Association of growth hormone deficiency (GHD) with anxiety and depression: experimental data and evidence from GHD children and adolescents.

Anxiety and depression are among the commonest emotional problems in children and young adolescents. They are encountered with even higher prevalence in children and adults with growth hormone deficiency (GHD). Alterations in the somatotropic axis, as observed in both GH/IGF1 deficiency and excess, can produce permanent changes in brain tissue structure. The growth hormone/insulin-like growth factor 1 (GH/IGF1) axis seems to exert a regulatory effect on brain function and neurogenesis, especially in the hippocampus, a brain region associated with mental and emotional disorders, such as depression and anxiety. There is evidence from animal models of the possible interrelationship of the endocrine system with the pathogenesis of emotional disorders. Moreover, clinical data support the association of GHD and mood disorders, which are often reversed by GH replacement therapy. However, the causal relationship and the mechanism underlying this association are to date obscure and remain to be clarified. The present review reports experimental data from animal models regarding the role of GH/IGF1 in emotional disorders and focuses on clinical data on the presence of these disorders in children with GHD and their response to GH therapy.

Cortisol response to adrenocorticotropin testing in non-classical congenital adrenal hyperplasia (NCCAH).

BACKGROUND: The adequacy of cortisol response in non-classical congenital adrenal hyperplasia (NCCAH) has not been fully elucidated. The aim was to evaluate cortisol response to adrenocorticotropin (ACTH) stimulation test in children and adolescents with NCCAH and heterozygotes for CYP21A2 gene mutations. METHODS: One hundred and forty-six children and adolescents, mean age 7.9 (0.7-17.5) years with clinical hyperandrogenism, were evaluated retrospectively. Thirty-one subjects had NCCAH, 30 were heterozygotes for CYP21A2 gene mutations, while 85 showed normal response to ACTH test. RESULTS: Baseline cortisol levels did not differ among NCCAH, heterozygotes, and normal responders: 15.75 (5.83-59.6) µg/dL vs. 14.67 (5.43-40.89) µg/dL vs. 14.04 (2.97-34.8) µg/dL, p=0.721. However, NCCAH patients had lower peak cortisol compared to heterozygotes and control group: 28.34 (12.25-84.40) vs. 35.22 (17.47-52.37) µg/dL vs. 34.92 (19.91-46.68) µg/dL, respectively, p=0.000. Peak cortisol was <18 µg/dL in 7/31 NCCAH patients and in one heterozygote. CONCLUSIONS: A percentage of 21.2% NCCAH patients showed inadequate cortisol response to ACTH stimulation. In these subjects, the discontinuation of treatment on completion of growth deserves consideration.