Search

Introduction: Growth hormone deficiency (GHD) may be associated with subtle cardiovascular abnormalities, reversible upon starting GH treatment. Data on vascular morphology and function in GHD children are scanty and inconclusive. The aim of our study was to evaluate the effects of GHD and GH treatment on endothelial function and intima-media thickness (IMT) in children and adolescents., Methods: We enrolled 24 children with GHD (10.85 ± 2.71 years) and 24 age-, sex-, and BMI-matched controls. We evaluated anthropometry, lipid profile, asymmetric dimethylarginine (ADMA), brachial flow-mediated dilatation (FMD), and IMT of common (cIMT) and internal (iIMT) carotid artery at study entry in all subjects and after 12 months of treatment in GHD children., Results: At baseline GHD, children had higher total cholesterol (163.17 ± 18.66 vs. 149.83 ± 20.68 mg/dL, p = 0.03), LDL cholesterol (91.18 ± 20.41 vs. 77.08 ± 19.73 mg/dL, p = 0.019), atherogenic index (AI) (2.94 ± 0.71 vs. 2.56 ± 0.4, p = 0.028), and ADMA (215.87 ± 109.15 vs. 164.10 ± 49.15 ng/mL, p < 0.001), compared to controls. GHD patients also exhibited increased higher waist-to-height ratio (WHtR) compared to controls (0.48 ± 0.05 vs. 0.45 ± 0.02 cm, p = 0.03). GH therapy resulted in a decrease in WHtR (0.44 ± 0.03 cm, p = 0.001), total (151.60 ± 15.23 mg/dL, p = 0.001) and LDL cholesterol (69.94 ± 14.40 mg/dL, p < 0.0001), AI (2.28 ± 0.35, p = 0.001), and ADMA (148.47 ± 102.43 ng/mL, p < 0.0001). GHD showed lower baseline FMD than controls (8.75 ± 2.44 vs. 11.85 ± 5.98%, p = 0.001), which improved after 1-year GH treatment (10.60 ± 1.69%, p = 0.001). Baseline cIMT and iIMT were comparable between the two groups, but slightly reduced in GHD patients after treatment., Conclusion: GHD children may exhibit endothelial dysfunction in addition to other early atherosclerotic markers like visceral adiposity, and altered lipids, which can be restored by GH treatment., (© 2023 S. Karger AG, Basel.)

Background: Coexistence of congenital adrenal hyperplasia (CAH) and congenital hypothyroidism (CH) due to TG mutation in the same non-consanguineous family is rare., Case Series: We report 4 siblings born to unrelated parents, the father being an asymptomatic carrier of homozygous p.V281L and heterozygous p.I172N CYP21A2 mutations. Sibling 1 had salt-wasting CAH (CYP21A2 genotype Intron 2 splice/p.I172N and p.V281L). She also had CH (TG genotype p.R296/ p.T1416Rfs*30) and learning difficulties. Poor compliance and morbid obesity resulted in short stature, precocious puberty, hirsutism, amenorrhoea, insulin insensitivity and a possible adrenal adenoma. Sibling 3 (CYP21A2 and TG genotype similar to sibling 1) is a boy presenting with salt-wasting CAH, CH, and developmental delay. He was overweight and underwent precocious puberty. Although siblings 2 and 4 (both females) share the same CYP21A2 genotype (Intron 2 splice/p.V281L), the former only had biochemical evidence of CAH, while the latter presented at 9.8 years of age with a history of pubarche at 7 years and advanced bone age., Conclusions: We report the unusual occurrence of 2 rare autosomal recessive diseases, CAH and CH. Our cases highlight the phenotypic variability of CAH and CH due to TG mutations, even within a single family, and illustrate the importance of optimal disease control.
., (© 2017 S. Karger AG, Basel.)

Background: The p.R63W mutation in the hepatocyte nuclear factor-4 alpha (HNF4A) results in macrosomia and atypical Fanconi syndrome, in addition to hyperinsulinaemic hypoglycaemia (HI). We describe 2 infants carrying this mutation, presenting with additional features. Cases Series: Patient 1, a male born with a birth weight of 1.7 SDS, was diagnosed with HI on day 2 of life. He responded to 3-10 mg/kg/day of diazoxide. Raised serum creatinine led to the investigation of renal tubular function, showing leaking of electrolytes and protein. The patient also had conjugated hyperbilirubinaemia with liver steatosis. Patient 2 was a male born with a weight of 0.36 SDS. His mother had renal Fanconi syndrome. He received parenteral nutrition and presented with HI at 1 month of age, while establishing enteral feeds. Biochemistry workup showed renal tubular leaking of calcium, sodium, and phosphate. A hypoglycaemia screen documented HI, and the patient was commenced on 2 mg/kg/day of diazoxide. Continuous glucose monitoring was performed in his mother, revealing overnight hypoglycaemia., Conclusion: Renal Fanconi syndrome represents the only HNF4A feature showing complete penetrance. Our cases suggest that the p.R63W HNF4A mutation must be considered in subjects with a normal birth weight and postulate the possibility of liver involvement as a part of this condition., (© 2016 S. Karger AG, Basel.)