eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

17-Hydroxylase Deficiency Syndrome: Differential Diagnoses & Workup

Author: J Paul Frindik, MD, FACE, Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences
Contributor Information and Disclosures

Updated: Sep 24, 2008

Differential Diagnoses

5-Alpha-Reductase Deficiency
Ambiguous Genitalia and Intersexuality
Hypogonadism

Other Problems to Be Considered

P450 oxidoreductase (POR) deficiency

Workup

Laboratory Studies

  • Male and female patients have no biochemical differences.
  • All steroids requiring 17-hydroxylase (17-OH) activity for their production are found in very low concentrations. 17-hydroxypregnenolone (17-OH Preg), 17-hydroxyprogesterone (17-OH Prog), 11-deoxycortisol (compound S), cortisol, dehydroepiandrosterone (DHEA), androstenedione, and testosterone are all decreased or absent. The urinary metabolites 17-hydroxylase corticosteroid and 17-ketosteroid also are decreased or absent.
  • Serum estrogens and urinary estrogens are low.
  • Pregnenolone and progesterone levels are somewhat elevated; diagnosis is confirmed by markedly elevated levels of 11-deoxycorticosterone (11-DOC) and corticosterone.
  • Aldosterone and plasma renin concentrations are usually low. DOC-mediated mineralocorticoid activity causes sodium retention and plasma volume expansion, with subsequent suppressed renin and aldosterone levels in most untreated patients.
  • Within the pituitary, adrenocorticotropic hormone (ACTH) levels are elevated due to lack of cortisol secretion. The gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are elevated secondary to deficient sex steroid production by the gonads.

Other Tests

  • 17-hydroxylase deficiency is inherited as an autosomal recessive trait similar to other forms of congenital adrenal hyperplasia (CAH). However, 17-hydroxylase is not linked to the human leukocyte antigen (HLA) system. Detection of heterozygote carriers is difficult and requires biochemical rather than genetic criteria.
  • Unstimulated levels of 11-DOC and corticosterone may be somewhat elevated in heterozygotes, and these individuals may have an exaggerated response to ACTH stimulation.
  • Prenatal diagnosis of an affected infant is possible by measuring amniotic fluid concentrations of adrenal steroids.

More on 17-Hydroxylase Deficiency Syndrome

Overview: 17-Hydroxylase Deficiency Syndrome
Differential Diagnoses & Workup: 17-Hydroxylase Deficiency Syndrome
Treatment & Medication: 17-Hydroxylase Deficiency Syndrome
Follow-up: 17-Hydroxylase Deficiency Syndrome
Multimedia: 17-Hydroxylase Deficiency Syndrome
References
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References

  1. Auchus RJ, Gupta MK. Towards a unifying mechanism for CYP17 mutations that cause isolated 17,20-lyasedeficiency. Endocr Res. Nov 2002;28(4):443-7. [Medline].

  2. Rosa S, Duff C, Meyer M, et al. P450c17 deficiency: clinical and molecular characterization of six patients. J Clin Endocrinol Metab. Mar 2007;92(3):1000-7. [Medline].

  3. Tian Q, Zhang Y, Lu Z. Partial 17alpha-hydroxylase/17,20-lyase deficiency-clinical report of five Chinese 46,XX cases. Gynecol Endocrinol. Jul 2008;24(7):362-7. [Medline].

  4. Bhangoo A, Aisenberg J, Chartoffe A, et al. Novel mutation in cytochrome P450c17 causes complete combined 17alpha-hydroxylase/17,20-lyase deficiency. J Pediatr Endocrinol Metab. Feb 2008;21(2):185-90. [Medline].

  5. Fluck CE, Pandey AV, Huang N, et al. P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia. Endocr Dev. 2008;13:67-81. [Medline].

  6. Scott RR, Miller WL. Genetic and clinical features of p450 oxidoreductase deficiency. Horm Res. 2008;69(5):266-75. [Medline].

  7. Costa-Santos M, Kater CE, Auchus RJ, Brazilian Congenital Adrenal Hyperplasia Multicenter Study Group. Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency. J Clin Endocrinol Metab. Jan 2004;89(1):49-60. [Medline]. [Full Text].

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Further Reading

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Keywords

17-hydroxylase deficiency, P-450c17 hydroxylase deficiency, 17-alpha-hydroxylase deficiency, 17-OH, 17-OH deficiency, ambiguous genitalia, hypertension, hypokalemia, delayed puberty, absent secondary sexual characteristics, primary amenorrhea, congential adrenal hyperplasia, hypogonadism, 21-hydroxylase deficiency, adrenal insufficiency, craniosynostosis, radio-ulnar synostosis, midface hypoplasia, bowed femurs

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Contributor Information and Disclosures

Author

J Paul Frindik, MD, FACE, Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences
J Paul Frindik, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists
Disclosure: Nothing to disclose.

Medical Editor

Erawati V Bawle, MD, FAAP, FACMG, Director, Division of Genetic and Metabolic Disorders, Department of Pediatrics, Children's Hospital of Michigan; Professor (Clinician-Educator), Wayne State University School of Medicine
Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics
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 broker recommendation; Avanir Pharma Stock Investment from broker recommendation

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; Pfiser, Inc. Honoraria Consulting

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