ELEVATION OF SERUM-FREE TRIIODOTHYRONINE, TOTAL TRIIODOTHYRONINE, THYROXINE-BINDING GLOBULIN, AND TOTAL THYROXINE LEVELS IN COMBAT-RELATED POSTTRAUMATIC-STRESS-DISORDER

Background: This study was designed to assess both central and periphe ral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine ( T-4) and total T-4 previously observed in pilot work. Methods: A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T-4, free T-4, total triiodothyr onine (T-3), free T-3, T-4-binding globulin, and thyrotropin. Results: The pilot observation of moderately elevated total T-4 levels with no elevation in free T-4 levels in patients with PTSD was confirmed, sug gesting the hypotheses that (1) there may be an increased peripheral c onversion of free T-4 by deiodination to T-3 or (2) there may be an in creased binding of T-4 secondary to elevated T-4-binding globulin leve ls. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T-3 and free T -3, as well as elevated T-3/T-4, ratios, supporting the increased T-3 conversion hypothesis. The PTSD groups also showed a marked and sustai ned increase in T-4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups. Conclusions: These findings demonstrate an unusual pa ttern of thyroid alterations, featuring substantial elevations in tota l T-3, free T-3, and T-4-binding globulin levels, in combat-related PT SD that differs from established endocrinopathies, such as classic hyp erthyroidism, T-3 thyrotoxicosis,or chronic T-4-binding globulin eleva tion.