title: A hypothesis on the mechanism of action of high-dose thyroid in refractory mood disorders.
abstract: Multiple lines of evidence suggest the hypothesis that high dose thyroid therapy corrects for cellular hypothyroidism found in bipolar disorders. Evidence indicates that bipolar disorders are associated with mitochondrial dysfunction which results in low cellular adenosine 5'-triphosphate (ATP) levels. Transport of thyroid hormones into cells is energy intensive and dependent on ATP except in the pituitary gland. Inadequate ATP levels makes it difficult to get thyroid hormone into cells leading to cellular hypothyroidism. This creates a condition where the blood and pituitary levels of thyroid hormone are normal but low in other tissues. High dose thyroid therapy produces a gradient that is sufficient for thyroid hormone to diffuse into cells correcting cellular hypothyroidism. If this hypothesis is correct there are number of implications. The two most important are: On average patients suffering from a bipolar disorder die 10-20years earlier than the general population. The medical sequelae associated with bipolar disorders cause far more deaths than suicide. If high dose thyroid corrects for cellular hypothyroidism it could well decrease the medical morbidity and mortality associated with bipolar disorders that are the result of cellular hypothyroidism. Thus high dose thyroid would be a first treatment that decreases the considerable medical morbidity and mortality associated with the bipolar disorders. This would stand in stark contrast to most psychiatric medications that can that increase morbidity and mortality. It would also reinforce the safety of HDT. The second implication is thyroid hormone blood levels in patients suffering from a bipolar disorder do not accurately reflect the true thyroid status.
authors.affiliation: George Washington University, GWU MFA Department of Psychiatry and Behavioral Sciences, 2120 L St NW, Suite 600, Washington DC 20037, United States; The Depression & Bipolar Clinic of Colorado, 400 East Horsetooth Road, Suite 300, Fort Collins, Colorado 80525, United States. Electronic address: TamKelly@comcast.net.
authors.forename: Tammas
authors.initials: T
authors.lastname: Kelly
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000339:Affect; D000465:Algorithms; D000818:Animals; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy; D008928:Mitochondria / Q000378:metabolism; D008962:Models, Theoretical; D019964:Mood Disorders / Q000150:complications / Q000188:drug therapy; D010902:Pituitary Gland / Q000378:metabolism; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D013961:Thyroid Gland / Q000503:physiopathology; D013963:Thyroid Hormones / Q000627:therapeutic use*; D013971:Thyrotoxicosis / Q000150:complications
chemical_list: D013963:Thyroid Hormones; D000255:Adenosine Triphosphate