Endocrine Abstracts

Introduction: Graves’ disease (GD) is unique among autoimmune endocrinopathies because the underlying immune disorder results in thyroid stimulation rather than functional or structural inhibition of the gland. However, thyrotropin-receptor antibodies (TRAbs), a specific and sensitive immunological marker for GD, are heterogeneous both in terms of their molecular structure and their biological activity. Stimulating TRAbs (TSIs) activate the thyrotropin (TSH) receptor. Blocking TRAbs reduce the action of TSH but can also be weak agonists. Neutral TRAbs have no effect on TSH binding. They are probably involved in the generation of oxidative radicals and the induction of apoptosis. Some TRAbs also inhibit agonist-independent ("constitutive") signaling and are called "inverse agonists". In fact, the clinical picture of GD is determined by the balance between the opposing activities of these antibodies, but this balance could change in the course of the disease.

Clinical case: A 67-year-old woman was admitted emergently to a cardiology unit due to acute heart failure based on high-frequency atrial fibrillation. The heart rate reached 167 beats per minute. During digitalization, normofrequency atrial fibrillation was achieved. Due to accompanying complaints of weight reduction, increased sweating and anxiety, thyroid function was also investigated, and thyrotoxicosis was established (TSH <0.004 mIU/ml, FT4 1 pmol/l, FT3 13.1 pmol/l). Based on the ultrasound of the thyroid gland (diffuse inhomogeneity with pseudonodulation and increased blood flow) and the examined immunological markers (thyroperoxidase antibodies (TPO Ab) <10 U/ml; TSI 5.7 IU/l), GD was diagnosed. Treatment with 1 mg propranolol and 1 mg thiamazole daily was initiated. Two months later, according to hormonal parameters (TSH 3.8 mIU/ml, FT4 8.1 pmol/l, FT3 4.1 pmol/l), the dose of thyrostatic was reduced to 1 mg daily. Restoration of sinus rhythm was also recorded. Control hormonal tests on the 4th month after diagnosis revealed severe hypothyroidism (TSH 101.25 mIU/ml, FT4 2.1 pmol/l, FT3 2.1 pmol/l) regardless of the reduced dose of thiamazole (1 mg daily). Analysis of immunological markers revealed high TRAbs titers (>40 IU/l) and reduced levels of stimulating immunoglobulins (TSI 2.11 IU/l). The therapeutic regimen was continued with 10 mg thiamazole in combination with 25 µg levothyroxine daily, but without β-blocker.

Conclusion: Both TRAK and TSI are useful for the diagnosis of GD, but their comparison is more important for treatment monitoring. The marked predominance of TRAbs over TSIs in the presented clinical case may be related to the presence of blocking/neutral TRAbs. This conclusion is supported by the observed clinical course of the disease.