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. 2017 Apr 13;1(6):577-587.
doi: 10.1210/js.2017-00069. eCollection 2017 Jun 1.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

Odelia Cooper  1 , Vivien Bonert  1 , Franklin Moser  2 , James Mirocha  3 , Shlomo Melmed  1
Affiliations

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

Odelia Cooper et al. J Endocr Soc. .

Abstract

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume.

Design: Prospective controlled study in an outpatient clinic.

Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC.

Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects.

Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

Keywords: PTSD; cortisol; hypothalamic-pituitary-adrenal axis; pituitary gland; pituitary volume.

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Figures

Figure 1.
Figure 1.
MRI images (coronal and sagittal) and volumetric analysis of (a) a 60-year-old woman with PTSD (geometric volume, 403 mm3, volumetrics, 566 mm3) and (b) a matched healthy control subject (volume, 1379 mm3, volumetrics, 1080 mm3).
Figure 2.
Figure 2.
Correlation of 24-hour UFC levels with age in (a) PTSD subjects and (b) control subjects. In PTSD subjects, UFC levels decreased with age, whereas there was no similar correlation in control subjects.
Figure 3.
Figure 3.
Correlation of pituitary volume and ACTH AUC. Mean pituitary volume was 729.7 mm3 (SD, 227.3 mm3) in PTSD subjects (circles) compared with 835.2 mm3 (SD, 302.8 mm3) in healthy control subjects (triangles). ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) in PTSD subjects vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects. In healthy control subjects (gray line), pituitary volume significantly correlated with ACTH AUC (Pearson correlation coefficient, 0.88; P = 0.0009) but not in PTSD subjects (dark line) (Pearson correlation coefficient, 0.29; P = 0.41).
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