Karen Lin-Su

Steroid 21 Hydroxylase Deficiency Congenital Adrenal Hyperplasia

Steroid 21 hydroxylase deficiency is the most common form of congenital adrenal hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied.

Congenital Adrenal Hyperplasia in Adolescents

Adolescent females who have irregular menstrual periods may have the nonclassical form of congenital adrenal hyperplasia due to a mild deficiency of steroid 21‐hydroxylase (NC 21‐OHD). Hyperandrogenic signs such as acne, frontal hair loss, hirsutism, and irregular menstrual periods should alert the physician to the diagnosis of NC 21‐OHD. An ACTH stimulation test in which serum hormone concentrations of 17‐OHP, Δ4‐androstenedione, and testosterone are determined will assist in the diagnosis of NC 21‐OHD, but the definitive diagnostic test is an analysis of the mutations in the CYP21A2 gene. Typical mutations in the CYP21A2 gene in patients with NC 21‐OHD are an exon 7 or an exon 1 mutation. Once the genotype establishes the diagnosis of NC 21‐OHD, treatment should be initiated. Typical treatment is dexamethasone, 0.25u2003mg HS, which generally reverses the hyperandrogenic signs.

Body Mass Index and Age at Menarche in an Adolescent Clinic Population

Body fatness as a determinant of menarche has been studied extensively, but limited to underweight females. Adolescent female patients were measured and interviewed. Subjects were divided into three groups based on body mass index (BMI) standard deviation score (SDS). Average age at menarche was 11.87 + 1.1 years in the obese group, 12.14 ± 0.9 years in the overweight group, and 12.20 ± 1.3 years in the normal weight group. Pearson correlation factor between BMI SDS and age at menarche was -0.24 (p<0.01). These findings suggest an important role of increased body fatness on menarche that extends beyond underweight girls.

Growth and pubertal characteristics in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

This retrospective study examined the pubertal characteristics and growth in patients with 21-hydroxylase deficiency (21-OHD). There were 18 males and 31 females with salt wasting (SW), simple virilizing (SV), or non-classical (NC) 21-OHD. Mean ages at onset of puberty (AOP) in SW, SV, and NC males were 9.2 +/- 1.9, 10.3 +/- 1.1, and 10.7 +/- 0.8 years, respectively; while mean AOP in SW, SV, and NC females were 9.3 +/- 1.7, 8.6 +/- 1.6, and 8.5 +/- 1.3 years, respectively. Mean final height (FH) in SW males (159.6 +/- 7.8 cm) was less than in SV (166.8 +/- 7.5 cm, p = 0.06) and NC (173.4 +/- 6.4 cm, p = 0.005) males. Mean FH in SW females (157.1 +/- 5.5 cm) was similar to SV (156.0 +/- 8.4 cm) but less than NC (161.3 +/- 5.4 cm, p = 0.01) females. In conclusion, while the patients as a group entered puberty earlier than the general population, SW males entered puberty the earliest and had the most compromised FH outcome.

Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body composition in children and adolescents infected with human immunodeficiency virus.

OBJECTIVEnTo evaluate the effects of protease inhibitors (PIs) as antiretroviral therapy in comparison with other antiretroviral (non-PI) medications on glucose tolerance, lipid metabolism, and body fat distribution in human immunodeficiency virus (HIV)-infected young patients.nnnMETHODSnWe conducted a cross-sectional clinical study in an outpatient HIV clinic. The study population consisted of 21 patients (15 female and 6 male) who had had at least 6 months of antiretroviral treatment. The mean age of the patients was 11.9 years (range, 6 to 16.5).nnnRESULTSnFifteen patients treated with PIs and 6 patients treated with non-PIs were enrolled in the study. We found no significant differences in the lipid panel and insulin resistance, as determined by using the Quantitative Insulin Sensitivity Check Index formula, in the PI group in comparison with the non-PI group. Lipodystrophy was observed in 47% (7 of 15) of the PI group and 33% (2 of 6) of the non-PI group (P = 0.66). In the presence of lipodystrophy, serum triglyceride levels were higher in the PI group than in the non-PI group (P = 0.046). No such difference was found between the treatment groups when no lipodystrophy was present. There was no significant difference in insulin resistance between the treatment groups in the presence or absence of lipodystrophy.nnnCONCLUSIONnOur study found the presence of lipodystrophy in HIV-infected young patients regardless of whether they were taking PIs or not. In the patients who had lipodystrophy, those treated with PIs had higher serum triglyceride levels than those not treated with PIs.

Effects of Adrenal Steroids on the Bone Metabolism of Children with Congenital Adrenal Hyperplasia

Abstract:u2002 The primary treatment for patients with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (21OHD) is glucocorticoid replacement therapy, which at supraphysiologic levels can result in diminished bone accrual and lead to osteopenia and osteoporosis. Unlike other diseases treated with chronic glucocorticoid therapy, previous studies of patients with 21OHD have not demonstrated a detrimental effect of glucocorticoid treatment on bone mineral density (BMD). It has been postulated that the elevated androgens typically found in these patients have a protective effect on bone integrity, but the precise mechanism remains unknown. We propose that the inhibitory effect of corticosteroid therapy on bone formation is counteracted by estrogens effect on bone resorption through the RANK‐L/osteoprotegerin (OPG) system. A better understanding of the mechanism by which patients with 21OHD are protected against bone loss may lead to novel therapeutic measures to prevent or treat osteopenia and osteoporosis in other conditions, including postmenopausal women.

Growth Hormone Treatment in Children with Congenital Adrenal Hyperplasia

Final adult height is often compromised in children with congenital adrenal hyperplasia (CAH). This report examines the impact of growth hormone (GH) with or without LHRH analogue (LHRHa) on final adult height in patients with CAH due to 21-hydroxylase deficiency. Boys and girls with CAH who had a predicted final height of more than 2 SD below their mid-parental target height or more than 2 SD below the population mean were eligible for treatment with GH. Other inclusion criteria included open epiphyses (bone age <14 years for boys and bone age <13 years for girls) and bone age ≥1 standard deviation above the mean for chronological age. Subjects received GH (starting dose of 0.3 mg/kg/week) until final adult height was reached. Final adult height was defined as growth velocity ≤1.5 cm/year over a 6-month period and bone age ≥15 in girls or ≥17 in boys. Patients with early central puberty were also treated with an LHRHa. The primary outcome variable was final adult height. Secondary outcome variables were gain in height (final height minus initial predicted height) and height discrepancy (final height minus target height). We report the results of 31 GH-treated CAH patients who have reached final adult height. Mean duration of growth hormone treatment was 4.5 years for girls and 4.9 years for boys. Mean duration of LHRHa therapy was 4.2 years. Girls (n = 15) reached a mean final adult height of 162.1 cm, in contrast to a mean initial predicted height of 153.0 cm.

Long-term Growth Hormone Therapy in an Adolescent Boy with 45,X/46,XidicY(p11)

A 17-year-old boy with chromosomal mosaicism resulting in a 45,X/46,X,idic(Y)(p11) karyotype came to medical attention at the age of 10 years because of short stature. He was treated with recombinant growth hormone for 6.6 years and has achieved a near final adult height of 172.5 cm. His clinical features included second-degree hypospadias, some stigmata of Turner syndrome, and spontaneous progression through puberty. We report long-term use of growth hormone in a male adolescent with isodicentric Yq.

Health-Related Quality of Life in Children with Congenital Adrenal Hyperplasia.

Background/Aims: Factors in congenital adrenal hyperplasia (CAH) that may affect quality of life (QOL) include the need for lifelong medication, the risk of adrenal crisis, and hyperandrogenic symptoms. The objectives were to evaluate health-related QOL (HRQOL) in children with CAH, and whether CAH poses an additional burden compared to other endocrine disorders. Methods: The validated PedsQL 4.0 generic core scales were administered to subjects (8-18 years) with CAH and hypothyroidism and their parents. The minimal clinically important difference (MCID) was determined for each scale score, allowing a comparison with the healthy population. A score of >1 standard deviation below the population mean was considered at risk for impaired HRQOL. Results: In CAH, the mean total HRQOL scores were >1 MCID below the population mean, and a higher percentage than expected had scores considered at risk. Conclusion: Compared to subjects with hypothyroidism, subjects with CAH self-reported lower school domain scores. CAH subjects more frequently reported peers not wanting to be friends.

Congenital adrenal hyperplasia in adults

Hyperandrogenism in congenital adrenal hyperplasia (CAH) results from overstimulation of adrenocorticotropic-driven androgen production in the adrenal cortex due to lack of cortisol feedback. The classical form is characterized by more-severe symptoms of hyperandrogenism, including virilization of the female genitalia. The milder nonclassical form presents with postnatal symptoms of hyperandrogenism. Presenting symptoms in adulthood may include acne, male-pattern alopecia, hirsutism, irregular menses/amenorrhea or infertility. The goal of therapy in CAH is to both correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH but new treatment strategies continue to be developed and studied.