Prevalence and natural history of adrenal incidentalomas.
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Clinically silent adrenal masses discovered by imaging studies performed for unrelated reasons, i.e. adrenal incidentalomas, have become a rather common finding in clinical practice. However, only limited studies of incidence, prevalence, and natural history of adrenal incidentalomas are available. A comprehensive review of the literature shows the prevalence of adrenal incidentalomas to be 2.3% at autopsy and 0.5-2% at abdominal computed tomography scan. Most lesions are adrenocortical adenomas at histology, whereas the prevalence of adrenocortical carcinomas is relatively low. The risk of malignancy over time for masses defined as benign at diagnosis is estimated at about 1/1000, even though 5-25% of masses increase in size during follow-up. Hyperfunction develops in about 1.7% of cases and the risk is higher in patients with lesions larger than 3 cm. Cortisol hypersecretion is the most likely disorder that may ensue, and it remains subclinical in about two-thirds of cases. The lack of controlled studies precludes making specific management recommendations. Large perspective controlled studies to define the epidemiology, natural history, and possible associated morbidity of adrenal incidentalomas and their impact on the quality of life of patients are needed. (+info)
Prolonged low-dose dexamethasone treatment, in early gestation, does not alter blood pressure or renal function in adult sheep.
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Low-dose dexamethasone treatment is used in pregnancies where the fetus is suspected to be at risk of congenital adrenal hyperplasia (CAH). In order to see if such treatment had long-term effects, pregnant ewes were treated with dexamethasone (20 micro g/kg maternal body weight) or saline from 25 to 45 days of gestation and blood pressure and renal function studied in offspring at 2 Years of age. There were 11 animals from dexamethasone treatment (six females and five males) and nine lambs from saline treatment (five females and four males). We aimed to study blood pressure and heart rate in the adult animals of both genders, and renal function only in the adult female animals. In both females and males, blood pressure and heart rate were similar between the two groups of animals. The excretion rates of sodium and potassium were similar between the two groups of animals. In addition, glomerular filtration rate was not different between the two groups of animals (112+/-11 ml/kg per h (S.E.M.) in saline-treated females vs 112+/-10 ml/kg per h in dexamethasone-treated females). There were no differences in body weight or weights of the kidney and heart between the treatments in both females and males. In conclusion, these results are reassuring for patients similarly exposed to prenatal dexamethasone treatment for CAH, as in our animal model no evidence of altered renal function or predisposition to adult hypertension was found. (+info)
Menstrual disorders in adolescence: investigation and management.
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Menstrual disorders in adolescence may present diagnostic and management challenges for the gynaecologist. This review will describe the common and uncommon menstrual disorders that may arise in early reproductive life, together with guidance on their investigation and management. (+info)
Improved specificity of newborn screening for congenital adrenal hyperplasia by second-tier steroid profiling using tandem mass spectrometry.
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BACKGROUND: Newborn screening for congenital adrenal hyperplasia (CAH) involves measurement of 17alpha-hydroxyprogesterone (17-OHP), usually by immunoassay. Because this testing has been characterized by high false-positive rates, we developed a steroid profiling method that uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure 17-OHP, androstenedione, and cortisol simultaneously in blood spots. METHODS: Whole blood was eluted from a 4.8-mm (3/16-inch) dried-blood spot by an aqueous solution containing the deuterium-labeled internal standard d(8)-17-OHP. 17-OHP, androstenedione, and cortisol were extracted into diethyl ether, which was subsequently evaporated and the residue dissolved in LC mobile phase. This extract was injected into a LC-MS/MS equipped with pneumatically assisted electrospray. The steroids were quantified in the selected-reaction monitoring mode by use of peak areas in reference to the stable-isotope-labeled internal standard. We analyzed 857 newborn blood spots, including 14 blood spots of confirmed CAH cases and 101 of false-positive cases by conventional screening. RESULTS: Intra- and interassay CVs for 17-OHP were 7.2-20% and 3.9-18%, respectively, at concentrations of 2, 30, and 50 microg/L. At a cutoff for 17-OHP of 12.5 microg/L and a cutoff of 3.75 for the sum of peak areas for 17-OHP and androstenedione divided by the peak area for cortisol, 86 of the 101 false-positive samples were within reference values by LC-MS/MS, whereas the 742 normal and 14 true-positive results obtained by conventional screening were correctly classified. CONCLUSION: Steroid profiling in blood spots can identify false-positive results obtained by conventional newborn screening for CAH. (+info)
The prevalence of late onset congenital adrenal hyperplasia in hirsute women from Central Anatolia.
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Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute women. Sixty-three patients with hirsutism were evaluated to determine the frequency of LO CAH by comparing them with their age and body mass index matched 28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20 were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11-desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and DHEA-S levels did not differ between groups. However, stimulated F levels were found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients with hirsutism met the criterion for 21 hydroxylase deficiency. We found no subject presumed to have 11-beta hydroxylase deficiency, but one subject in control group (3.57%) and two patients among PCOS subjects (4.65%) had exaggerated DHEA-S response which was suggestive of mild 3-beta hydroxysteroid dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia. Mild 3-beta HSD deficiency may also be an underlying cause for hirsutism and it may be seen without any clinical presentation. Adrenal hyperactivity is likely to be the main reason of hyperandrogenemia in women with hirsutism. (+info)
A method for specific amplification and PCR sequencing of individual members of multigene families: application to the study of steroid 21-hydroxylase deficiency.
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Mutations at the human HLA-linked CYP21B locus are responsible for 21-hydroxylase deficiency, a recessively inherited disorder of steroidogenesis. The scope for PCR-based analysis of the CYP21B gene has been restricted by the very high sequence homology between CYP21B and a closely related pseudogene, CYP21A. Here we describe a novel PCR sequencing strategy that allows the independent amplification of the entire CYP21B coding sequence and the subsequent enzyme-mediated conversion of the PCR product to a single-stranded form for dideoxy sequencing. We have used this approach to characterize the 21-hydroxylase deficiency allele associated with HLA-B55, the most frequent HLA marker associated with a CYP21B point mutation in the British population, and also an HLA-B35 associated allele of Asian origin. Allele-specific oligonucleotide (ASO) hybridization analyses have confirmed the selective amplification of CYP21B genes and the identity of the pathological mutations. The method can be adapted to permit selective amplification and PCR sequencing of individual closely related members of other multigene families and small-copy-number repetitive DNA families. (+info)
Steroid 21-hydroxylase deficiency: three additional mutated alleles and establishment of phenotype-genotype relationships of common mutations.
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Lesions in the gene encoding steroid 21-hydroxylase [steroid hydrogen-donor: oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] result in defective adrenal steroid synthesis; the severe forms are known as congenital adrenal hyperplasia. To facilitate complete characterization of mutations in this region of tandemly repeated genes, we have developed selective PCR amplification and direct sequencing of full-length nonpseudogene steroid 21-hydroxylase genes. This technique identifies known mutations, characterizes or excludes unknown mutations, and determines the gene-copy number. Three additional defective alleles were found. A Gly-292----Ser mutation and a frameshift mutation at Arg-484 (GG----C) were identified in patients with severe steroid 21-hydroxylase deficiency. An allele with three additional sequence variations--C----T at 4 bases upstream of translation initiation, Pro-106----Leu, and Pro-454----Ser--were identified in two siblings with late-onset deficiency. Pro-454 is conserved in four species, indicating its importance for normal enzyme function. Functional consequences of individual alleles have been determined in vivo by studying individuals with only one steroid 21-hydroxylase gene. Detailed analyses of clinical data revealed that genotyping could predict the clinical course of the disease. The locations of disease-causing mutations on different haplotypes of the steroid 21-hydroxylase gene region are described. (+info)
The prevalence, molecular analysis and HLA typing of late-onset 21-hydroxylase deficiency in Turkish woman with hirsutism and polycystic ovary.
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We studied the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 2l-hydroxylase (21-OH) deficiency, its molecular genotype expression, and its association with the major histocompatibility complex in 61 women with hirsutism and polycystic ovary. Ultrasound, clinical and hormonal parameters were used to define polycystic ovary syndrome (PCOS). Baseline and ACTH stimulated 17alpha-hydroxyprogesterone (17-OHP) levels were measured for screening of LOCAH during follicular phase. Forty-one women were diagnosed as having PCOS (67%) and 20 women were diagnosed as having had LOCAH due to 2l-OH deficiency (33%). In LOCAH patients, the most common mutation (Val281-Leu, V281L) was found in 10 patients (7 heterozygous/3 homozygous). The frequency of V281L mutation was found as 32.5% in 20 patients. All patients with the V281L mutation presented HLA-B14 (100%) and six of them presented DR1 (60%), confirming that LOCAH is linked to the histocompatibility complex. Although molecular analysis is a better and more accurate means for an exact and precise definition of LOCAH, it is not routinely available in our country. So, ACTH stimulation test combined with HLA-B14 typing should be more widely utilized in these patients. As a result, LOCAH due to 21-OH deficiency is unexpectedly high in Turkish patients with hirsutism and PCO. (+info)