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Cited by 28Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchPituitary Gland Disorders and Treatments

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Epidemiology of Pediatric Traumatic Brain Injury and Hypothalamic-Pituitary Disorders in Arizona

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Abstract

Traumatic brain injury (TBI) in children can result in long-lasting social, cognitive, and neurological impairments. In adults, TBI can lead to endocrinopathies (endocrine system disorders), but this is infrequently reported in children. Untreated endocrinopathies can elevate risks of subsequent health issues, such that early detection in pediatric TBI survivors can initiate clinical interventions. To understand the risk of endocrinopathies following pediatric TBI, we identified patients who had experienced a TBI and subsequently developed a new-onset hypothalamic regulated endocrinopathy (n=498). We hypothesized that pediatric patients who were diagnosed with a TBI were at higher risk of being diagnosed with a central endocrinopathy than those without a prior diagnosis of TBI. In our epidemiological assessment, we identified pediatric patients enrolled in the Arizona Health Care Cost Containment System (AHCCCS) from 2008-2014 who were diagnosed with one of 330 TBI International Classification of Diseases (ICD)-9 codes and subsequently diagnosed with one of 14 central endocrinopathy ICD-9 codes. Additionally, the ICD-9 code data from over 600,000 Arizona pediatric patients afforded an estimate of the incidence, prevalence, relative risk, odds ratio, and number needed to harm, regarding the development of a central endocrinopathy after sustaining a TBI in Arizona Medicaid pediatric patients. Children with a TBI diagnosis had 3.22 times the risk of a subsequent central endocrine diagnosis compared with the general population (±0.28). Pediatric AHCCCS patients with a central endocrine diagnosis had 3.2-fold higher odds of a history of a TBI diagnosis than those without an endocrine diagnosis (±0.29). Furthermore, the number of patients with a TBI diagnosis for one patient to receive a diagnosis of a central endocrine diagnosis was 151.2 (±6.12). Female subjects were more likely to present with a central endocrine diagnosis after a TBI diagnosis compared to male subjects (64.1% vs 35.9%). These results are the first state-wide epidemiological study conducted to determine the risk of developing a hypothalamic-pituitary disorder after a TBI in the pediatric population. Our results contribute to a body of knowledge demonstrating a TBI etiology for idiopathic endocrine disorders, and thus advise physicians with regard to TBI follow-up care that includes preventive screening for endocrine disorders.

Overview

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TL;DR

In Arizona Medicaid pediatric patients from 2008–2014, children with a TBI diagnosis had about 3.2 times the risk of a subsequent central endocrine diagnosis compared with those without TBI, with a number needed to harm of about 151. Female patients accounted for 64.1% of TBI-plus-endocrine cases and showed higher prevalence and earlier onset than male patients.

Key findings

  • Among 498 unique patients with TBI and a subsequent central endocrine diagnosis, overall prevalence was 0.103 (±0.003 at 90% CI), incidence was 0.0014 (±0.0002), relative risk was 3.22 (±0.29), odds ratio was 3.24 (±0.29), and number needed to harm was 151.19 (±6.12).
  • The highest prevalence of endocrine diagnosis after TBI occurred at ages 7–11 years. Female patients (n = 319) outnumbered male patients (n = 179); female prevalence was 0.758 versus male prevalence 0.278, and female subjects were 64.06% versus male 35.94% of TBI-plus-endocrine cases.
  • The predominant TBI ICD-9 code was 959.01 (head injury, unspecified), comprising ~64% of subjects by text (66.4% in Table 4). The predominant endocrine code was 259.10 (precocious sexual development and puberty, not elsewhere classified), comprising ~59% of subjects (59.4% in Table 4), followed by 253.30 (pituitary dwarfism) at 9% by text (9.5% in Table 4).
  • A total of 107,458 children were diagnosed with a TBI before or at age 18; AHCCCS provided care for an average of 643,212 (±19,097 at 90% CI) pediatric patients per year.

Methods

  • Retrospective epidemiological analysis of de-identified Arizona Health Care Cost Containment System (AHCCCS) Medicaid records from 2008–2014. Patients were ≤18 years old, continuously enrolled with no more than a 30-day gap in coverage per year, and had TBI diagnoses from 330 ICD-9 codes followed by central endocrine diagnoses from 14 ICD-9 codes; endocrine diagnosis prior to TBI was excluded.
  • Patients were grouped into four cohorts: TBI+/Endo+, TBI+/Endo−, TBI−/Endo+, and TBI−/Endo−. Prevalence, incidence, relative risk, odds ratio, attributable risk, and number needed to harm were calculated and stratified by age and male/female sex using Python 3.7.3.
  • The study protocol was approved by the Phoenix Children's Hospital Institutional Review Board (IRB 15-021) and deferred by the University of Arizona and Arizona State University; written informed consent was provided by participants' legal guardian/next of kin.

Limitations

  • The authors state that the AHCCCS Medicaid sample represents a unique low-income population and may not generalize to the entire population; ICD-9 coding limitations, including the predominant unspecified head injury code 959.01, prevented meaningful analysis between TBI type/severity and endocrine disorder.
  • The authors state that the dataset lacked injury severity indicators and case details/imaging, so the relationship between mode of TBI and pituitary or hypothalamic damage could not be determined; patients over age 18 were excluded, so late-teen TBI followed by later endocrine disorder may have been missed, and TBI/endocrine symptoms may be underreported.
  • Evident from the text but not framed as limitations by the authors: the study is observational and cannot establish causality; sex was analyzed only as binary male/female entries; and the 18-year upper age limit creates an arbitrary ceiling effect on the data.

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Integrity signals

Registry

Crossref · 10.3389/fneur.2019.01410

Cites

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Figures

Figure 1 Pediatric patients with a traumatic brain injury (TBI) who were diagnosed with a hypothalamic-pituitary disorder showed the highest prevalence in ages 7–11. (A) Patients (n = 498) with a TBI and subsequent endocrine diagnosis were indexed by age. Here, we sorted all patients of our group of interest by age with patient index referring to the fraction of the total. The black line represents the age of each patient when they were diagnosed with a TBI, and the dot tracking along the x-axis from the line indicates the subsequent onset of their first endocrine diagnosis. (B) Prevalence of an endocrine diagnosis after a TBI stratified by age at the endocrine diagnosis. Here, prevalence was calculated as the number of TBI patients with an endocrine diagnosis divided by those TBI patients without an endocrine. Children aged 7–11 years had the highest prevalence of an endocrine disorder diagnosis after a TBI diagnosis compared to other age groups.
Figure 1 Pediatric patients with a traumatic brain injury (TBI) who were diagnosed with a hypothalamic-pituitary disorder showed the highest prevalence in ages 7–11. (A) Patients (n = 498) with a TBI and subsequent endocrine diagnosis were indexed by age. Here, we sorted all patients of our group of interest by age with patient index referring to the fraction of the total. The black line represents the age of each patient when they were diagnosed with a TBI, and the dot tracking along the x-axis from the line indicates the subsequent onset of their first endocrine diagnosis. (B) Prevalence of an endocrine diagnosis after a TBI stratified by age at the endocrine diagnosis. Here, prevalence was calculated as the number of TBI patients with an endocrine diagnosis divided by those TBI patients without an endocrine. Children aged 7–11 years had the highest prevalence of an endocrine disorder diagnosis after a TBI diagnosis compared to other age groups.CC BY · PubMed Central
Figure 2 Female subjects show a higher incidence, and an early age of onset, of hypothalamic-pituitary disorder following TBI compared to male subjects. (A) Male and female patients with a TBI diagnosis and subsequent endocrine diagnosis were indexed by age, as a fraction of the total number of subjects in each group. The lines represent male (n = 179; blue) and female (n = 319; red) age of each patient when they were diagnosed with a TBI, and the dots tracking along the x-axis from the line indicate male (blue) and female (red) age at the time of their first endocrine diagnosis. (B) Endocrine diagnosis incidence rates after TBI were calculated for male/female patients in blocks of 4-year age groups, with children older than 0 and ≤ 4 years old in the first block, followed by children >4 years old and ≤ 7.5 years old in the second block, etc. Female subjects diagnosed with a TBI (red line) were more likely to have a central endocrine diagnosis at an earlier age compared with male subjects diagnosed with a TBI (blue line). The overall incidence of endocrine dysfunction peaked between ages 7 and 11. This is driven by the higher overall incidence of post-TBI endocrine diagnoses in female patients, compared to male patients, whose incidence peaks between ages 11 and 15. Incidence rate was calculated as the number of new cases per year of endocrine diagnoses in TBI patients divided by the cumulative population of TBI patients. (C) Data stratified by male/female indicated female patients showed a shorter time gap between diagnosis of TBI and subsequent endocrine diagnosis compared with male subjects, but not necessarily reflect the onset of undiagnosed symptoms.
Figure 2 Female subjects show a higher incidence, and an early age of onset, of hypothalamic-pituitary disorder following TBI compared to male subjects. (A) Male and female patients with a TBI diagnosis and subsequent endocrine diagnosis were indexed by age, as a fraction of the total number of subjects in each group. The lines represent male (n = 179; blue) and female (n = 319; red) age of each patient when they were diagnosed with a TBI, and the dots tracking along the x-axis from the line indicate male (blue) and female (red) age at the time of their first endocrine diagnosis. (B) Endocrine diagnosis incidence rates after TBI were calculated for male/female patients in blocks of 4-year age groups, with children older than 0 and ≤ 4 years old in the first block, followed by children >4 years old and ≤ 7.5 years old in the second block, etc. Female subjects diagnosed with a TBI (red line) were more likely to have a central endocrine diagnosis at an earlier age compared with male subjects diagnosed with a TBI (blue line). The overall incidence of endocrine dysfunction peaked between ages 7 and 11. This is driven by the higher overall incidence of post-TBI endocrine diagnoses in female patients, compared to male patients, whose incidence peaks between ages 11 and 15. Incidence rate was calculated as the number of new cases per year of endocrine diagnoses in TBI patients divided by the cumulative population of TBI patients. (C) Data stratified by male/female indicated female patients showed a shorter time gap between diagnosis of TBI and subsequent endocrine diagnosis compared with male subjects, but not necessarily reflect the onset of undiagnosed symptoms.CC BY · PubMed Central

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Metadata

Authors
Ortiz, J. B., Sukhina, A., Balkan, B., Harootunian, G., Adelson, P. D., Lewis, K. S., Oatman, O., Subbian, V., Rowe, R. K., & Lifshitz, J.
Affiliations
  • Barrow Neurological Institute (US)
  • University of Arizona (US)
  • Arizona State University (US)
  • Phoenix Children's Hospital (US)
Corresponding author
Lifshitz, Jonathan
Venue
Frontiers in Neurology
Published
2020-01-22
Volume
10
Pages
1410-1410
ISSN
1664-2295 (ISSN-L)
OpenAlex
W3001464871
Cited by
28
References
54
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 9 · 2022: 2 · 2021: 4 · 2020: 3
FWCI
2.29
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Neurology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Foundation (1838745)
  • Science Foundation Arizona
  • Arizona State University
Topics
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
pediatric traumatic brain injury, hypothalamic-pituitary dysfunction, incidence and prevalence, Medicaid, sex differences, endocrine screening

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