eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Congenital Adrenal Hyperplasia: Follow-up

Author: Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Contributor Information and Disclosures

Updated: Nov 18, 2009

Follow-up

Further Outpatient Care

• Closely monitor patients with adrenal hyperplasia for adequacy of dosing of glucocorticoids, mineralocorticoids, or both.
  • Too little glucocorticoid results in symptoms of adrenal insufficiency (eg, anorexia, nausea, vomiting, abdominal pain, asthenia) and progressive virilization and advancement of skeletal maturation in virilizing forms.
  • Too much glucocorticoid results in excess weight gain, Cushingoid features, hypertension, hyperglycemia, cataracts, and growth failure.
• Growth failure is one of the more sensitive indicators of excess exposure to glucocorticoids. Short stature in adulthood is frequently the outcome in virilizing forms of adrenal hyperplasia because of the effect of uncontrolled adrenal androgens on skeletal maturation or the effects of excess glucocorticoid administration on growth (see Media file 5).
• Some patients develop precocious puberty, perhaps secondary to the advanced growth and skeletal maturation that occurs with androgen exposure. This may be treated with GnRH analogue therapy.
• As puberty progresses, monitor for adrenal rests within the gonads. If ACTH is inadequately suppressed, these maybe mistaken for gonadal tumors and may cause gonadal pain. Adrenal rests are more commonly found in the testes than in the ovaries.
• As adulthood approaches, vaginal adequacy should be assessed because many females with adrenal hyperplasia suffer from dyspareunia due to vaginal stenosis.

Deterrence/Prevention

• Prenatal testing using amniocentesis or chorionic villus sampling has been successful in diagnosing congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency and 11-beta-hydroxylase deficiency if a sibling had a known mutation or deletion in a previous pregnancy. Because these disorders are consistent with normal development and survivable if treated, the choice to terminate an affected pregnancy is rare. Prenatal diagnosis is usually part of prenatal treatment.
• Prenatal treatment of congenital adrenal hyperplasia appears to be somewhat successful in preventing the virilization due to 21-hydroxylase deficiency in a female fetus. According to the protocol Carlson et al proposed in 1999, the mother is treated with 20 mcg/kg/d of dexamethasone divided into 3 doses as soon as the pregnancy is recognized to suppress fetal ACTH secretion and to prevent the fetal adrenal gland from overproducing adrenal androgens.⁸
• Dexamethasone treatment is discontinued if chorionic villus sampling (done at 8-12 weeks' gestation) or amniocentesis (done at 18-20 weeks' gestation) indicates that the fetus is male or if genetic analysis indicates that the fetus is unaffected.
  • Because only the female fetus is at risk of disfigurement from virilization, this strategy results in unnecessary treatment in 7 of 8 fetuses. However, because virilization occurs within the first 12 weeks' gestation, the virilization of an affected female fetus will have already occurred if one waits until the sex and diagnosis of the fetus are known.
  • So far, this strategy has not resulted in an increase in fetal wastage or congenital malformations in treated pregnancies.⁹ However, it is associated with considerable maternal adverse effects during the pregnancy.
  • Long-term follow-up studies are ongoing and required to determine whether dexamethasone treatment in early pregnancy results in any long-term adverse effects.
• Methods have been developed to screen neonates for congenital virilizing adrenal hyperplasia secondary to 21-hydroxylase deficiency by measuring 17-hydroxyprogesterone from heel blood samples collected on filter paper.
  • This approach has permitted early identification of newborns with this disorder. This strategy has prevented salt-wasting crises in males whose condition is unrecognized at birth and resulted in the identification of both completely virilized females who may be mistaken for males with cryptorchidism and patients of both sexes with simple virilizing adrenal hyperplasia, enabling early treatment before undue advancement in skeletal maturation.
  • Whether these benefits are deemed to be worth the economic cost of screening to justify more global screening remains to be determined.¹⁰

Complications

• Complications of congenital adrenal hyperplasia are common. Too little glucocorticoid results in adrenal insufficiency and further virilization in the virilizing forms. Complications of excessive administration of glucocorticoids include growth failure, obesity, striae, hypertension, hyperglycemia, and cataracts. The complications of excess mineralocorticoid administration include hypertension and hypokalemia.
• Short stature is a frequent complication of virilizing forms of congenital adrenal hyperplasia. In general, patients have final heights 1-2 standard deviations below their estimated genetic potential. This difference results from exposure to excessive concentrations of adrenal androgens that cause rapid skeletal maturation or from excessive exposure to glucocorticoids that limit growth. Early central puberty is often observed in children with advanced skeletal maturation and can contribute to the limitation in growth (see Media file 5).
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  Short stature in a male patient with congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency. His compliance with medical therapy was poor, and early growth and skeletal maturation was advanced, resulting in early puberty and completion of growth. This 12-year-old boy has reached final adult height, which is well below that of his mother.

  [ CLOSE WINDOW ]

  

  Short stature in a male patient with congenital adrenal hyperplasia secondary to 21-hydroxylase deficiency. His compliance with medical therapy was poor, and early growth and skeletal maturation was advanced, resulting in early puberty and completion of growth. This 12-year-old boy has reached final adult height, which is well below that of his mother.

• Female patients with virilizing forms of adrenal hyperplasia have a decreased fertility rate.¹¹ The reasons are believed to be multifactorial and include abnormal genital anatomy, vaginal stenosis, and poor control of adrenal androgen production that results in diminished ovulation. When pregnancy does occur, the baby is generally born by means of caesarian delivery because of vaginal stenosis or an android pelvis. Virilization of female infants born to mothers with congenital adrenal hyperplasia has not been reported but is potentially possible if the condition is uncontrolled.
• Males with uncontrolled congenital adrenal hyperplasia may develop masses in the testes (adrenal rests or adrenal tissue) because the gonads and adrenal glands are derived from the same embryologic anlage. Because the adrenal rests are under ACTH control, the adrenal rests enlarge when ACTH concentrations are elevated. The adrenal rests may cause discomfort and may be mistaken for testicular tumors, resulting in unnecessary surgery. Furthermore, these rests may cause oligospermia or azoospermia and infertility.

Prognosis

• With adequate medical and surgical therapy, the prognosis is good. However, problems with psychological adjustment are common and usually stem from the genital abnormality that accompanies some forms of congenital adrenal hyperplasia.
• Short stature and infertility are common.
• Gender identity in females with virilizing adrenal hyperplasia is usually female if female gender assignment is made early in life, if adequate medical and surgical support are provided, and if the family (and eventually the patient herself) is given adequate education to understand the disease. 
• Females with virilizing adrenal hyperplasia may have more masculine interests.
• Females with adrenal hyperplasia have reduced fertility rates, but fertility is possible with good metabolic control.
• Early death may occur if patients are not provided with stress doses of glucocorticoid in times of illness, trauma, or surgery.

Patient Education

• Educate the caretakers and patients about the nature of the disease in order for them to understand the importance of replacement of the deficient adrenal cortical hormones.
• Patients must also understand the need for additional glucocorticoids in times of illness and stress in order to avoid an adrenal crisis.
• Patients must know the importance of IM injections of glucocorticoids and be educated in the technique of IM administration.
• Useful Web sites for patients and parents include the National Adrenal Diseases Foundation and the Congenital Adrenal Hyperplasia Research Education and Support (CARES) Foundation.

Miscellaneous

Medicolegal Pitfalls

• Education is essential for parents and affected children to understand the pathophysiology of their disease and the importance of glucocorticoid and mineralocorticoid replacement.
  • As with all forms of adrenal insufficiency, the need for coverage with stress doses of glucocorticoids must be emphasized and reemphasized periodically because caretakers are often reluctant to provide stress doses when needed and are particularly reluctant to administer injectable glucocorticoids when the patient is unable to take oral medication or when he or she is severely lethargic. Disastrous consequences can result.
  • Encourage patients to wear medical alert identification tags stating that they are taking glucocorticoids.
  • Advise patients to seek medical help early if they are ill.
• The care of infants with ambiguous genitalia is problematic because major decisions must be made for the child regarding gender assignment without the input of the child.
  • Some intersex patient groups advocate no surgery until the child can participate in these momentous decisions, citing loss of clitoral sensation as a consequence of clitoral recession techniques. This approach is reasonable in a mildly virilized female. 
  • With adequate suppression of adrenal androgen production and growth of the child (but not the clitoris), the genital abnormality may become less apparent over time. 
  • Although postponement of surgery until the child can make the decision certainly reduces the responsibility of the parents and physician for making these decisions on behalf of the patient, in the case of a severely virilized female, it may leave the patient and parents with ambiguities about sex and gender identity through childhood and may expose the child to the risk of further embarrassment.  
  • This is a decision that must be individualized for each family based on the careful education of the parents regarding the available options. 
  • If surgery is to be performed, it must be performed by a surgeon experienced in dealing with disorders of sexual differentiation.

Special Concerns

• Some patient groups have been vocal in criticizing the treatment (particularly the surgical treatment) of patients with congenital virilizing adrenal hyperplasia or other disorders of sexual differentiation. These groups are to be commended for attempting to educate the public about these conditions and to improve society's tolerance for intersex conditions. 
• However, the author is concerned that the vocality of such groups (some of which are composed of dissatisfied patients who underwent poor medical management in an era of low sensitivity to the feelings of the child and unsophisticated genital reconstruction techniques) restricts physicians and parents who struggle to arrive at decisions that are in the best interest of children born with this difficult condition.

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