Anterior Pituitary Dysfunction Post ABI

 

Author/Year/
Country/ Sample Size 

Methods

Outcomes

Cuesta et al. (2016)
Ireland
Case Control
N=249
Population: TBI. Case Group (n=112): Mean Age=31yr; Gender: Male=77, Female=35; Mean Time Post Injury=19mo; Mean GCS=8. Control Group (n=137): Mean Age=35yr; Gender: Male=113, Female=24; Mean Time Post Injury=17mo; Mean GCS=8.
Intervention: Participants with symptoms suggestive of pituitary dysfunction (cases) were compared to a consecutive group without symptoms (controls).
Outcome Measures: Hormone levels (GH, GnRH, ACTH, TSH, ADH).
  1. Men with hypogonadism symptoms had greater deficiency of GH (p=0.003), GnRH (p<0.0001), and TSH (p=0.03) than those without.
  2. Women with menstrual dysfunction had greater deficiency of GH (p=0.001), ACTH (p<0.0001), and GnRH (p<0.0001), and more pituitary hormone deficits (p=0.003) than those without.
Marina et al. (2015)
Germany
Observational
N=163

Population: ABI. TBI (n=111); Mean Age=42.7yr; Gender: Male=83, Female=28; Mean Time Post Injury=20.7d; Mean GCS=10.2. Non-TBI (52): Mean Age=47.9yr; Gender: Male=28, Female=24; Mean Time Post Injury=28.6d; Mean GCS=11.3.
Treatment: Participants admitted to neurorehabilitation were assessed at 3mo and 1yr follow-up.
Outcome Measures: Stress hormone levels (PRL, IGF-1, cortisol), Gonadal hormone levels, Thyroid hormone levels, Functional Independence Measure (FIM), Glasgow Outcome Scale Extended (GOSE).

  1. At 3mo, 68% showed elevated stress hormones.
  2. At 1yr, lower FIM and GOSE scores were associated with elevated stress hormones (p<0.01).
  3. At 3mo, 32% showed suppressed gonadal or thyroid hormones.
  4. At 1yr, lower FIM and GOSE scores were associated with supressed gonadal/thyroid hormones (p<0.01).
Nemes et al. (2015)
Hungary
Observational
N=126
Population: TBI; Mean Age=42.4yr; Gender: Male=103, Female=23; Mean Time Post Injury=2.0yr; Injury Severity: Moderate=50, Severe=76.
Intervention: Participants were assessed during neurological follow-up.
Outcome Measures: Hormone deficiency (GH, LH, FSH, ACTH, TSH, ADH).
  1. At admission, 57.1% had major anterior pituitary failure.
  2. At follow-up, 31.7% presented significant changes in deficiencies: 16 developed new deficiencies and 10 had previous deficiencies resolved.
  3. GCS score was an independent predictor of hormone deficiencies (OR: 3.25, p=0.002).
Prasanna et al. (2015)
India
Observational
N=100
Population: TBI; Mean Age=32.3yr; Gender: Male=88, Female=12; Injury Severity: Moderate=52, Severe=48.
Intervention: Participants admitted to an Intensive Care Unit were assessed at 1d and 7d post injury.
Outcome Measures: Hormone levels (GH, TSH, PRL, fT3, fT4, cortisol), Glasgow Outcome Scale (GOS).
  1. GH was the most common hormone to increase in participants (p<0.005).
  2. Cortisol was the most common hormone to decrease in participants (p<0.005).
  3. Pituitary dysfunction was associated with lower GCS and GOS scores, and high intracranial pressure (p<0.05). 

Kopczak et al. (2014)
Germany
Observational
N=509

Population: ABI; TBI Group: N=340; Mean Age=39yr; Gender: Male=257, Female=83; SAH Group: N=169; Mean Age=49yr; Gender: Male=67, Female=102.
Treatment: Basal anterior pituitary hormone levels assessed at median 7wk post injury. Subsequent stimulation tests were offered if insufficiency was suspected following the initial hormone screening.
Outcome Measure: Hormone levels (fT4, cortisol, testosterone [men], estradiol [women], PRL, and IGF-1).

  1. Overall, 56.8% of patients with TBI showed abnormal laboratory values in the screening program, compared to 56.2% patients with SAH.

  2. In total, 145 patients (28.5%) showed low laboratory values in one pituitary axis and 23 patients (4.5%) in at least two or more axes.

Hannon et al. (2013)
Ireland
Observational
N=100
Population: TBI; Mean Age=33yr; Gender: Male=84, Female= 16; Mean GCS=8.59.
Intervention: Participants were recruited and assessed for anterior pituitary hormone deficiency (levels of ACTH, GH, LH, FSH, TSH, PRL) at >6mo follow-up.
Outcome Measures: Anterior Pituitary Hormone Deficiency (APHD).
  1. APHD was analyzed in only 32 participants at follow-up: 19% had ACTH deficiency, 19% had GH deficiency, 3% had FSH deficiency, and none were TSH or PRL deficient.
  2. All participants with APHD at 6mo had either DI or hypocortisolemia during 1-10d.

Olivecrona et al. (2013)
Sweden
Observational
N=45

Population: TBI; Mean Age=35.7yr; Gender: Male=30, Female=15; Median GCS=6.
Treatment: Evaluation of changes in anterior pituitary hormone levels from day 1 to day 4 post TBI. Clinical outcomes were obtained at 3mo post injury.
Outcome Measure: Hormone measurement (cortisol, GH, PRL, IGF-1, TSH, fT3, fT4, FSH, LH, and testosterone), Glasgow Outcome Scale (GOS) at 3 mo.

  1. GOS at 3mo was significantly predicted by day 1 LH, along with FSH (p<0.001). This was also true when predicting mortality (dead/alive; p<0.002) and unfavourable/favourable outcome (p<0.01).

Prodam et al. (2013)
Italy
Observational
N=54
Population: TBI. Case Group (n=15): Mean Age=46.4yr; Gender: Male=14, Female=1; Mean Time Post Injury=7.4yr; Injury Severity: Moderate=5, Severe=5. Control Group (n=39): Mean Age=37.1yr; Gender: Male=24, Female=15; Mean Time Post Injury=5.1yr; Injury Severity: Moderate=4, Severe=35.    
Intervention: Participants admitted to tertiary care were assessed, comparing those with hypopituitarism (case) and those without (control).
Outcome Measures: Hypopituitarism.
  1. 27.8% had hypopituitarism: 9.3% had total, 7.4% had multiple, and 11.1% had isolated.
  2. Cases had higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) than controls.
  3. Cases were predominantly male (p<0.01) and older (p<0.02), as well as had longer comas (p<0.003) and greater epilepsy rate (p<0.03) than the control group.
Rosario et al. (2013)
USA
Observational
N=59
Population: TBI; Mean Age=44.4yr; Gender: Male=59, Female=0; Mean Time Post Injury=34.3d; Mean GCS=7.1. 
Intervention: Hypothalamic-pituitary dysfunction was assessed relative to functional improvement.
Outcome Measure: Hormone levels (testosterone, IGF-1, GH, fT4), Functional Independence Measure (FIM).
  1. Nearly 70% of patients were classified as having some degree of hypothalamic-pituitary dysfunction.
  2. No significant differences were found between individuals with and without endocrine abnormalities when comparing injury severity, length of stay, admission FIM score, or age; however, those with endocrine abnormalities were on average 10yr younger.
  3. FIM gain/day significantly decreased in patients with hypopituitarism compared to those with normal hormone levels (p=0.04).
Ulfarsson et al. 
(2013)
Sweden
Case Series
N=51

Population: TBI; Mean Age=37.9yr; Gender: Male=38, Female=13; Mean Time Post Injury=68.0mo; GCS<8.
Intervention: Participants were assessed for post-traumatic hypopituitarism (PTHP).
Outcome Measures: Hormone levels (GH, GHRH, LH, FSH, TSH, ACTH, IGF-1, SHBG, fT4, testosterone, estrogen), Glasgow Outcome Scale Extended (GOSE), 36-Item Short Form Health Survey (SF-36).

  1. 27.5% had PTHP; 21.6% had isolated GHD.
  2. Participants with PTHP had higher BMI at follow-up (p=0.01), which was partially explained by the PTHP (p=0.001).
  3. There was no significant correlation between PTHP and GOSE, SF-36, or ADL.

Moreau et al. (2012)
France
Observational
N=55

Population: TBI; Mean Age=36.1yr; Gender: Male=46, Female=9; Mean Time Post Injury=79.2mo.
Intervention: Anterior pituitary function was assessed post injury. 
Outcome Measures: Anterior pituitary deficiencies including hyperprolactinemia, gonadotropic deficiency (GD), thyrotropin releasing hormone deficiency (TRH), corticotropin deficiency (CD), and growth hormone deficiency (GHD).

  1. 42 (76.4%) patients developed at least one pituitary deficiency.
  2. Severe GHD, CD, TD and GD were not significantly related to age, clinical severity of the initial trauma, and presence of specific brain lesions noted on the initial CT scan and MRI performed 3mo later.

Bondanelli et al. (2007)
Italy
Observational
N=72

Population: TBI; Mean Age=37.2yr; Gender: Male=56, Female=16; Injury Severity: Moderate=10, Severe=62; Mean Time Post Injury=240.5d.
Intervention: Anterior pituitary function was assessed at least once between 6 and 12mo post injury.
Outcome Measure: Hormone levels (IGF-1, TSH, fT4, ACTH, LH, FSH, PRL, cortisol, testosterone or estradiol). 

  1. Pituitary dysfunction occurred in 22 patients (30.5%). Isolated anterior pituitary hormone deficiency was detected in 14 patients (19.4%) (LH/FSH=7, GH=6, TSH=1), double deficiencies in 4 patients (5.5%), and complete hypopituitarism in 1 patient (1.4%).
  2. No significant difference was observed in occurrence of hypopituitarism between patients with moderate and severe TBI.
  3. Disability Rating Score values at discharge were higher in patients with hypopituitarism, indicating an unfavourable outcome as compared with those with normal pituitary function (12.70±1.71 versus 8.03±0.94; p=0.014).

     

Klose et al. (2007)
Denmark
Observational
N=104

Population: TBI; Median Age=41yr; Gender: Male=78, Female=26; Mean Time Post Injury=13mo; Injury Severity: Mild=44, Moderate=20, Severe=40.
Intervention: Anterior pituitary function was assessed post injury.
Outcome Measures: Hormone levels (TSH, fT4, LH, FSH, PRL, testosterone or estradiol).

  1. 16 (15.4%) patients demonstrated hypopituitarism; 10 had an isolated dysfunction (all GH deficient), 4 had two dysfunctional axes, and 2 had more than two impaired axes.
  2. Hypopituitarism was independently associated with the female gender (p=0.02) and higher BMI (p=0.005), but not age.
  3. Patients with hypopituitarism were also likely to have a severe injury (p<0.001).

     

Tanriverdi et al. (2007)
Spain
Observational
N=104

Population: TBI; Mean Age=38.8yr; Gender: Male=78, Female=26; Time Post Injury <24hr; Injury Severity: Mild=49, Moderate=24, Severe=31.
Intervention: Anterior pituitary function was assessed within 24hr of trauma.
Outcome Measure: Hormone levels (cortisol, fT3, fT4, TSH, PRL, ACTH, FSH, LH, IGF-1, GH, testosterone or estradiol). 

  1. No significant differences were noted in mean age, fT3, TSH, cortisol, ACTH, FSH, LH, IGF-I, GH and testosterone levels among patients with mild, moderate, and severe TBI.
  2. Mortality following TBI was associated with old age (p=0.003) and low GCS score (p=0.0001), but not with basal pituitary hormone levels.
  3. The following pituitary hormone deficiencies were noted: TSH deficiencies in 4/104 (3.8%), gonadotropin (LH/FSH) deficiency in 38/95 (40%), ACTH deficiency in 9/95 (8.8%), and GH deficiency in 19/95 (20%).

     

Schneider et al. (2006)
Germany
Observational
Ninitial=78, Nfinal=70

 

 

 

 

*Schneider et al. (2008)

Population: TBI; Mean Age=36yr; Gender: Male=52, Female=26; Mean GCS=7.4.
Intervention: Anterior pituitary function was assessed 3mo±2wk (T1) and 12mo± 4wk (T2) post injury.
Outcome Measure: Hormone levels (IGF-1, TSH, fT4, T3, LH, FSH, PRL, GH, ACTH, testosterone or estradiol). 

 

 

*Follow-up to Schneider et al. (2006)

  1. At T1, impairments of at least one pituitary axis were seen in 44 (56%) of 78 patients; 8 patients had combined impairments of two axes.
  2. At T1, no differences were found in initial GCS, modified Rankin scale, age, BMI or prevalence of hyperprolactinemia between patients with and without hypopituitarism.
  3. At T2, 36% continued to have hormonal disturbances.
  4. At T2, patients with hypopituitarism at 12mo were older than those without (41.7±14.6 versus 36.9±14.0yr; p=0.01), but no differences were found in the initial GCS, modified Rankin scale, BMI, or prevalence of hyperprolactinemia.
  5. Testing at both T1 and T2 indicated that greater diffuse axonal injury, age, and basal skull fracture were associated with a higher risk of pituitary impairment in at least one of the axes (p<0.05).

Aimaretti et al. (2005)
Italy
Observational
N=102

Population: ABI; TBI Group (n=70): Mean Age=39.31yr; Gender: Male=50, Female=20; Severity of Injury: Mild=33, Moderate=22, Severe=15; SAH Group (n=32): Mean Age=51.9yr; Gender: Male=12, Female=20.
Intervention: Pituitary function was assessed 3 and 12mo post injury.
Outcome Measure: Hormone levels (cortisol, fT4, TSH, FSH, LH, GH, IGF-1, PRL).

 

TBI Group (n=70):

  1. At 3mo, hypopituitarism (H) was seen in 32.8% of patients with TBI. Panhypopituitarism (PH), multiple (MH), and isolated hypopituitarism had been noted in 5.7%, 5.7%, and 21.4%, respectively.
  2. At 12mo, H, PH, MH, and IH were seen in 22.7%, 5.7%, 4.2%, & 12.8%, respectively.
  3. The occurrence of H was not associated with GCS (OR=1.08).

SAH Group (n=32):

  1. At 3mo, H was noted in 46.8% of patients with SAH. MH and IH had been demonstrated in 6.2 and 40.6%, respectively.
  2. At 12mo, H, MH, and IH were seen in 37.5%, 6.2%, and 31.3%, respectively.
  3. The occurrence of H was not associated with the Fisher’s scale (OR=0.95).
  4. The frequency of H was comparable between TBI and SAH patients both at 3 and 12mo testing.

Agha et al. (2005)
Ireland
Observational
Ninitial=50, Nfinal=48

Population: TBI; Mean Age=37yr; Gender: Male=38, Female=12; Median Time Post Injury=12d; Injury Severity: Moderate=18, Severe=32.
Intervention: Anterior pituitary function was assessed at acute phase, and at 6 and 12mo post injury.
Outcome Measure: Hormone levels.

  1. Anterior pituitary abnormalities occurred soon after injury and were transient; most patients recovered within 6mo.

Agha et al. (2004)
Ireland
Observational
N=102

Population: TBI; Median Age=28yr; Gender: Male=85, Female=17; Median Time Post Injury=17mo; Median GCS Score=8.
Intervention: Anterior pituitary function was assessed at least 6mo post injury (median 17mo).
Outcome Measure: Hormone levels (GH, ACTH, FSH, LH, fT4, TSH, PRL, IGF-I, cortisol, testosterone or estradiol).

  1. At least one anterior pituitary hormone deficiency was found in 29 (28.4%) of 102 patients studied.
  2. Of these 29, 23 patients had isolated hormone deficiencies (gonadotropic deficiency=9, ACTH deficiency=8, GH deficiency=6), while 6 had multiple hormone deficiencies.

     

Bondanelli et al. (2004)
Italy
Observational
N=50

Population: TBI; Mean Age=37.6yr; Gender: Male=40, Female=10; Time Post Injury Range=12–64mo; Injury Severity: Mild=16, Moderate=7, Severe=27.
Intervention: Anterior pituitary function was assessed at least once within 5yr of injury. 
Outcome Measure: Hormone levels (IGF-1, TSH, fT4, ACTH, LH, FSH, PRL, cortisol, testosterone or estradiol).

  1. Anterior pituitary dysfunction was observed in 27 (54%) patients: 14 (51.8%) had partial or severe GHD, hypogonadism in 7 (25.9%), hypothyroidism in 5 (18.5%), hyperprolactinemia in 4 (14.8%), and hypoprolactinemia in 4 (14.8%); 6 (22.2%) patients had multiple abnormalities.
  2. GCS was significantly lower in those with pituitary dysfunctions than those without (8.3±0.5 versus 10.2±0.6; p<0.02). 

     

Lieberman et al. (2001)
USA
Observational
N=87

 

Population: ABI=17, TBI=70; TBI Group (n=70): Mean Age=31.5yr; Gender: Male=46, Female=24; Mean Time Post Injury=49mo; Injury Severity: Severe=32, Mild/Moderate=6, Unknown=49.
Intervention: Initial anterior pituitary assessments were followed-up with appropriate dynamic tests (e.g. GnRH stimulation, TRH stimulation, or GH stimulation with L-dopa) if patients showed abnormalities.
Outcome Measure: Hormone levels (GH, TSH, fT4, PRL, IGF-I, ACTH, cortisol, testosterone, menstrual history).

 

  1. 36 (51.4%) of 70 patients had a single abnormal axis (ACTH=26, TH=8, GH=2), and 12 (17.1%) had dual abnormalities.
  2. Severe injury was not related to the number of abnormal pituitary axes.

     

Kelly et al. (2000)
USA
Observational
N=22

Population: ABI (TBI=20, SAH=2); Mean Age=28yr; Gender: Male=18; Female=4; Median Time Post Injury=26mo; Median GCS=7.
Intervention: Anterior pituitary function was assessed using dynamic pituitary testing. 
Outcome Measures: Hormone levels (TSH, fT4, LH, FSH, GH, PRL, IGF-1, cortisol, testosterone or estradiol), Glasgow Outcome Scale (GOS).

  1. 8 (36.4%) patients with head injury had a subnormal response in at least one hormonal axis, including 5 (22.7%) with two axes deemed deficient.
  2. Of individuals with moderate or severe head injury, 8 (42.1%) of 19 displayed an abnormal response in at least one hormonal axis; no patient with mild brain injury had dysfunction.
  3. Good recovery (GOS=5) was achieved in only 1 (12.5%) of 8 patients with anterior hormone insufficiency compared with 9 (64.3%) of 14 patients without hormone insufficiency (p<0.05).