Alterations in Lipid and Carbohydrate Metabolism in Patients with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Abstract

Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. Aim: To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis. Patients and Methods: Twenty-seven Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Clinical parameters, hormonal status and genotype were assessed in all patients. Lipid parameters, including relative (%) and absolute (mg/dl) small-dense low-density lipoproteins subfractions (sd-LDL) were measured in patients and controls. Oral glucose tolerance tests were performed in both groups. Results: sd-LDL (%) was significantly higher in patients than controls (39.7 ± 5.9 vs. 35.5 ± 5.7%; p = 0.008). The same applies for absolute sd-LDL (mg/dl) (42.6 ± 11.9 vs. 36.4 ± 7.5; p = 0.029). HDL-cholesterol was lower in patients (p = 0.032). Fasting glucose and insulin were significantly higher in patients. Similar differences were noticed for HOMA-IR (p = 0.001), IRI (p = 0.001) and HOMA-B (p = 0.002). IRI correlated directly and significantly with the total hydrocortisone dose and the duration of treatment. Fasting glucose correlated with absolute sd-LDL. No obvious differences were seen between clinical forms or genotype groups. Conclusions: Substitution therapy should be adapted particularly at young ages to prevent early atherogenesis and cardiovascular risk in later life.

Obesity and Familial Predisposition Are Significant Determining Factors of an Adverse Metabolic Profile in Young Patients with Congenital Adrenal Hyperplasia

“…Several studies have revealed unfavorable trends in the cardiovascular status and metabolic risk of adults with CAH [11,15,22,23,24]; however, the data on children and adolescents with CAH are limited.…”

“…In young CAH patients, increased obesity prevalence [14], lipid levels [15,16] and insulin resistance [17] compared with controls have been reported. However, these previous studies were inconclusive because they included patients with both the classical and nonclassical forms of CAH who were receiving a mixture of GC regimes along with different approaches for hormonal control during the course of CAH management.…”

Health Problems in Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

“…Overweight and obese adults with classic CAH had similar lipid profiles to patients with normal BMI [33]. Decreased HDL levels and increased small-dense LDL were found in 27 children and young adults [49]. A larger and more homogeneous cohort of 61 females showed an even higher HDL/LDL ratio in CAH women older than 30 years (n = 34) compared to controls [39].…”

Hiperplasia adrenal congênita em mulheres adultas: manejo de antigos e novos desafios

“…Além disso, essas mulheres têm maior prevalência de obesidade, resistência à insulina, dislipidemia e hipertensão (24). Esses fatores em conjunto traduzem a síndrome metabólica, com consequente risco cardiovascular aumentado (7,59,60). No entanto, ainda não foi demonstrada maior morbidade ou mortalidade cardiovascular ou risco de diabetes tipo 2 nessas mulheres (9).…”