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Fertility and Sterility Jan 2019Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid... (Review)
Review
Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible. Prenatal genetic diagnosis via amniocentesis or chorionic villus sampling was used to determine the need for continuing fetal therapy (dexamethasone), allowing cessation if the fetus was unaffected. Newer methods now allow diagnosis earlier in gestation, further shortening the treatment time for unaffected female fetuses who will not develop genital ambiguity. Preimplantation genetic testing permits transfer only of an unaffected female or male fetus. Analysis of maternal cell-free DNA based on quantitative differences in the amount of allele parental DNA permits affected pregnancies to be differentiated from unaffected pregnancies.
Topics: Adrenal Hyperplasia, Congenital; Embryo Transfer; Female; Genetic Counseling; Genetic Testing; Humans; Male; Pregnancy; Preimplantation Diagnosis; Prenatal Diagnosis
PubMed: 30611408
DOI: 10.1016/j.fertnstert.2018.11.041 -
Best Practice & Research. Clinical... Apr 2009In adult patients with congenital adrenal hyperplasia (CAH) the presence of testicular adrenal rest tumours (TART) is an important cause of gonadal dysfunction and... (Review)
Review
In adult patients with congenital adrenal hyperplasia (CAH) the presence of testicular adrenal rest tumours (TART) is an important cause of gonadal dysfunction and infertility. In the last decade several papers have focused on the origin and pathogenesis of these tumours. In this paper we review the embryological, histological, biochemical and clinical features of TART and discuss the treatment options. Furthermore, we propose a new five-stage classification of TART, based on sonographic, clinical and biochemical parameters, that may lead to a better follow up and treatment of patients with TART.
Topics: Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Adult; Female; Humans; Male; Ovarian Neoplasms; Testicular Neoplasms
PubMed: 19500764
DOI: 10.1016/j.beem.2008.09.007 -
Hormone Research 2008During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization... (Review)
Review
During childhood, the main aims of the medical treatment of congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase are to prevent salt loss and virilization and to attain normal stature and normal puberty. As such, there is a narrow therapeutic window through which the intended results can be achieved. In adulthood, the clinical management has received little attention, but recent studies have shown the relevance of long-term follow-up of these patients. The aims here are to review the multiple clinical, hormonal and metabolic abnormalities that could be found in adult CAH patients as such a decrease in bone mineral density, overweight and disturbed reproductive functions. In women with classic CAH, a low fertility rate is reported, and is probably the consequence of multiple factors including neuroendocrine and hormonal factors, feminizing surgery, and psychological factors. Men with CAH may present hypogonadism either through the effect of adrenal rests or from suppression of gonadotropins resulting in infertility. Therefore a multidisciplinary team with knowledge of CAH should carefully follow up these patients, from childhood through to adulthood, to avoid these complications and to ensure treatment compliance and tight control of the adrenal androgens.
Topics: Adrenal Hyperplasia, Congenital; Adult; Humans; Infertility; Metabolism, Inborn Errors; Obesity; Osteoporosis; Steroid 21-Hydroxylase
PubMed: 18204267
DOI: 10.1159/000113020 -
Journal of Pediatric Endocrinology &... May 2006Congenital adrenal hyperplasia (CAH) is generally regarded as a paediatric endocrine disease, but nowadays nearly all patients reach adulthood as a result of improved... (Review)
Review
Congenital adrenal hyperplasia (CAH) is generally regarded as a paediatric endocrine disease, but nowadays nearly all patients reach adulthood as a result of improved diagnosis and treatment. It is now increasingly recognised that treatment goals shift during life: one of the major treatment goals in childhood and puberty, i.e. normal growth and development, is no longer relevant after childhood, whereas other aspects, such as fertility and side effects of long-term glucocorticoid treatment, become more important in adulthood. This paper focuses on fertility in male and female adult patients with CAH. In males with CAH the fertility rate is reduced compared with the normal population, the most frequent cause being testicular adrenal rest tumours. Development and growth of these tumours is assumed to be ACTH dependent and undertreatment may play an important role. If intensifying glucocorticoid treatment does not lead to tumour decrease, surgical intervention may be considered, but the effect on fertility is not yet known. In females with CAH the degree of fertility depends on the phenotype of the CAH. Most fertility problems are seen in the classic salt-wasting type. Age of menarche and regularity of the menstrual cycle depends on the degree of adrenal suppression. Not only adrenal androgens have to be normalised but also the levels of adrenal progestins (progesterone and 17-OH-progesterone) that interfere with normal ovulatory cycles. The regularity of menstrual cycles can be considered as an important measure of therapeutic control in adolescent females with CAH and therefore as a therapeutic goal from (peri)pubertal years on. Other factors that contribute to impaired fertility in females with CAH are ovarian hyperandrogenism (polycystic ovary syndrome), ovarian adrenal rest tumours, genital surgery and psychological factors. Subfertility in CAH can have its origin already in the peripubertal years and is therefore of interest to the paediatric endocrinologist.
Topics: Adrenal Hyperplasia, Congenital; Adult; Female; Fertility; Humans; Male
PubMed: 16789634
DOI: 10.1515/jpem.2006.19.5.677 -
The Turkish Journal of Pediatrics 2022Type 1 pseudohypoaldosteronism (PHA1) is a rare condition characterized by the resistance of the kidney to the effect of aldosterone. Secondary PHA1 is a syndrome that...
BACKGROUND
Type 1 pseudohypoaldosteronism (PHA1) is a rare condition characterized by the resistance of the kidney to the effect of aldosterone. Secondary PHA1 is a syndrome that is most often related to urinary tract anomalies (UTAs) and/or urinary tract infections (UTIs). A similar pattern of electrolyte impairment is seen in congenital adrenal hyperplasia (CAH) and secondary PHA1, and CAH is a condition that requires urgent treatment. In our study, eight patients aged between 15 days and 8 months (seven males and one female) were included in the evaluation. It was aimed to evaluate cases of secondary PHA1 in our clinic and to identify the problems encountered in diagnosis and follow-up.
METHODS
The records of the patients who presented to our hospital between February 2010 and 2021 were retrieved and retrospectively scanned.
RESULTS
In all cases, hyponatremia, hyperkalemia, hyperaldosteronism, and hyperreninemia were detected. Other biochemical and hormonal tests were normal. Leukocytosis was detected in urine analysis, and urine cultures were productive. UTA was detected in five cases. Nine episodes of PHA1 occurred in eight patients and fungal infections were responsible for causing two episodes. Four episodes of PHA1 needed mineralocorticoid treatment. On the third day, serum electrolytes normalized. Fludrocortisone treatment was continued for 1 week. In one case, UTIs were repeated with PHA1, but in the follow-up, there were no additional problems.
CONCLUSIONS
Secondary PHA1 should be kept in mind when hyponatremia and hyperkalemia are seen, especially in infants aged under 3 months or older, up to 8 months, who present with non-specific symptoms. Fungal infections should not be forgotten in UTI etiology because PHA1 episodes can be initiated. If CAH is suspected, mineralocorticoid treatment should be rapidly initiated.
Topics: Adrenal Hyperplasia, Congenital; Female; Humans; Hyperkalemia; Hyponatremia; Infant; Male; Mineralocorticoids; Pseudohypoaldosteronism; Retrospective Studies; Urinary Tract Infections
PubMed: 35899562
DOI: 10.24953/turkjped.2021.1443 -
Frontiers in Endocrinology 2023
Topics: Humans; Adrenal Hyperplasia, Congenital; Steroid 21-Hydroxylase
PubMed: 38075037
DOI: 10.3389/fendo.2023.1332962 -
Advances in Clinical and Experimental... Mar 20213β-HSD deficiency is a rare type of congenital adrenal hyperplasia (CAH), which is caused by HSD3B2 gene mutations.
BACKGROUND
3β-HSD deficiency is a rare type of congenital adrenal hyperplasia (CAH), which is caused by HSD3B2 gene mutations.
OBJECTIVES
In order to improve the understanding and diagnosis of the disease, we analyzed and summarized the clinical characteristics, genetic variants and treatment for 3 children with 3β-HSD deficiency in this study.
MATERIAL AND METHODS
A summary of the clinical data, hormone levels (17-hydroxyprogesterone, adrenocorticotropic hormone, cortisol, testosterone, dehydroepiandrosterone, androstenedione, renin, and aldosterone), therapeutic drugs, and gene sequencing results from 3 3β-HSD deficiency patients was created.
RESULTS
The 3 patients developed external genital abnormalities and adrenal insufficiency in infancy. Steroid hormone levels were consistent with 3β-hydroxysteroid dehydrogenase deficiency. Gene sequencing for the 3 patients detected complex heterozygous mutations in the HSD3B2 gene, which confirmed the diagnosis of 3β-HSD deficiency type II. Among the mutation types, c.154_162delinsTCCTGTT and c.674T>A have not been reported in the literature. The 3 children were treated with glucocorticoid and mineralocorticoid replacement, which controlled the adrenal insufficiency satisfactorily. In 2 male patients, external genital dysplasia manifested as hypospadias and small penis. After long-acting testosterone intramuscular injection to increase the penis size, the hypospadias were repaired. Mild masculinization in the female patient resulted in skin pigmentation and clitoral hypertrophy; however, no surgical intervention was required.
CONCLUSIONS
The main clinical manifestations of 3β-HSD deficiency were adrenal insufficiency and sex hormone synthesis dysfunction. There was a strong phenotype correlation between the observed clinical manifestations in conjunction with steroid hormone levels and HSD3B2 mutations. The novel mutations c.154_162delinsTCCTGTT and c.674T>A were classified as pathogenic variants. Adrenal cortical function control was satisfactory after hormone replacement therapy, and hypospadias and small penis were attenuated using testosterone replacement therapy during mini-puberty for optimal surgical outcome.
Topics: Adrenal Hyperplasia, Congenital; Child; Female; Heterozygote; Humans; Hydrocortisone; Male; Mineralocorticoids
PubMed: 33757164
DOI: 10.17219/acem/131220 -
Archives of Disease in Childhood Sep 2003The surgical management of children born with ambiguous genitalia has always been difficult, subject to evolving attitudes and techniques, and at times controversial.... (Review)
Review
The surgical management of children born with ambiguous genitalia has always been difficult, subject to evolving attitudes and techniques, and at times controversial. Standard protocols have stressed the need for early diagnosis, gender assignment, and appropriate surgery in infancy.(1) In recent years some authors, backed by patient support groups, have claimed that such surgery is damaging or mutilating and, as it is essentially cosmetic, should not be performed until the fully informed consent of the patient could be obtained-that is, when the child becomes "Gillick competent".(2-)(4) There are, however, so many specific issues related to the different diagnostic groups that such a policy would seem to be too prescriptive.
Topics: Adrenal Hyperplasia, Congenital; Androgen-Insensitivity Syndrome; Child; Child, Preschool; Disorders of Sex Development; Female; Genitalia; Humans; Infant; Infant, Newborn; Male; Sex Determination Analysis; Time Factors
PubMed: 12937103
DOI: 10.1136/adc.88.9.799 -
Endocrine Jun 2023To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults.
PURPOSE
To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults.
METHODS
A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity.
RESULTS
Of the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively.
CONCLUSION
Cardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.
Topics: Female; Humans; Young Adult; Adult; Male; Adrenal Hyperplasia, Congenital; Diabetes Mellitus, Type 2; Obesity; Hypertension; Prevalence; Hyperinsulinism; Cardiovascular Diseases; Osteoporosis
PubMed: 36857009
DOI: 10.1007/s12020-023-03330-w -
Archives of Disease in Childhood Oct 1951
Topics: Adrenal Gland Diseases; Adrenal Glands; Adrenal Hyperplasia, Congenital; Fetus; Humans; Hyperplasia
PubMed: 14886050
DOI: 10.1136/adc.26.129.423