Case report of an adult female with neglected Congenital Adrenal hyperplasia (CAh) / Journal of the ASEAN Federation of Endocrine Societies

@#An apparently well 27-year-old phenotypically male adult was seen at the endocrine clinic for gender assignment. Patient had been raised as a male and identifies as such. Abdominal CT scan showed a unilateral left adrenal mass and karyotyping revealed 46 XX female karyotype. She was diagnosed to have simple virilizing CAH and needed thorough counselling with subsequent management by a multidisciplinary team

Management framework paradigms for disorders of sex development

Until 2005, questions regarding medical treatment and diagnostic information on Disorders of Sex Development (DSD) were not systematically discussed with both the patients and their families; however, the way these patients are currently treated have been changing with time. Interventional changes in the clinical-psychotherapeutic-surgical areas of DSD determine not only different medical recommendations but also help to place the patient and the family into the decisional process of therapy. We must consider two paradigmatic periods that have influenced and transformed the clinical management framework of patients with DSD: a) The "Money era" (1955), which emphasized the role of the gonads as the diagnostic criterion, having the environment as determinant of the sex identity; and b) The Chicago Consensus (2005) phase, in which the role of genetics and molecular biology was critical for an early identification, as well as in building a proper sex identity, emphasizing ethical questions and the "stigma culture". In addition, recent data have focused on the importance of interdisciplinarity and statements on questions concerning Human Rights as key factors in treatment decision making. Despite each of these management models being able to determine specific directions and recommendations regarding the clinical handling of these patients, we verify that a composite of these several models is the clinical routine nowadays. In the present paper, we discuss these several paradigms, and pinpoint clinical differences and their unfolding regarding management of DSD patients and their families.

Variables Influencing 17-Hydroxyprogesterone Values in Newborn Screening for Congenital Adrenal Hyperplasia

PURPOSE: Congenital adrenal hyperplasia(CAH), which is classified into salt-wasting, simple virilization and non-classic type according to clinical features, is difficult to detect in early stages. Failure to diagnose it in the initial state may lead to life-threatening adrenal crisis, inappropriate male sex assignment in the genetic female, acceleration of skeletal maturation and subsequent short stature. Therefore, we studied the variables increasing the 17-hydroxyprogesterone(OHP) values for more specific and sensitive diagnosis of CAH. METHODS: We classified 3,532 newborns into variable factors; gestational age, birth weight, gender, delivery type, sampling date and stress. Then, we analysed the relationships between 17-OHP values and variable factors. RESULTS: The mean value of 17-OHP was 4.21+/-0.03ng/ml. There were significant differences among the variable factors except gender. The mean value of male was 4.26ng/ml, and that of female was 4.15ng/ml(P=0.10). The mean value of 17-OHP in vaginal delivered newborn was higher than C-section delivered ones(4.71ng/ml, 3.34ng/ml, P=0.0001). It was also higher in low birth weight(P=0.0001), in prematurity(P=0.001), those sampled within 4 days(P=0.0001), stressful condition and ventilator care-assisted(P=0.004). CONCLUSION: 17-OHP value in neonatal screening is influenced by several variables such as vaginal delivery, ventilator management, low birth weight, sampling date and prematurity. If the 17-OHP value is increased, we have to consider the variables influencing the increase in value and follow up with time interval or analysis of genetic mutations.

Variables Influencing 17-Hydroxyprogesterone Values in Newborn Screening for Congenital Adrenal Hyperplasia

PURPOSE: Congenital adrenal hyperplasia(CAH), which is classified into salt-wasting, simple virilization and non-classic type according to clinical features, is difficult to detect in early stages. Failure to diagnose it in the initial state may lead to life-threatening adrenal crisis, inappropriate male sex assignment in the genetic female, acceleration of skeletal maturation and subsequent short stature. Therefore, we studied the variables increasing the 17-hydroxyprogesterone(OHP) values for more specific and sensitive diagnosis of CAH. METHODS: We classified 3,532 newborns into variable factors; gestational age, birth weight, gender, delivery type, sampling date and stress. Then, we analysed the relationships between 17-OHP values and variable factors. RESULTS: The mean value of 17-OHP was 4.21+/-0.03ng/ml. There were significant differences among the variable factors except gender. The mean value of male was 4.26ng/ml, and that of female was 4.15ng/ml(P=0.10). The mean value of 17-OHP in vaginal delivered newborn was higher than C-section delivered ones(4.71ng/ml, 3.34ng/ml, P=0.0001). It was also higher in low birth weight(P=0.0001), in prematurity(P=0.001), those sampled within 4 days(P=0.0001), stressful condition and ventilator care-assisted(P=0.004). CONCLUSION: 17-OHP value in neonatal screening is influenced by several variables such as vaginal delivery, ventilator management, low birth weight, sampling date and prematurity. If the 17-OHP value is increased, we have to consider the variables influencing the increase in value and follow up with time interval or analysis of genetic mutations.

Prenatal diagnosis of a heterozygote of salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency by genetic linkage analysis

For the purpose of prenatal diagnosis of CAH, genetic linkage analysis by HLA genotyping with lymphocytes and cultured amniotic cells were performed in a family at risk in which two consecutive children had been affected with SW CAH. In addition, the response of serum 17-OHP to intravenous ACTH was determined in obligate carrier parents, and 17-OHP concentration of amniotic fluid was also measured at 16 weeks of gestation. As might be expected, the baseline levels of 17-OHP in obligate parents were significantly higher than that of normal control. Although the post stimulation response of 17-OHP to ACTH in the mother (I-2) was significantly higher than that of normal control, the post stimulation levels of 17-OHP were in normal range in the father (I-1). The 17-OHP level (5.7 ng/ml) in the amniotic fluid showed intermediate value compared to Pang's report (normal less than 30 ng/ml, CAH greater than 12.0 ng/ml) suggesting heterozygote of the fetus. Genetic linkage analysis by HLA genotyping with cultured amniotic cells revealed heterozygote in their fetus (II-3) who has received one chromosome No,6 containing HLA haplotype A24, B40, Cw3 (normal allele for 21-OH) from the father and the other chromosome No,6 containing HLA haplotype A2, Bw62, Cw4 (mutant allele for 21-OH D) from the mother. In conclusion, attempts to detect heterozygote for 21-OH deficiency by ACTH stimulation test were partially successful and prenatal diagnosis of CAH by the hormone studies in ammiotic fluid requires reliable values in normal, heterozygotes and patients group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)