Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood

Probably not a substantial claim: may not pass S3 (load-bearing).

The cohort's injuries were classified as 64 inflicted and 134 accidental.

“Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental.”

• Also stated in: § Results · plain

  “Sixty-four participants (32%) sustained inflicted and 134 (68%) accidental TBI.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

One female had possible mild central hypothyroidism initially, but her thyroid function normalized one month later.

“One female had possible mild central hypothyroidism on initial assessment, free T 4 of 10.6 pmol/liter (11-22 pmol/liter), free T 3 of 6.8 pmol/liter (3-10 pmol/liter), and TSH of 1.1 mU/liter (1.6 mU/liter).She was clinically well, and thyroid function normalized a month later”

May combine two claims.

Among those with peak GH below 5 μg/L, mean height SDS was 1.0 and mean BMI SDS was 2.8.

“Among subjects with GH under 5 g/liter (with apparent GH deficiency), mean height SDS was 1.0 Ϯ 1.2 and BMI SDS 2.8 Ϯ 0.8, whereas both IGF-I and IGFBP-3 were within the normal range for all subjects (Table 2).”

May combine two claims.

On repeat GH testing in five cases, all but one had a peak GH above 5 μg/L; the exception was likely affected by severe obesity.

“Repeat GH was more than 5 g/liter in all but one case, likely confounded by severe obesity (BMI SDS 4.2).”

May combine two claims.

No participant had hypernatremia or high serum osmolality.

“No participants had hypernatremia or high serum osmolality.”

May combine two claims.

Six participants (3%) had height below -2 SDS, and seven (4%) had height corrected for genetic potential below -2 SDS.

“There were six subjects (3%) who had height below Ϫ2 SDS at assessment and seven (4%) with height corrected for genetic potential below Ϫ2 SDS.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One female had a history of transient posttraumatic diabetes insipidus and had been asymptomatic off treatment for three years at assessment.

“One female had a history of transient posttraumatic diabetes insipidus and had been off treatment and asymptomatic for 3 yr at the time of assessment.”

May combine two claims.

In those with peak GH below 5 μg/L, IGF-I and IGFBP-3 values were normal, and their growth was normal.

“Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth.”

• Also stated in: § GH-IGF-I axis · boosted

  “whereas both IGF-I and IGFBP-3 were within the normal range for all subjects (Table 2).This group was followed in growth clinics for a period of 6 -36 months, and all demonstrated normal height velocity (Table 2).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Seven participants had mildly elevated prolactin levels that were not considered clinically significant.

“Seven subjects had mildly elevated prolactin levels (range 370 -750 mIU/liter) that were not considered clinically significant.”

Classified as probably not a substantial claim. May combine two claims. The quote only partly states this claim.

The study enrolled 198 children who had survived structural traumatic brain injury in early childhood; their mean age at injury was 1.7 years, and they were assessed a mean of 6.5 years later at a mean age of 8.3 years.

“We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 Ϯ 1.5 yr) 6.5 Ϯ 3.2 yr after injury.”

• Also stated in: § Results · plain

  “As a result, 198 participants were studied, whose baseline characteristics are outlined in Table 1.”

• Also stated in: § Endocrine evaluation · plain

  “Patients were assessed 6.5 Ϯ 3.2 yr after injury, at an age of 8.3 Ϯ 3.3 yr.”

May combine two claims.

On repeat Synacthen testing of all 17 with low cortisol, 13 reached the target peak cortisol, four remained low, one declined further testing, and three had appropriate metyrapone responses.

“All 17 underwent repeat Synacthen tests, 13 of which achieved peak cortisol above target.Four remained low, one declined additional assessment (peak cortisol 490 nmol/liter), and three responded appropriately to metyrapone.”

May combine two claims.

Mean basal cortisol was 270 nmol/L and mean peak cortisol was 695 nmol/L.

“Basal cortisol was 270 Ϯ 150 nmol/liter and peak 695 Ϯ 152 nmol/liter.”

May combine two claims.

The incidence of precocious puberty was one in 116 boys and one in 82 girls.

“The incidence of precocious puberty among boys was one in 116 and among girls was one in 82.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One case had a specific pituitary abnormality, posterior hemorrhage, associated with transient diabetes insipidus.

“Specific pituitary abnormality (posterior hemorrhage) was reported in only one case and was associated with transient diabetes insip-idus.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Most participants had severe to critical structural TBI, while just under half had moderate to severe injury by GCS.

“Most subjects had severe to critical structural TBI, although just under half had moderate to severe injury by GCS (Table 1).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Mean hospital stay was 10.5 days, and 40% were admitted to intensive care.

“Average length of stay in hospital was 10.5 d, and 40% were admitted to intensive care (Table 1).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A prior meta-analysis of adult TBI reported a long-term hypopituitarism rate of 27.5%, most often involving GH or gonadotropins.

“A recent meta-analysis of adult TBI data reported the rate of long-term hypopituitarism as 27.5%, most commonly affecting GH or gonadotropins (3).”

• cites [3]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Not all participants had reached the usual age of pubertal onset, so the prevalence estimate might be an underestimate.

“Nonetheless, not all subjects in our study had reached the normal age of pubertal onset, so that our prevalence data might also have been an underestimate.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Recruitment was the main challenge, largely because of difficulty obtaining current contact details.

“The major challenge for this study was recruitment, mostly due to difficulty in obtaining up-to-date case contact details.”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

From 770 identified TBI admissions, exclusions and nonparticipation resulted in 198 participants being studied.

“This study identified 770 TBI admissions of children under 5 yr of age.”

• Also stated in: § Results · plain

  “As a result, 198 participants were studied, whose baseline characteristics are outlined in Table 1.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study received hospital and regional ethics approval, and guardians gave written informed consent.

“This study was approved by the hospital (Auckland District Health Board) and regional (Northern X) ethics committees.”

• Also stated in: § Starship · plain

  “Written informed consent was obtained from guardians of all participants.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Inflicted brain injuries are usually repeated and severe and occur in very young infants.

“Inflicted brain injuries are typically repeated and severe and affect very young infants, yet no hypopituitarism was found.”

Classified as probably not a substantial claim.

Hormone values were compared with reference ranges adjusted for age, sex, and where appropriate pubertal stage.

“Baseline hormone values were compared with age-, sex-, and (where appropriate) pubertal stage-adjusted normal reference ranges provided by Auckland Healthcare Laboratory Services.”

Classified as probably not a substantial claim.

GH deficiency was diagnosed by combining stimulated GH peak, IGF-I, IGFBP-3, and growth parameters.

“The diagnosis of GH deficiency was based on the integrated assessment of stimulated GH peak, IGF-I, IGFBP-3, and growth parameters.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Endocrine assessment was complete in 191 participants; four declined GH stimulation tests, one also declined Synacthen testing, and thyroid function was unavailable in three.

“Endocrine assessment was complete in 191; four participants declined GH stimulation tests, and one additionally declined the Synacthen test.Thyroid function was not available in three cases.”

Classified as probably not a substantial claim.

ACTH deficiency was diagnosed only after consistently subnormal results, using repeat low-dose Synacthen testing and, if needed, a metyrapone test.

“The diagnosis of ACTH deficiency was based on consistently subnormal results.Participants with peak stimulated cortisol below 500 nmol/liter underwent a second low-dose Synacthen test, and those with a second subnormal response underwent a short metyrapone test”

Probably not a substantial claim: may not pass S3 (load-bearing).

The proposed mechanism for traumatic hypopituitarism is vascular.

“The mechanism of traumatic hypopituitarism is proposed to be vascular.”

• cites [13]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The findings may not apply to adolescents, whose physical characteristics and injury types are more like those of adults.

“Note that these findings may not be applicable to adolescents, whose physical characteristics and types of injury more closely resemble those seen in adults.”

May combine two claims.

Inflicted injuries may result from shaking, impact, or both, and these mechanisms can produce the same brain pathology.

“Inflicted injuries can be caused by shaking or impact (or a combination of both), and either mechanism can produce identical pathological changes in the brain (14).”

• cites [14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Structural TBI is likely a better way than GCS to identify significant head injury and predict pituitary damage in young children.

“Structural TBI is likely to be a more robust way to define significant head injury, and therefore predict pituitary damage, in young children.”

May combine two claims.

GH tests are poorly reproducible, and repeated tests in the same individual give highly variable results.

“In addition, GH tests are poorly reproducible; individuals who undergo repeated tests have highly variable results (34).”

• cites [34]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Growth velocity was monitored for at least six months in participants whose peak GH was below 5 μg/L.

“Growth velocity was monitored over a minimum of 6 months among participants with peak stimulated GH below 5 g/liter”

May combine two claims.

The population prevalence of precocious puberty is not well described, and the reference data came from the Danish national registry.

“The population prevalence of precocious puberty is not well described, and our reference data were derived from the Danish national registry (26).”

• cites [26]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The mechanisms of inflicted TBI and infant head and neck anatomy may make infants especially susceptible to pituitary injury.

“The mechanisms by which inflicted TBI is produced, and the anatomy of the infant head and neck, may make infants particularly vulnerable to pituitary injury (14).”

• cites [14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The association between GCS-defined TBI severity and hypopituitarism has been weak, possibly because GCS is an indirect measure of pituitary damage.

“The relationship between TBI severity as defined by GCS and hypopituitarism has been weak and may reflect the indirect nature of GCS as an assessment tool for pituitary damage.”

May combine two claims.

Among contacted families, 75% accepted participation, and there was probable selection bias toward children with chronic disability.

“Overall, the rate of acceptance among those contacted was high (75%), with probable selection bias toward children with chronic disability, who would be expected to be at greater risk of hypopituitarism.”

Classified as probably not a substantial claim. May combine two claims.

Screening for pituitary dysfunction after moderate to severe TBI has been recommended for adults and extended to children.

“Routine pituitary assessment after moderate to severe TBI has been recommended for adult populations (11) and extrapolated to children as well (12).”

• cites [11]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [12]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Those prior pediatric TBI studies were small, with fewer than 50 participants, and used nonstandardized methods to assess and diagnose pituitary function.

“All have been small studies (n Ͻ 50) and used nonstandardized methods to assess and diagnose pituitary function.”

• cites [4]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [5]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [6]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [7]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [8]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [9]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [10]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The Glasgow Coma Scale is commonly used to grade TBI severity, but presentation interval, prehospital care, and limited interobserver reliability can affect scores.

“The Glasgow Coma Scale (GCS) is widely used to define severity (15), although a variety of factors such as interval to hospital presentation, prehospital interventions, and limited interobserver reliability can affect scores (16,17).”

• cites [15]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [16]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [17]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Some participants may have already recovered from transient hormone deficiency, but the importance of this is unclear.

“It is possible that some of our subjects had already recovered from transient hormone deficiency, but the significance of this would be unclear.”

May combine two claims.

Stimulated GH levels are inversely related to BMI in childhood, and low GH levels suggesting deficiency are especially common in obese children.

“Stimulated GH levels are inversely associated with BMI in childhood (33), and misleadingly low GH levels (suggestive of deficiency) are especially common in obese children.”

• cites [33]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

The timing of assessments varied among participants.

“Another potential limitation was the variable timing of assessments.”

May combine two claims.

Scoring preverbal children is harder, and a single score may be less meaningful after the repeated injuries often seen in inflicted TBI.

“Scoring preverbal children presents further difficulty (18), and a single score may be less meaningful after the repeated injury commonly seen in inflicted TBI (19).”

• cites [18]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [19]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.