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Elevation of Serum Free Triiodothyronine, Total Triiodothyronine, Thyroxine-Binding Globulin, and Total Thyroxine Levels in Combat-Related Posttraumatic Stress Disorder

John Mason, MD; Steven Southwick, MD; Rachel Yehuda, PhD; Sheila Wang, PhD; Sherry Riney; Douglas Bremner, MD; David Johnson, PhD; Hadar Lubin, MD; Dudley Blake, PhD; Gang Zhou; Fred Gusman, MSW; Dennis Charney, MD
Arch Gen Psychiatry. 1994;51(8):629-641. doi:10.1001/archpsyc.1994.03950080041006.
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Background:  This study was designed to assess both central and peripheral 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 (T4) and total T4 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 T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin.

Results:  The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups.

Conclusions:  These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.


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