Context: The long-lived thyroid cell generates, for the synthesis of thyroid hormones, important amounts of H₂O₂ which are toxic in other cell types. The review analyses the protection mechanisms of the cell and the pathological consequences of disorders of this system.

Evidence acquisition: The literature on H₂O₂ generation and disposal, thyroid hormone synthesis, and their control in the human thyroid is analyzed.

Evidence synthesis: In humans, H₂O₂ production by DUOXes and consequently thyroid hormone synthesis by thyroperoxidase are controlled by the phospholipase C-Ca²⁺-diacylglycerol arm of TSH receptor action. H₂O₂ in various cell types, and presumably in thyroid cells, is a signal, a mitogen, a mutagen, a carcinogen, and a killer. The various protection mechanisms of the thyroid cell against H₂O₂ are analyzed. They include the separation of the generating enzymes (Dual activity oxidases, DUOX), their coupling to thyroperoxidase in a proposed complex, the thyroxisome, and H₂O₂ degradation systems.

Conclusions: It is proposed that various pathologies can be explained, at least in part, by overproduction and lack of degradation of H₂O₂ (tumorigenesis, myxedematous cretinism, thyroiditis) and by failure of the H₂O₂ generation or its positive control system (congenital hypothyroidism).

I. GENERAL EFFECTS OF H₂O₂

A H₂O₂ in signal transduction