Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study


Marianne Christina Klose, Department of Medical Endocrinology, PE2131, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen. Tel: +45 35 45 87 39; Fax: +45 35 45 22 40; E-mail:


Objective  To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations.

Design  A 12-month prospective study.

Patients  Forty-six consecutive patients with TBI (mild: N = 22; moderate: N = 9; severe: N = 15).

Measurements  Baseline and stimulated hormone concentrations were assessed in the early phase (0–12 days post-traumatically), and at 3, 6 and 12 months postinjury. Pituitary tests included the Synacthen-test (acute +6 months) and the insulin tolerance test (ITT) or the GHRH + arginine test if the ITT was contraindicated (3 + 12 months). Insufficiencies were confirmed by retesting.

Results  Early post-traumatic hormone alterations mimicking central hypogonadism or hypothyroidism were present in 35 of the 46 (76%) patients. Three months post-traumatically, 6 of the 46 patients failed anterior pituitary testing. At 12 months, one patient had recovered, whereas none developed new insufficiencies. All insufficient patients had GH deficiency (5 out of 46), followed by ACTH- (3 out of 46), TSH- (1 out of 46), LH/FSH- (1 out of 46) and ADH deficiency (1 out of 46). Hypopituitary patients had more frequently been exposed to severe TBI (4 out of 15) than to mild or moderate TBI (1 out of 31) (P = 0·02). Early endocrine alterations including lowered thyroid and gonadal hormones, and increased total cortisol, free cortisol and copeptin were positively associated to TBI severity (P < 0·05), but not to long-term development of hypopituitarism (P > 0·1), although it was indicative in some.

Conclusion  Long-term hypopituitarism was frequent only in severe TBI. During the 3–12 months follow-up, recovery but no new insufficiencies were recorded, indicating manifest hypothalamic or pituitary damage already a few months postinjury. Very early hormone alterations were not associated to long-term post-traumatic hypopituitarism. Clinicians should, nonetheless, be aware of potential ACTH deficiency in the early post-traumatic period.