Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
The Task Force recommends that screening for 21-hydroxylase deficiency be incorporated into all newborn screening programs (1|++OO), using a two-tier protocol (initial immunoassay with further evaluation of positive tests by liquid chromatography/tandem mass spectrometry).
The Task Force recommends standardization of first-tier screening tests to a common technology with a single consistent set of norms stratified by gestational age (1|++OO).
The Task Force recommends that infants with positive newborn screens for congenital adrenal hyperplasia (CAH) be followed up according to specific regional protocols (1|++OO).
Prenatal Treatment of CAH
The Task Force recommends that prenatal therapy continue to be regarded as experimental. Thus the Task Force does not recommend specific treatment protocols.
The Task Force suggests that prenatal therapy be pursued through protocols approved by Institutional Review Boards at centers capable of collecting outcomes data on a sufficiently large number of patients so that risks and benefits of this treatment can be defined more precisely (2|++OO).
Diagnosis of Nonclassic CAH (NCCAH)/CAH after Infancy
The Task Force recommends obtaining with an early morning baseline serum 17-hydroxyprogesterone (17-OHP) in symptomatic individuals (1|++OO).
The Task Force recommends obtaining a complete adrenocortical profile following a cosyntropin stimulation test to differentiate 21-hydroxylase deficiency from other enzyme defects, and to make the diagnosis in borderline cases (1|++OO).
The Task Force suggests genotyping only when results of the adrenocortical profile following cosyntropin stimulation test are equivocal or for purposes of genetic counseling (2|+OOO).
Medical Treatment of CAH in Growing Patients
The Task Force recommends maintenance therapy with hydrocortisone tablets in growing patients with classic CAH (1|+++O).
The Task Force recommends against the use of oral hydrocortisone suspension, and against the chronic use of long-acting potent glucocorticoid (GCs), in growing patients (1|++OO).
The Task Force recommends monitoring patients for signs of GC excess, as well as for signs of inadequate androgen suppression (1|++OO).
The Task Forces recommends that all patients with classic CAH be treated with fludrocortisone and sodium chloride supplements in the newborn period and early infancy (1|++OO).
The Task Force recommends increasing the GC dosage of CAH patients in situations such as febrile illness (>38.5°C), gastroenteritis with dehydration, surgery accompanied by general anesthesia, and major trauma (1|++OO).
The Task Force recommends against the use of increased GC doses in mental and emotional stress, minor illness, and before physical exercise (1|+OOO).
The Task Force recommends against the use of stress doses of GC in patients with nonclassic CAH unless their adrenal function is suboptimal or iatrogenically suppressed (1|+OOO).
The Task Force suggests that patients who require treatment always wear or carry medical identification indicating that they have adrenal insufficiency (2|+OOO).
The Task Force recommends monitoring treatment by consistently timed hormone measurements (1|+OOO).
The Task Force recommends that endogenous adrenal steroid secretion not be completely suppressed in order to avoid adverse effects of over-treatment (1|++OO).
The Task Force suggests regular monitoring of height, weight, and physical examination; annual bone age x-ray assessment is also suggested after age 2 years (2|+OOO).
Treatment of NCCAH
The Task Force suggests treating NCCAH children with inappropriately early onset and rapid progression of pubarche or bone age, and adolescent patients with overt virilization (2|++OO).
The Task Force recommends against treatment in asymptomatic individuals with NCCAH (1|++OO).
The Task Force suggests that previously treated NCCAH patients be given the option of discontinuing therapy when symptoms resolve (2|++OO).
Complications of CAH
The Task Force recommends close monitoring for iatrogenic Cushing syndrome in all GC-treated patients (1|++OO).
The Task Force suggests against the routine evaluation of bone mineral density in children (2|+OOO).
The Task Force suggests that adrenal imaging be reserved for those patients who have an atypical clinical or biochemical course (2|+OOO).
The Task Force suggests that for severely virilized (Prader stage ≥3) females clitoral and perineal reconstruction be considered in infancy, and performed by an experienced surgeon in a center with similarly experienced pediatric endocrinologists, mental health professionals, and social work services (2|++OO).
The Task Force suggests neurovascular-sparing clitoroplasty and vaginoplasty using total or partial urogenital mobilization (2|+OOO).
The Task Force suggests continued long-term outcome studies of early surgery.
The Task Force suggests that children with CAH who have a predicted height standard deviation (SD) ≤-2.25 be considered for experimental treatment in appropriately controlled trials (2|+OOO).
The Task Force recommends against use of experimental treatment approaches outside of formally approved clinical trials (1|++OO).
The Task Force suggests further prospective, randomized, and carefully controlled studies to determine whether the use of growth-promoting drugs increases adult height in patients with CAH (2|+OOO).
The Task Force suggests that bilateral adrenalectomy be considered only in select cases that have failed medical therapy, especially in rare cases of adult females with salt-wasting (SW) CAH and infertility. Risk for noncompliance must be evaluated prior to surgery (2|+OOO).
The Task Force suggests the development of new treatment approaches that minimize daily GC exposure and aim to achieve physiological cortisol replacement.
The Task Force suggests additional research concerning epinephrine deficiency in the stress response.
The Task Force suggests continued research concerning novel therapies.
The Task Force suggests that further study of alternative treatment approaches consider growth, metabolic, reproductive and neuropsychiatric endpoints.
CAH in Adulthood
The Task Force recommends that NCCAH screening with an early morning serum measurement of 17-OHP be confirmed when needed through a cosyntropin (ACTH) stimulation test (1|++OO).
The Task Force suggests treatment of adults with NCCAH with patient-important hyperandrogenism or infertility (2|+OOO). The Task Force suggests clinicians not prescribe daily GC substitution in adult males with NCCAH (2|+OOO).
The Task Force suggests that adult patients with classic CAH be treated with hydrocortisone or long-acting GCs (2|+OOO).
The Task Force suggests the monitoring of GC and mineralocorticoid (MC) treatment include at least annual physical examination and appropriate hormone measurements.
The Task Force recommends that genetic counseling be given to parents at birth of a CAH child, and to adolescents at the transition to adult care (1|+OOO).
The Task Force suggests that pediatric and adult endocrinologists, reproductive endocrinologists, gynecologists, and urologists have joint clinics for transfer of patients with CAH to adult care (2|+OOO).
The Task Force suggests a gynecological history and examination under anesthesia in adolescent females with CAH.
The Task Force suggests against the routine use of pelvic ultrasound in CAH patients with regular menstrual cycles (2|+OOO).
The Task Force suggests all males with classic CAH be periodically screened from adolescence for testicular adrenal rest tumors by ultrasound (2|+OOO).
The Task Force suggests that CAH patients with impaired fertility consult a reproductive endocrinologist and/or fertility specialist (2|+OOO).
The Task Force suggests that pregnant women with CAH be followed jointly by endocrinologists and obstetricians.
The Task Force recommends that patients with CAH who become pregnant continue their pre-pregnancy doses of hydrocortisone/prednisolone and fludrocortisone therapy (1|++OO). GC doses should be adjusted if symptoms and signs of GC insufficiency occur. The Task Force recommends against the use of GCs that traverse the placenta, such as dexamethasone, for treatment of pregnant patients with CAH (1|++OO). Stress doses of GCs should be used during labor and delivery.
The Task Force suggests that patients with CAH and psychosocial problems associated with disorders of sexual development be referred to mental health staff with specialized expertise in managing such problems (2|++OO).
The Task Force suggests the development, evaluation, and implementation in long-term clinical trials and in clinical practice of valid and responsive patient-reported assessments of their quality of life in response to treatment regimens (2|+OOO).
Quality of Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
Strength of Recommendation
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."