Review | Thyroid Updates 2025 | Paediatrics | Critical Care 

Beyond the Bruise: The Quiet Threat of Central Hypothyroidism After Traumatic Brain Injury in Paediatric Patients

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This article is a compilation of recent studies published in a number of peer-reviewed publications. It is not intended to represent original research, nor is it intended to replace the original research.  Access the full Disclaimer Information.

 

Traumatic brain injury (TBI) can cause structural damage to the pituitary stalk and anterior pituitary gland, resulting in anterior pituitary dysfunction (APD). First noted in 1918, APD was initially considered rare, but subsequent studies—primarily in adults—have shown it to be more common than previously thought. However, research in children and adolescents remains limited, which is of concern given their developmental vulnerability.

One particular consequence of APD is central hypothyroidism (CH), which remains under-recognised in paediatric populations following TBI. A key challenge is that the clinical features of CH often mimic the neurological sequelae of brain injury, making diagnosis difficult and potentially delaying treatment. This is troubling, as early identification and management of CH is critical for supporting recovery, growth, and neurodevelopment.

Despite the central role of the hypothalamic–pituitary axis in child and adolescent development, high-quality data on post-TBI CH in this population is lacking.

Based on these concerns, the primary aim of this study was to evaluate the rate of CH and characterise the clinical presentation and laboratory findings associated with this complication in a longitudinal cohort of children and adolescents with TBI. A secondary aim was to compare hormone levels in this cohort with those in patients with a history of TBI but without APD.

Study Methodology

Researchers Graca & Aguiar et al. analysed 31 paediatric patients with a history of TBI, all of whom were followed for at least one year.

Evaluations were conducted at hospital admission and every three months thereafter. Clinical assessments included neurological examination, brain CT scans, and comprehensive hormone profiling. 

Central hypothyroidism (CH) was diagnosed based on clinical presentation, abnormal laboratory findings, and the patient’s response to a therapeutic trial of levothyroxine.


Study Findings

Of the 48 paediatric patients assessed at baseline, 17 were followed for less than one year and were, therefore, excluded from further analysis. The remaining 31 patients—who had a mean age of 14.3 years at the time of traumatic brain injury (TBI)—underwent comprehensive endocrine evaluations over at least a 12-month period.

The folowing were recorded:

Hormonal Abnormalities Post-TBI

Among 31 patients:
 

5 (16.1%) developed chronic hypothyroidism (CH)

7 showed abnormalities in the growth hormone (GH)–insulin-like growth factor 1 (IGF-1) axis

1 developed isolated central adrenal insufficiency (CAI)

18 had no evidence of anterior pituitary dysfunction (non-APD group)

Thyroid Function Patterns

In the CH group:

Four of the five patients had serum-free T4 (ft4) values in the lowest quartile (0.80–1.10 ng/dL) at the 3-month follow-up, and all five had low ft4 values by the 12-month mark.

Three patients experienced a >20% drop in fT4 levels relative to baseline during the first year.

Two patients recorded persistently low fT4 values (<0.8 ng/dL) at 17 months and 9.2 years post-TBI, respectively.
 

Interestingly, five of the 18 patients in the non-APD group also had fT4 values in the lowest quartile at follow-up (n=2 at 3 months, n=3 at 12 months), but none exhibited clinical symptoms of hypothyroidism.

GH–IGF-1 Axis Findings

GH function was assessed using a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) stimulation:
 

Three CH patients and two non-APD patients showed a robust GH peak response (>30 ng/mL).

Despite these peaks, three patients in the CH group had IGF-1 levels below −2 standard deviation scores (SDS) before levothyroxine treatment, indicating impaired GH axis activity.

The remaining two CH patients had IGF-1 values of −1.49 SDS and −0.69 SDS, still below average and suggestive of a trend toward GH suppression.

These findings suggest a potential interplay between thyroid dysfunction and GH–IGF-1 axis impairment in the post-TBI setting.


Response to Levothyroxine Therapy

All CH patients began a therapeutic trial of levothyroxine between 13 and 35 months post-injury:
 

Clinical symptoms were resolved in all five patients.

Median fT4 levels rose from 0.92 ng/dL pre-treatment to 1.47 ng/dL on therapy.

Treatment interruptions—due to patient or family decisions—led to temporary declines in fT4 (median 1.02 ng/dL), with recovery to 1.37 ng/dL once therapy was resumed.

The highest fT4 level during treatment was 1.77 ng/dL.

At the time of final follow-up, all five patients remained on levothyroxine, highlighting the sustained clinical benefit and the likely need for long-term thyroid hormone replacement in this group.


Discussion

Over a median follow-up of 6.5 years, CH was diagnosed in 16% of patients, a higher rate than reported in most studies (0–14.2%). Most significantly, these cases were only identified beyond the first year post-TBI, emphasising the importance of long-term follow-up.

This longer follow-up period of 12 months, coupled with the standardised monitoring in relation to previous studies and the use of a therapeutic trial with levothyroxine, which was rarely applied in earlier studies, may have resulted in the higher incidence evidenced here.

Clinical symptoms, low or declining fT4, and low IGF-1 levels supported the CH diagnosis. Levothyroxine treatment in these patients resulted in significant biochemical and clinical improvements, which were reversed when the treatment was withheld, confirming CH. Interestingly, despite CH usually being associated with blunted GH response, the CH group demonstrated higher GH peaks, possibly due to decreased IGF-1 feedback or neurosecretory dysfunction related to the TBI.

The study found no significant differences in clinical severity or imaging findings between the CH and non-APD groups.  However, the synchrony between IGF-1 and ft4 and the asynchrony between IGF-1 and GH levels point to a nonclassical, potentially overlooked form of post-TBI CH.


In Conclusion

The researchers concluded that their study demonstrated that a longer follow-up period, careful consideration of clinical signs and symptoms, use of nontraditional laboratory markers, and a diagnostic trial with levothyroxine uncovered a significantly higher incidence of central hypothyroidism (CH) following traumatic brain injury (TBI) in children and adolescents than previously reported in the literature. 

These findings suggest that post-TBI CH may be substantially underdiagnosed without a comprehensive and proactive evaluation strategy.

 

 

Original Study

Graca, G. M., Aguiar, L. R., & De Lacerda, L. (2025). New diagnostic approach to central hypothyroidism after traumatic brain injury in children and adolescents. European thyroid journal, 14(1), e240184.  https://etj.bioscientifica.com/view/journals/etj/14/1/ETJ-24-0184.xml

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