Pituitary dysfunction after traumatic brain injury in children: is there a need for ongoing endocrine assessment?

BACKGROUND: Hypopituitarism has been widely described in adults after traumatic brain injury (TBI); however, the available data in paediatric populations are scarce. Here, we report the results of a prospective, long-term study in children, adolescents and young adults. STUDY GROUP: Thirty-seven children (age, 2 months to 19·9 years) of 51 eligible patients were followed for 1 year. Clinical and baseline endocrine variables were assessed in all 3 and 12 months after TBI; children ≥ 6 years underwent two stimulation tests (glucagon stimulation and megatest). RESULTS: In the group ≥6 years, 11 of 23 patients (47·8%) had a subnormal GH peak 3 months after TBI that persisted in 8 of 23 patients (34%) after 1 year. The GH response showed no correlation with injury severity (GCS, Marshall classification). Growth velocity was normal in all patients, except for one. Body mass index (BMI) SDS increased significantly in the group with low GH response. A suboptimal cortisol was observed in 10 of 23 subjects, which normalized in all but three, 1 year thereafter. All patients but one showed a pubertal response to GnRH testing. No clinical or hormonal abnormalities were detectable in children <6 years. CONCLUSION: Our results recommend to prospectively follow children after TBI: firstly, because the impairment of pituitary function cannot be predicted, and secondly, to avoid the potential consequences of pituitary dysfunction. Prospective clinical trials are needed before recommending a systematic screening after TBI and/or GH therapy either in postpubertal children or in prepubertal children who grow normally.

Low-birth weight children develop lower sex hormone binding globulin and higher dehydroepiandrosterone sulfate levels and aggravate their visceral adiposity and hypoadiponectinemia between six and eight years of age.

BACKGROUND: Most children born small for gestational age (SGA) normalize their body size by late infancy. Between 2 and 6 yr, such SGA children develop higher circulating levels of insulin, lower levels of adiponectin, and more visceral fat than appropriate-for-gestational-age (AGA) controls, even in the absence of overweight. Here we report on their further course between 6 and 8 yr. STUDY DESIGN AND POPULATION: Longitudinal study over 2 yr comparing data from 32 AGA vs. 32 SGA children, matched for gender, height, weight, and body mass index at the age of 6 yr. MAIN OUTCOMES: Fasting insulin, dehydroepiandrosterone sulfate (DHEAS), SHBG, high-molecular-weight (HMW) adiponectin, leptin, IGF-I; body composition by absorptiometry; and abdominal fat partitioning by magnetic resonance imaging. RESULTS: Between 6 and 8 yr, novel AGA-vs.-SGA divergences emerged (higher DHEAS and lower SHBG in SGA; P < 0.001), and some earlier divergences widened further (HMW adiponectin, visceral fat; P < 0.001), whereas others stabilized (fasting insulin, IGF-I). At age 8 yr, the most discerning features of SGA children were a high ratio of visceral over sc fat in the abdominal region (69% of SGA children), HMW hypoadiponectinemia (41%), fasting hyperinsulinemia (34%), and elevated circulating IGF-I levels (31%). CONCLUSION: SGA children with spontaneous catch-up growth develop relatively high DHEAS and low SHBG levels and become more often HMW hypoadiponectinemic and viscerally adipose between 6 and 8 yr of age.

Visceral adiposity without overweight in children born small for gestational age.

CONTEXT: Children born small for gestational age (SGA) tend to develop catch-up growth in infancy and become overweight by the age of 6 yr. Weight control is advocated as a preventive measure, but it is unknown whether such control suffices to prevent visceral fat excess and hypoadiponectinemia. SETTING: The study was performed at a university hospital. STUDY POPULATION AND DESIGN: A total of 64 children (32 matched pairs) aged 6 yr, of whom 32 were born appropriate for gestational age and 32 were born SGA, and had subsequently developed spontaneous catch-up growth were included in the study; matching was performed for gender, height, weight, and, thus, body mass index. MAIN OUTCOMES: Fasting insulin, IGF-I, high molecular weight adiponectin, leptin, visfatin, and lean and fat mass were calculated by absorptiometry, and abdominally sc and visceral fat by magnetic resonance imaging. RESULTS: After strict matching, SGA children had a total lean mass, total fat mass, leptinemia, and visfatinemia comparable to those in the appropriate for gestational age children, but they still had higher fasting insulin and IGF-I levels (P < 0.01), much lower high molecular weight adiponectin levels (P < 0.0001), and a striking shift from abdominally sc to visceral fat (P < 0.0001). Fasting insulin (r = 0.52; P < 0.00001) was a major determinant of visceral fat in boys and girls, explaining 28% of its variance. CONCLUSIONS: SGA children tend to be viscerally adipose and hypo-adiponectinemic, even if they are not overweight. Therefore, measures beyond weight control seem to be needed to allow most SGA children to normalize their body composition and endocrine-metabolic homeostasis.

Early development of visceral fat excess after spontaneous catch-up growth in children with low birth weight.

CONTEXT: The sequence of prenatal growth restraint and infantile catch-up of weight is by the age of 4 yr associated with hyperinsulinemic adiposity. We studied whether the adiposity of post-catch-up children born small for gestational age (SGA) is further amplified between age 4 and 6 yr and whether visceral fat excess has already emerged by the age of 6 yr. SETTING: The study took place at a university hospital. STUDY POPULATION AND DESIGN: A longitudinal cohort (age 2-6 yr) of 22 children born appropriate for gestational age (AGA) and 29 born SGA were studied. Auxological, endocrine, metabolic, and body composition (by absorptiometry) assessments were made at 2, 4, and 6 yr, and visceral fat was assessed (by magnetic resonance imaging) at 6 yr. MAIN OUTCOMES: Outcome measures included fasting glucose, insulin, IGF-I, neutrophil to lymphocyte ratio, lean mass, and total, abdominal, and visceral fat mass. RESULTS: Between ages 4-6 yr, the relative adiposity of SGA children was further amplified. Between ages 2-6 yr, SGA children gained more total and abdominal fat and raised their insulin, IGF-I, and neutrophil to lymphocyte ratio more than did AGA children (all P<0.0001). At age 6 yr, the average amount of visceral fat was in SGA children more than 50% higher than in AGA children (P<0.005). The 0- to 2-yr increment in weight Z-score together with the 2- to 6-yr increment in fasting insulin accounted for 62% of visceral fat variability at age 6 yr. CONCLUSION: The amount of visceral fat is in post-catch-up SGA children excessive by the age of 6 yr. In populations at risk for type 2 diabetes or metabolic syndrome after fetal growth restraint, the time window for early intervention may have to be advanced into prepubertal childhood.