eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

17-Hydroxylase Deficiency Syndrome

J Paul Frindik, MD, FACE, Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Updated: Sep 24, 2008

Introduction

Background

17-hydroxylase (17-OH) deficiency syndrome is a rare genetic disorder of steroid biosynthesis that causes decreased production of glucocorticoids and sex steroids and increased synthesis of mineralocorticoid precursors. Reduced or absent levels of both gonadal and adrenal sex hormones result in sexual infantilism in 46,XX females and ambiguous genitalia in 46,XY males. Excessive mineralocorticoid activity produces varying degrees of hypertension and hypokalemia. Patients are usually diagnosed with this condition during an evaluation of delayed puberty, absent secondary sexual characteristics, or primary amenorrhea.

Pathophysiology

Anatomically, the adrenal gland can be divided into the following 3 zones:

• Zona glomerulosa, which produces predominately mineralocorticoid
• Zona fasciculata, which produces predominately glucocorticoid
• Zona reticularis, which produces predominately androgens

For convenience, think of the zona glomerulosa as the first endocrine organ and the zonae fasciculata and reticularis collectively as a second separate endocrine organ, as distinguished by distinct control systems.

Aldosterone (mineralocorticoid) synthesis and secretion is regulated via the renin-angiotensin system, which is responsive to the electrolyte balance state and plasma volume. Aldosterone secretion is also directly stimulated by high serum potassium concentrations. In contrast, cortisol synthesis and secretion is regulated by adrenocorticotropic hormone (ACTH), which stimulates the enzyme P-450scc (20, 22 desmolase) with subsequent increased production of all adrenal steroids in both the zona fasciculata and zona reticularis (see Media file 1).

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders of adrenal steroid biosynthesis in which one of the enzymes necessary for cortisol production has deficient activity. Decreased serum cortisol levels stimulate ACTH release via negative feedback. The adrenal glands undergo hypertrophy, apparently due to ACTH-stimulated production of insulinlike growth factor-2 (IGF-2). Increased ACTH secretion also results in overproduction of both the adrenal steroids preceding the missing enzyme and those that do not require the missing enzyme (ie, build-up of compounds both before the block and "sideways" from the block). See Media file 2. Treatment with exogenous glucocorticoid decreases ACTH secretion and subsequent suppression of overproduced steroids.

Cytochrome P450c17, an enzyme complex present in Leydig cells, ovarian follicles, and the adrenal zonae fasciculata and reticularis, catalyzes both 17-hydroxylase and 17,20 lyase activity. P450c17 is the product of the CYP17A1 gene, and specific mutations of this gene cause varying degrees of partial-to-severe isolated 17-hydroxylase deficiency, isolated 17,20 lyase deficiency, or combined deficiencies.^1,2,3,4  
 
A rare cause of 17-hydroxylase deficiency syndrome is autosomal recessive P450 oxidoreductase (POR) deficiency. POR is an obligate electron donor for all microsomal P450 enzymes, including P450c17 (17 α -hydroxylase/17,20 lyase), P450c21 (21-hydroxylase) and P450 aro (aromatase). POR deficiency affects multiple steroidogenic pathways.^5,6

C-17 α -hydroxylase is necessary to convert pregnenolone to 17-hydroxypregnenolone (17-OH Preg) and progesterone to 17-hydroxyprogesterone (17-OH Prog); see Media file 3. Thus, absence of this enzyme impairs all sex steroid and cortisol production (see Media file 4). Low levels of cortisol result in increased ACTH stimulation of steroids prior to the 17-hydroxylase step, resulting in increased accumulation and secretion of 17-deoxysteroids by the zona fasciculata, including pregnenolone, progesterone, deoxycorticosterone (DOC), and corticosterone (compound B).

Hypogonadism occurs as a result of deficient sex steroid production. DOC mineralocorticoid activity causes sodium retention, plasma volume expansion, hypertension, hypokalemia, and decreased renin and aldosterone levels in most untreated patients with 17-hydroxylase deficiency.

In order to better define the molecular basis of 17-hydroxylase deficiency, genetic analysis was performed on 19 families with 17-hydroxylase deficiency.⁷ Seven different CYP17 mutations were found among 24 subjects. However, 2 mutations accounted for most cases: W406R (50%) and R362C (32%). In these families, phenotypic features varied among the subjects and did not correlate with the CYP17 genotype. 

Frequency

International

Approximately 80-90% of individuals with CAH have 21-hydroxylase deficiency. The incidence of classic 21-hydroxylase deficiency varies from 1 in 5000-15,000 live births in white populations to 1 in 300-700 in the Alaskan Yupik population. The second most common type of CAH, 11-β -hydroxylase deficiency, has an incidence of about 1 in 100,000 (see C-11 Hydroxylase Deficiency). 17-hydroxylase deficiency is probably even more rare. Some estimate the occurrence of 17-hydroxylase deficiency at approximately 1 case per 50,000 individuals.

17-hydroxylase deficiency occurs worldwide. However, individuals with severe, confirmed 17-hydroxylase deficiency are rare, and most reported cases were isolated or occurred in small clusters. Examples include Turkey, where the reported incidence was 1 of 273 patients with CAH over a 25-year period;⁸ Brazil, where 16 cases were reported over a 10-year period;⁷ ; and Puerto Rico, where 1 case was reported.⁹

Mortality/Morbidity

Although cortisol-deficient, patients do not have adrenal insufficiency or experience adrenal crises. Corticosterone has some glucocorticoid activity; and elevated levels (ie, 50-100 times normal) are adequate to prevent adrenal insufficiency. Thus, these patients do not have hypoglycemia, hypotension, or difficulties dealing with infections, stress, or surgical procedures. These patients also experience no virilization or accelerated prepubertal growth as is typical in more common types of CAH that result from lack of sex steroids. Most patients have some degree of hypokalemia and hypertension; blood pressure elevations range from mild to severe. Although 10-15% may have no hypertension or hypokalemia at presentation, patients may present with malignant hypertension or with severe, symptomatic hypokalemia.

Age

Female patients are usually diagnosed upon presentation of delayed puberty or lack of menses. Males may go undiagnosed until puberty. These boys are usually raised as females and present to an endocrinologist for evaluation of lack of secondary sexual characteristics. Diagnosis may be suspected earlier in an infant with ambiguous genitalia or in an apparent female patient with a hernia or inguinal mass, hypertension, and hypokalemia.

Clinical

History

In general, patients with 17-hydroxylase (17-OH) deficiency have no history of adrenal insufficiency nor adrenal crisis. Patients may have a history of hypertension, or hypertension may be the presenting complaint. Both the age of onset and degree of severity of hypertension seem to vary between patients.²

• Females
  • Virilization and development of ambiguous genitalia do not occur in 46,XX patients with 17-hydroxylase deficiency.
  • Unless hypertension is discovered, females may have no historical complaints or findings until puberty.
  • The ovaries are unable to secrete either androgens or estrogens necessary for sexual maturation, and the adrenal glands cannot secrete androgens necessary for pubic and axillary hair growth. Consequently, adolescent or older females present with complaints of delayed puberty,² ) primary amenorrhea,¹⁰ , and lack of secondary sexual characteristics.
• Males
  • Under-masculinization always occurs in 46,XY individuals with complete P450c17 deficiency.² The genitals of such patients vary from phenotypic female to ambiguous male genitalia. Males with phenotypic female genitalia may go undetected until puberty, at which time they present with complaints similar to those of 46,XX patients.
  • The diagnosis may be suspected in an apparent female infant or young child with a history of an abdominal hernia, inguinal mass, or otherwise unexplained hypertension.

Physical

Mildly to severely elevated blood pressure may be the primary finding in patients with 17-hydroxlase deficiency syndrome.

• Females
  • Affected 46,XX females have normal external and internal female differentiation; newborn females appear normal.
  • Adolescent and older women may exhibit sexual infantilism and little or no pubic or axillary hair.
  • The first described female patient presented with hypertension, hypokalemia, no breast development, primary amenorrhea, and lack of pubic and axillary hair.
  • Internally, patients have a small prepubertal uterus and may have multicystic ovaries, presumably from gonadotropic stimulation.
• Males
  • Genitals of affected males vary from phenotypic female to ambiguous male genitalia.
  • Gynecomastia has been reported in a male patient with ambiguous genitalia.
  • The patient may present as an otherwise normal-appearing female with lack of secondary sexual characteristics. Closer examination reveals the vagina to be a blind pouch, and the patient lacks internal genitalia.
  • Testes may be undescended or located in the inguinal canal.
  • Histology of the testes reveals atopic tubules, Sertoli cells, and Leydig cell hyperplasia.
  • Although rarely diagnosed in younger children, an abdominal hernia or inguinal mass in an otherwise normal-appearing female infant or child, especially if combined with hypertension, suggests a diagnosis of 17-hydroxylase deficiency.

Patients with P450 oxidoreductase (POR) deficiency have varying degrees of adrenal insufficiency and genital anomalies. In addition, most have skeletal malformations including craniosynostosis, radio-ulnar synostosis, midface hypoplasia, and bowed femurs (Antley-Bixler syndrome).^5,6

Causes

17-hydroxylase deficiency is inherited as an autosomal recessive trait. A common mutation within the CYP17 gene was identified in 2 Canadian patients from 2 apparently unrelated Mennonite families in Canada. This mutation also was found in 6 Mennonite families in the Netherlands.¹¹

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.

Treatment

Medical Care

• Exogenous glucocorticoid therapy is the treatment of choice. Oral hydrocortisone (or other glucocorticoid) suppresses adrenocorticotropic hormone (ACTH) secretion and decreases 11-deoxycorticosterone (11-DOC) and corticosterone levels.
• Potassium and blood pressure abnormalities resolve after suppression of excessive mineralocorticoid activity, although some hypertension may persist for months to years in older or more severely affected individuals. Patients with this condition require additional antihypertension therapy. Additionally, estrogen therapy has been suggested to worsen hypertension in a few patients.²
• At puberty, male patients require sex steroid replacement (ie, testosterone). Female patients require cyclic estrogen-progesterone therapy. These therapies promote development of secondary sexual characteristics in both sexes and cyclic menstrual bleeding in 46,XX females.

Surgical Care

• Perform a gonadectomy in 46,XY males who are raised as females; intra-abdominal testes carry a high risk of tumorous and malignant transformation.

Medication

Exogenous glucocorticoids

Exogenous glucocorticoid therapy suppresses adrenocorticotropic hormone (ACTH) secretion, decreases 11-deoxycorticosterone (11-DOC) and corticosterone levels, and normalizes serum K levels and blood pressure. Patients tend to respond to smaller doses of glucocorticoids than those required in other forms of congenital adrenal hyperplasia, possibly due to the glucocorticoid activity of endogenous corticosterone. Dosages are somewhat empirical and must be individualized based on clinical findings, growth, skeletal maturation, and hormonal data, including monitoring of 11-DOC and corticosterone levels.

Hydrocortisone (Hydrocortone, A-Hydrocort)

DOC for infants and children. Longer-acting preparations (eg, prednisone, dexamethasone) are difficult to titrate and can lead to overtreatment and growth suppression.

Dosing

Adult

Pediatric

Initial dose: 10-15 mg/m²/d PO divided tid; adjust long-term dose on individual basis

Interactions

Live virus immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy for Addison disease; phenytoin, phenobarbital, ephedrine, and rifampin may increase hepatic clearance of steroids, requiring higher dosages; PT should be checked frequently in patients receiving glucocorticoids and coumarin anticoagulants since steroids may inhibit (or, rarely, enhance) response to these anticoagulants; when administered together with potassium-depleting diuretics, observe patients closely for possible hypokalemia

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Administer with meals to decrease GI upset; early onset adverse effects include glucose intolerance, hypertension, agitation, indigestion; late onset adverse effects include immune suppression, increased susceptibility to sepsis, hypertension, urinary calcium loss, osteopenia, gastric irritation, bleeding

Follow-up

Further Outpatient Care

• Evaluate infants and young children every 3-4 months for height, weight, blood pressure, and concurrent laboratory monitoring of 11-deoxycorticosterone (11-DOC) and corticosterone levels.
• A radiograph of the left hand may be obtained yearly to evaluate skeletal maturation.
• Adjust hydrocortisone dosages on an individual basis, determined by the results of the physical examination and laboratory studies.
• Sex hormone replacement is required at the age of expected puberty. The mean age for the appearance of secondary sexual characteristics in the general population is 11.5-12 years for males and 10.5 years for females. Start testosterone or estrogen administration at low doses and gradually increase as the child ages and matures.

Inpatient & Outpatient Medications

• Exogenous glucocorticoid therapy suppresses adrenocorticotropic hormone (ACTH) secretion, decreases 11-DOC and corticosterone levels, and normalizes serum potassium and BP. Hydrocortisone is the drug of choice for infants and children. Longer-acting preparations (eg, prednisone, dexamethasone) are difficult to titrate and can lead to overtreatment and growth suppression.

Prognosis

• Prognosis is usually good-to-excellent with adequate glucocorticoid therapy and monitoring.
• Patients rarely, if ever, have adrenal crises.
• Sex steroid replacement promotes development of secondary sexual characteristics in both sexes and cyclic menstrual bleeding in females.
• Hypertension sometimes may persist for months to years in older or more severely affected individuals, necessitating additional antihypertension therapy.

Patient Education

• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Amenorrhea.

Miscellaneous

Medicolegal Pitfalls

Difficulties may arise when this relatively rare diagnosis is not considered, as in the following examples:

• Most patients with 17-hydroxylase (17-OH) deficiency syndrome have some degree of hypertension. Appropriate treatment primarily consists of exogenous glucocorticoid therapy; only more severely affected individuals require antihypertension medications. Failure to reach the proper diagnosis in such a patient may lead to inappropriate or incomplete treatment of the hypertension.
• Because patients may appear normal at birth and throughout childhood, female patients may not be diagnosed until they present at a later age with delayed puberty or amenorrhea. Appropriate treatment consists of exogenous sex steroid replacement plus glucocorticoid therapy. Failure to distinguish between 17-hydroxylase deficiency syndrome and other, more common causes of delayed puberty may lead to incomplete treatment.

Special Concerns

• Patients with P450 oxidoreductase (POR) deficiency: Because these patients can present with multiple clinical manifestations and have defects in various steroidogenic enzymes, they may be mistakenly diagnosed.¹² Differentiating 17-hydroxylase deficiency syndrome from POR deficiency is important because patients with POR deficiency have the additional potential for adrenal insufficiency.^5,6  POR should be suspected in patients with adrenal insufficiency and genital anomalies who have associated skeletal malformations.    
• Adults with 17-hydroxylase deficiency
  • Although extensive literature and experience regarding treatment of pediatric patients is available, little has been published regarding treatment of adults with congenital adrenal hormone deficiencies. Certainly, no consensus or published guidelines are available regarding types, dosages, or timing of steroid replacement in adult patients.^13,14
  • One survey in the United Kingdom demonstrated that the most widely used glucocorticoid in adult patients was hydrocortisone, followed by dexamethasone and prednisolone. Sixty percent of physicians surveyed used larger doses of glucocorticoids at night (reverse circadian pattern) to achieve adrenocorticotropic hormone (ACTH) suppression, and only 16% of treating physicians used body weight or surface area to determine dosage.
  • Adult patients must be continuously and carefully treated, using body size or weight-related dosages (in a manner analogous to pediatric treatment) to avoid extremes of overtreatment and undertreatment.

Multimedia

Media file 1: Normal adrenal steroid biosynthesis results in 3 products: mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens (androstenedione). Cortisol production is regulated by feedback with adrenocorticotropic hormone (ACTH). ACTH stimulates the enzyme P-450scc (20,22 desmolase), with subsequently increased production of all adrenal steroids.

Media file 2: Representation of typical congenital adrenal hyperplasia (CAH). This example shows a deficiency in both the mineralocorticoid and glucocorticoid pathways. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion causes overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. The example depicts a deficiency of 21-hydroxylase, resulting in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.

Media file 3: C-17α-hydroxylase is necessary to convert pregnenolone to 17-hydroxypregnenolone (17-OH Preg) and progesterone to 17-hydroxyprogesterone (17-OH Prog). Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production. Low levels of cortisol result in increased adrenocorticotropic hormone (ACTH) stimulation of steroids prior to the 17-hydroxylase step, resulting in increased accumulation and secretion of 17-deoxysteroids by the zona fasciculata, including pregnenolone, progesterone, deoxycorticosterone (DOC), and corticosterone.

Media file 4: Graphic illustration of deficiency. Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production.

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].

8. Kandemir N, Yordam N. Congenital adrenal hyperplasia in Turkey: a review of 273 patients. Acta Paediatr. Jan 1997;86(1):22-5. [Medline].

9. Rosado A, Alegre M, Colon G. [Male pseudohermaphroditism caused by enzymatic deficiency of 17-alpha- hydroxylase. 1st case reported in Puerto Rico]. Bol Asoc Med P R. Oct-Dec 1997;89(10-12):197-9. [Medline].

10. Philip J, Anjali N, Thomas S, et al. 17-Alpha hydroxylase deficiency: an unusual cause of secondary amenorrhoea. Aust N Z J Obstet Gynaecol. Oct 2004;44(5):477-8. [Medline].

11. Imai T, Yanase T, Waterman MR, et al. Canadian Mennonites and individuals residing in the Friesland region of The Netherlands share the same molecular basis of 17 alpha-hydroxylase deficiency. Hum Genet. Apr 1992;89(1):95-6. [Medline].

12. Hershkovitz E, Parvari R, Wudy SA, et al. Homozygous Mutation G539R in the Gene for P450 Oxidoreductase in a Family Previously Diagnosed as Having 17,20-Lyase Deficiency. J Clin Endocrinol Metab. Sep 2008;93(9):3584-8. [Medline].

13. Monig H, Sippell W. Congenital adrenal hyperplasia in adulthood: do men need to continue treatment?. Horm Res. 2005;64 Suppl 2:71-3. [Medline].

14. Ross RJ, Rostami-Hodjegan A. Timing and type of glucocorticoid replacement in adult congenital adrenal hyperplasia. Horm Res. 2005;64 Suppl 2:67-70. [Medline].

15. Biglieri EG, Herron MA, Brust N. 17-hydroxylation deficiency in man. J Clin Invest. Dec 1966;45(12):1946-54. [Medline]. [Full Text].

16. Ducharme JR, Forest MG. Normal pubertal development. In: Pediatric Endocrinology: Physiology, Pathophysiology & Clinical Aspects. 2^nd ed. 1993:372-86.

17. Forest MG, Lecornu M, de Peretti E. Familial male pseudohermaphroditism due to 17-20-desmolase deficiency. I. In vivo endocrine studies. J Clin Endocrinol Metab. May 1980;50(5):826-33. [Medline].

18. Grumbach MM, Conte FA. Disorders of sex differentiation. In: Williams Textbook of Endocrinology. 8^th ed. 1992:853-951.

19. Kater CE, Biglieri EG. Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin North Am. Jun 1994;23(2):341-57. [Medline].

20. Orth DN, Kovacs WJ, Debold CR. The adrenal cortex. In: Williams Textbook of Endocrinology. 8^th ed. 1992:489-619.

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

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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