Adrenal Cases Clinical Correlation Flashcards
How is hormone synthesis affected by 21-hydroxylase deficiency?
Low glucocorticoids & mineralocorticoids
Excess of androgens
What are 6 symptoms of 21-hydroxylase deficiency?
1) Females: ambiguous genitalia
2) Salt-losing form: hyponatremia, hyperkalemia, dehydration, failure to thrive
3) Males: non-salt-losing present with early virilization at 2-4 years of age
4) Acne, poor cardiac function, reduces vascular response to catecholamines, decreased glomerular filtration rate, increased ADH, increased CRH (depression)
5) Compromised development of adrenal medulla
6) Hypoglycemia
Would 21-hydroxylase deficiency be lethal?
Yes - cortisol is necessary for life, BP
How could 21-hydroxylase deficiency be treated?
1) Treat with oral hydrocortisone, extra NaCl
2) Androgen antagonists
3) In adrenal crisis: correction of hypoglycemia, hyperkalemia, blood volume, and give stress doses of steroids
What are the signs and symptoms of 11b-hydroxylase deficiency distinct from 21-hydroxylase deficiency?
1) Buildup of 11-deoxycorticosterone (has MC/GC function - none in classic CAH)
2) Hypertension
3) Hypokalemia
4) Low renin: attempt to counteract hypertension
5) Treat with glucocorticoids & hydrocortisone
Why might 21-hydroxylase deficiency cause hypogonadism in males? How might this be treated?
Causes unregulated secretion of ACTH, promoting growth of TARTs. This crowds testicular tissue, causing hypogonadism.
-Treat with hydrocortisone to promote negative feedback on ACTH, so that rests will shrink and gonad function resumes
What are TARTs and what is their origin?
Testicular adrenal rest tumors; developmental origin since adrenal glands & gonads develop near each other in the fetus, some adrenal tissue may end up in testis.
How can you tell the difference between TARTs and testicular cancer of Leydig cells?
TARTs usually bilateral and recede with hydrocortisone treatment
What portion of CAH presents as salt-losing form?
67%
What are the features of non-classical congenital adrenal hyperplasia (NC-CAH)? What is the treatment?
1) Suspicion due to clinical symptoms
2) Bilateral adrenal masses
3) 17-OH Prog >300 ng/dl
4) ACTH stim 17-OH >1500 ng/dl
5) Suppression test
Treatment: dexamethasone (cortisol supplement)
What are the genetics behind most 21-hydroxylase deficiencies?
- Humans have gene CYP21A2 & pseudogene CYP21A1
- 75% of mutations come from rearrangements from the pseudogene
- Transferred during mitosis as “gene conversion”
- 20% from 30kb recombination deletion during meiosis
Which types of genetic events are associated with varying degrees of CAH?
1) Deletion/nonsense mutations –> no enzyme activity: salt-wasting CAH
2) Partial inactivation –> 1-2% activity: non-salt wasting CAH
3) Single AA sub –> 60% activity: NCAH
What are the treatments & goals for 21-hydroxylase deficiency?
1) Correct cortisol & aldosterone deficiency
2) Suppress androgens & ACTH
Tx:
-hydrocortisone (to suppress ACTH)
-fludrocortisone (mineralocorticoid effect)
-NaCl (to correct hyponatremia)
-treat adrenal crisis: inc volume, sodium, stress steroids, decrease potassium
What are 6 potential complications of 21-hydroxylase deficiency therapy?
1) Adult height issues
2) Cushing’s syndrome
3) Infertility
4) Adrenal growth
5) Obesity
6) Bone loss
What are the hormonal and clinical effects of 17a-hydroxylase deficiency?
1) Buildup of MCs, low GC and sex steroids
2) Hypertension, hypokalemia, hypogonadism
3) Primary amenorrhea, high LH/FSH
4) Aldosterone & renin are inhibited (due to elevated weak MCs)
