL) Head & Neck
Surgery, Aarhus University Hospital, Nørrebrogade 44, 8000
Aarhus C, Denmark
Department of Clinical Medicine, Aarhus University, Palle Juul-
Jensens Boulevard 82, 8200 Aarhus N, Denmark
Department of ORL Head & Neck Surgery, Odense University
Hospital, J.B. Winsløws Vej 4, 5000 Odense C, Denmark
Department of ORL Head & Neck Surgery, Aalborg University
Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark
Department of Endocrinology, Odense University Hospital,
Kløvervænget 6, 5000 Odense C, Denmark
Department of Plastic and Breast surgery, Aarhus University
Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark