Congenital adrenal hyperplasia is any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of mineralocorticoids , glucocorticoids or sex steroids from cholesterol by the adrenal glands steroidogenesis. Symptoms can include:. Due to inadequate mineralocorticoids :. Due to insufficient androgens and estrogens: [ citation needed ].
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NCBI Bookshelf. Ifeanyi I. Momodu ; Gurdeep Singh. Authors Ifeanyi I. Momodu 1 ; Gurdeep Singh 2. Most of these diseases involve the excessive or deficient production of sex steroids that can alter the development of primary or secondary sex characteristics in some affected infants, children, or adults.
Universal newborn screening for CAH, done in the U. The estimated prevalence is one case per 60 individuals in the general population but increases to one in three in select genetically isolated communities with a smaller gene pool. For example, almost CYP21A2 mutations have been identified, making genotyping these individuals a cumbersome undertaking. Since all forms of CAH have an autosomal recessive pattern of inheritance, both sexes are equally affected.
However, because of the accumulated testosterone or precursor hormones, the phenotypic expression may be different in both genders. CAH is usually obvious at birth or soon after because of the ambiguous genitals, early virilization, or salt wasting. Atypical cases may be recognized around puberty with the presence of virilizing signs or oligomenorrhea in females.
The pathway for steroid synthesis is mediated by various enzymes, including hydroxylase, beta-hydroxylase, and alpha-hydroxylase. Deficiency of either of these enzymes impairs production of the major steroids stimulating corticotropin mediated accumulation of cortisol precursors, causing a shift in steroid pathogenesis towards androgen production.
Fetal androgen excess leads to various degrees of virilization at birth. CAH is associated with a defective gene. Milder degrees of inefficiency leads to excessive sex hormone effects in childhood or adolescence. The mildest form interferes with ovulation and fertility in adults. Under-virilization may occur in XY males, which may cause female external genitalia. In females, hypogonadism may cause sexual infantilism or abnormal pubertal development and infertility.
Females less severely affected may present with early pubarche. Most males have no signs of CAH at birth. However, some may present with hyperpigmentation and penile enlargement while those with salt-wasting disease present early with hyponatremia and hypovolemia.
Males with non-salt-wasting disease present later with signs of virilization. In rare forms, males are under-masculinized. The initial screening test is done by measuring serum 17OHP to screen for hydroxylase deficiency. If positive, then repeat 17OHP test should be obtained along with measurement of the serum electrolyte panel. Salt-wasting patients may have higher 17 alpha-hydroxyprogesterone levels than non-salt-wasting patients. In many countries, children are screened for hydroxylase at birth.
This test will detect elevated levels of hydroxyprogesterone. A second tier test using liquid chromatography-tandem mass spectrometry allows diagnosis of CAH due to other enzyme defects such as beta-hydroxylase. Patients with inconclusive results may need further evaluation using a cosyntropin stimulation test followed by complete adrenocortical profile.
Unless hemorrhage is suspected in the adrenal glands, imaging studies are not required in evaluating patients with CAH. However, in patients with ambiguous genitalia, pelvic ultrasound may be done to assess for other anomalies and define the anatomy of the urogenital tract. The goal of medical treatment of CAH differs by the age of the patient. CAH is a recessive gene, so both the mother and father must be recessive carriers.
During infancy and childhood, treatment aims to prevent adrenal crises, early virilization, promote normal growth, avoid electrolyte abnormalities and dehydration. To achieve this balance requires close monitoring. Educating parents, caregivers, and older patients with CAH about the signs, symptoms, prevention, and emergency treatment of adrenal crises is an integral part of the management of CAH. All patients with CAH are advised to wear medical identification and have a glucocorticoid emergency injection kit for use in adrenal crises.
Supply enough glucocorticoids to reduce hyperplasia and reduce the overproduction of androgens and mineralocorticoids. Provide replacement of mineralocorticoids and extra salt if deficient. Provide testosterone or estrogen replacement at puberty if deficient.
Additional therapy, as needed, to optimize growth by delaying puberty or delaying bone maturation. Infants with ambiguous genitalia need a surgical consult for corrective surgery. The risks and benefits of early versus delayed operation should be carefully discussed with the child's parents by a multidisciplinary team of specialists involving the pediatric endocrinologist, urologist, surgeon, and anesthesiologist.
Surgery should only be done in centers that specialize in genitoplasty. Surgery is only undertaken in a few selected infants and must be done by experienced surgeons. In the past, some infants required bilateral adrenalectomies to manage severe virilization and prevent premature skeletal maturation- however, today, this procedure is rarely done.
Patients with CAH need lifelong follow up to monitor the doses of glucocorticoids and mineralocorticoids and monitor the side effects of these hormones.
Patients with CAH should have routine screening for cardiovascular and metabolic diseases as the general population. If the disorder is promptly diagnosed and treated, the prognosis for most patients is good.
However, even though the physical deficits can be overcome, most patients have lifelong emotional issues that stem from the ambiguous genitalia. Other problems that can occur in these patients include:. The defect results in adrenal hyperplasia. Cortisol deficiency in CAH is usually partial. The synthesis of cortisol shares steps with the creation of aldosterone, testosterone, and estradiol.
CAH is a relatively common disorder, but the clinical presentation does vary with the severity of enzyme deficiency. Thus, CAH is best managed by an interprofessional team that includes a geneticist, endocrinologist, a pediatric surgeon, a fertility expert, and a nurse specialist.
Pharmacists review medicines prescribed and drug-drug interactions. Specialty care nurses provide teaching to patients and parents. Nurses communicate changes in patient to conditions the team. Referral to a mental health counselor may be appropriate because many patients develop emotional distress over the ambiguous genitals. These infants need lifelong monitoring because too little or too much glucocorticoids can have detrimental effects.
Even as adults, many of these patients need assessment of their genitals because problems like vaginal stenosis and dyspareunia are not uncommon. To access free multiple choice questions on this topic, click here. This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. National Center for Biotechnology Information , U.
StatPearls [Internet]. Search term. Congenital Adrenal Hyperplasia Ifeanyi I. Author Information Authors Ifeanyi I. Lipoid deposits which represent cholesterol esters that could not enter the mitochondria for steroid synthesis. History and Physical The symptoms of CAH include: Mineralocorticoids Inadequacy Vomiting because of salt-wasting leads to dehydration, hypovolemia, shock, and death. Females: ambiguous genitalia, menstrual irregularity, infertility because of anovulation, enlarged clitoris, and shallow vagina.
Some centers routinely screen infants for the hydroxylase deficiency before a life-threatening salt-wasting crisis develops. Medical therapy General principles in the treatment of CAH include: Supply enough glucocorticoids to reduce hyperplasia and reduce the overproduction of androgens and mineralocorticoids.
Spironolactone should be avoided in salt-wasting CAH due to increased risk for dehydration. Surgical therapy Surgery is not required for the majority of infants with mild forms of virilization.
Long-Term Monitoring Patients with CAH need lifelong follow up to monitor the doses of glucocorticoids and mineralocorticoids and monitor the side effects of these hormones. Prognosis If the disorder is promptly diagnosed and treated, the prognosis for most patients is good.
Other problems that can occur in these patients include: Infertility. Complications Growth failure. Prevention Prenatal chorionic villus sampling or amniocentesis can detect CAH during pregnancy. Enhancing Healthcare Team Outcomes CAH is a relatively common disorder, but the clinical presentation does vary with the severity of enzyme deficiency. Questions To access free multiple choice questions on this topic, click here.
References 1. Revisiting the association of HLA alleles and haplotypes with CYP21A2 mutations in a large cohort of patients with congenital adrenal hyperplasia. Al-Mendalawi MD. Comment on: Growth characteristics in children with congenital adrenal hyperplasia. Saudi Med J. Sexual orientation of 46, XX patients with congenital adrenal hyperplasia: a descriptive review. J Pediatr Urol. Arch Sex Behav. Front Endocrinol Lausanne. Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia.
Horm Res Paediatr.
Congenital Adrenal Hyperplasia
Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed. Congenital adrenal hyperplasia CAH is an inherited endocrine disorder caused by a steroidogenic enzyme deficiency that is characterized by adrenal insufficiency and variable degrees of hyper or hypo androgeny manifestations, depending of the type and the severity of the disease.
Congenital adrenal hyperplasia is an autosomal recessive disorder of congenital cortisol synthesis enzyme deficiency:. Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys. Updating… Please wait. Unable to process the form.