ABSTRACT
A 14-year-old female (social gender) patient was admitted to the hospital due to severe hypertension for 11 days. The patient had primary amenorrhea. The blood pressure was 146/90 mm Hg. The skin color was slightly black. The development of secondary sexual characteristics was poor. The labia majora could be observed in the vulva. However, the labia minora, clitoris, vagina, and hymen were absent. The levels of renin, cortisol, and sex hormone were low, while the levels of adrenocorticotropic hormone and gonadotropin were high. The levels of blood potassium and aldosterone were both normal. Radiography indicated retardation of bone age. Ultrasound examination revealed that the ovary and uterus were both absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome sequencing revealed two homozygous mutations, c.985T>C and c.987delC, in exon 6 of the CYP17A1 gene of the patient and heterozygous mutations in the same sites of the parents. The patient was diagnosed with congenital adrenal hyperplasia-17α-hydroxylase deficiency. After treatment with hydrocortisone for 2 months, blood pressure returned to normal and the level of adrenocorticotropic hormone was reduced. According to the request of the patient and the parents, hydrocortisone was replaced with estrogen to allow the patient to live as a female. The patient also received surgical excision of cryptorchid testes to prevent gonadal malignancy. It is concluded that in the differential diagnosis of pediatric hypertension, sexual development should be considered and the levels of adrenocorticotropic hormone and cortisol should be evaluated. The rare disease 17α-hydroxylase deficiency should be considered for patients with low-renin hypertension and gonadal dysgenesis.
ABSTRACT
Objective: To prepare naringenin-loaded solid lipid nanoparticles (NRG-SLN) lyophilized powder, and investigate its physicochemical properties and release characteristics, then to investigate the pharmacokinetic characteristics in rats after pulmonary delivery. Methods: NRG-SLN were prepared by solvent emulsification-evaporation method, the formulation was optimized by orthogonal design, with encapsulation efficiency as reference, and the measurements of particle size, morphology, Zeta potential, the polydispersity index (PDI) and in vitro drug release behavior were performed. To screen the best lyoprotectants in appearance, color, and redispersibility as indexes the differential scanning calorimetry (DSC) was used to analyze its material phase of the drug in nanoparticles. The study on pulmonary pharmacokinetics in rats was carried out by pulmonary instillation. Results: The NRG-SLN assumed a spherical shape with an even distribution of diameter and particle size of (97.69±2.84) nm, the PDI was 0.207±0.010, Zeta potential was (-26.20±0.45) mV, entrapment efficiency was (81.09±1.37)%, and drug loading was (8.30±0.04)% (n=3). Mannitol (5%) was the best protective agent for lyophilized powder of NRG-SLNs. The characterization indicated that the drug to amorphous state dispersed in a lipid. In vitro dissolution experiments showed NRG-SLN compared with pure drugs had obviously sustained release. After pulmonary administration to rats, the pharmacokinetic parameters of NRG-SLN and solution were as follows: Cmax (163.00±23.05) and (269.00±35.34) ng/mL, AUC0-t (929.32±190.28) and (3 390.23±533.68) ng∙h/mL, t1/2 (5.13±0.23) and (18.93±7.90) h, MRT (7.19±0.44) and (23.29±9.27) h. Conclusion: The technique of preparing NRG-SLN by solvent emulsification-evaporation has small particle size, high entrapment efficiency, and good stability, and the process is simple. Compared with the naringenin solution, the SLN show the sustained-release characteristics and can significantly improve the bioavailability after pulmonary administration.