scholarly journals An 11-year-old girl with genital ambiguity: a case of non-classical congenital adrenal hyperplasia

2020 ◽  
Vol 10 (3) ◽  
pp. 204-206
Author(s):  
Aleya Ferdush Monni ◽  
Rezwana Sobhan ◽  
Md Faruque Pathan ◽  
Faria Afsana ◽  
Feroz Amin
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Stage Iv ◽  
External Genitalia ◽  
Lower Limbs ◽  
Breast Development ◽  
Growth Spurt ◽  
Normal Female ◽  
Adrenal Hyperplasia ◽  
Excessive Sweating ◽  
Genital Ambiguity

Congenital adrenal hyperplasia (CAH) describes a group of autosomal disorders where there is impairment of cortisol biosynthesis. Here is a case of 11-year-old girl who presented with enlargement of external genitalia, excessive growth of hair in pubis, axilla, face and lower limbs along with growth spurt, excessive sweating and deepening of voice for 4 years. On examination she had normal body habitus, hirsutism (modified Ferriman- Gallwey Score-8), acanthosis nigricans in neck and axillary region, Tanner staging revealed stage-II breast development and stage IV female pattern pubic hair. Genitalia examination showed clitoromegaly with normal labia majora, minora and urethral position. Chromosomal analysis showed a normal female 46XX karyotype with normal uterus and bilateral ovaries on ultrasonography. Serum testosterone was elevated and 17- hydroxyprogesterone (17 OHP) was mildly elevated, raising the suspicion of non-classical congenital adrenal hyperplasia which was confirmed later by performing short Synacthen test. Patient and her parents were counseled regarding the diagnosis and clitoroplasty was done and prednisolone 5 mg daily at night in reverse circadian rhythm started. After 3 months of treatment, her hirsutism significantly reduced and menstruation had begun. Birdem Med J 2020; 10(3): 204-206

scholarly journals So, and if it is not congenital adrenal hyperplasia? Addressing an undiagnosed case of genital ambiguity

2021 ◽  
Author(s):  
Reinaldo Luna de Omena Filho ◽  
Reginaldo José Petroli ◽  
Fernanda Caroline Soardi ◽  
Débora de Paula Michelatto ◽  
Taís Nitsch Mazzola ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Treatment Options ◽  
External Genitalia ◽  
Autosomal Recessive Disorder ◽  
Missense Variant ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genital Ambiguity ◽  
21 Hydroxylase Deficiency

Abstract The Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene. In this disorder/difference of sex development, the conversion of androstenedione into testosterone is impaired. The appearance of external genitalia of 46,XY individuals varies from typically male to almost female. We report on a child presenting severe ambiguous genitalia. Due to access constraints, specialized care did not start until the child was 10 months old. Parents are consanguineous and were born in an area of high isonymy that is a cluster for rare recessive diseases. A new homozygous missense variant c.785G > T was found in exon 10 of the HSD17B3 gene. Researchers-clinicians and researchers-researchers collaborative efforts to elucidate the genetic basis of this disease were critical since this etiologic investigation is not available through the public health system. This case exemplifies the families’ pilgrimage in cases of genital ambiguity due to a rare genetic condition. Recognizing the etiology was the baseline to provide information on prognosis and treatment options, and to shelter family and child doubts and hopes in order to better support their decisions.

Rationale of a lower dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on pharmacokinetic modelling

2021 ◽  
Author(s):  
Viktoria Stachanow ◽  
Uta Neumann ◽  
Oliver Blankenstein ◽  
Uwe Fuhr ◽  
Wilhelm Huisinga ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Stochastic Simulations ◽  
Minimum Effective Dose ◽  
Adrenal Hyperplasia ◽  
Androgen Excess ◽  
Nonlinear Mixed Effects Model ◽  
Dexamethasone Therapy ◽  
Fit For Purpose ◽  
Pituitary Adrenal Axis

Context: Prenatal dexamethasone therapy is used in female foetuses with congenital adrenal hyperplasia to suppress androgen excess and prevent virilisation of the external genitalia. The traditional dexamethasone dose of 20 µg/kg/d has been used since decades without examination in clinical trials and is thus still considered experimental. Objective: Because the traditional dexamethasone dose potentially causes adverse effects in treated mothers and foetuses, we aimed to provide a rationale of a reduced dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on a pharmacokinetics-based modelling and simulation framework. Methods: Based on a published dexamethasone dataset a nonlinear mixed-effects model was developed describing maternal dexamethasone pharmacokinetics. In stochastic simulations (n=1000) a typical pregnant population (n=124) was split into two dosing arms receiving either the traditional 20 µg/kg/d dexamethasone dose or reduced doses between 5 and 10 µg/kg/d. Target maternal dexamethasone concentrations, identified from literature, served as threshold to be exceeded by 90% of mothers at steady state to ensure foetal hypothalamic‐pituitary‐adrenal axis suppression. Results: A two-compartment dexamethasone pharmacokinetic model was developed and subsequently evaluated to be fit for purpose. The simulations, including a sensitivity analysis regarding the assumed foetal:maternal dexamethasone concentration ratio, resulted in 7.5 µg/kg/d to be the minimum effective dose and thus our suggested dose. Conclusions: We conclude that the current experimentally used dexamethasone dose is 3-fold higher than needed, possibly causing harm in treated foetuses and mothers. The clinical relevance and appropriateness of our recommended dose should be tested in a prospective clinical trial.

scholarly journals Validation and Preliminary Results of the Parental Assessment of Children's External Genitalia Scale for Females (PACE-F) for Girls With Congenital Adrenal Hyperplasia

Urology ◽  
2019 ◽  
Vol 130 ◽  
pp. 132-137
Author(s):  
Konrad M. Szymanski ◽  
Benjamin Whittam ◽  
Patrick O. Monahan ◽  
Martin Kaefer ◽  
Heather Frady ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Adrenal Hyperplasia ◽  
Preliminary Results ◽  
Parental Assessment

Therapeutic challenges in a patient with the simple virilizing (SV) form of congenital adrenal hyperplasia (CAH) due to the P30L/I172N genotype

2019 ◽  
Vol 32 (5) ◽  
pp. 543-547 ◽  
Author(s):  
Maja Tankoska ◽  
Violeta Anastasovska ◽  
Marina Krstevska-Konstantinova ◽  
Michel Naydenov ◽  
Mirjana Kocova
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Polymerase Chain Reaction Amplification ◽  
Point Mutations ◽  
External Genitalia ◽  
High Serum ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Her Family ◽  
Simple Virilizing ◽  
21 Hydroxylase Deficiency

Abstract Background Steroid 21-hydroxylase deficiency is an autosomal recessive disorder, present in 90–95% of all cases with congenital adrenal hyperplasia (CAH). The classical simple virilizing (SV) form of the disease causes virilization of the external genitalia in newborn females and pseudo-precocious puberty in both sexes, due to reactive androgen overproduction. Case presentation We describe a 3.5-year-old girl presenting with pubarche, P2 according to Tanner, advanced bone age of 6 years and 10 months, and high serum levels of 17-hydroxyprogesterone (17-OHP). Molecular analysis of the nine most common pseudogene-derived CYP21A2 point mutations was performed in the patient and her family members using the polymerase chain reaction/amplification-created restriction site (PCR/ACRS) method. We detected the P30L/I172N genotype in the patient. She had inherited a mild P30L mutation from her mother and a severe I172N mutation from her father. Conclusions Although the CAH phenotype is determined by the allele that produces most of the enzyme activity and the mild non-classical (NC) phenotype should be expected, the mild P30L known to be more virilizing probably induced the classical SV phenotype in our patient. A continuous regimen of hydrocortisone at a recommended dose failed to decrease the 17-OHP sufficiently. Careful tapering of the dose did not help, and her pubic hair advanced to P3 according to Tanner. Individually tailored treatment is warranted in this patient.

scholarly journals Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency*

2000 ◽  
Vol 21 (3) ◽  
pp. 245-291 ◽  
Author(s):  
Perrin C. White ◽  
Phyllis W. Speiser
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
External Genitalia ◽  
Clinical Severity ◽  
Sodium Balance ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Gene Encoding ◽  
Salt Wasting ◽  
Direct Mutation ◽  
21 Hydroxylase Deficiency

Abstract More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal “salt wasting” crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions—transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed.

scholarly journals Congenital Adrenal Hyperplasia in Patients with Disorders of Sexual Differentiation

2020 ◽  
Vol 1 (3) ◽  
pp. 25-30
Author(s):  
Warda Fatima ◽  
Tayyaba Rafiq ◽  
Saqib Mahmood
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Sexual Differentiation ◽  
Tertiary Care ◽  
Female Gender ◽  
Chromosomal Analysis ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Genital Ambiguity ◽  
Disorders Of Sexual Differentiation ◽  
21 Hydroxylase Deficiency

Congenital Adrenal Hyperplasia (CAH) is considered to be the most common cause of genital ambiguity in children. According to World’s literature, 90-95% of this disease is caused by 21-hydroxylase deficiency that impairs the synthesis of cortisol and aldosterone. The consequent excess in androgen production leads to virilization in the affected females. This study was aimed to find the number of cases with CAH (21-hydroxylase deficiency) in the children presented with disorders of sexual differentiation. For this purpose, 100 patients presented to The Children’s hospital for gender assessment were taken and their 17- OH progesterone levels were measured to confirm 21-hydroxylase deficiency, and chromosomal analysis was done to confirm chromosomal sex. Results indicated that out of 100 patients 49 were suffering from CAH. 63.2% of CAH patients were initially presented as males. Out of these, 44.8% were reassigned female gender on chromosomal analysis. So, it is concluded that the majority of patients presented with genital ambiguity in the tertiary care health facility have the ambiguity due to congenital adrenal hyperplasia.

scholarly journals A neglected case of treatable genetic disorder

2016 ◽  
Vol 4 (04) ◽  
pp. 01-03
Author(s):  
C. Rekha ◽  
R. Paramaguru ◽  
Vimala Sarojini ◽  
Dinisha Einstien ◽  
A. Prathiba
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Genetic Disorder ◽  
External Genitalia ◽  
Female Child ◽  
Ambiguous Genitalia ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Adrenal Hormones ◽  
Stage 4 ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia(CAH) is a autosomal recessive genetic disorder involving adrenal hormones resulting in excessive production of androgens and hence their effects. Here we report a case of CAH which was diagnosed very late but was treated successfully. 12 years old female child came to us with ambiguous genitalia. Examination showed praders stage 4 external genitalia. Evaluated further and confirmed as a case of classic type of simple virilising congenital adrenal hyperplasia due to 21 hydroxylase deficiency. She was successfully treated with steroids and surgical correction was also done. Now child has also attained menarche and on follow up at our pediatric out patient department.

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