PUBERTAL VIRILIZATION IN AN ADOLESCENT WITH 46, XY DISORDER OF SEXUAL DEVELOPMENT: A NOVEL MUTATION IN NR5A1 GENE.

Background: NR5A1 [Steroidogenic factor 1 (SF1)] is a nuclear receptor that is essential for the development of gonads and adrenal glands as well as the establishment of steroidogenesis in these organs. The clinical findings of the mutations of NR5A1 gene in 46, XY individuals are variable. Virilization at puberty can be seen in some of the 46, XY children who have a female phenotype and are raised as female.A girl aged 13 years and 10 months old was brought by the family for deepening of her voice. On physical examination, her breast development was Tanner stage 2, axillary hair (+) and pubic hair was Tanner stage 4. She had labioscrotal fusion and 4.4 cm phallus (External Masculinisation Score was 6). Hypergonadotropic hypogonadism, low AMH and high testosterone levels were detected in laboratory tests. Uterus was not visualized in pelvic ultrasonography. Karyotype analysis was reported as 46, XY. Sequence analysis of the NR5A1 gene revealed a novel heterozygote c.1075_1089del (p.Leu359_Leu363del) variant. The patient was raised as a female and oestrogen replacement was started following gonadectomy. Conclusion: It should be kept in mind that virilization may develop at puberty in individuals with 46, XY disorder of sexual development due to NR5A1 mutation.

What should be the primary treatment in atrial fibrillation: ventricular rate control or sinus rhythm control with long-term anticoagulation?

Recent trials have favoured ventricular rate control in atrial fibrillation (AF) management, however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were randomized and received sinus rhythm control with either aspirin (group 1) or warfarin (group 2), or they were given ventricular rate control (group 3). Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 (91.1%) of them. After 3 years' follow-up there were 12, two and 15 embolic events in groups 1, 2 and 3 respectively (significant difference between groups 1 and 2, and 2 and 3) and overall mortalities were four, two and 12, respectively (significant difference between groups 2 and 3). It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality.

Role of enoxaparin resistance in recurrent chest pain in the intensive care unit.

To investigate the relationship between anticoagulation treatment and drug resistance in chest pain, levels of factor Xa residual activity were determined in patients seen in intensive care with recurrent chest pain and compared with levels in patients who had no ischaemic events during hospitalization. A total of 122 patients aged 18 - 75 years who were admitted to hospital with acute coronary syndrome and treated with enoxaparin were included. Of these, 62 patients had recurrent chest pain while hospitalized (group A) and 60 patients had an uneventful follow-up period (group B). Patients requiring primary percutaneous transluminal coronary angioplasty and/or treatment with glycoprotein IIb/IIIa inhibitors, and those with renal failure, a high risk of bleeding or receiving anti-inflammatory drugs were excluded from the study. Median levels (+/- interquartile range) of factor Xa residual activity were significantly higher in group A compared with group B (0.68 +/- 0.29 IU/ml versus 0.34 +/- 0.33 IU/ml). It is concluded that enoxaparin resistance, resulting in high levels of factor Xa residual activity, should be considered in patients with recurrent ischaemia.