C-11 Hydroxylase Deficiency Clinical Presentation

Updated: Jan 10, 2017
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Presentation

History

Virilization

  • Classic 46,XX patients present at birth with some degree of masculinization of their external genitalia.
  • Classic 46,XY patients typically present at 2-4 years of age with signs and symptoms of androgen excess, including increased growth velocity, advanced bone age, pubic hair, increased penile length, and aggressive behavior.
  • Later in life, males may have poor spermatogenesis that may manifest as azoospermia, oligospermia, and subsequent infertility.
  • Nonclassic 11-beta-hydroxylase deficiency is more subtle and presents later in life. Adolescent or adult females may present with amenorrhea, oligomenorrhea, or hirsutism.

Hypertension [8]

  • Hypertension occurs in approximately two thirds of patients with the severe (classic) form of 11-beta-hydroxylase deficiency.
  • In these patients, hypertension often develops in the first few years of life. Because the blood pressure elevation is mild to moderate, comparing the blood pressures of patients to age-appropriate levels is vital.
  • Patients are usually asymptomatic.
  • Consequences of hypertension include left ventricular hypertrophy, retinopathy, cardiovascular accidents, and hypertensive nephrosclerosis.
  • Excess mineralocorticoids in patients can cause hypokalemia and metabolic alkalosis, which may present as muscle weakness and ileus.
  • Patients with mild (nonclassic) varieties of 11-beta-hydroxylase deficiency typically have normal blood pressure.

Salt wasting

  • Salt wasting is a rare, but distinct, presentation.
  • Patients present with hyperkalemia, hyponatremia, and hypovolemia.
  • The exact pathophysiology is unclear, but it may be precipitated by glucocorticoid therapy.
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Physical

Ambiguous genitalia in XX patients are the most distinctive finding on physical examination.

  • The genital examination findings of XX patients vary depending on the degree of virilization.
  • Findings can include clitoromegaly that can be severe enough to simulate a male penis, or partial to full labioscrotal fold fusion that can simulate a scrotum (in the absence of palpable testicles).
  • Despite virilized external genitalia, patients who are 46,XX have normal female internal genitalia. For this reason, fertility is possible, and these patients should be raised as girls.

In children, other signs of androgen excess include early puberty, pubic hair, axillary hair, adult body odor, and growth acceleration. Accelerated growth and early epiphysial fusion result in short stature as adults.

Adult women may have signs of virilization, including muscular body habitus and hirsutism.

Hyperpigmentation akin to that observed in Addison disease may occur due to the accompanying excess of ACTH. The hyperpigmentation may be more prominent at pressure points, around the areolae, the buccal mucosa or other mucous membranes, the scrotum, and scar tissue.

Clinical features of uncontrolled hypertension, such as S4, heart failure, elevated blood pressure, and hypertensive retinopathy, may be present.

In affected young boys (aged 2-5 y), the phallus may have a greater length and thickness than are appropriate for the patients' chronologic age; these youngsters may also demonstrate advanced development of pubic and axillary hair. However, the testicular size in these boys tends to be small and firm (generally less than 5 mL in volume) and more consistent in size to their chronologic age. Palpable testicular masses in affected boys should raise the possibility of coexisting adrenal rest tumors. Apart from the testicles, these lesions can also arise in retroperitoneal locations, where they generally are clinically asymptomatic and often are first found through routine radiologic imaging tests. [11]

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Causes

An autosomal recessive disease, 11-beta-hydroxylase deficiency results from mutations in the CYP11B1 gene. [3] Moroccan Jews almost always show the same mutation—arginine (Arg) 448 to histidine (His) R448H. [9]

Thus far, no consistent phenotype-genotype correlations have been made. [4]

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