scholarly journals High-Dose Hook Effect in 17-Hydroxyprogesterone Assay in a Patient with 21-Hydroxylase Deficiency

2015 ◽  
Vol 7 (4) ◽  
pp. 329-332 ◽  
Author(s):  
Mesut Parlak ◽  
Hamit Yaşar Ellidağ ◽  
Doğa Türkkahraman
Keyword(s):  
High Dose ◽  
Hydroxylase Deficiency ◽  
Hook Effect ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

scholarly journals Ovarian intratumoral 21-hydroxylase deficiency in a postmenopausal hirsute woman

2012 ◽  
Vol 56 (9) ◽  
pp. 672-676 ◽  
Author(s):  
Selma B. Souto ◽  
Pedro V. Baptista ◽  
Filomena Barreto ◽  
Pedro F. Sousa ◽  
Daniel C. Braga ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Left Ovary ◽  
Serum Testosterone Level ◽  
Hydroxylase Deficiency ◽  
Postoperative Serum ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Hormone Analysis

Virilising ovarian tumours are a rare cause of hyperandrogenism in women, accounting for less than 5% of all ovarian neoplasms. It occurs most often in - and postmenopausal women. We report a case of a 64 year-old woman with signs of virilisation that had started 3 years before. Blood hormone analysis revealed increased levels of testosterone, and 17-hydroxyprogesterone. The tetracosactin test revealed 21-hydroxylase deficiency. Radiological imaging demonstrated a nodule in her left ovary. The patient was submitted to bilateral laparoscopic oophorectomy, and histopathological examination revealed a luteoma of the left ovary. Postoperative serum testosterone level and 17-hydroxyprogesterone returned to normal levels in one month. Virilism regressed within six months. Our patient also showed an elevation in 17-OHP serum levels. Normalization of 17-OHP after oophorectomy suggests a case of intratumoral 21-hydroxylase deficiency. To our knowledge, this is the first description of ovarian intratumoral 21-hydroxylase deficiency in a postmenopausal woman. Arq Bras Endocrinol Metab. 2012;56(9):672-6

scholarly journals Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency in patients with unilateral and bilateral adrenal incidentalomas

2002 ◽  
pp. 349-355 ◽  
Author(s):  
A Patocs ◽  
M Toth ◽  
C Barta ◽  
M Sasvari-Szekely ◽  
I Varga ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Tumor Formation ◽  
Adrenal Incidentalomas ◽  
Hydroxylase Deficiency ◽  
Similar Frequency ◽  
Specific Pcr ◽  
Large Gene ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Hormonal Evaluation

OBJECTIVE: The aims of the present study were (a) to examine the occurrence of 21-hydroxylase gene (CYP21) mutations in patients with unilateral and bilateral adrenal incidentalomas and (b) to correlate the results of mutation screening with hormonal parameters of 21-hydroxylase deficiency. DESIGN: The frequency of the eight commonly occurring CYP21 mutations in blood DNA samples of 19 patients with bilateral, as well as in blood and tumoral tissue DNA samples of 31 patients with unilateral adrenal incidentalomas, was determined. In all patients, hormonal evaluation for 21-hydroxylase deficiency was performed using measurements of basal and ACTH-stimulated plasma 17-hydroxyprogesterone (17-OHP) concentrations. METHODS: Blood and tumoral DNA samples were analyzed by allele-specific PCR for the detection of the eight commonly occurring CYP21 mutations (deletion/large gene conversion, intron 2 splicing, Ile172Asn, exon 6 cluster, Val281Leu, Leu307insT, Gln318Stop and Arg356Trp mutations). Plasma 17-OHP concentrations were measured by radioimmunoassay. RESULTS: Of the 19 patients with bilateral adrenal incidentalomas, one patient had homozygous (Val281Leu) and three patients had heterozygous germline CYP21 mutations (Val281Leu in two cases and Arg356Trp in one case). Heterozygous germline CYP21 mutations were also detected in five of the 31 patients with unilateral adrenal incidentalomas (Ile172Asn in three cases and Val281Leu in two cases). Mutation screening of tumoral DNA in unilateral incidentalomas showed the presence of corresponding germline mutations but no additional somatic mutations were found. ACTH-stimulated plasma 17-OHP concentrations were above 1500 ng/dl in all patients with bilateral incidentalomas who had homozygous and heterozygous CYP21 mutations, but heterozygous carriers with unilateral incidentalomas had highly variable ACTH-stimulated plasma 17-OHP levels (between 111 and 1705 ng/dl). CONCLUSIONS: These results suggest a similar frequency of germline CYP21 mutations in patients with bilateral and unilateral adrenal incidentalomas (21.1% and 16.1% respectively). Therefore, it cannot be ruled out that, in at least some patients, CYP21 mutations may play a role in the pathomechanism of bilateral and unilateral adrenal incidentalomas. However, the lack of clear association of CYP21 mutations with increased ACTH-stimulated plasma l7-OHP response, especially in patients with unilateral incidentalomas, suggests that the effect of CYP21 mutations on adrenocortical tumor formation may also involve mechanism(s) independent of ACTH-induced changes in 17-OHP secretion.

The prevalence of the non-classical form of congenital adrenal hyperplasia as exemplified (by the population of the Moscow region)

2013 ◽  
Vol 59 (4) ◽  
pp. 18-22
Author(s):  
T A Ionova ◽  
A N Tiul'pakov ◽  
S G Kalinenkova
Keyword(s):  
Neonatal Screening ◽  
Moscow Region ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
True Incidence ◽  
Monogenic Diseases ◽  
Frequent Mutations ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency ◽  
Autosomal Recessive Pattern

The non-classical form of 21-hydroxylase deficiency (NC21OH) is one of the most common monogenic diseases inherited in the autosomal-recessive pattern. The incidence of this condition in the Russian population, unlike that of its classical variant, remains to be elucidated. Aim. The objective of the present study was to estimate the true incidence of NC21OH based on the prevalence of the two most frequent mutations associated with this disease. A total of 998 randomly selected blood spots were obtained in the course of neonatal screening of the children born within one calendar year at the territory of the Moscow region. The incidence of the disease was calculated with the use of Hardi-Weinberg equation. The minimal prevalence rate of NC21OH in the population of the Moscow region was estimated to be 1:2206. The level of 17-hydroxyprogesterone (17-OHP) calculated based on the results of the screening studies can not be used to identify the carriers of the pathology of interest whereas neonatal screening allows to diagnose no more than 90% of the cases of NC21OH.

Development of a Direct Fluoroimmunoassay for Serum Levels of 17-Hydroxyprogesterone

1988 ◽  
Vol 25 (1) ◽  
pp. 35-41 ◽  
Author(s):  
B A El-Gamal ◽  
S A Eremin ◽  
D S Smith ◽  
J Landon
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Sodium Salicylate ◽  
Serum Levels ◽  
Adrenal Hyperplasia ◽  
Initial Sample ◽  
Hydroxylase Deficiency ◽  
Sample Extraction ◽  
Analytical Recovery ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

A direct, rapid and highly specific fluoroimmunoassay for determining serum levels of 17-hydroxyprogesterone has been developed. It is based on the use of a sheep antiserum covalently coupled to magnetisable particles and fluorescein-labelled steroid. Sodium salicylate is employed to eliminate interference from endogenous binding proteins in serum. The sensitivity of 0·5 nmol/L is adequate for clinical purposes. Analytical recovery, linearity and precision are satisfactory and the results obtained correlate closely with those of an established radioimmunoassay using 3H-labelled steroid and the same antiserum after initial sample extraction and chromatography. The values found for serum from normal adult subjects ranged from 1·0 to 12·6 nmol/L while those from treated and untreated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency were 1·5 to 190 and 28·0 to 655 nmol/L, respectively.

scholarly journals Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche

2011 ◽  
Vol 165 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Lucia Ghizzoni ◽  
Marco Cappa ◽  
Alessandra Vottero ◽  
Graziamaria Ubertini ◽  
Daniela Carta ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Serum Levels ◽  
Cortisol Response ◽  
Operating Characteristics ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
17 Hydroxyprogesterone ◽  
Italian Children ◽  
21 Hydroxylase Deficiency ◽  
Premature Pubarche

ObjectivePremature pubarche (PP) is the most frequent sign of nonclassic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency in childhood. The aim of this study was to assess the relationship between the CYP21A2 genotype and baseline and ACTH-stimulated 17-hydroxyprogesterone (17-OHP) and cortisol serum levels in patients presenting with PP.Patients and methodsA total of 152 Italian children with PP were studied. Baseline and ACTH-stimulated 17-OHP and cortisol serum levels were measured and CYP21A2 gene was genotyped in all subjects.ResultsBaseline and ACTH-stimulated serum 17-OHP levels were significantly higher in NCCAH patients than in both heterozygotes and children with idiopathic PP (IPP). Of the patient population, four NCCAH patients (7.3%) exhibited baseline 17-OHP values <2 ng/ml (6 nmol/l). An ACTH-stimulated 17-OHP cutoff level of 14 ng/ml (42 nmol/l) identified by the receiver-operating characteristics curves showed the best sensitivity (90.9%) and specificity (100%) in distinguishing NCCAH patients. This value, while correctly identifying all unaffected children, missed 9% of affected individuals. Cortisol response to ACTH stimulation was <18.2 μg/dl (500 nmol/l) in 14 NCCAH patients (28%) and none of the heterozygotes or IPP children. Among the 55 NCCAH patients, 54.5% were homozygous for mild CYP21A2 mutations, 41.8% were compound heterozygotes for one mild and one severe CYP21A2 gene mutations, and 3.6% had two severe CYP21A2 gene mutations.ConclusionIn children with PP, baseline 17-OHP levels are not useful to rule out the diagnosis of NCCAH, which is accomplished by means of ACTH testing only. The different percentages of severe and mild CYP21A2 gene mutations found in PP children compared with adult NCCAH patients is an indirect evidence that the enzyme defect is under-diagnosed in childhood, and it might not lead to the development of hyperandrogenic symptoms in adulthood. Stress-dose glucocorticoids should be considered in patients with suboptimal cortisol response to ACTH stimulation.

scholarly journals The Application of a New Highly-Sensitive Radioimmunoassay for Plasma 21-Deoxycortisol to the Detection of Steroid-21-Hydroxylase Deficiency

1994 ◽  
Vol 31 (1) ◽  
pp. 56-64 ◽  
Author(s):  
Jean Fiet ◽  
Jean-Marie Villette ◽  
Hervé Galons ◽  
Philippe Boudou ◽  
Jean-Michel Burthier ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Late Onset ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Hydroxylase Deficiency ◽  
Classical Form ◽  
Standard Curve ◽  
Basal Plasma ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11-hydroxylation of 17-hydroxyprogesterone. This metabolic pathway is minor in normal subjects, in whom basal plasma concentrations range from 0·03 to 0·63 nmol/L and from 0·865 to 1·50 nmol/L after adrenocorticotropic hormone (ACTH; Synacthène Immédiat, Ciba/Geigy, France). However, this metabolic pathway becomes major in 21-hydroxylase-deficient patients: in those who have the classical form of congenital adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deoxycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albumin (BSA), as well as the corresponding iodinated E and Z 21-DF-3-CMO-histamine tracers. We developed a very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF-3-CMO-BSA-E isomer antibody to an iodinated 21-DF histamine-Z isomer (standard curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the classical form of CAH in untreated newborn (basal 21-DF levels greater than 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than 11 · 54 nmol/L), and also permitted detection of 21-hydroxylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2·02 and 9·52 nmol/L).

17-HYDROXYPROGESTERONE IN THE COSYNTROPIN TEST: RESULTS IN NORMAL AND HIRSUTE WOMEN AND IN MILD CONGENITAL ADRENAL HYPERPLASIA

1979 ◽  
Vol 90 (3) ◽  
pp. 481-489 ◽  
Author(s):  
M. Gourmelen ◽  
M. T. Pham-Huu-Trung ◽  
M. G. Bredon ◽  
F. Girard
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Adrenal Hyperplasia ◽  
Acth Stimulation ◽  
Hydroxylase Deficiency ◽  
Individual Values ◽  
Minimum Concentration ◽  
The Mean ◽  
17 Hydroxyprogesterone ◽  
The Individual ◽  
21 Hydroxylase Deficiency

ABSTRACT The variations in plasma cortisol, testosterone and 17-hydroxyprogesterone (17-OHP) induced by an im injection of 0.25 mg cosyntrophin were studied in three groups of subjects: 16 healthy women, 16 hirsute women (HW) and 10 mild cases of congenital adrenal hyperplasia (CAH). The basal values of cortisol and testosterone were comparable between the three groups. In the patients with mild CAH, the mean 17-OHP concentration was increased: 483.9 ng/100 ml (113-1200 ng), but it should be noted that the individual values could overlap with the normal concentrations found in the controls and the HW during the luteal phase of the cycle. One hour after the injection of cosyntropin, a massive response of 17-OHP was observed in the mild cases of CAH, the mean basal concentration was multiplied by ten: 4843 ng/100 ml. The minimum concentration reached was 1740 ng/100 ml which is still 3-fold the highest level seen either in normal women (400 ng/ml) or in hirsute women (550 ng/100 ml). Determination of 17-OHP following a short-term ACTH stimulation, therefore provides evidence of partial 21-hydroxylase deficiency.

scholarly journals 11-oxygenated androgens useful in the setting of discrepant conventional biomarkers in 21-hydroxylase deficiency

2020 ◽  
Author(s):  
Smita Jha ◽  
Adina F Turcu ◽  
Ninet Sinaii ◽  
Brittany Brookner ◽  
Richard J Auchus ◽  
...  
Keyword(s):  
Disease Control ◽  
Good Control ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Menstrual Irregularity ◽  
Hydroxylase Deficiency ◽  
Natural History Study ◽  
Clinical Center ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Context Serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) are the conventional biomarkers used to assess disease control in patients with 21-hydroxylase deficiency (21OHD). However, discrepancy between the two is not uncommon, limiting interpretation. Objective To evaluate 11-oxyandrogens in discriminating good versus poor disease control in 21OHD in the setting of discrepant 17OHP and A4. Setting and Participants Retrospective analysis of 2,738 laboratory assessments obtained as part of Natural History Study of CAH at the NIH Clinical Center. Patients with discrepant 17OHP and A4 and available sera were selected. Methods A 15-steroid mass-spectrometry panel was performed in sera from patients with 21OHD and age- and sex-matched controls. Patients were categorized in “good” or “poor” control based on clinical assessment (bone age advancement, signs and symptoms of precocious puberty, menstrual irregularity, hirsutism, or hypogonadotrophic hypogonadism). Results Discrepant 17OHP and A4 was found in 469 (17%) laboratory assessments. Of these, 403 (86%) had elevated 17OHP with A4 in reference range. Of 46 patients with available sera, 30 (65%) were in good control. Median fold elevation relative to controls was higher in patients with poor versus good control for 11OHT (median [interquartile range], 2.82 [1.25-5.43] vs. 0.91 [0.49- 2.07], P= 0.003), and 11KT (3.57 [2.11-7.41] vs. 1.76 [1.24-4.00], P = 0.047). Fold elevation of 11OHT between 3.48 (sensitivity 97%, specificity 47%) and 3.88 (sensitivity 100%, specificity 40%) provided the best discrimination between poor vs. good control. Conclusion 11-oxyandrogens, especially 11OHT, may be useful in the management of CAH when conventional biomarkers are inconclusive.

Sign in / Sign up

Export Citation Format

Share Document