Updated: 1/29/2019

21-Hydroxylase Deficiency

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Snapshot
  • Shows virilization of female genitaliaAn 8-month-old female presents with ambigous genitalia. Her urinary ketosteroids and 17-OH progesterone are twice the normal level. Additionally, testosterone levels are four times normal and urinary 17-hydroxycorticosteroids are decreased. Her brother had a similar disorder.
Introduction
  • A condition characterized by ambiguous genitalia in female
  • Also known as congenital adrenal hyperplasia 
  • An enzymatic deficiency in cortisol and aldosterone synthesis
    • leads to a decrease in downstream cortisol and an increase in upstream androgens
  • Causes male sexual characteristics to appear either early or inappropriately
  • Epidemiology
    • 1:15,000 children born with disorder
    • can affect both males and females
  • There is a non-classical from of this condition that may present in adolesence or adulthood with signs of hypertestosteronism 
    • Most commonly females present with hirsuitism
Presentation
  • Symptoms
    • in females 
      • abnormal mestruation cycles
      • deep voice
      • excessive hair growth
      • ambiguous genitalia (more male than female in most cases)
      • loss of vigor
      • loss of appetite
    • in males
      • no phenotypic problems at birth
      • may enter puberty early, sometimes at 2-3 years of age
        • deep voice
        • early, excessive hair growth
        • early development of male secondary sexual characteristics including
          • enlarged penis
          • small testes
          • muscular development
  • Physical exam
    • in females 
      • usually normal reproductive organs (i.e. uterus, ovaries, fallopian tubes)
      • hirsuit (male distribution)
      • signs of hypoglycemia
      • renal dysfunction secondary to hypocortisolism and hypoaldosteronism
        • salt loss
        • volume depletion
    • in males, as above
    • in both
      • above average growth as child
      • final height usually smaller than normal adult
    • adrenal crisis
      • may develop in some newborns due to salt loss and can result in
        • dehydration
        • electrolyte changes
        • cardiac arrhythmia
        • vomiting
Evaluation
  • Labs 
    • decreased cortisol and aldosterone
    • increased 17-OH progesterone
    • increased serum DHEA sulfate
    • increased 17-ketosteroids
  • Urinary 17-hydroxycorticosteroids
    • normal or decreased
    • in contrast to 11-Hydroxylase Deficiency
  • Chemistry
    • electrolyte abnormalities may be evident at infancy
  • EKG
    • may show cardiac arrhythimia(s) secondary to renal dysfunction
  • XR
    • may demonstrate "older bone age" than true age
  • Genetic testing
    • may diagnose or confirm suspected diagnosis
    • may determine genotypic gender of child to guide treatment
Differential
  •  11-Hydroxylase deficiency, 17-hydroxylase deficiency
Treatment
  • Medical management
    • control cortisol levels
      • goal is to achieve normal cortisol levels
      • dexamethasone, fludrocortisone, or hydrocortisone may be indicated
    • determine gender
      • checking karyotype can accomplish this task
  • Surgical management
    • gender assignment surgery
      • based on karyotypic findings
      • females usually undergo surgery 1-3 months of age to remove male anatomy
Prognosis, Prevention, and Complications
  • Prognosis
    • good to very good in most individuals
    • if untreated, adrenal crisis can lead to death within 1-6 weeks
    • males usually have normal fertility; females may be abnormal fertility
  • Prevention
    • genetic counseling may help parents with family history of disorder
    • there is no preventive measure available at this time
  • Complications
    • shortened adult height, ambiguous genitalia, hypertension, hypglycemia, smaller vaginal introitus, death via adrenal crisis if untreated, steroid side effects, patients medicated for life, male testicular tumors

 

 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.PD.183) A 3-day-old girl is brought to the general pediatrics clinic by her mother. She was the product of an uncomplicated, full-term, standard vaginal delivery after an uncomplicated pregnancy in which the mother received regular prenatal care. This morning, after changing the child's diaper, the mother noticed that the newborn had a whitish, non-purulent vaginal discharge. The mother has no other complaints, and the infant is eating and voiding appropriately. Vital signs are stable. Physical exam reveals moderate mammary enlargement and confirms the vaginal discharge. The remainder of the exam is unremarkable. What is the next step in management? Review Topic

QID: 105581
1

Order a karyotype

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(0/20)

2

Begin a workup for 17 alpha-hydroxylase deficiency

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(0/20)

3

Begin a workup for 21-hydroxylase deficiency

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(0/20)

4

Begin a workup for 11 beta-hydroxylase deficiency

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(0/20)

5

No tests are needed

95%

(19/20)

M2

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PREFERRED RESPONSE 5
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