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Advances in Pediatrics Aug 2022Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth... (Review)
Review
Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth and adult height even when the body maintains endogenous GH production. In the United States, there are 8 Food and Drug Administration (FDA)-approved indications for pediatric GH therapy: GH deficiency, Prader-Willi Syndrome, small for gestational age (SGA) without catch-up growth, idiopathic short stature, Turner syndrome, SHOX gene haploinsufficiency, Noonan Syndrome, and chronic renal insufficiency. We characterize the growth patterns and effects of GH treatment in each of these indications. We also review patterns of growth that warrant referral to a pediatric endocrinologist, as well as safety updates. This review is intended to guide practitioners on the initial evaluation and management of patients with short stature, and the indications for GH therapy.
Topics: Adult; Child; Dwarfism; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Prader-Willi Syndrome; Turner Syndrome; United States
PubMed: 35985710
DOI: 10.1016/j.yapd.2022.03.005 -
Frontiers in Endocrinology 2020Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex.... (Review)
Review
Disorders of Sex Development (DSD) are congenital anomalies in which there is a discordance between chromosomal, genetic, gonadal, and/or internal/external genital sex. In XY individuals, the process of fetal sex differentiation can be disrupted at the stage of gonadal differentiation, resulting in gonadal dysgenesis, a form of early fetal-onset primary hypogonadism characterized by insufficient androgen and anti-Müllerian hormone (AMH) production, which leads to the development of ambiguous or female genitalia. The process of sex differentiation can also be disrupted at the stage of genital differentiation, due to isolated defects in androgen or AMH secretion, but not both. These are forms of fetal-onset hypogonadism with dissociated gonadal dysfunction. In this review, we present a perspective on impaired testicular endocrine function, i.e., fetal-onset male hypogonadism, resulting in incomplete virilization at birth.
Topics: Disorders of Sex Development; Humans; Hypogonadism; Male
PubMed: 32351452
DOI: 10.3389/fendo.2020.00211 -
Journal of Clinical Medicine Nov 2020In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification... (Review)
Review
In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification of disorders or anomalies of sex development. Anomalies in sex determination without sex ambiguity include gonadal dysgenesis, polysomies, male XX, and Klinefelter syndrome (dysgenesis and polysomies with a female phenotype; and sex reversal and Klinefelter with a male phenotype). Other infertility situations could also be included here as minor degrees of dysgenesis. Anomalies in sex determination with sex ambiguity should (usually) include testicular dysgenesis and ovotesticular disorders. Among the anomalies in sex differentiation, we include: (1) males with androgen deficiency (MAD) that correspond to those individuals whose karyotype and gonads are male (XY and testes), but the phenotype can be female due to different hormonal abnormalities. (2) females with androgen excess (FAE); these patients have ovaries and a 46,XX karyotype, but present varying degrees of external genital virilization as a result of an enzyme abnormality that affects adrenal steroid biosynthesis and leads to congenital adrenal hyperplasia; less frequently, this can be caused by iatrogenia or tumors. (3) Kallman syndrome. All of these anomalies are reviewed and analyzed herein, as well as related fertility problems.
PubMed: 33158283
DOI: 10.3390/jcm9113555 -
Best Practice & Research. Clinical... Jan 2022Cryptorchidism, i.e., undescended testis, is one of the most common genital malformations in newborn male babies. The birth rate of cryptorchidism varies from 1.6 to 9.0... (Review)
Review
Cryptorchidism, i.e., undescended testis, is one of the most common genital malformations in newborn male babies. The birth rate of cryptorchidism varies from 1.6 to 9.0 %. Etiology of disrupted testicular descent is complex and predisposing causes include genetic, hormonal, environmental, lifestyle and maternal factors. Testicular descent occurs in two major steps and testicular hormones and normal function of hypothalamic-pituitary-testicular axis are important for normal descent. Several gene mutations are associated with syndromic cryptorchidism but they are rarely found in boys with isolated undescended testis. Testicular regression can also cause an empty scrotum. Normal male genital phenotype indicates that the boy has had functioning testis during development. Torsion of the testis can cause testicular regression but in many cases the reason for vanishing testis remains elusive. In this narrative review we discuss genetics of cryptorchidism and testicular regression.
Topics: Cryptorchidism; Female; Gonadal Dysgenesis, 46,XY; Humans; Male; Mutation; Testis
PubMed: 35193821
DOI: 10.1016/j.beem.2022.101619 -
Frontiers in Endocrinology 2022Turner syndrome (TS) is a chromosomal disorder affecting females characterized by short stature and gonadal dysgenesis. Untreated girls with TS reportedly are... (Review)
Review
Turner syndrome (TS) is a chromosomal disorder affecting females characterized by short stature and gonadal dysgenesis. Untreated girls with TS reportedly are approximately 20-cm shorter than normal girls within their respective populations. The growth patterns of girls with TS also differ from those of the general population. They are born a little smaller than the normal population possibly due to a mild developmental delay in the uterus. After birth, their growth velocity declines sharply until 2 years of age, then continues to decline gradually until the pubertal age of normal children and then drops drastically around the pubertal period of normal children because of the lack of a pubertal spurt. After puberty, their growth velocity increases a little because of the lack of epiphyseal closure. A secular trend in height growth has been observed in girls with TS so growth in excess of the secular trend should be used wherever available in evaluating the growth in these girls. Growth hormone (GH) has been used to accelerate growth and is known to increase adult height. Estrogen replacement treatment is also necessary for most girls with TS because of hypergonadotropic hypogonadism. Therefore, both GH therapy and estrogen replacement treatment are essential in girls with TS. An optimal treatment should be determined considering both GH treatment and age-appropriate induction of puberty. In this review, we discuss the growth in girls with TS, including overall growth, pubertal growth, the secular trend, growth-promoting treatment, and sex hormone replacement treatment.
Topics: Child; Female; Humans; Turner Syndrome; Human Growth Hormone; Growth Hormone; Puberty; Hormone Replacement Therapy
PubMed: 36714599
DOI: 10.3389/fendo.2022.1068128 -
Annales D'endocrinologie Aug 2022Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of...
Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11-12years of age until the normal age of natural menopause of around 53-54years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed.
Topics: Cryopreservation; Female; Fertility; Fertility Preservation; Humans; Infertility; Pregnancy; Primary Ovarian Insufficiency; Quality of Life; Turner Syndrome
PubMed: 35728697
DOI: 10.1016/j.ando.2022.06.001 -
Cells May 2023Turner syndrome (TS), a genetic disorder due to incomplete dosage compensation of X-linked genes, affects multiple organ systems, leading to hypogonadotropic... (Review)
Review
Turner syndrome (TS), a genetic disorder due to incomplete dosage compensation of X-linked genes, affects multiple organ systems, leading to hypogonadotropic hypogonadism, short stature, cardiovascular and vascular abnormalities, liver disease, renal abnormalities, brain abnormalities, and skeletal problems. Patients with TS experience premature ovarian failure with a rapid decline in ovarian function caused by germ cell depletion, and pregnancies carry a high risk of adverse maternal and fetal outcomes. Aortic abnormalities, heart defects, obesity, hypertension, and liver abnormalities, such as steatosis, steatohepatitis, biliary involvement, liver cirrhosis, and nodular regenerative hyperplasia, are commonly observed in patients with TS. The gene plays a crucial role in short stature and abnormal skeletal phenotype in patients with TS. Abnormal structure formation of the ureter and kidney is also common in patients with TS, and a non-mosaic 45,X karyotype is significantly associated with horseshoe kidneys. TS also affects brain structure and function. In this review, we explore various phenotypic and disease manifestations of TS in different organs, including the reproductive system, cardiovascular system, liver, kidneys, brain, and skeletal system.
Topics: Humans; Female; Pregnancy; Turner Syndrome; Heart Defects, Congenital; Primary Ovarian Insufficiency; Karyotype; Karyotyping; Liver Diseases; Short Stature Homeobox Protein
PubMed: 37408200
DOI: 10.3390/cells12101365 -
Journal of Cardiovascular Development... Oct 2021Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian... (Review)
Review
Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian failure, congenital heart defects, endocrine disorders, lymphedema, and webbed neck. People with Turner syndrome have significantly increased mortality risk primarily due to cardiovascular abnormalities. The mechanisms that lead to these defects are not completely understood and are obscured by the significant variability of both karyotype and phenotype without consistent correlation between the two. This paper presents a review of the recent literature surrounding the symptoms, mechanisms, diagnosis, and treatment of Turner syndrome with a focus on cardiovascular manifestations. With technological advancements in genetics, the molecular processes of Turner syndrome have begun to be dissected. Certain genes on the X chromosome that typically escape inactivation have been implicated in both specific manifestations and broader risk categories. Recently identified genome-wide epigenetic changes may help explain the variability in presentation. It remains unclear as to how the combination of these factors results in the overall clinical picture, but advances in genomic, genetic, epigenetic, and -omics technology hold promise for providing insights that will improve the medical management of individuals with Turner syndrome.
PubMed: 34821691
DOI: 10.3390/jcdd8110138