Circulating MicroRNAs as Potential Biomarkers for Traumatic Brain Injury-Induced Hypopituitarism

Traumatic brain injury (TBI), a worldwide public health problem, has recently been recognized as a common cause of pituitary dysfunction. Circulating microRNAs (miRNAs) present in the sera are characteristically altered in many pathological conditions and have been used as diagnostic markers for specific diseases. It is with this goal that we planned to study miRNA expression in patients with TBI-induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43 +/- 18 years) who had been admitted to the neurosurgery intensive care unit due to TBI were included in the acute phase of the study. In the chronic phase, miRNA expression profile blood samples were drawn from 25 patients who had suffered TBI 5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute adrenocorticotropic hormone deficiency). In the chronic phase eight of 25 patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar healthy controls (25 male, 22 female, mean age: 41 +/- 14 years) were included in the study. In order to identify potential candidate miRNA/miRNAs whose levels had been altered in response to TBI-induced hypopituitarism, 740 miRNA expression analyses were performed in the sera of TBI patients by high throughput real-time polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126-3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following TBI. In addition, miRNA-3907 showed statistically significant and constant dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the patients with TBI. Our results indicated that altered expression of miR-126-3p and miR-3610 may play an important role in the development of TBI-induced hypopituitarism.