Title:A Novel TSH Receptor Gene Variant Associated with Non-Autoimmune
Hyperthyrotropinemia: A Case Report
Volume: 24
Issue: 2
Author(s): Ilaria Piva, Simona Censi, Jacopo Manso, Susi Barollo, Loris Bertazza, Carla Scaroni, Caterina Mian and Mattia Barbot*
Affiliation:
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Keywords:
Non-autoimmune hyperthyrotropinemia, novel tsh receptor gene mutation, tsh receptor, thyroid, hyperthyrotropinemia, familial hyperthyrotropinemia.
Abstract:
Background: Resistance to TSH is defined as reduced sensitivity to normal, biologicallyactive
TSH, and abnormally high levels of TSH are needed to achieve normal levels of thyroid hormones.
Case Presentation: A 15-year-old female patient, having been treated since childhood with levothyroxine
for hyperthyrotropinemia was referred to our institution complaining of tachycardia after the levothyroxine
therapy had been increased. Thyroid ultrasound features were normal, and thyroid antibodies were
negative. The therapy was gradually tapered in light of the symptoms, although subclinical hypothyroidism
was evident at thyroid function tests. First-degree relatives were tested for thyroid function, and the
father was also found to have a previously-unknown subclinical hypothyroidism. The patient underwent
genetic testing for TSH receptor (TSHR) gene mutations, which revealed a gene variant hitherto not
described: p.C598R (c.1792T>C). The father was also tested and was found to carry the same mutation,
while other first-degree relatives were wild-type for the TSHR gene. An in-silico analysis was performed,
which revealed a loss-of-function phenotype corresponding to the described variant, suggesting a novel
loss-of-function TSH receptor gene mutation.
Conclusion: In this case report, we present a novel loss-of-function gene mutation in the TSH receptor
gene associated with a TSH resistance phenotype.