Prospective Trial of Functional Thyrotropin Receptor Antibodies in Graves Disease.

Abstract

CONTEXT:

Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD).

OBJECTIVE:

To evaluate the clinical utility and predictive value of TSAb/TBAb.

DESIGN:

Prospective 2-year trial.

SETTING:

Academic tertiary referral center.

PATIENTS:

One hundred consecutive, untreated, hyperthyroid GD patients.

METHODS:

TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibition).

MAIN OUTCOME MEASURES:

Response versus nonresponse to a 24-week methimazole (MMI) treatment defined as biochemical euthyroidism versus persistent hyperthyroidism at week 24 and/or relapse at weeks 36, 48, and 96.

RESULTS:

Forty-four patients responded to MMI, of whom 43% had Graves orbitopathy (GO), while 56 were nonresponders (66% with GO; P < 0.01). At baseline, undiluted serum TSAb but not thyroid binding inhibitory immunoglobulins (TBII) differentiated between thyroidal GD-only versus GD + GO (P < 0.001). Furthermore, at baseline, responders demonstrated marked differences in diluted TSAb titers compared with nonresponders (P < 0.001). During treatment, serum TSAb levels decreased markedly in responders (P < 0.001) but increased in nonresponders (P < 0.01). In contrast, TBII strongly decreased in nonresponders (P = 0.002). All nonresponders and/or those who relapsed during 72-week follow-up period were TSAb-positive at week 24. A shift from TSAb to TBAb was noted in 8 patients during treatment and/or follow-up and led to remission.

CONCLUSIONS:

Serum TSAb levels mirror severity of GD. Their increase during MMI treatment is a marker for ongoing disease activity. TSAb dilution analysis had additional predictive value.

• Authors: George J Kahaly, Tanja Diana, Michael Kanitz, Lara Frommer, Paul D Olivo
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 105 Issue 4 (04 01 2020) ISSN: 1945-7197 [Electronic] United States
• PMID: 31865369 (Publication Type: Journal Article)
• Copyright: © Endocrine Society 2019.

Chemical References

• Autoantibodies
• Biomarkers
• Receptors, Thyrotropin
• Thyrotropin

Topics

• Adolescent
• Adult
• Autoantibodies (blood, immunology)
• Biomarkers (blood)
• Female
• Follow-Up Studies
• Graves Disease (blood, drug therapy, immunology)
• Humans
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Receptors, Thyrotropin (immunology)
• Thyrotropin (therapeutic use)
• Young Adult