Premature pubarche in a child with abnormal 3<i>β</i>‐hydroxysteroid dehydrogenase function and Klinefelter syndrome: the intriguing relationship between androgen deficiency and excess

Gortakowski, Michele; Conroy, Rushika; Aguiar, Luisa; Allen, Holley

doi:10.1002/ccr3.742

Cited by 6 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…He was found to have karyotype 47XXY, and a post hoc molecular analysis showed that a pathogenic variant in HSD3B2 and not CYP21A2 was the cause of the disease. The association of Klinefelter syndrome and CAH is extremely rare, with very few cases reported in the literature [ [39] , [40] , [41] ]. More details of this case will be presented in a future manuscript.…”

Section: Discussionmentioning

confidence: 99%

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Umaña-Calderón

Acuña-Navas

Alvarado

et al. 2021

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

Steroid 21-hydroxylase deficiency accounts for 95% of congenital adrenal hyperplasia (CAH) cases. Newborn screening has allowed for early detection of the disease, and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design Observational, retrospective, descriptive study based on the review of patient records who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 ( N = 58). Objective To describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency at the National Children's Hospital “Dr. Carlos Sáenz Herrera”, Caja Costarricense de Seguro Social (CCSS) in Costa Rica. Results 53% (31/58) of the patients were male and 80% (37/46) were born full term; 72% (42/58) had salt wasting phenotype, 9% (5/58) simple virilizing phenotype and 19% (11/58) non-classic phenotype. The most frequent variants were c.292+5G>A in 26% (15/58) of patients and Del/Del in 21% (12/58) of them. Conclusions The most frequent mutation in our study population was the c.292+5G>A, which was found in 15/58 patients. This rare variant has only been reported in three other studies so far but as an infrequent mutation in CAH patients. The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect.

show abstract

Section: Discussionmentioning

confidence: 99%

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Umaña-Calderón

Acuña-Navas

Alvarado

et al. 2021

Molecular Genetics and Metabolism Reports

View full text Add to dashboard Cite

show abstract

“…So, we can speculate that high adrenal androgen secretion by CAH had a greater relevance than the low testicular androgen production, typical of KS. Till now there are 5 reported cases of co-occurrence of KS with CAH, one of them had 3BHSD2 deficiency but with a different presentation and the rest of them had 21-OH deficiency ( 23 , 24 , 25 , 26 , 27 ). Four of them were detected in boys and another one in a 51-year-old male.…”

Section: Discussionmentioning

confidence: 99%

A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity

Shehab

Mahmood

Hasanat

et al. 2018

Endocrinology, Diabetes &Amp; Metabolism Case Reports

View full text Add to dashboard Cite

SummaryCongenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3β-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3β-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3β-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well.Learning points:Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH.High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3β-HSD enzyme deficiency.Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations.Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism.Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.

show abstract

“…The patient was administered testosterone supplementation therapy, after which he underwent mammary plastic surgery. The fourth reported case was a boy who was diagnosed with CAH associated with 3β-Hydroxysteroid dehydrogenase deficiency at 8 years of age and KS at 9 years of age because he had a 47, XXY karyotype (10). He had a short stature and exhibited premature pubarche at 6 years of age.…”

Section: Ohd Is the Most Common Cause Of Cah Which Is Caused By Patho...mentioning

confidence: 99%

Treatment of congenital adrenal hyperplasia and Klinefelter Syndrome with central precocious puberty: a case report

Li¹,

Zhang²,

Пин³

2022

Transl Pediatr

View full text Add to dashboard Cite

The simultaneous occurrence of Klinefelter syndrome (KS) and congenital adrenal hyperplasia (CAH) is extremely rare, as the former causes androgen deficiency, while the latter results in androgen excess. In addition, central precocious puberty (CPP) will occur, which is caused by the activation of the hypothalamic-pituitary-gonadal (HPG) axis by androgens. We present the 7th reported case of simultaneous KS and CAH in a boy with CPP due to protopathy of CAH. He presented with increased gonadotropin and excessive androgen levels, and was diagnosed with KS due to his unexpected karyotype analysis results. This is the first reported case of an association between KS and CAH to undergo gonadotropin-releasing hormone analog (GnRHa) and recombinant human growth hormone (rhGH) therapy to increase his predicted final height. His predicted adult height was approximately 160 cm by estimation using the bone age as well as current height, which is much taller than the estimated height before treatment. Although KS may cause hypogonadism, the patient should be administered GnRHa and rhGH therapy if simultaneous CAH, CPP, and KS are present to increase the patient's predicted final height. Excessive androgen levels may mask the symptoms of KS-related hypogonadism during childhood; however, the patient should be made aware of the possibility of hypogonadism developing in the future.

show abstract

Premature pubarche in a child with abnormal 3β‐hydroxysteroid dehydrogenase function and Klinefelter syndrome: the intriguing relationship between androgen deficiency and excess

Abstract: Key Clinical MessageDisorders of androgen excess may coexist with disorders of androgen deficiency, such as Klinefelter syndrome, and can create diagnostic and therapeutic challenges.

Cited by 6 publications

References 10 publications

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity

Treatment of congenital adrenal hyperplasia and Klinefelter Syndrome with central precocious puberty: a case report

Contact Info

Product

Resources

About