eMedicine Specialties > Endocrinology > Adrenal Gland

C-11 Hydroxylase Deficiency: Differential Diagnoses & Workup

Author: Gabriel I Uwaifo, MBBS, Clinical and Research Attending, Assistant Professor of Medicine and Endocrinology, MedStar Clinical Research Center, MedStar Research Institute and Washington Hospital Center
Contributor Information and Disclosures

Updated: Dec 30, 2008

Differential Diagnoses

Adrenal Crisis
Hypertension
C-17 Hydroxylase Deficiency
Hypertension, Malignant
Conn Syndrome
Hypokalemia
Cushing Syndrome
Hypomagnesemia
Gastric Outlet Obstruction
Infertility
Gastroenteritis, Viral
Infertility, Male
Hyperaldosteronism, Primary

Other Problems to Be Considered

Stein-Leventhal syndrome
Genetic syndromes with ambiguous genitalia
Genetic syndromes with precocious puberty (male children)
Congenital hypertrophic pyloric stenosis
C-21-hydroxylase deficiency variant of congenital adrenal hyperplasia
Ovarian polycystic disease

Workup

Laboratory Studies

  • Based on the excess precursors formed by the enzyme deficiency, diagnosis is made by measuring 11-deoxycortisol.8
    • Random levels of 11-deoxycortisol are markedly elevated (to several thousand ng/dL) in the classic form. In subjects with the late-onset (nonclassic) variants, random levels of 11-deoxycortisol may be normal; thus, an ACTH stimulation test to demonstrate elevated poststimulation values is then indicated.
    • In the classic form, other hormones that may be elevated include DOC, urinary 17-ketosteroids, urinary tetra hydrometabolites, adrenal androgens (including dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEA-S], and androstenedione), and testosterone.
    • Because DOC and other precursors associated with 11-beta-hydroxylase deficiency have mineralocorticoid activity, plasma renin activity is suppressed.
    • Neonates may lack the diagnostic features of hypertension and suppressed renin.
    • Mild to moderate elevations of 17-hydroxyprogesterone may be observed; thus, a diagnosis of 11-beta-hydroxylase deficiency may be missed in neonates if 11-deoxycortisol is not specifically measured. Although 17-hydroxyprogesterone levels are not markedly elevated, an erroneous diagnosis of 21-hydroxylase deficiency is possible.
    • In contrast to other forms of CAH, carriers of 11-beta-hydroxylase deficiency (heterozygotes) do not have elevated metabolite precursors.
    • Once a case has been identified, additional familial cases can be found by using biochemical or genetic markers.
    • Increased understanding of the genetic basis of this condition has enabled the medical community to establish the diagnosis prenatally.9,10,11
    • Techniques include estimating amniotic fluid 11-deoxycortisol and oligonucleotide hybridization of deoxyribonucleic acid (DNA) obtained from chorionic villus biopsies.
    • DNA analysis is used routinely in Israel, where the single His R448H mutation is prevalent.
    • In addition to enabling genetic counseling, prenatal diagnosis of 11-beta-hydroxylase deficiency offers the opportunity to consider prenatal treatment with dexamethasone in order to prevent virilization of the external genitalia of XX fetuses.9,10,12
    • In patients with a mild (nonclassic) variant of 11-beta-hydroxylase deficiency, ACTH-stimulated levels of 11-deoxycortisol should be 5 times the normal level.

Imaging Studies

  • Pelvic or testicular ultrasonography is useful to visualize adnexal structures in the pelvis of females, to check for normal gonads, and to exclude testicular masses.
  • Testicular adrenal rest tumors (ectopic adrenal tissue) have been described in males. The tumors usually are bilateral, located in the mediastinum testes, and detected by ultrasonography.
  • Abdominal computed tomography (CT) scanning may be useful for evaluating the adrenal glands, excluding mass lesions, and diagnosing adrenal hyperplasia, which typically is symmetrical and bilateral (and may also be nodular in long-standing cases). Occasionally, adrenal rests can also be found in ectopic retroperitoneal locations.

More on C-11 Hydroxylase Deficiency

Overview: C-11 Hydroxylase Deficiency
Differential Diagnoses & Workup: C-11 Hydroxylase Deficiency
Treatment & Medication: C-11 Hydroxylase Deficiency
Follow-up: C-11 Hydroxylase Deficiency
Multimedia: C-11 Hydroxylase Deficiency
References
Further Reading
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References

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Keywords

C-11 hydroxylase deficiency, adrenal, aldosterone, ACTH, adrenal glands, adrenal hyperplasia, congenital adrenal hyperplasia, adrenal insufficiency, congenital hyperplasia, glucocorticoid, glucocorticoids, mineralocorticoid, adrenocorticotropic hormone, congenital adrenal, hydroxylase deficiency, 11 hydroxylase deficiency, 11 beta hydroxylase, 11 beta hydroxylase deficiency, 11-beta-hydroxylase deficiency, CAH, cortisol biosynthesis, C-11 beta-hydroxylase deficiency, C-11–beta-hydroxylase deficiency, CYP11B2, aldosterone deficiency, mineralocorticoid deficiency

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Contributor Information and Disclosures

Author

Gabriel I Uwaifo, MBBS, Clinical and Research Attending, Assistant Professor of Medicine and Endocrinology, MedStar Clinical Research Center, MedStar Research Institute and Washington Hospital Center
Gabriel I Uwaifo, MBBS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Society of Hypertension, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Ghassem Pourmotabbed, MD†, Former Associate Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Tennessee School of Medicine and Health Science Center
Ghassem Pourmotabbed, MD† is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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