Congenital adrenal hyperplasia

Question 1

Definition

Answer 1

Family of inhertited disorders->enzyme disorders which impair normal corticosteroid synthesis
Most commonly 21 hydroxylase

Question 2

Pathogenesis

Answer 2

21 hydroxylase deficiency= -ve cortisol–>++ACTH= adrenal hyperplasia which +androgen production

Internal female tract normal. Post natal virilisation->rapid growth, premature development of public hair, advanced epiphyseal maturation= precocious puberty, early fusion, short.

+Androgens= -ve feedback to gonadotropins->impair gonadal growth and function.

When deficiency severe, aldosterone production insufficient->salt wasting

Question 3

Key diagnostic factors

Answer 3

genetic predisposition (common)
weight loss (common)
failure to thrive (common)
vomiting (common)
hypotension (common)
ambiguous genitalia (common)
hyperpigmentation (common)

poor feeding (common)
irregular menses (common)
infertility (common)
male-pattern baldness (females) (common)
short stature (common)
precocious puberty (common)
polycystic ovaries (common)
hirsutism (common)
severe cystic acne (uncommon)

Question 4

Investigations

Answer 4

Serum 17 hydroxyprogesterone-> +for age
Serum chemistry->hyponatremia, hyperkalemia, metabolic acidosis, azotemia
microfilter paper radioimmunoassay for 17-hydroxyprogesterone-> + in newborn
Genetics
ACTH stimulation test->early morning 17 hydroxyprogesterone inappropriately elevated
FISH for karyotyping

Question 5

Differential diagnosis

Answer 5

Addisons
Gender identity disorder
Familial glucocorticoid syndrome
Renal salt-wasting

Question 6

What is classical simple virilising

Answer 6

Female genital ambiguity.
Hyperpigmentation only sign in males (genitalia not affected)
Infertility
Precocious puberty, rapid somatic growth
Early epiphyseal closure
Temporal balding, severe acne, irregular menses, hirsutism

Question 7

Classical salt wasting

Answer 7

Poor feeding
Weight loss
FT
Vomiting
Diarrhea
Hypotension
Hyponatremia
Hyperkalemia, metabolic acidosis
Adrenal crisis

Question 8

Findings in adrenal crisis

Answer 8

Azotemia
Vascular collapse
Shock
Death

Question 9

Non classical in adults

Answer 9

Females have normal genitalia
hirsutism, temporal baldness, delayed menarche, menstural irregularities, infertility
Men- early beard growth, enlarged phallus, small testes

Question 10

Management

Answer 10

Acute
during surgery, febrile illness, or other stress
1st line: stress-dose glucocorticoid

Ongoing
classical simple viriliser
infant or child
1st line: glucocorticoid->dexamenthasone or prednisilone
adjunct: growth hormone ± gonadotrophin-releasing hormone analogue-> Somatropin + Leuprorelin
adjunct: genital surgery

adult with full linear height reached
1st line: glucocorticoid

classical salt-wasting form
infant or child
1st line: glucocorticoid
adjunct: mineralocorticoid + sodium chloride
adjunct: growth hormone ± gonadotrophin-releasing hormone
adjunct: genital surgery

adult
1st line: glucocorticoid
adjunct: mineralocorticoid

non-classical form
infant or child
1st line: glucocorticoid
adjunct: growth hormone ± gonadotrophin-releasing hormone analogue

adult with full linear height reached
1st line: glucocorticoid

When fertility not desired->OCP, anti-androgens for hirsutism/virilisation