Q1. We would expect endocrine disruptors to affect all tissues including the pituitary, surely patients would present with abnormal TFTs? ARTH seems extremely unlikely.
A1. Toxicology testing traditionally addresses poisoning and cancer risk. For potential thyroid hormone disruptors current testing consists of feeding substances to rodents, assaying total T4 and TSH and observing thyroid pathology. Total T4 gives an indication of thyroid secretion. TSH is marker for hormone feedback to the pituitary. Thyroid pathology will reveal abnormal structure or cancers.
Consequently, substances that produce abnormal blood test results are rejected. Substances that are safe, or harmful but give normal blood test results are accepeted. Perversely, only EDCs that cannot be detected by TFTs are marketed.
Q2. Why me? Why aren’t family members or work colleagues affected?
Understanding susceptibility is important, not just for therapy but also for diagnosis. If we can discover the reasons for susceptibility we can target susceptible individuals for investigation and therapy.
Hydroxylated PBDEs are more potent disruptors. PBDE Hydroxylation is mediated by the cytochrome P450 enzyme CYP2B6. Expression of CYP2B6 between individuals varies by up to 200x and activity by up to 80x. Perhaps susceptibility is determined by CYP2B6 activity. We don’t know why some individuals are susceptible, variations in CYP2B6 activity levels is a strong possibility. Unfortunately, this can only be assessed by invasive techniques and might need ethical approval. Although ARTH is not a genetic disease it is quite likely that genes play a role in susceptibility and so this form of hypothyroidism may run in families.