MUTATIONS IN THE C-ERBA-BETA(1) GENE - DO THEY UNDERLIE EUTHYROID FIBROMYALGIA

Fibromyalgia, a chronic condition of widespread pain, stiffness, and f atigue, has proven unresponsive to drugs, the use of which is based on the 'serotonin-deficiency hypothesis'. An alternative hypothesis - fa iled transcription regulation by thyroid hormone can explain the serot onin deficiency and other objective findings and symptoms of euthyroid fibromyalgia. Virtually every feature of fibromyalgia corresponds to signs or symptoms associated with failed transcription regulation by t hyroid hormone. In hypothyroid fibromyalgia, failed transcription regu lation would result from thyroid-hormone deficiency. In euthyroid fibr omyalgia, failed transcription regulation may result from low-affinity thyroid hormone receptors coded by a mutated c-erbA beta(1) gene, yie lding partial peripheral resistance to thyroid hormone. The hypothesis of this paper is that, in euthyroid fibromyalgia, a mutant c-erbA bet a(1) gene (or alternately, the c-erbA alpha(1) gene) results in low-af finity thyroid-hormone receptors that prevent normal thyroid hormone r egulation of transcription. As in hypothyroidism, this would cause a s hift toward alpha-adrenergic dominance and increases in both cyclic ad enosine 3'-5'-phosphate phosphodiesterase and inhibitory G(i) proteins . The result would be tissue-specific hypothyroid-like symptoms despit e normal circulating thyroid-hormone levels.