Thyroid-Stimulating Hormone Deficiency

Author/Year/
Country/Study Design/N

Methods

Outcomes

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

Population: ABI; TBI Group (n=30): Mean Age=39yr; Gender: Male=257, Female=83; SAH Group (n=169): Mean Age=49yr; Gender: Male=67, Female=102.
Intervention: Basal thyrotropic hormone levels were assessed at median 7wk post injury. Normal range: fT4 0.93–1.7 ng/dL.
Outcome Measure: Level of fT4.

  1. Low fT4 was detected in 30 patients (5.9%), while elevated fT4 levels were detected in 37 patients (7.3%).

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

Population: TBI; Mean Age=35.7yr; Gender: Male=30, Female=15; Median GCS=6.
Intervention: Changes in thyrotropic hormone levels were assessed 1-4d post TBI. Clinical outcomes were obtained at 3mo post injury. Normal ranges: fT4 12–22 pmol/L, fT3 3.1–6.8pmol/L, TSH 0.27–4.2 mIU/L.
Outcome Measure: Levels of TSH, fT3 and fT4, Glasgow Outcome Scale (GOS).

 

  1. Mean serum fT4 and fT3 decreased significantly from 1d to 4d (p<0.0001 for both), while mean serum TSH increased significantly during the same period (p<0.03).
  2. No significant differences in fT4 levels between the deceased and alive patients or in the unfavourable (i.e., GOS 1-3) versus favourable (i.e., GOS 4-5) outcome groups at 3mo.
  3. fT3 levels were significantly lower in those with unfavorable outcome at 3mo than those with favorable outcome (p<0.02).
  4. TSH levels were significantly lower in patients deceased at 3mo compared to survivors, both at 1d (p<0.02) and 4d (p<0.03).

     

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: A consecutive population of patients with TBI screened for hypothalamic-pituitary dysfunction in relation to gains in FIM score. Normal range: fT4 0.77-61 ng/mL.
Outcome Measure: Level of fT4

  1. fT4 deficiencies were found in 46% of the cases.
  2. No significant difference was found between those with low levels of fT4 and those with normal levels (p=0.8).

     

Zetterling et al. (2013)
Sweden
Observational
N=20
Population: SAH; Mean Age=58.4yr; Gender: Male=7, Female=13; Severity: Mild=6, Moderate=10, Severe=4.
Intervention: Participants were recruited within 1d of injury and assessed daily for 7d, with a follow-up after 6mo.
Outcome Measures: Levels of TSH, T3, and T4.
  1. TSH levels significantly increased (p=0.03) while levels significantly decreased for T3 (p=0.005) and T4 (p=0.02) in all participants 0-7d.
  2. There was a significant positive correlation between 7d mean levels of T3 and Glasgow Outcome Scale scores at 6mo (r=0.45, p<0.05).

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: Thyrotropic functions were assessed post injury to assess the frequency of TD. Blood samples of fT4 and TSH were obtained. TD definition: low fT4 level with normal or low TSH.
Outcome Measures: Incidence of TD. 

  1. 42 (76.4%) patients presented with at least one pituitary deficiency; TD was noted in 12 cases (21.8%).
  2. There was a trend toward an association between TD and poor performance on the digit span forward test, and digit span backward test, but these associations were not significant (p>0.05).

     

Kleindienst et al. (2009)
Germany
Observational
N=71

Population: TBI; Mean Age=53yr; Gender: Male=57, Females=14; Mean GCS=9.6.
Intervention: Thyrotropic functions assessed via basal TSH, fT4 and tT3 measurements on admission, days 3 and 7, and at follow-up (24–36mo post injury). Normal ranges: TSH >0.45 µU/mL, fT4 >0.77 ng/dL, and tT3 >0.8 ng/mL.
Outcome Measure: Incidence of TD.

  1. TD was noted in 12 (17%) on admission, in 17 (24%) on day 3, in 6 (8%) on day 7, and in none at follow-up.
  2. Severe injury was associated with low TSH levels on day 3 (p=0.036) and low fT4 levels on day 7 (p=0.008).
  3. Patients who received ventilation for >24hr had significantly reduced tT3 levels on days 0, 3, and 7 (p=0.043, p<0.001, p=0.002), reduced fT4 levels on days 3 and 7 (both p<0.001), and reduced TSH levels on day 3 (p<0.001).

     

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

Population: TBI; Mean Age=37.2yr; Gender: Males=56, Female=16; Severity of Injury: Moderate=10, Severe=62; Mean Time Post Injury=240.5d; Injury Severity: Moderate=10, Severe=62.
Intervention: Thyrotropic function was assessed at least once between 6 and 12mo post TBI to assess the frequency of hypothyroidism. Blood samples of TSH and fT4 were obtained. Hypothyroidism definition: basal serum fT4 <10.3 pmol/L (<0.8 ng/dL) in the presence of normal or ‘low’ TSH levels (0.4-4.2 mIU/L).
Outcome Measure: Incidence of hypothyroidism. 

  1. Hypothyroidism was noted in 3 patients, who showed low blood fT4 levels with low or normal TSH concentrations.

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

Population: TBI; Median Age=41yr; Gender: Males=78, Females=26; Mean Time Post Injury=13mo; Injury Severity: Mild=44, Moderate=20, Severe=40.
Intervention: Thyrotropic functions assessed post TBI via baseline measurements of TSH and fT4. TD definition: serum fT4 <12 pmol/L with inappropriately ‘low’ TSH.
Outcome Measures: Incidence of TD. 

  1. TD was confirmed in 2 patients.

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

Population: TBI; Mean Age=38.8yr; Gender: Male=78, Female=26; Severity of Injury: Mild=49, Moderate=24, Severe=31; Time Post Injury <24hr; Injury Severity: Mild=49, Moderate=24, Severe=31.
Intervention: Blood samples of TSH, fT4 and fT3 from patients were obtained within 24hr of trauma to assess post-injury thyrotropic functions. TD definition: serum fT4 <8 pg/L without inappropriate elevation in serum TSH.
Outcome Measure: Incidence of TD.

  1. No significant differences were noted in mean TSH levels among patients with mild, moderate, and severe TBI (0.9±0.8 versus 0.99±1.3 versus 1.3±1.2 mIU/mL).
  2. 42 of 97 patients (43.3%) had low T3 syndrome (i.e., normal fT4, normal TSH but low fT3 levels).
  3. No differences were found in mean fT3 and TSH levels between deceased (n=20) and surviving (n=84) patients.

     

 

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

 

*Schneider et al. (2008)

Population: TBI; Mean Age=36yr; Gender: Males=52, Female=26; Mean GCS Score=7.4.
Intervention: Thyrotropic function assessed 3 mo±2wk (T1) and 12 mo±4wk (T2) post injury. Basal fasting measurements of fT4, TSH, and tT3 were obtained. Hypothyroidism definition: fT4 <0.93 ng/dL, and TSH not elevated beyond the standard range (0.27-4.4 µIU/mL).
Outcome Measure: Incidence of hypothyroidism.

*Follow-up to Schneider et al. 2006

  1. At T1, Hypothyroidism was seen in 6 patients.
  2. At T2, only 2 patients had persistent hypothyroidism.
  3. After 12 mo, impairment of TSH was positively associated with age and basal skull fracture, and negatively associated with cranial vault fracture.

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: Thyrotropic function was assessed at acute phase, and at 6 and 12mo post injury via basal blood collections of TSH and fT4. TD definition: low serum fT4 with inappropriately low serum TSH concentration.
Outcome Measure: Incidence of TD.

  1. 1 patient had TD but recovered by 6mo; a new patient developed TD at 6mo, which persisted into 12mo follow-up.

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

Population: ABI; TBI Group (n=70): Mean Age=39.31yr; Gender: Male=50, Female=20; Injury Severity: Mild=33, Moderate=22, Severe=15; SAH Group (n=32): Mean Age=51.9yr; Gender: Male=12, Female=20.
Intervention: Pituitary function tested was 3 and 12mo post injury. Hypothyroidism definition: fT4 <8 ng/L with normal or ‘low’ TSH.
Outcome Measure: Incidence of hypothyroidism.

TBI Group (n=70):

1. Percentage of patients with hypothyroidism stayed the same from 3 to 12mo (5.7%).

SAH Group (n=32):

2. Percentage of patients with hypothyroidism stayed the same from 3 to 12mo (9.3%).

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

Population: TBI; Mean Age=37.6yr; Gender: Male=40, Female=10; Injury Severity: Mild=16, Moderate=7, Severe=27.
Intervention: Thyrotropic functions were assessed once between 12 and 64 mo post TBI to assess the frequency of hypothyroidism. Basal blood samples of TSH and fT4 were obtained. Hypothyroidism definition: basal TSH <0.4-4.2 mIU/L, or basal fT4 <10.3–19.4 pmol/L. 
Outcome Measure: Incidence of hypothyroidism.

  1. 5 (10%) of 50 patients had low blood fT4 concentrations with low or normal TSH concentrations (hypothyroidism).

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

Population: TBI; Median Age=28yr; Gender: Male=85, Female=17; Median GCS Score=8; Median Time Post Injury=17 mo. 
Intervention: Thyrotropic function was assessed at least 6mo post injury. Baseline serum samples of fT4 and TSH were obtained. TD definition: low serum fT4 level without appropriate elevation in serum TSH.
Outcome Measure: Incidence of TD.

 

  1. TD was present in 1 patient.

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

 

Population: TBI; Median Age=28yr; Gender: Male=85, Female=17; Median GCS Score=8; Median Time Post Injury=17 mo. 
Intervention: Thyrotropic function was assessed at least 6mo post injury. Baseline serum samples of fT4 and TSH were obtained. TD definition: low serum fT4 level without appropriate elevation in serum TSH.
Outcome Measure: Incidence of TD.

  1. In 2 of 69 (2.9%) patients, fT4 and TSH levels were well below the lower limit of the normal range; 6 patients had low fT4 with normal TSH; 7 had normal fT4 with low TSH; 15 (21.7%) had at least one abnormality in the thyroid axis.
  2. 27 received TRH stimulation; 4 (14.8%) showed abnormal increase in TSH.

     

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

Population: Head Injury; Mean Age=28yr; Gender: Male=18; Female=4; Median Time Post Injury=26mo.
Intervention: Thyrotropic function was assessed at median 26mo post injury via TRH stimulation test. Normal range: TSH 0.4-4.2 mU/L.
Outcome Measures: Incidence of TD.

  1. 1 patient (4.5%) displayed an insufficient response to the TRH stimulation test.
  2. Despite therapy, which lasted approximately 2mo, the patient did not improve in thyrotropic function.

     

Cernak et al. (1999)
Yugoslavia
Observational
N=31

Population: TBI; Age Range=18-38yr; Gender: Male=31, Female=0; Injury Severity: Mild=8, Severe=10, Other=13.
Intervention: Thyrotropic function was assessed in patients at admission, and at 1, 2, 3, 5 and 7d after injury. Normal reference values for were obtained from 10 healthy age-matched male controls, and were defined as 1.220±0.090 IU/L for TSH, 1.6±0.06 nmol/L for T3, and 95.5±3.65 nmol/L for T4.
Outcome Measure: Levels of TSH, T3, and T4.

  1. Relative to control, TSH levels were elevated for the first 3d of injury in those who had sustained a mild TBI (p<0.05), whereas TSH levels in those with severe injuries remained low for 7d following injury (p<0.01).
  2. T3 levels remained low in those with a severe injuries for the entire duration of the study (p<0.05 relative to control).
  3. T4 levels appeared to be unchanged regardless of the severity of injury.