scholarly journals A Giant Ovarian Cyst in a Neonate with Classical 21-Hydroxylase Deficiency with Very High Testosterone Levels Demonstrating a High-Dose Hook Effect

2012 ◽  
Vol 4 (3) ◽  
pp. 151-153 ◽  
Author(s):  
Tülay Güran ◽  
Gözde Yeşil ◽  
Ömer Güran ◽  
Suna Cesur ◽  
Oktav Bosnalı ◽  
...  
Keyword(s):  
Ovarian Cyst ◽  
High Dose ◽  
Hydroxylase Deficiency ◽  
Testosterone Levels ◽  
Hook Effect ◽  
21 Hydroxylase Deficiency ◽  
Very High

scholarly journals Failure of Cortisone Acetate Treatment in Congenital Adrenal Hyperplasia because of Defective 11β-Hydroxysteroid Dehydrogenase Reductase Activity*

1999 ◽  
Vol 84 (4) ◽  
pp. 1210-1213 ◽  
Author(s):  
Anna Nordenström ◽  
Claude Marcus ◽  
Magnus Axelson ◽  
Anna Wedell ◽  
E. Martin Ritzén
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Reductase Activity ◽  
Urinary Metabolites ◽  
Hydroxysteroid Dehydrogenase ◽  
Cortisone Acetate ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genetic Lesion ◽  
21 Hydroxylase Deficiency ◽  
Very High

Congenital adrenal hyperplasia in children is often treated with cortisone acetate and fludrocortisone. It is known that certain patients with congenital adrenal hyperplasia require very high substitution doses of cortisone acetate, and a few patients do not respond to this treatment at all. A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2·day), was examined. The activation of cortisone to cortisol was assessed by measuring urinary metabolites of cortisone and cortisol. The patient’s inability to respond to treatment with cortisone acetate was found to be caused by a low conversion of cortisone to cortisol, assumed to be secondary to low 11β-hydroxysteroid dehydrogenase activity (11-oxoreductase deficiency). All exons and exon/intron junctions of the 11β-hydroxysteroid dehydrogenase type1 gene (HSD11L) were sequenced without finding any mutations, but a genetic lesion in the promoter or other regulatory regions cannot be ruled out. The deficient 11-oxoreductase activity seems to have been congenital, in this case, but can possibly be attributable to a down-regulation of the enzyme activity. The results support the use of hydrocortisone, rather than cortisone acetate, for substitution therapy in adrenal insufficiency.

Serum total testosterone levels in a patient with late onset 21-hydroxylase deficiency and a twin gestation

2007 ◽  
Vol 87 (5) ◽  
pp. 1212.e5-1212.e8 ◽  
Author(s):  
Lindsay M. Mains ◽  
Ruth B. Lathi ◽  
Richard O. Burney ◽  
Michael H. Dahan
Keyword(s):  
Late Onset ◽  
Total Testosterone ◽  
Hydroxylase Deficiency ◽  
Testosterone Levels ◽  
21 Hydroxylase Deficiency

scholarly journals Huge ovarian cyst in a neonate with classical 21-hydroxylase deficiency

2021 ◽  
Vol 30 (1) ◽  
pp. 57-60
Author(s):  
Yasmine Abdelmeguid ◽  
Nada Yakout ◽  
Ahmed Oshiba ◽  
Mostafa Zain ◽  
Mostafa Kotb
Keyword(s):  
Ovarian Cyst ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

Adrenocortical Tumor in a Patient with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

PEDIATRICS ◽  
1981 ◽  
Vol 68 (2) ◽  
pp. 242-246
Author(s):  
Songja Pang ◽  
Dorothy Becker ◽  
James Cotelingam ◽  
Thomas P. Foley ◽  
Allan L. Drash
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
High Dose ◽  
Base Line ◽  
Cortical Tissue ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Serum Progesterone ◽  
High Dose Dexamethasone ◽  
Dexamethasone Therapy ◽  
21 Hydroxylase Deficiency

An adrenal cortical tissue tumor developed in a patient with poorly controlled salt-losing congenital adrenal hyperplasia. A 16-year-old girl became progressively virilized from 13 to 16 years of age. Base line serum progesterone, 17-hydroxyprogesterone, and testosterone levels were high and there was a diurnal pattern of the hormones. Initially elevated urinary 17-ketosteroid and serum steroid levels were decreased by high dose dexamethasone therapy, and at laparotomy an adenoma was found in the cortex of the hyperplastic left adrenal gland. It is inferred that persistent adrenocorticotropic hormone stimulation may result in neoplastic transformation of hyperplastic adrenal cortical tissue in patients with congenital adrenal hyperplasia.

scholarly journals Initial high dose hydrocortisone (HDC) treatment for 21-hydroxylase deficiency (21-OHD) does not affect linear growth during the first three years of life

2012 ◽  
Vol 59 (11) ◽  
pp. 1001-1006 ◽  
Author(s):  
Kei Takasawa ◽  
Makoto Ono ◽  
Kentrao Miyai ◽  
Yohei Matsubara ◽  
Fumihiko Takizawa ◽  
...  
Keyword(s):  
Linear Growth ◽  
High Dose ◽  
Hydroxylase Deficiency ◽  
21 Hydroxylase Deficiency

scholarly journals Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children

2020 ◽  
Author(s):  
Zhuo Chang ◽  
Wei Lu ◽  
Zhu-Hui Zhao ◽  
Li Xi ◽  
Xiao-Jing Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Testosterone Levels ◽  
Novel Variants ◽  
Novel Variant ◽  
Threatening Condition ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Background Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. Results Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p. 279GfsX17) and c.651 + 2T > G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p. 108S > X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399 + 1G > A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein. Conclusions We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.

scholarly journals Pitfalls of Prenatal Diagnosis guiding Postnatal Management in Congenital Adrenal Hyperplasia(CAH)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A150-A151
Author(s):  
Deepa Badrinath Murthy ◽  
Melissa Kaori Litao ◽  
Bina Cherryl Shah ◽  
Brenda Kohn ◽  
Emily Nicole Breidbart
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Urogenital Sinus ◽  
High Dose ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Postnatal Management ◽  
Genotype Phenotype Correlation ◽  
Classic Cah ◽  
21 Hydroxylase Deficiency

Abstract Background: 21-hydroxylase deficiency is the most common form of CAH and is associated with a variety of clinical phenotypes (salt wasting SW, simple virilizing SV and non-classic NCCAH). Commonly, there is a strong genotype-phenotype correlation for SW and NCCAH, but this is less predictable with the SV forms. We present a case with prenatal diagnosis of classic CAH which demonstrated genotype-phenotype discordance. Clinical Case: Ex 39 weeker female born to non-consanguineous parents was prenatally diagnosed with CAH based on routine genetic screen. Mother was noted to be a carrier for Intron 2G and father was a carrier of p.I172N both known to be pathogenic variants on CYP21A2. At 23 weeks gestational age, DNA analysis revealed fetus was compound heterozygous for both mutations which is most commonly associated with either SV or SW phenotype. At birth, infant had mild edema of the labia majora which resolved; the clitoris was not enlarged. There was no genital virilization or urogenital sinus. Newborn screen sent at 15 hours of life:17 OHP 132 ng/ml, repeat on DOL 3:77 ng/ml and DOL 13:59.9 ng/ml. High dose cosyntropin stim test on DOL 3 at 0 min: Cortisol not done, 17 OHP 1279 ng/dl; 60 min: Cortisol 12.3mcg/dl, 17OHP 3394 ng/dl. DOL 5 at 0 min: Cortisol 2.7 mcg/dl, ACTH 164.5 pg/ml, 17OHP 803.7 ng/dl; 60 minute: Cortisol 7.6mcg/dl, 17OHP 5920 ng/dl. Using available 17OHP normograms, the infant’s stimulated 17 OHP levels were not consistent with classic CAH. Unstimulated testosterone on DOL 3: 25ng/dl, DOL 5: 14 ng/dl. Ultrasound showed adrenal gland thickness 4mm bilaterally (upper limit of normal). Hydrocortisone (HC) was started on DOL 5 at 35 mg/m2/day after the stim test. On DOL 7, HC was increased to 100 mg/m2/day; fludrocortisone 0.1 mg twice daily and NaCl 0.5 g/day were started (Na 131, K 6.5, plasma renin activity 80.2). Upon discharge (DOL 13), infant was on HC 35 mg/m2/day, Fludrocortisone 0.1mg twice daily and NaCl 2g/day. Doses were adjusted accordingly during outpatient follow up. Currently infant is 4 months of age, thriving and remains on HC 11.3 mg /m2/day, Fludrocortisone 0.05 mg twice daily and NaCl 750 mg daily. Postnatal genetic analysis confirmed prenatal genotype. Conclusion: In general, genotype-phenotype correlation has 80–90% concordance. However clinicians should be aware of genotype/phenotype discrepancies that exist in order to carefully guide postnatal management based on prenatal genetic analysis. Our patient’s 17-ohp was done by LC/MS, which is standard now for most specialized endocrine laboratories. However, the 17-ohp nomograms for CAH, which are frequently used for subtype categorization, are based on RIA levels. Further studies would be helpful in creating an updated normogram using LCMS specifically for the neonatal period, as confirmatory screening of CAH will become more common with the rise in parental prenatal carrier screening.

scholarly journals Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children

2020 ◽  
Author(s):  
Zhuo Chang ◽  
Wei Lu ◽  
Zhu-Hui Zhao ◽  
Li Xi ◽  
Xiao-Jing Li ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Information ◽  
Hydroxylase Deficiency ◽  
Primary Adrenal Insufficiency ◽  
Salt Wasting ◽  
Testosterone Levels ◽  
Novel Variants ◽  
17 Hydroxyprogesterone ◽  
21 Hydroxylase Deficiency

Abstract Background: Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.Methods: Seventy children were enrolled. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.Results: Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p.279GfsX17) and c.651+2T>G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p.108S>X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399+1G>A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399+1G>A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein.Conclusions: We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.

scholarly journals Genetic, anthropometric and metabolic features of adult Norwegian patients with 21-hydroxylase deficiency

2012 ◽  
Vol 167 (4) ◽  
pp. 507-516 ◽  
Author(s):  
Ingrid Nermoen ◽  
Ingeborg Brønstad ◽  
Kristian J Fougner ◽  
Johan Svartberg ◽  
Marianne Øksnes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Fat Mass ◽  
Normal Population ◽  
Final Height ◽  
Population Based ◽  
Hydroxylase Deficiency ◽  
Cross Sectional ◽  
Testosterone Levels ◽  
21 Hydroxylase Deficiency

ObjectiveThe aim of this study was to determine the genetic, anthropometric and metabolic features in an unselected population of adult Norwegian patients with 21-hydroxylase deficiency (21OHD).Patients, methods and designSixty-four 21OHD patients participated (23 men and 41 women; median age 38.5 years; range 19–72 years) in a cross-sectional study including DNA sequencing ofCYP21A2, anthropometric measurements including dual X-ray absorptiometry scanning and biochemical analyses. The results were compared with reference cohorts from the general population.ResultsWe identified four novel and plausibly disease-causingCYP21A2mutations. Gene deletions/conversions (42.1% of alleles), the splice mutation I2 splice (23.0%) and point mutation I172 N (22.2%) were common. The genotype corresponded to clinical phenotype in 92% of the patients. The prevalence of osteopenia was 48% in males and 34% in females. Both men and women had normal BMI but markedly increased fat mass compared with the normal population. Diastolic blood pressure was higher than normal. Thirty-nine per cent of the women had testosterone levels above the normal range; 13% of the men had testosterone levels below normal. Reduced final height was more pronounced in men (median −11.2 cm, −1.77 SDS) than in women (−6.3 cm, −1.07 SDS).ConclusionsIn this population-based survey of 21OHD, we identified four novel mutations and high concordance between genotype and phenotype. The patients had increased fat mass, increased diastolic blood pressure, reduced final height and high frequency of osteopenia among males. These results show unfavourable metabolic features in 21OHD patients indicating a need for improvement of treatment and follow-up.

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