Andrea Esposito

Cluster of cardiometabolic risk factors in children with GH deficiency: a prospective, case–control study

Growth hormone (GH) deficiency (GHD) in adults is associated with increased cardiovascular (CV) risk. Although some authors have documented the presence of early CV risk factors in untreated GHD children, results are still inconsistent. Aim of this study was to evaluate the effects of GHD and GH therapy on early cardiometabolic risk factors in a large cohort of children.

Bone health in children with long-term idiopathic subclinical hypothyroidism.

BackgroundSubclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.AimTo evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS).Patients and MethodsTwenty-five children and adolescents (11 males) aged 9.8 ± 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 ± 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the non-dominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) and bone transmission time (BTT).ResultsMean BMD Z-score was −0.4 ± 1.36 in patients and −0.2 ± 1.2 in controls. Mean Ad-SoS Z-score was 0.01 ± 1.0 in patients and 0.1 ± 1.2 in controls and mean BTT Z-score was −0.03 ± 0.8 and 0.04 ± 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups.ConclusionBone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.

Long-term effects of growth hormone (GH) replacement therapy on hematopoiesis in a large cohort of children with GH deficiency.

The aim of our prospective case-control study was to evaluate long-term effects of GH replacement therapy on erythrocytes parameters, leukocytes, and platelets numbers in a large cohort of children with isolated GH deficiency (GHD). Hemoglobin (Hb) concentration, hematocrit (Hct), mean corpuscular volume, mean corpuscular hemoglobin, red cell distribution width, number of erythrocytes, leukocytes, neutrophils, lymphocytes, monocytes and platelets, ferritin, and C-reactive protein were evaluated in 85 children with isolated GHD (10.20xa0±xa03.50xa0years) before and annually during the first 5xa0years of GH replacement therapy and in 85 healthy children age and sex comparable to patients during 5xa0years of follow-up. Compared with controls, GHD children at study entry showed lower Hb (−1.18xa0±xa00.87 vs. −0.40xa0±xa00.90 SDS, pxa0<xa00.0001), red cells number (−0.24xa0±xa00.81 vs. 0.25xa0±xa01.14 SDS, pxa0<xa00.0001), and Hct (−1.18xa0±xa00.86 vs. −0.68xa0±xa00.99 SDS, pxa0<xa00.0001). Twelve GHD patients (14xa0%) showed a normocytic anemia. GH therapy was associated with a significant increase in Hb, Hct, and red cells number which became all comparable to controls within the first 2xa0years of treatment. Moreover, hemoglobin levels normalized in all anemic GHD patients after 5xa0years of therapy. No difference between patients and controls was found in leukocytes and platelets numbers neither at baseline nor during the study. GHD in childhood is associated with an impairment of erythropoiesis which causes a normocytic anemia in a considerable percentage of patients. GH replacement therapy exerts a beneficial effect leading to a significant increase of erythrocytes parameters and recovery from anemia. Neither GHD nor GH replacement treatment exerts effects on leukocytes or platelets numbers.

Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature.

BackgroundAutoimmune polyendocrine syndrome type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy, is a rare autosomal recessive disease due to pathogenic variants in the AIRE gene. Classic features of the syndrome are mucocutaneous candidiasis, chronic idiopathic hypoparathyroidism and Addison disease. However, other endocrine and non-endocrine components, may occur with a different prevalence. In addition to ectodermal features, which are quite common features of the disease, APS 1 patients may experience other types of skin alterations, such as vasculitic skin rash. An early diagnosis of APS 1 can be very challenging, due to the high clinical heterogeneity, and a considerable delay may occur between the appearance of symptoms and the diagnosis.Case presentationWe report on a girl affected by APS 1 who presented with cutaneous vasculitis when she was seven-months old, some years before the onset of the common components of the disease.ConclusionClinical picture of APS 1 may be characterized by isolated rare or atypical autoimmune or immune-mediated manifestations, even years before the onset of the classic components of the disease. Among these uncommon features, skin rashes of variable form and duration may occur, most of them being associated with histopathological features of vasculitis. Our case suggests that cutaneous vasculitis may represent a first sign of APS 1. The clinical significance of cutaneous vasculitis in the context of APS 1 is still debated. It may represent a rare, unusual, early component of the disease or a clinical manifestation secondarily related to the typical APS 1 components (i.e. autoimmune thyroid disease), which are frequently associated with rheumatologic-like signs and symptoms. Alternatively, it may be the expression of an independent disease co-occuring with APS 1. In conclusion, our case suggests that children presenting with unexplained vasculitic skin rash should be followed-up in order to early identify APS 1.

Glucose homeostasis in GHD children during long-term replacement therapy: a case−control study

PurposeTo evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy.MethodsWe evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years.ResultsNo difference was detected at baseline between GHD patients and controls in glucose (79.58u2009±u20099.96 vs. 77.18u2009±u20098.20u2009mg/dl), insulin (4.50u2009±u20093.24 vs. 4.30u2009±u20092.60u2009µU/ml), HbA1c (5.20u2009±u20090.31 vs. 5.25u2009±u20090.33%) levels, and HOMA-IR (0.93u2009±u20090.72 vs. 0.86u2009±u20090.61). One year of GH was associated with a significant increase in insulin (7.21u2009±u20094.84, pu2009<u20090.001) and HOMA-IR (1.32u2009±u20090.98, pu2009<u20090.001) in GHD children, which became different from controls (pu2009<u20090.001 and pu2009=u20090.004). These parameters did not change further during the following years of treatment in GHD subjects. In contrast, controls did not show significant changes in insulin (4.40u2009±u20092.60) and HOMA-IR (0.82u2009±u20090.60) during the first year; however, at the fifth year of the study a significant increase in insulin (6.50u2009±u20093.50, pu2009=u20090.004) and HOMA-IR (1.29u2009±u20090.54, pu2009<u20090.001) was documented, making these parameters comparable between patients and controls.ConclusionsOur results suggest that growth hormone (GH) treatment is not associated with significant impairment of insulin sensitivity in GHD children. The slight impairment observed in GHD adolescents after long-term GH is comparable to that physiologically occurring in healthy pubertal subjects.

Muscle and skeletal health in children and adolescents with GH deficiency

In addition to promoting linear growth, GH plays a key role in the regulation of bone and muscle development and metabolism. Although GH deficiency is frequently listed among the causes of secondary osteoporosis in children, its impact on bone and muscle health and on fracture risk is still not completely established. Current data suggest that childhood-onset GH deficiency can affect bone and muscle mass and strength, with GH replacement therapy exerting beneficial effects. Moreover, GH withdrawal at final height can result in reduced peak bone and muscle mass, potentially leading to increased fracture risk in adulthood. Thus, the muscle-bone unit in GH deficient subjects should be monitored during childhood and adolescence in order to prevent osteoporosis and increased fracture risk and GH replacement should be tailored to ensure an optimal bone and muscle health.