New diagnostic approach to central hypothyroidism after traumatic brain injury in children and adolescents

Abstract

Background: Pituitary lesions after traumatic brain injury (TBI) are frequent in children and adolescents, but the rate of post-TBI central hypothyroidism remains uncertain.

Objective: To identify the long-term incidence of post-TBI CH and the clinical and laboratory characteristics of this complication in children and adolescents.

Methods: The analysis included 31 patients with a history of TBI with at least 1 year of follow-up. Patients were evaluated at hospital admission and every 3 months thereafter. Assessments included clinical evaluation, brain CT and hormone assessments (basal fT4, IGF-1, cortisol and adrenocorticotropic hormone; insulin tolerance test/thyrotropin-releasing hormone test with TSH, growth hormone and cortisol measurement; and corticotropin-releasing hormone test, if indicated). The CH diagnosis was based on clinical and laboratory findings and a therapeutic trial with levothyroxine.

Results: Overall, five patients (16%) developed CH (3 with associated adrenal insufficiency). At 3 and 12 months, median fT4 values were lower in patients with CH compared with those without anterior pituitary dysfunction (n = 18; P = 0.01). Patients with CH received levothyroxine and progressed with clinical resolution and increased median fT4 (from 0.92 to 1.47 ng/dL) and IGF-1 (from -2.08 to -0.22 standard deviation scores (SDS)) levels. Temporary suspension of levothyroxine was accompanied by decreased median fT4 (1.02 ng/dL) and IGF-1 (-1.07 SDS) levels and reappearance of clinical symptoms, which resolved once levothyroxine was reinitiated.

Conclusions: The longer follow-up, valorization of clinical manifestations, nontraditional laboratory approach and therapeutic trial with levothyroxine in the present study revealed a higher rate of post-TBI CH in children and adolescents than that reported in the literature.

Keywords: GH; IGF-1; adolescents; central hypothyroidism; children; traumatic brain injury.

Figure 1

Individual and combined (median) free thyroxine (fT4) levels in five patients with central hypothyroidism secondary to TBI. The sequence of time points shown indicates values measured at hospital admission, at the 3- and 12-month follow-up visits, before levothyroxine (LT4) treatment (pre-Tx), during LT4 treatment (on LT4), LT4 interruption (off LT4) and LT4 reinitiation (on LT4).

Figure 2

Individual and combined (median) IGF-1 values in five patients with central hypothyroidism secondary to TBI. The sequence of time points shown indicates values measured at hospital admission, at the 3- and 12-month follow-up visits, before levothyroxine (LT4) treatment (Pre-Tx), during LT4 treatment (on LT4), LT4 interruption (off LT4) and LT4 reinitiation (on LT4).

Figure 3

Peak GH values (median, minimum and maximum values) during the insulin tolerance test (ITT) combined with the TRH stimulation test in patients with central hypothyroidism secondary to TBI (n = 5) versus those without anterior pituitary dysfunction (n = 18) at the 3-month and 12-month follow-up visits. Nonparametric Mann–Whitney test (*P = 0.02).