Definition Congenital adrenal hyperplasia can affect both boys and girls. People with congenital adrenal hyperplasia lack an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone. Without these hormones, the body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia. Signs and Symptoms Girls will usually have normal female reproductive organs (ovaries, uterus, and fallopian tubes).
They may also have the following changes: * Abnormal menstrual periods * Deep voice * Early appearance of pubic and armpit hair * Excessive hair growth and facial hair * Failure to menstruate * Genitals that look both male and female (ambiguous genitalia), often appearing more male than female Boys won’t have any obvious problems at birth.
However, they may appear to enter puberty as early as 2 – 3 years of age. Changes may include: * Deep voice * Early appearance of pubic and armpit hair * Early development of male characteristics * Enlarged penis * Small testes Well-developed muscles Both boys and girls will be tall as children but much shorter than normal as adults.
Some forms of congenital adrenal hyperplasia are more severe and cause adrenal crisis in the newborn due to a loss of salt. Newborns with these forms develop severe symptoms shortly after birth, including: * Cardiac arrhythmias * Dehydration * Electrolyte changes * Vomiting Pathophysiology The clinical manifestations of each form of congenital adrenal hyperplasia are related to the degree of cortisol deficiency and/or the degree of aldosterone deficiency.
In some cases, these manifestations reflect the accumulation of precursor adrenocortical hormones.
When present in supraphysiologic concentrations, these precursors cause abnormalities such as virilization or hypertension. The phenotype depends on the degree or type of gene deletion or mutation and the resultant deficiency of the steroidogenic enzyme. The enzymes and corresponding genes are displayed in the image below. Enzymes and genes involved in adrenal steroidogenesis. Two copies of an abnormal gene are required for disease to occur, and not all mutations and partial deletions result in disease.
The phenotype can vary from clinically inapparent disease (occult or cryptic adrenal hyperplasia) to a mild form of disease that is expressed in adolescence or adulthood (nonclassic adrenal hyperplasia) to severe disease that results in adrenal insufficiency in infancy with or without virilization and salt wasting (classic adrenal hyperplasia). The most common form of adrenal hyperplasia (due to a deficiency of 21-hydroxylase activity) is clinically divided into 3 phenotypes: salt wasting, simple virilizing, and nonclassic.
CYP21A is the gene that codes for 21-hydroxylase, CYP11B1 codes for 11-beta-hydroxylase, and CYP17 codes for 17-alpha-hydroxylase. Many of the enzymes involved in cortisol and aldosterone syntheses are cytochrome P450 (CYP) proteins. Diagnostic Test Tests to diagnose congenital adrenal hyperplasia include: * Physical exam. Your child’s doctor will examine your child and evaluate symptoms. If, based on these findings, the doctor suspects congenital adrenal hyperplasia, the next step is to confirm the diagnosis with blood and urine tests. Blood and urine tests. Tests used to diagnose congenital adrenal hyperplasia measure levels of hormones manufactured by the adrenal glands — cortisol, aldosterone and androgens. A diagnosis can be made when there are abnormal levels of these hormones. In many states, doctors are required to conduct hormonal tests for congenital adrenal hyperplasia in newborns during the first few days of life. Blood is drawn with a heel prick of the newborn and analyzed. Prenatal testing Doctors have the tools to screen and diagnose congenital adrenal hyperplasia in fetuses.
These tools are used most often when siblings have the disease or family members are known to carry the gene defect. If you’re pregnant and have the condition or a family history of the condition, your doctor may recommend one of the following tests: * Amniocentesis. This procedure uses a needle to withdraw a sample of cells from the amniotic fluid in the womb and determine in the laboratory whether the condition is present. * Chorionic villus sampling. This test involves withdrawing cells from the placenta for analysis in the laboratory.
If the condition is diagnosed before birth, treatment can be started in the womb. Prenatal diagnosis and therapy may be able to reduce the risk of complications. Testing to determine a child’s sex After birth, your child may have ambiguous external genitalia, so you may not sure of your child’s sex. In that case, genetic blood tests can analyze chromosomes — in a test called karyotyping — to determine the sex of your child. In addition, a pelvic ultrasound can be used to produce images of female reproductive structures — the cervix, uterus and fallopian tubes — to confirm whether your child is a girl.
Additional: * Abnormal salt levels in blood (serum electrolytes) and urine * High levels of 17-OH progesterone * High levels of serum DHEA sulfate * High levels of urinary 17-ketosteroids * Low levels of aldosterone and cortisol * Normal or low urinary 17-hydroxycorticosteroids * X-ray for bone age (shows older bones than normal for the person’s age) Genetic tests can help diagnose, confirm, and manage the disease. This disease may also affect the results of the following tests: * Estriol – serum * Estriol – urine Pregnanediol Medical Inteventions Infants with ambiguous genitalia should be closely observed for symptoms and signs of salt wasting while a diagnosis is being established. Clinical clues include abnormal weight loss or lack of expected weight gain. Electrolyte abnormalities generally take from a few days to 3 weeks to appear because the placenta maintains the fetal electrolytes in utero. In mild forms of salt-wasting adrenal hyperplasia, salt wasting may not become apparent until an illness stresses the child. Patients with dehydration, hyponatremia, or hyperkalemia and a possible salt-wasting form of adrenal hyperplasia should receive an intravenous (IV) bolus of isotonic sodium chloride solution (20 mL/kg or 450 mL/m2) over the first hour, as needed, to restore their intravascular volume and blood pressure. * This dosage may be repeated if the blood pressure remains low. * Dextrose must be administered if the patient is hypoglycemic and must be included in the rehydration fluid after the bolus dose to prevent hypoglycemia. After samples are obtained to measure electrolyte, blood sugar, cortisol, aldosterone, and 17-hydroxyprogesterone concentrations, the patient should be treated with glucocorticoids based on suspected adrenal insufficiency. Treatment should not be withheld while confirmatory results are awaited because it may be life preserving (see Medication). * After the patient’s condition is stabilized, treat all patients who have adrenal hyperplasia with long-term glucocorticoid or aldosterone replacement (or both), depending on which enzyme is involved and on whether cortisol and/or aldosterone synthesis is affected. Another approach currently under investigation is the combined use of glucocorticoid (to suppress ACTH and adrenal androgen production), mineralocorticoid (to reduce angiotensin II concentrations), aromatase inhibitor (to slow skeletal maturation), and flutamide (an androgen blocker to reduce virilization). * Some patients develop precocious puberty, which further compromises adult height. Suppression of puberty with long-acting gonadotropin-releasing hormone (GnRH) agonists while simultaneously stimulating growth with growth hormone may partially improve the patient’s height.
The Endocrine Society’s 2010 clinical practice guidelines note the following: * Prenatal treatment for CAH should be regarded as experimental. * Glucocorticoid therapy should be carefully titrated to avoid Cushing syndrome. * Mineralocorticoid replacement is encouraged. In infants, mineralocorticoid replacement and sodium supplementation are encouraged. * Use of agents to delay puberty and promote growth are experimental. * Psychiatric support should be encouraged for patients with adjustment problems. * Medication should be used judiciously during pregnancy and in symptomatic patients with nonclassical CAH. Surgical Interventions
Infants with ambiguous genitalia require surgical evaluation and, if needed, plans for corrective surgery. * The traditional approach to the female patient with ambiguous genitalia due to adrenal hyperplasia is clitoral recession early in life followed by vaginoplasty after puberty. * Vocal groups of patients with disorders of sexual differentiation (eg, Intersex Society of North America) have recently challenged this approach. * Some female infants with adrenal hyperplasia have only mild virilization and may not require corrective surgery if they receive adequate medical therapy to prevent further virilization. Bilateral adrenalectomies have been suggested in the management of virilizing forms of adrenal hyperplasia in order to prevent further virilization and advancement of skeletal maturation. This approach is experimental and should be considered only in the context of a controlled study. The Endocrine Society’s 2010 clinical practice guidelines note the following: * Adrenalectomy should be avoided. * While surgical reconstruction may not be necessary during the newborn period in mildly virilized girls, it may be appropriate in severely virilized girls.
It should be a single stage genital repair, performed by experienced surgeons. Drug Study Generic Name| Brand Name| Indications| Action| Side Effects| Nursing Considerations| Hydrocortisone| Hydrocortisone acetate| · Replacement therapy in adrenal cortical insufficiency-Hypercalcemia associated with cancer· Short-term inflammatory and allergic disorders, such as rheumatoid arthritis, collagen diseases (SLE), dermatologic diseases (pemphigus), status asthmaticus, and autoimmune disorders· Hematologic isorders–thrombocytopenic purpura, erythroblastopenia· Trichinosis with neurologic or myocardial involvement· Ulcerative colitis, acute exacerbations of multiple sclerosis, and palliation in some leukemias and lymphomas· Intra-articular or soft-tissue administration: Arthritis, psoriatic plaques· Retention enema: For ulcerative colitis, proctitis· Dermatologic preparations: To relieve inflammatory and pruritic manifestations of dermatoses that are steroid responsive· Anorectal cream, suppositories: To relieve discomfort of hemorrhoids and perianal itching or irritation| Enters target cells and binds to cytoplasmic receptors; initiates many complex reactions that are responsible for its anti-inflammatory, immunosuppressive (glucocorticoid), and salt-retaining (mineralocorticoid) actions. Some actions may be undesirable, depending on drug use. Vertigo, headache, paresthesias, insomnia, convulsions, psychosisHypotension, shock, hypertension and CHF secondary to fluid retention, thromboembolism, thrombophlebitis, fat embolism, cardiac arrhythmias secondary to electrolyte disturbancesThin, fragile skin; petechiae; ecchymoses; purpura; striae; subcutaneous fat atrophyCataracts, glaucoma (long-term therapy), increased intraocular pressureAmenorrhea, irregular menses, growth retardation, decreased carbohydrate tolerance and diabetes mellitus, cushingoid state (long-term therapy), hypothalamic-pituitary-adrenal (HPA) suppression systemic with therapy longer than 5 daysPeptic or esophageal ulcer, pancreatitis, abdominal distention, nausea, vomiting, increased appetite and weight gain (long-term therapy)Na+ and fluid retention, hypokalemia, hypocalcemia, increased blood sugar, increased serum cholesterol, decreased serum T1 and T4 levelsAnaphylactoid or hypersensitivity reactionsMuscle weakness, steroid myopathy and loss of muscle mass, osteoporosis, spontaneous fractures (long-term therapy)| Systemic administrationWARNING: Give daily before 9 AM to mimic normal peak diurnal corticosteroid levels and minimize HPA suppression. Space multiple doses evenly throughout the day. Do not give IM injections if patient has thrombocytopenic purpura. Rotate sites of IM repository injections to avoid local atrophy. Use minimal doses for minimal duration to minimize adverse effects. Taper doses when discontinuing high-dose or long-term therapy.
Arrange for increased dosage when patient is subject to unusual stress. Ensure that adequate amount of Ca2+ is taken if prolonged administration of steroids. Use alternate-day maintenance therapy with short-acting corticosteroids whenever possible. WARNING: Do not give live virus vaccines with immunosuppressive doses of hydrocortisone. Provide antacids between meals to help avoid peptic ulcer. Topical dermatologic administrationUse caution with occlusive dressings; tight or plastic diapers over affected area can increase systemic absorption. Avoid prolonged use, especially near eyes, in genital and rectal areas, on face, and in skin creases. |
Generic Name| Brand Name| Indications| Action| Side Effects| Nursing Considerations| Dexamethasone| Cortastat, Dalalone, Decadrol, Decaject, Deronil, Dexacorten, Dexameth, Dexasone, Dexone, Hexadrol, Primethasone, Solurex| Management of cerebral edemaDiagnostic agent in adrenal disordersRelieves inflammationAllergic disordersAsthmaArthritis| Enters target cells and binds to specific receptors, initiating many complex reactions that are responsible for its antiinflammatory and immunosuppressive effects. | AcneDecreased wound healingDepressionVomitingEasy bruisingHeadacheIncreased hair growthInsomniaRestlessnessStomach irritationIrregular or absent menstruationDizziness| For systemic administration, do not give drug to nursing mothers; drug is secreted in breast milk. WARNING: Give daily doses before 9 AM to mimic normal peak corticosteroid blood levels. Increase dosage when patient is subject to stress. Taper doses when discontinuing high-dose or long-term therapy.
Do not give live virus vaccines with immunosuppressive doses of corticosteroids. For respiratory inhalant, intranasal preparation, do not use respiratory inhalant during an acute asthmatic attack or to manage status asthmaticus. Do not use intranasal product with untreated local nasal infections, epistaxis, nasal trauma, septal ulcers, or recent nasal surgery. WARNING: Taper systemic steroids carefully during transfer to inhalational steroids; adrenal insufficiency deaths have occurred. For topical dermatologic preparations, use caution when occlusive dressings, tight diapers cover affected area; these can increase systemic absorption. Avoid prolonged use near the eyes, in genital and rectal areas, and in skin creases. |