Hyperreninemic Hypoaldosteronism in Combat-Related Posttraumatic Stress Disorder
Authors: David J. Houlihan
Journal: Psychotherapy and Psychosomatics (2013)

Combat-related posttraumatic stress disorder (PTSD) has been posited a unique contributor to an elevated risk of early-onset primary care provider-diagnosed illnesses [1]. The causality linking PTSD and physical disease development remains unclear. Much literature has focused on the role of cortisol in predisposing individuals to medical comorbidities. The renin-angiotensin-aldosterone system (RAAS) has been largely unexplored in this population [2]. The following is the description of 6 PTSD veterans discovered to have hyperreninemic hypoaldosteronism (HH) during an endocrine workup of medical comorbidities.The cohort consisted of 6 Caucasian male outpatients, aged 34-64 years (mean 54.1 years) at the time of the workup. All were combat veterans of the Persian Gulf (n = 2) or Vietnam conflict (n = 4). They were all diagnosed with PTSD by DSM-IV-TR criteria [3]. Duration since trauma exposure was 48-540 months (mean 384 months). Two had comorbid major depressive disorder and alcohol dependence, in remission. All met the clinimetric definition of allostatic overload (AO) [4] and were considered disabled due to the severity of their psychiatric symptoms.The cohort had the following medical comorbidities: endocrine/nutritional/metabolic disease [obesity (n = 4), hyperlipidemia (n = 5), diabetes mellitus (n = 3), and hypogonadism (n = 4)], nervous system disorders [chronic pain (n = 6)], circulatory disease [myocardial infarction (n = 2)], hypertension (n = 5), respiratory disease [asthma, chronic obstructive pulmonary disease (n=2)], digestive disease [irritable bowel disorder, gastric ulcer, gastroesophageal reflux (n = 2)], and musculoskeletal disease (n = 6). Vital signs were in the normal range on the date of the workup for all 6. HH was defined as a plasma renin activity greater than 2 ng/ml/h and a plasma aldosterone concentration to plasma renin activity ratio of less than 2 (table 1). Abnormal a.m. cortisol was observed in patient 1. The remaining cohort had values within the reference range. Diurnal cortisol variation was not determined in the cohort. All had adrenocorticotropic hormone levels within the reference range. Three patients showed evidence of proinflammatory profiles by elevated interleukin-6 and erythrocyte sedimentation rate. The group was prescribed between 6 and 14 medications (mean 10.5). There was no medication common to all 6 patients.Recent studies have demonstrated statistically significant differences in diverse biomarkers between subjects with and without clinimetrically defined AO [5]. The clinical use of these biological markers in individuals is still unclear. HH description in humans has largely been confined to a subgroup of critically ill patients [6,7]. This report, though observational in nature, is important in being the first description of HH occurring in a noncritically ill population as an apparent result of exposure to chronic psychological stress. These findings support Kubzansky and Adler [2] in the need to further explore the role of the RAAS in the development of medical comorbidities as a result of chronic stress. Aguilera et al. [8] demonstrated the development of HH after chronic physical-psychological stress in an animal model. These authors suggested renin stimulation due to sympathetic activation, and aldosterone secretion inhibition due to late steroidogenic pathway inhibition, underlying the development of HH. This report suggests an analogous occurrence in a subgroup of PTSD patients.The etiology of HH in this population is currently unclear. The allostatic model of maintaining stability through change is an intriguing possibility. This model posits that vulnerable individuals develop AO as a result of attempted allostatic accommodation to chronic uncontrollable stress. The brain, as the primary regulator of allostatic accommodation, potentially develops maladaptive alterations in the hypothalamic-pituitary-adrenocortical axis and sympathetic-adrenal-medullary stress axis to maintain homeostasis in the presence of AO [1,9,10]. This multisystem dysfunction has been hypothesized to lead to a cascade of events resulting in a predisposition to medical comorbidities as a result of chronic stress. The above cases, though observational in nature, suggest psychoneuroendoimmunologic disruption as a possible predisposing factor for the development of comorbidities in vulnerable populations.The allostatic theory would not suggest that PTSD leads to medical comorbidities. PTSD, however, may be a relatively early manifestation of morbidity in the presence of AO. Such a possibility needs further exploration.Treatment approaches to HH are limited. Critical care literature is cautionary in treating isolated abnormalities due to possible iatrogenic consequences within the larger dysfunctional system. The allostatic model argues that it may be more advantageous to focus on physiological and psychological stressors that drive the overall dysfunction. Such an approach in PTSD populations would argue for aggressive management of factors such as insomnia, anxiety, and pain which are well-recognized allostatic loads [7]. Close medical and psychiatric coordination in managing such a population, although speculative, would appear prudent.In conclusion, the above cohort description contributes to the growing literature suggesting RAAS involvement in responses to stress and resulting psychiatric and medical comorbidities. Future investigations are needed to clarify the range, prevalence, and course of RAAS abnormalities as well as its role in medical comorbidities. There is a need to explore identification, prevention, and treatment options in vulnerable populations as well.The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.There is no conflict of interest.This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.