Endocrine and metabolic complications in children and adolescents with Sickle Cell Disease: an Italian cohort study

Abstract

BackgroundChildren with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents.MethodsFifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3–18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters.ResultsHeight-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase.ConclusionsMetabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients.Electronic supplementary materialThe online version of this article (10.1186/s12887-019-1423-9) contains supplementary material, which is available to authorized users.

Response to Letter to the Editor: Impact of Bariatric Surgery on Outcomes of Patients with Sickle Cell Disease: a Nationwide Inpatient Sample Analysis, 2004–2014

“…Based upon our study design and nature of the Nationwide Inpatient Sample database, the authors further describe that our study does not provide important information on variants of SCD. However, as they have clearly suggested, and based upon previous literature, it is highly likely that patients included in our analysis had milder forms of disease [3,4]. Even though these patients may have milder forms of disease, the findings of this Nationwide Inpatient Sample study advocate for an important role of weight reduction surgery in the management of this specific population.…”

A Meta-analysis on Vitamin D Deficiency in Patients with Sickle Cell Disease

“…Hamdy et al [49] showed a significant correlation between serum vitamin D level and the biomarkers of hemolysis (lower level of hemoglobin and a higher level of aspartate aminotransferase, lactate dehydrogenase, and bilirubin), and the clinical course and complications of SCD (frequency of blood transfusions and hospitalization, occurrence of vaso-occlusive crises, and recurrent infections). Similarly, Mandese et al [44] demonstrated the significant negative correlation between levels of vitamin D and clinical indicators of the SCD severity (hospitalization and number of days of hospital admissions).…”

“…Several peculiar characteristics of SCD could explain the high prevalence and increased risk of VDD among patients with SCD, such as: impaired absorption by the damaged intestinal mucosa as a complication of SCD; decreased level of vitamin D binding protein due to the inflammatory condition in SCD; increased physiological demands due to the fast turnover in the process of erythrocytosis in SCD; and reduced levels of nutritional status, physical activity, and exercise in patients with SCD [12,28,30,40,44,46,49].…”

“…Full texts of 40 studies were screened, and 15 studies were subsequently excluded because of insufficient data to estimate the outcomes of interest (Figure 1). A total of 25 studies published from 1993 to 2019 that met the eligibility for data were used for qualitative and quantitative syntheses: 10 studies from the Americas [12,[28][29][30][31][32][33][34][35][36]; six studies from Asia [37][38][39][40][41][42]; five studies from Europe [43][44][45][46][47]; two studies from Africa [48,49], one study that used samples from both Jamaica and West Africa [50], and one study that used samples from both Brazil and Nigeria [51].…”

Male hypogonadism with its systemic complications

“…Such decrease in gonadotropins could occur in other types of anemia like Fanconi anemia [36] which is intertwined with genetic disorder. Also, sickle cell anemia could lead to hypogonadism by occluding pituitary or/and testicular vessels and leading to their infarction [37] [38]. Introducing testosterone supplementation in treatment of patients with lowered androgens levels as a result of aging or hypogonadism, treated for anemia have positive impact on hemoglobin concentration and production of erythropoietin, ferroportin, and transferrin receptors [39].…”