MON-471 A New Look at the Endocrinology of Posttraumatic Stress Disorder (PTSD)

Background Typically, individuals with PTSD have: [a] decreased rapid eye movement (REM) sleep, [b] low cortisol (F) response to ACTH after dexamethasone suppression (dex-ACTH) despite elevated ACTH levels, and [c] are often hypertensive. However, there has been no comprehensive understanding of the underlying endocrinology of PTSD. Without REM sleep, PTSD patients would be expected to be GH deficient, but this has yet to be confirmed. Children in severely stressed environments, perhaps equivalent to PTSD, have decreased REM sleep, poor growth and a low GH response to testing. Children with isolated GH deficiency have a decreased F response to dex-ACTH, but their corticosterone (B) response to dex-ACTH is exaggerated. Treatment with exogenous hGH for 3 days stimulates 17-hydroxylase and restores the normal F to B ratio after dex-ACTH. B measurements after dex-ACTH have not been made in patients with PTSD. We have recently reported the discovery of Ionotropin. Ionotropin shares a structural element (a 5-membered lactone ring) with spironolactone. Ionotropin seems to function as an endogenous equivalent. High levels of Ionotropin are frequently observed in patients with hypertension. New synthesis The lack of REM sleep suggests that many patients with PTSD are functionally GH deficient. This would restrict 17-hydroxylase activity and lead to increased B and decreased F. Both B and F are glucocorticoids. However, B is a potent mineralocorticoid but F much less so. Mineralocorticoids, such as B, stimulate the Na+ channel, leading to Na+ retention and K+ wasting. To compensate for the K+ wasting, a patient would synthesize Ionotropin, which would cause hypertension. K+ wasting (including hypokalemia) is known to be associated with mental problems. One example is Bartter's syndrome. Affected patients benefit from therapy with triamterene or amiloride. New approaches to therapy Evaluate REM sleep and confirm low IGF levels. Choose drugs known to improve REM sleep, rather than anti-depressants. Confirm elevated B to F ratios, either episodically or after ACTH administration. Test if a short course of hGH or IGF1 therapy restores normal B to F ratios. Amiloride and triamterene are K+ sparing diuretics and block synthesis of the Na+ channel, which is a key part of the response to mineralocorticoids. This therapy could reduce K+ wasting, reducing Ionotropin synthesis, and lead to lower blood pressures. Strict low Na+ diets might also be helpful. Monitoring IGF and/or Ionotropin levels might be useful markers to evaluate new therapies. Notes This hypothesis does not imply that all patients with PTSD have this trilogy. There may be multiple diseases that present with the PTSD psychiatric phenotype. As women with pre-eclampsia have high levels of a digoxin-like material, which might be Ionotropin, this might be the explanation why pregnant women with PTSD are at increased risk of developing pre-eclampsia.