scholarly journals Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

2012 ◽  
Vol 166 (4) ◽  
pp. 687-694 ◽  
Author(s):  
Laetitia Martinerie ◽  
Yves Morel ◽  
Claire-Lise Gay ◽  
Catherine Pienkowski ◽  
Marc de Kerdanet ◽  
...  
Keyword(s):  
Adult Height ◽  
Pubertal Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Gender Assignment ◽  
Gh Treatment ◽  
Difficult Decision ◽  
Final Stature ◽  
Low Levels ◽  
End Of Puberty

ContextGender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys.ObjectiveThe purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys.MethodsThis is a multicenter retrospective study.ResultsMean age at study was 25.6±2.4 years. Eighty-five percent of the patients presented a ‘classical’ mixed gonadal dysgenetic phenotype at birth. Puberty was initially spontaneous in all but three boys, although in six other patients, testosterone therapy was subsequently necessary for completion of puberty. Sixty-seven percent of the remaining patients presented signs of declined testicular function at the end of puberty (increased levels of FSH and low levels of testosterone and/or inhibin B). Moreover, an abnormal structure of the Y chromosome, known to alter fertility, was found in 10 out of 16 (63%) patients. Two patients developed testicular cancer. Half of the patients have adult penile length of <80 mm. Mean adult height is 156.9±2 cm, regardless of GH treatment.ConclusionsIn summary, 45,X/46,XY children born with ambiguous genitalia and raised as boys have an altered pubertal course and impaired fertility associated with adult short stature, which should, therefore, be taken into consideration for the management of these patients.

scholarly journals Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

2018 ◽  
Vol 179 (3) ◽  
pp. 181-190 ◽  
Author(s):  
Laurence Dumeige ◽  
Livie Chatelais ◽  
Claire Bouvattier ◽  
Marc De Kerdanet ◽  
Capucine Hyon ◽  
...  
Keyword(s):  
Cell Function ◽  
Pubertal Development ◽  
External Genitalia ◽  
Growth Spurt ◽  
Normal Male ◽  
Early Management ◽  
Abnormal Growth ◽  
Renal Malformations ◽  
Male Phenotype ◽  
End Of Puberty

Objective Few studies of patients with a 45,X/46,XY mosaicism have considered those with normal male phenotype. The purpose of this study was to evaluate the clinical outcome of 45,X/46,XY boys born with normal or minor abnormalities of external genitalia, notably in terms of growth and pubertal development. Methods Retrospective longitudinal study of 40 patients followed between 1982 and 2017 in France. Results Twenty patients had a prenatal diagnosis, whereas 20 patients had a postnatal diagnosis, mainly for short stature. Most patients had stunted growth, with abnormal growth spurt during puberty and a mean adult height of 158 ± 7.6 cm, i.e. −2.3 DS with correction for target height. Seventy percent of patients presented Turner-like syndrome features including cardiac (6/23 patients investigated) and renal malformations (3/19 patients investigated). Twenty-two patients had minor abnormalities of external genitalia. One patient developed a testicular embryonic carcinoma, suggesting evidence of partial gonadal dysgenesis. Moreover, puberty occurred spontaneously in 93% of patients but 71% (n = 5) of those evaluated at the end of puberty presented signs of declined Sertoli cell function (low inhibin B levels and increased FSH levels). Conclusion This study emphasizes the need to identify and follow-up 45,X/46,XY patients born with normal male phenotype until adulthood, as they present similar prognosis than those born with severe genital anomalies. Currently, most patients are diagnosed in adulthood with azoospermia, consistent with our observations of decreased testicular function at the end of puberty. Early management of these patients may lead to fertility preservation strategies.

scholarly journals Pubertal development in 46,XY patients with NR5A1 mutations

Endocrine ◽  
2021 ◽  
Author(s):  
Isabel Mönig ◽  
Julia Schneidewind ◽  
Trine H. Johannsen ◽  
Anders Juul ◽  
Ralf Werner ◽  
...  
Keyword(s):  
Pubertal Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Gene Encoding ◽  
Steroidogenic Factor 1 ◽  
Sex Development ◽  
Sex Assignment ◽  
Internal Genitalia ◽  
Differences Of Sex Development ◽  
Pubertal Transition

Abstract Purpose Mutations in the NR5A1 gene, encoding the transcription factor Steroidogenic Factor-1, are associated with a highly variable genital phenotype in patients with 46,XY differences of sex development (DSD). Our objective was to analyse the pubertal development in 46,XY patients with NR5A1 mutations by the evaluation of longitudinal clinical and hormonal data at pubertal age. Methods We retrospectively studied a cohort of 10 46,XY patients with a verified NR5A1 mutation and describe clinical features including the external and internal genitalia, testicular volumes, Tanner stages and serum concentrations of LH, FSH, testosterone, AMH, and inhibin B during pubertal transition. Results Patients who first presented in early infancy due to ambiguous genitalia showed spontaneous virilization at pubertal age accompanied by a significant testosterone production despite the decreased gonadal volume. Patients with apparently female external genitalia at birth presented later in life at pubertal age either with signs of virilization and/or absence of female puberty. Testosterone levels were highly variable in this group. In all patients, gonadotropins were constantly in the upper reference range or elevated. Neither the extent of virilization at birth nor the presence of Müllerian structures reliably correlated with the degree of virilization during puberty. Conclusion Patients with NR5A1 mutations regardless of phenotype at birth may demonstrate considerable virilization at puberty. Therefore, it is important to consider sex assignment carefully and avoid irreversible procedures during infancy.

scholarly journals Ambiguous genitalia: clinical management of adult female with male assigned gender: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mahamudu Ayamba Ali ◽  
Raymond Saa-Eru Maalman ◽  
Yaw Otchere Donkor ◽  
James Edward Mensah
Keyword(s):  
Adult Female ◽  
Surgical Intervention ◽  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Surgical Reconstruction ◽  
Successful Outcome ◽  
Early Assessment ◽  
Gender Assignment ◽  
Her Family

Abstract Background Disorders of sex development are anomalies in which the development of urogenital ridge is undifferentiated for the male and female child. Imaging plays a vital role in investigating the gross anatomy and associated anomalies. Ultrasonography, such as genitography and magnetic resonance, is the primary modality for demonstrating internal gonads and genitalia. Early multidisciplinary approach in the management of ambiguous genitalia including early surgical intervention is the predominant practice, with few current considerations on deferral of genital reconstruction until adolescent age. Case presentation We report the rare case of a 24-year-old adult female from a majority ethnic group of the Volta region, Ghana who was diagnosed and raised as male, now requiring surgical restoration to the female gender. The surgical team decided to assign external genitalia to correspond with the already intact internal organs, thus constructing the vulva. Consent was given by the client and her family members for management and surgical intervention. The surgery was scheduled and duly performed with a successful outcome. Understanding and consent was sought from the patient for the purpose of using her images for teaching, scientific publication, and demonstrations. Conclusion The advantages of deferring surgical reconstruction with psychological counseling after early assessment need to be considered to prevent inappropriate gender assignment.

scholarly journals Disorder Of Sex Development : Ambiguous Genitalia, Partial Androgen Insensitivity Syndrome

2018 ◽  
Vol 3 (2) ◽  
pp. 1
Author(s):  
Rajuddin Rajuddin ◽  
Fauzan Fauzan
Keyword(s):  
Disorders Of Sex Development ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Androgen Insensitivity Syndrome ◽  
Gender Assignment ◽  
Androgen Insensitivity ◽  
Sex Development ◽  
Molecular Term ◽  
Congenital Condition ◽  
Partial Androgen Insensitivity Syndrome

Disorders of sex development (DSDs) also known as “intersex” are congenital condition by mismatch in which chromosomal, gonadal and anatomical. One in 4.500 infants is born with abnormalities of External genitalia, and mostly unexplained in molecular term. Androgen Insensitivity Syndrome (AIS) is a common cause of DSDs. Partial Androgen Insensitivity Syndrome (PAIS) is one of three broad subdivided phenotypes of AIS. Typically, characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. In males characterized, Pais is common to observe a micropenis, hypospadias, and cryptorchidism. Individuals with PAIS that are characterized as women have been observe to have clitoromegaly and a fused labia during puberity . We reported a 13 year old child, with chief complaint primer amenorrhea. The patient admit as a girl but not yet got her menstruation. Patient was referred by Endocrinology Fertility and Reproductive Consultant of OBGYN, that has done Cromosomal and Hormonal analysis. We perform a laparascopy Exploratif and we get no uterus, fallopian tubal and ovarium that are exist. But, we found testis in inguinal canal.  Decision regarding gender assignment are still confronted between patient”s Family and medical staff. The prognosis is depends on the ambiguity of genital, Physical, and Physicosocial adjustment for sex assignment.

Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil

2020 ◽  
Vol 33 (11) ◽  
pp. 1449-1455
Author(s):  
Suzana Nesi-França ◽  
Rodrigo B. Silveira ◽  
Juliana Cristina R. Rojas Ramos ◽  
Adriane A. Cardoso-Demartini ◽  
Monica N. Lima Cat ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Neonatal Screening ◽  
Adult Height ◽  
Screening Program ◽  
Pubertal Development ◽  
Z Score ◽  
Normal Range ◽  
Adequate Treatment ◽  
Increased Risk ◽  
Puberty Onset

AbstractObjectivesAdequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients.MethodsClinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls).ResultsMedian chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 μg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04).ConclusionsIn this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

Idiopathic Short Stature

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
A.M. Pasquino ◽  
A. Albanese ◽  
M. Bozzola ◽  
G.E. Butler ◽  
F. Buzi ◽  
...  
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Idiopathic Short Stature ◽  
Psychological Benefits ◽  
Normal Children ◽  
Gh Treatment ◽  
Number Of Children ◽  
The Status ◽  
Gonadotrophin Releasing Hormone

AbstractIdiopathic short stature (ISS) is a term used to describe the status of children with short stature that cannot be attributed to a specific cause. Many children diagnosed as having ISS have partial GH insensitivity, which can result from disturbances at various points of the GH-IGF-I axis. Several clinical studies on spontaneous growth in ISS showed that adult height was almost in the range of target height. GH treatment led to adult height not significantly higher than the pretreatment predicted adult height in most reports. No metabolic side effects have been observed, even when the dose was higher than in GH deficiency. Manipulation of puberty with gonadotrophin releasing hormone analogues reported by a few authors in a small number of children has shown conflicting results. Long-term psychological benefits of GH therapy for short normal children have not been demonstrated to date.

scholarly journals 45,X/46,XY mosaicism: report on 14 patients from a Brazilian hospital. A retrospective study

2014 ◽  
Vol 132 (6) ◽  
pp. 332-338 ◽  
Author(s):  
Rafael Fabiano Machado Rosa ◽  
Willy Francisco Bartel D'Ecclesiis ◽  
Raquel Papandreus Dibbi ◽  
Rosana Cardoso Manique Rosa ◽  
Patrícia Trevisan ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Turner Syndrome ◽  
Early Recognition ◽  
External Genitalia ◽  
Ambiguous Genitalia ◽  
Referral Hospital ◽  
Clinical Genetics ◽  
Sex Development ◽  
Genital Ambiguity ◽  
The Individual

CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism.DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil.METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records.RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype.CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management.

HERMAPHRODITISM: CLASSIFICATION, DIAGNOSIS, SELECTION OF SEX AND TREATMENT

PEDIATRICS ◽  
1955 ◽  
Vol 16 (3) ◽  
pp. 287-302
Author(s):  
Lawson Wilkins ◽  
Melvin M. Grumbach ◽  
Judson J. Van Wyk ◽  
Thomas H. Shepard ◽  
Constantine Papadatos
Keyword(s):  
External Genitalia ◽  
Exploratory Laparotomy ◽  
Ambiguous Genitalia ◽  
Urogenital Sinus ◽  
Sex Characteristics ◽  
Normal Female ◽  
Anatomic Structure ◽  
Before School ◽  
And Behavior ◽  
Made In

The different types of ambisexual development have been described. It is most important in earliest infancy to differentiate, on the basis of the 17-ketosteroid excretion, female pseudohermaphroditism due to congenital adrenal hyperplasia from other forms of ambisexual development. The female pseudohermaphrodites should be reared as girls and treated with cortisone according to the methods described. Surgical exploration is not indicated. If the clitoris is enlarged it should be removed before school age and the urogenital sinus corrected to form a separate vagina. With cortisone therapy continued normal female development can be assured. When the adreno-genital syndrome has been excluded, all patients with ambiguous genitalia should be submitted to careful urethroscopic study and exploratory laparotomy. This applies also to individuals who appear to be cryptorchid males with hypospadias and those resembling females with gonads in the groins or labia. These procedures should be carried out in the earliest months of life and a definite decision made as to the sex in which the child is to be reared. Abundant evidence has been accumulated that an individual's gender role and erotic orientation are established through the cumulative experiences of years of living as a boy or a girl. Irrespective of chromosomes, gonads or hormones, the child who from earliest infancy has been steadfastly accepted as a girl or as a boy, particularly if the external genitals have been altered to conform to this sex, will not question his own gender and will conform to the habits and behavior of the sex of rearing. When there is prolonged doubt and uncertainty on the part of the parents or when a change of sex is imposed after an early age and before late adolescence the child will be confused and perplexed and psychologic difficulties result. Accordingly, every effort should be made in early infancy to decide the sex of rearing and the parents should be given support, guidance and reassurance. Necessary corrective operations should be undertaken as early in life as possible. No change from the original decision should be made in later childhood. It is advisable to select the sex of rearing according to the anatomic structure of the external genitalia rather than the type of gonads or the sex chromosomal pattern. To attempt to make a boy of an individual who does not have a fairly well-developed phallus is unwise and condemns the patient to a life of misery. Male pseudohermaphrodites who have external genitalia of female configuration invariably feminize at puberty, so that orchidectomy is not necessary to prevent masculinization. Its only indication might be to avoid the possible risk of testicular malignancy. Male pseudohermaphrodites whose genitalia resemble the male or are ambiguous may either masculinize or feminize at puberty. If it is decided to raise such a child as a female because of the small size of the phallus, orchidectomy may be performed in infancy to avoid the risk of masculinization or it may be postponed until masculinization begins. The former course often seems preferable. At puberty estrogen should be given in doses adequate to develop female sex characteristics. In these cases gonadectomy cannot be considered a mutilating operation or one which deprives the patient of fertility. On the contrary it is one which enables the patient to continue as a reasonably normal individual in the sex in which he has been reared and prevents the disastrous psychologic upheaval of a sex reversal.

Disorders of sex development

2017 ◽  
Author(s):  
David F.M. Thomas
Keyword(s):  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Surgical Reconstruction ◽  
Adrenal Hyperplasia ◽  
Specialist Care ◽  
Gender Assignment ◽  
Developmental Abnormalities ◽  
Sex Development

The aetiology of disorders of sex development (DSD) is multifactorial and includes chromosomal defects, developmental abnormalities of the gonads, and defects of hormonal synthesis and expression. Infants born with ambiguous genitalia require urgent investigation because of the risk of hyponatraemia associated with congenital adrenal hyperplasia (CAH) and to permit an informed decision on gender assignment. CAH is the commonest form of DSD, accounting for around 80% of all infants born with ambiguous genitalia. Despite controversy regarding timing and consent, feminizing genitoplasty in early childhood remains the accepted management for girls with significant clitoromegaly. Surgical reconstruction for 46XY DSD is guided by several factors, notably the size of the phallus and gonadal phenotype. The majority of individuals with disorders of sex development will require ongoing specialist care and long-term multidisciplinary follow-up and support.

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