Horm Metab Res 2011; 43(7): 500-504
DOI: 10.1055/s-0031-1277184
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Prolonged Inappropriate TSH Suppression During Hypothyroidism After Thyroid Ablation in a Patient with Nonautoimmune Familial Hyperthyroidism

H. Jaeschke1 , M. Eszlinger1 , J. Lueblinghoff1 , R. Coslovsky2 , R. Paschke1
  • 1Department for Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
  • 2Endocrine Unit, Kaplan Medical Center, Rehovot, Israel
Further Information

Publication History

received 03.02.2011

accepted 12.04.2011

Publication Date:
17 May 2011 (online)

Abstract

Prolonged TSH suppression was reported in a patient with nonautoimmune hyperthyroidism. These observations were made during L-thyroxine treatment and it was not possible to investigate a possible increase in serum TSH concentrations to levels observed in untreated hypothyroidism. We describe nonautoimmune familial hyperthyroidism identified in an Israeli woman, which is remarkable for the prolonged inappropriate TSH suppression after thyroid ablation. After 2 radioiodine treatments for several years, her TSH was always lower than 0.03 mU/l with 1.6 μg/kg/day (100 μg) thyroxine. 14 years after the radioiodine treatments, she discontinued thyroxine for 3.5 months and developed myxoedema with fT4 <6.0 and fT3 1.3 pmol/l and TSH of only 4.4 mU/l, which rose to only 8.6 after TRH. Genomic analysis showed a germline substitution M626I in the TSHR gene. Both exons of the thyroid-releasing hormone receptor revealed no mutations in this gene. Functional in vitro characterization of M626I showed a cell surface expression of 70% compared with the wt (100%), a significant increase of basal activity (5-fold over wt basal), which was confirmed by linear regression analysis (LRA) (slope: M626I=7, wt=1). No TRH-receptor mutation was detected. Therefore, this is the first patient with nonautoimmune hyperthyroidism with unequivocal evidence for inappropriately prolonged TSH suppression documented by a clearly insufficient TSH increase during clinical hypothyroidism. The in vitro characterization of the TSH-receptor mutation did not show any explanations for the prolonged TSH suppression. Therefore, other possible candidate genes remain to be investigated for potential explanations for this prolonged TSH suppression.

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Correspondence

Prof. Dr. R. Paschke

Department for Endocrinology

and Nephrology

University of Leipzig

Liebigstraße 20

04103 Leipzig

Germany

Phone: +49/341/971 3201

Fax: +49/341/971 3239

Email: ralf.paschke@medizin.uni-leipzig.de

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