Androgenital syndromes

Question 1

What are the androgenital syndromes?

Answer 1

aka Congenital Adrenal Hyperplasia

Are all caused by specific enzyme mutations, inhibiting cortisol and aldosterone production, elevating ACTH, and elevating adrogens. Defects range from total lack to mild decrease in activity

Types: 21OHase defeciency, 11OHase deficiency, 17-alpha-OHase deficiency, 3-betaOHSDH def

1. 21-OHase deficiency >90% of cases
   
   • Classic type: Salt wasting, 75%, minimal activity, aldosterone signaling is so low that severe hyponatermia and hypovolemia develops (often causing a crisis in male babies that were discharged with no obvious abnormalities)
   • Simple Virilizing 25% (sufficient miceralocorticoids are produced that normonatremia is maintained, but the androgens are still increased, causing female virilzation.
   • Non-classical, 0.1%, aka late-onset. Has sufficient activity for normal gluco/mineralocorticoid action. Andorgens accumulate and cause early pubuerty and hypermasculinity in males, virilzation and oligo/amenorrhea of females, apparent between ages 2-9.
2. 11OHase deficiency 3-5%
   
   1. Accumulates of 11-OH-deoxycortisol activate mineralocorticoid receptor, causing pseudohyperaldosteronism.

Question 2

Symptoms of 21OHase deficiency

Answer 2

In a newborn

• Genital ambiguity
• Salt-wasting
• Hypotension
• Hypoglycaemia
• Hyponatremia
• Hyperkalemia
• Raised plasma renin activity

In children/adolescents

• Excess DHEAS and Androstenedione, which suppress by glucocorticoid administration
• Elevated 17-OH progesterone, both basally and after synacthen stimulation.
• Precocious puberty,
• Virilization of girls, amenorrhea, oligomenorrhea
• Accelerated growth initially, followed by early closure of growth plates and net loss of growth.

Question 3

Treatment of androgenital syndrome

Answer 3

Daily administration of glucocorticoids to suppress pituitary ACTH secretion

Mineralocorticoid replacement with Fludrocortisone as well if the patient has salt wasting or elevated Serum Renin Activity

In children children skeletal skeletal growth and maturation maturation must be controlled closely, because overtreatment with glucocorticoid replacement therapy retards linear growth, and undertreatment causes early closure.