eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Congenital Adrenal Hyperplasia: Differential Diagnoses & Workup

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

Differential Diagnoses

3-Beta-Hydroxysteroid Dehydrogenase Deficiency
Familial Glucocorticoid Deficiency
5-Alpha-Reductase Deficiency
Fluid, Electrolyte, and Nutrition Management of the Newborn
Adrenal Hypoplasia
Hyperkalemia
Adrenal Insufficiency
Hypokalemia
Ambiguous Genitalia and Intersexuality
Hyponatremia
Androgen Insensitivity Syndrome
Pyloric Stenosis, Hypertrophic
Congenital Adrenal Hyperplasia
Sexuality: Gender Identity
Cystic Fibrosis
Sexuality: Sexual Orientation
Denys-Drash Syndrome
Small-Bowel Obstruction
Failure to Thrive
WAGR Syndrome

Other Problems to Be Considered

Bilateral adrenal hemorrhage
Cryptorchidism
Defects in testosterone synthesis
Mixed gonadal dysgenesis
Polycystic ovary syndrome
Pseudohypoaldosteronism
Renal salt wasting
Obstructive uropathy

Workup

Laboratory Studies

  • The diagnosis of congenital adrenal hyperplasia depends on the demonstration of inadequate production of cortisol, aldosterone, or both in the presence of accumulation of excess concentrations of precursor hormones. For example, the distinguishing characteristic of 21-hydroxylase deficiency is a high serum concentration of 17-hydroxyprogesterone (usually >1000 ng/dL) and urinary pregnanetriol (metabolite of 17-hydroxyprogesterone) in the presence of clinical features suggestive of the disease (eg, salt wasting, clitoromegaly or ambiguous genitalia [in a female patient], precocious pubic hair, excessive growth, premature phallic enlargement in the absence of testicular enlargement, hirsutism, oligomenorrhea, female infertility).
  • Likewise, 11-beta-hydroxylase deficiency is indicated by excess concentrations of 11-deoxycortisol and deoxycorticosterone or by an elevation in the ratio of 24-hour urinary tetrahydrocompound S (metabolite of 11-deoxycortisol) to tetrahydrocompound F (metabolite of cortisol). Both are accompanied by elevated levels of 24-hour urinary 17-ketosteroids, the urinary metabolites of adrenal androgens.
  • 3-beta-hydroxysteroid dehydrogenase deficiency is indicated by an abnormal ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone and dehydroepiandrosterone to androstenedione.
  • Salt-wasting forms of adrenal hyperplasia are accompanied by low serum aldosterone concentrations, hyponatremia, hyperkalemia, and elevated plasma renin activity (PRA), indicating hypovolemia. In contrast, hypertensive forms of adrenal hyperplasia (ie, 11-beta-hydroxylase deficiency and 17-alpha-hydroxylase deficiency) are associated with suppressed PRA and, often, hypokalemia.
  • Subtle forms of adrenal hyperplasia (as in nonclassic forms of 21-hydroxylase deficiency and nonclassic 3-beta-hydroxysteroid dehydrogenase deficiency) often require a synthetic corticotropin (Cortrosyn) stimulation test to demonstrate the abnormal accumulation of precursor steroids. Nomograms are available for interpreting the results.5

Imaging Studies

  • Imaging studies of the adrenal gland are generally not useful in the evaluation of patients with suspected adrenal hyperplasia. However, CT scanning of the adrenal gland can be useful in excluding bilateral adrenal hemorrhage in patients with signs of acute adrenal failure without ambiguous genitalia or other clues of adrenal hyperplasia.
  • Pelvic ultrasonography may be performed in an infant with ambiguous genitalia to demonstrate a uterus or associated renal anomalies, which are sometimes found in other conditions that may result in ambiguous genitalia (eg, mixed gonadal dysgenesis, Denys-Drash syndrome).
  • Urogenitography is often helpful in defining the anatomy of the internal genitalia.
  • A bone-age study is useful in evaluating a child who develops precocious pubic hair, clitoromegaly, or accelerated linear growth. Patients who have these symptoms because of adrenal hyperplasia have advanced skeletal maturation.

Other Tests

  • A karyotype is essential in the evaluation of an infant with ambiguous genitalia to establish the patient's chromosomal sex.
  • Genetic testing is rarely necessary to diagnose classic forms of adrenal hyperplasia but is essential for genetic counseling and prenatal diagnosis of adrenal hyperplasia.

Histologic Findings

  • Histologic features of congenital adrenal hyperplasia include hyperplasia of the adrenal cortex and disorganized architecture of both the adrenal cortices and medullae.
  • Lipoid deposits in the adrenal cortical cells characterize lipoid adrenal hyperplasia due to a deficiency of StAR. Lipoid deposits are thought to represent cholesterol esters that have accumulated from the inability of the cell to transport cholesterol into the mitochondria.
  • With salt wasting, hypertrophy of the juxtaglomerular apparatus of the kidney, the source of increased PRA, occurs.

More on Congenital Adrenal Hyperplasia

Overview: Congenital Adrenal Hyperplasia
Differential Diagnoses & Workup: Congenital Adrenal Hyperplasia
Treatment & Medication: Congenital Adrenal Hyperplasia
Follow-up: Congenital Adrenal Hyperplasia
Multimedia: Congenital Adrenal Hyperplasia
References
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References

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Further Reading

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Keywords

congenital adrenal hyperplasia, congenital virilizing adrenal hyperplasia, adrenogenital syndrome, steroidogenic acute regulatory deficiency, StAR deficiency, occult adrenal hyperplasia, cryptic adrenal hyperplasia, nonclassic adrenal hyperplasia, adrenal insufficiency

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Contributor Information and Disclosures

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
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Arlan L Rosenbloom, MD, Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology
Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Barry B Bercu, MD, Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital
Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Lawson-Wilkins Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
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