TSH-receptor antistoffen - van stimuleren naar blokkeren en vice versa

In dit onderzoek gaat het om blokkerende en stimulerende TSH-receptor antistoffen. TSH-receptor antistoffen (TBII/TRAb) binden zich aan het celmembraan van een schildkliercel. Zij nemen de plaats in van TSH op de TSH-receptor. Op die manier doen zij TSH na. TSH is een hormoon dat de schildklier stimuleert om schildklierhormoon te maken. Blijkbaar komt bij sommige patiënten voor dat die antistoffen zorgen voor afwisselend hypo- en hyperthyreoïdie en andersom.

Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for ‘switching’.

TSHR / TSI antibodies

Thyrotropin receptor (TSHR / TSI) antibodies that stimulate the thyroid (TSAb) cause Graves’ hyperthyroidism.

TBAb / TBI antibodies

TSHR antibodies which block thyrotropin action (TBAb / TBI) are occasionally responsible for hypothyroidism.


TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction.

Factors that may impact the shift include:
  • LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels;
  • antithyroid drug treatment decreases thyroid autoantibody levels;
  • hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity;
  • immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum;
  • maternally transferred IgG transiently impacts thyroid function in neonates until metabolized;
  • a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates.

Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo.


Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves’ disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition. The occurrence of ‘switching’ emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare ‘switch’ patients and appropriate Graves’ and Hashimoto’s controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity.