Fibromyalgia, a chronic condition of widespread pain,
stiffness, and fatigue, has proven unresponsive to drugs, the
use of which is based on the 'serotonin-deficiency
hypothesis'. An alternative hypothesis-failed transcription
regulation by thyroid hormone-can explain the serotonin
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 thyroid hormone.
In hypothyroid fibromyalgia, failed transcription regulation
would result from thyroid-hormone deficiency. In euthyroid
fibromyalgia, failed transcription regulation may result from
low-affinity thyroid hormone receptors coded by a mutated
c-erbA beta 1 gene, yielding partial peripheral resistance to
thyroid hormone. The hypothesis of this paper is that, in
euthyroid fibromyalgia, a mutant c-erbA beta 1 gene (or
alternately, the c-erbA alpha 1 gene) results in low-affinity
thyroid-hormone receptors that prevent normal thyroid hormone
regulation of transcription.
As in hypothyroidism, this would cause a shift toward
alpha-adrenergic dominance and increases in both cyclic
adenosine 3'-5'-phosphate phosphodiesterase and inhibitory
Gi proteins. The result would be tissue-specific hypothyroid-like
symptoms despite normal circulating thyroid-hormone levels.