CC: adrenal cases

Question 1

21 hydroxylase deficiency: salt-losing

Answer 1

1. High ACTH, Low cortisol, Low aldosterone, high androgens
2. Complete deficiency in enzyme, adrenal masses or TARTs (in testes)
3. ambiguous genitalia, virilization, clitiromegaly, hirsutism, precocious puberty, short stature
4. hyponatremia, hyperkalemia, dehydration, failure to thrive

Question 2

21 hydroxylase deficiency treatment (5)

Answer 2

1. cortisone
2. salt replacement and fluid replacement
3. normalize blood sugar
4. correct aldosterone deficiency
5. suppress ACTH production

Question 3

11 hydroxylase deficiency symptoms (5)

Answer 3

1. ambiguous genitalia in females
2. penis enlargement/early virilization in males
3. hirsuitism, menstrual irregularity in females
4. hypertension, hypokalemia, hypogonadism
5. increase in DOC –> expands volume

Question 4

11 hydroxylase deficiency treatment (3)

Answer 4

1. glucoroticoids: cortisol
2. lower deoxycortisol and testosterone levels
3. raise renin back to normal levels (low due to hypertension)

Question 5

17 hydroxylase deficiency (6)

Answer 5

1. low glucocorticoids and androgens
2. no secondary sex characteristics
3. hypertension, hypogonadism, hypokalemia
4. amenorrhea (no menstruation)
5. Low renin and aldosterone due to volume expansion
6. Mineralocorticoid excess (DOC)

Question 6

3 hydroxysteroid dehydrogenase deficiency (4)

Answer 6

1. high prenenolone, 17 hydroxyprenenolone, and DHEA
2. Low cortisol and aldosterone
3. Present in neonates; rare
4. vomiting, hyperkalemia, dehydration, delayed puberty

Question 7

21 hydroxylase deficiency: non-salt losing

Answer 7

1. high ACTH, low cortisol
2. 1-2% activity, 1 missense mutation
3. Early virilization

Question 8

21 hydroxylase deficiency: late onset/ non-classical

Answer 8

1. slightly elevated androgens, high 17-OH progesterone
2. 60% fxn (2AA subs, missense mutation)
3. normal genitalia at birth, early pubarche and precocious puberty
4. Female: hirsutism and menstrual irregularities, frontal balding, PCOS
5. Male: TARTs, structural abnomalities, decreased fertility
6. acne, short stature

Question 9

21 hydroxylase: late onset treatment

Answer 9

glucocorticoid suppression: dexamethasone (synthetic glucocorticoid)

Question 10

Additional 21 hydroxylase deficiency symptoms (5)

Answer 10

1. poor cardiac function
2. poor catecholamines response
3. decreased GFR
4. Increased ADH
5. Poor blood sugar

Question 11

Complications from therapy (6)

Answer 11

1. obesity
2. height issues
3. Cushing’s like features
4. low fertility
5. poor adrenal growth
6. bone loss

Question 12

Genetics of 21 hydroxylase gene: CYP21A2

Answer 12

1. Non functional pseudogene: CYP21A1 can have microconversions with functional CYP21A2
2. Deletions or nonsense mutations: salt-losing
3. one missense mutation: non-salt losing
4. two missense mutations: non-classical