Experience of a Pituitary Clinic for US Military Veterans With Traumatic Brain Injury

Abstract

Context: Traumatic brain injury (TBI) is considered the "signature" injury of veterans returning from wartime conflicts in Iraq and Afghanistan. While moderate/severe TBI is associated with pituitary dysfunction, this association has not been well established in the military setting and in mild TBI (mTBI). Screening for pituitary dysfunction resulting from TBI in veteran populations is inconsistent across Veterans Affairs (VA) institutions, and such dysfunction often goes unrecognized and untreated.

Objective: This work aims to report the experience of a pituitary clinic in screening for and diagnosis of pituitary dysfunction.

Methods: A retrospective analysis was conducted in a US tertiary care center of veterans referred to the VA Puget Sound Healthcare System pituitary clinic with a history of TBI at least 12 months prior. Main outcome measures included demographics, medical history, symptom burden, baseline hormonal evaluation, brain imaging, and provocative testing for adrenal insufficiency (AI) and adult-onset growth hormone deficiency (AGHD).

Results: Fatigue, cognitive/memory problems, insomnia, and posttraumatic stress disorder were reported in at least two-thirds of the 58 patients evaluated. Twenty-two (37.9%) were diagnosed with at least one pituitary hormone deficiency, including 13 (22.4%) AI, 12 (20.7%) AGHD, 2 (3.4%) secondary hypogonadism, and 5 (8.6%) hyperprolactinemia diagnoses; there were no cases of thyrotropin deficiency.

Conclusion: A high prevalence of chronic AI and AGHD was observed among veterans with TBI. Prospective, larger studies are needed to confirm these results and determine the effects of hormone replacement on long-term outcomes in this setting.

Keywords: GH; TBI; adrenal insufficiency; growth hormone deficiency; head trauma; hypopituitarism.

Figure 1.

CONSORT diagram. CONSORT diagram displaying patients’ progression through clinical evaluation. ^aIt is possible that patients with central hypothyroidism may present with mildly elevated thyrotropin; however, to err on the side of caution, we report these patients as primary; ^bprovocative testing not indicated because early-morning cortisol was above 15 µg/dL; ^cprovocative testing not indicated because of lack of symptoms consistent with adult growth hormone deficiency and/or contraindication to growth hormone replacement. ACTH, adrenocorticotropin; CONSORT, Consolidated Standards of Reporting Trials; COVID, SARS coronavirus 2; GST, glucagon stimulation test; ITT, insulin tolerance test.

Figure 2.

Symptomatic burden of pituitary clinic patients. Frequency of symptoms reported by patients who were evaluated in clinic and completed baseline laboratory assessment (n = 58). Fatigue, cognitive problems, memory problems, and insomnia were recorded according to severity, and erectile dysfunction (ED), low libido, and mood problems were recorded as categorical variable (presence or absence).

Figure 3.

Symptomatic burden based on traumatic brain injury (TBI) severity. Frequency of symptoms reported by patients who were evaluated in clinic and completed baseline laboratory assessment with mild TBI (A, n = 41) or moderate/severe TBI (B, n = 17). Fatigue, cognitive problems, memory problems, and insomnia were recorded according to severity, and erectile dysfunction (ED), low libido, and mood problems were recorded as categorical variable (presence or absence).

Figure 4.

Laboratory values throughout the insulin tolerance test. Laboratory values for A, cortisol; B, growth hormone; and C, glucose measured throughout administration of the insulin tolerance test (n = 15).

Figure 5.

Deficiencies in pituitary clinic patients. Prevalence of pituitary dysfunction categorized by individual deficiencies; total indicates frequency of patients with a single deficiency and frequency of patients with more than one deficiency.

Figure 6.

Prevalence of symptoms and hormone deficiencies. Prevalence of symptoms reported between patients with or without A, AGHD and B, between patients with or without adrenal insufficiency (AI). *P less than or equal to .05. AGHD, adult growth hormone deficiency; ED, erectile dysfunction.