Consensus Statement on Treatment of 21-Hydroxylase Deficiency

Print Version (3 page PDF file)

JCEM 87(9):4048-4053, 2002.

1.   Clinical Evaluation

Endocrinology consult if:

• Clinical suspicion of CAH

• Infant with ambiguous genitalia

• Abnormal newborn screening result (high 17-OH Progesterone for age)

• Complete history and physical exam – check for maternal virilism

• Ultrasound exam of internal genitalia and adrenal glands

• Karyotype or FISH for sex chromosome material

• Serial 17-OH Progesterone levels in premature babies

2.   Newborn Screening

• Detects classical CAH and some cases of nonclassical CAH

• Sample ideally obtained at 48-72 hours of age

• Positive result requires validation with second test

  • Serum/plasma 17-OH progesterone

  • Urine steroid profile

  • ± CYP21 gene analysis

• Confirm salt wasting status with:

  • Serial serum/plasma and urine electrolytes

  • Plasma renin activity or direct renin

  • ± CYP 21 gene analysis

3.   Prenatal Diagnosis and Treatment

Treatment effective if started by 9 weeks after mother’s LMP
No adverse effects to fetus reported (although some theoretical concerns)
Mothers have edema, striae, weight gain, but no diabetes or hypertension
Only 1 of 8 fetuses will continue treatment to end of pregnancy (6 unaffected, 1 male will not need therapy)

Inclusion criteria:

1. previously affected sib or first degree relative with known mutations causing classical CAH, proven by DNA analysis
2. reasonable expectation that father is same as the proband’s
3. availability of genetic analysis
4. therapy starts before 9 weeks after mother’s LMP
5. no plans for abortion
6. reasonable expectation of adherence to regimen

Optimal dose of dexamethasone is 20 ug/kg/day divided t.i.d.

Monitor maternal BP, urine glucose, HbA1c, weight, plasma cortisol, DHEA-S, and androstenedione at start and q 2 months

Measure urine estriol after 15-20 weeks gestation.

Treatment should only be undertaken after full discussion. This is NOT standard of care in the community. Written consent MUST be obtained. Preferably done under supervision of IRB and in context of a study

4.   Surgical Management

Decision should be made by parents

Goals of surgery are:

1. genital appearance compatible with gender
2. unobstructed urinary emptying without incontinence or infections
3. good adult sexual and reproductive function

Once decision made to raise child as female:

• If high proximal junction between vagina and urethra

  • Best time is 2-6 months of age (technically easier than at later times)

  • Experienced surgeon

• If junction between vagina and urethra is near perineum

  • Surgery may not be necessary

  • Anatomical studies required to make best decision

  • Clitoroplasty may not be necessary

  • If clitoroplasty is performed, must preserve neurovascular bundle, glans, preputial skin related to the glans

  • If surgery done early, should be one-stage repair using newest techniques of vaginoplasty, clitoral, and labial surgery at a center with at least 3-4 cases per year. (designated surgical team)

  • Revision vaginoplasty often required at adolescence

  • Surgery between 12 months of age and adolescence not recommended in the absence of complications causing medical problems

  • Vaginal dilation before adolescence contradindicated

  • Minimize genital exams and photographs to those that are necessary

• For virilized 46 X,X patients with late presentation, consider sex re-assignment only after psychological evaluation of patient and family and period of endocrine replacement therapy

5.      Psychological Issues

Females with CAH show behavioral masculinization

• Most pronounced in gender role behavior

• Less so in sexual orientation

• Rarely in gender identity

Must consider societal setting when making decision about sex assignment/re-assignment

6.   Treatment Considerations

Goals are:

• Replace deficient steroids

• Minimize sex steroid and glucocorticoid excess

• Prevent virilization

• Optimize growth

• Protect potential fertility

Glucocorticoid Use

• Typical dose of hydrocortisone is 10-15 mg/m2/day divided t.i.d.

• Especially in infancy, doses may need to be higher (25 mg/m2/day)

• Crushed hydrocortisone tablets preferred to oral suspension

• Complete adrenal suppression causes Cushingoid features, obesity and poor linear growth

• When growth is complete, longer acting steroids may be used

• Prednisolone at 2-4 m/m2/day divided bid is preferred

• Dexamethasone can be given at 0.25-0.375 mg once daily

• GnRH agonist may be required for central precocious puberty

Mineralocorticoid Use

• All classical CAH patients should receive fludrocortisone at diagnosis (0.05-0.30 mg/day)

• Sodium chloride supplements often needed in infants (1-3 g/day = 17-51 mEq/day) divided in several feedings

• Need for continuing therapy based on measures of blood pressure and renin

Diagnosis and Treatment of Nonclassical CAH

• Diagnostic test is 60 minute ACTH test [250 ug (1-24)ACTH IV bolus]

• Morning serum 17 OH Progesterone can be used as a screening tool

• Treat only if symptomatic (bone age and poor height prediction, hirsutism, severe acne, menstrual irregularities, testicular masses, infertility)

Monitoring Treatment of Classical CAH

• Physical Findings

  • Growth rate

  • Cushingoid features

  • Blood pressure

• Laboratory (not all are necessary)

  • Serum/plasma electrolytes

  • 17 OH Progesterone

  • Androstenedione

  • Testosterone

  • Plasma renin activity or direct renin

• Measure labs q 3 months during infancy and then q 4-12 months thereafter

• Patients receiving adequate hormone therapy may have lab values above the normal range

Stress Dosing

• Carry and wear medical ID

• Need emergency supply of  IM hydrocortisone or glucocorticoid suppositories

• Give 2-3 times normal glucocorticoid dose for stress related to:

  • Fever >38.5ºC

  • Vomiting

  • Anorexia

  • Trauma

  • Pre-operatively

  • ±Endurance sports

• Parenteral steroids needed if:

  • Vomiting

  • Unable to take oral steroid

  • Trauma

  • Surgery

Stress IV hydrocortisone doses

May need IV glucose and sodium chloride

Management in adolescence

• Perform genital exam only if there is a clinical or laboratory indication:

  • Poor control of sex steroid production

  • Pubertal progress

  • Clitoral size

  • Counseling about use of tampons or sexual activity

• Explain reason to patient and family for doing genital exam

Psychological Well Being

• Assess need for counseling routinely

• Offer sex- and age-appropriate counseling, regarding sexual function, future surgery, gender role, issues related to living with a chronic disease

Care During Transition to Adulthood

• Transition team include endocrinologists, gynecologist, urologist, psychologist with specific expertise

• Males should be counseled that treatment improves fertility and reduces risk of palpable testicular masses

• Periodic exams, ultrasound and MRI to assess extent of testicular masses.

• Surgical removal of a glucocorticoid unresponsive mass may preserve or improve fertility

Women need assessment of genital repair and counseling if sexual dysfunction is concern

Women with nonclassical CAH should be counseled about risk of infertility (actual risk unknown)

Management of a Pregnant Woman with CAH

• Require tertiary care

• Treat with Prednisone or Hydrocortisone (do not cross placenta)

• Avoid dexamethasone, unless fetus has CAH

• Adjust doses to keep maternal testosterone level at high normal for pregnancy

• Elective C/S reconstructive surgery has been done

• Pediatrician at delivery if baby diagnoses with CAH pre-natally

Copyright 2002
Medical College of Georgia
All rights reserved.

Pediatric Endocrinology
Department of Pediatrics | Medical College of Georgia
Please email comments, suggestions or questions to:
Andrew Muir, M.D., amuir@mcg.edu

February 27, 2004