Congenital adrenal hyperplasia
Key points
Approximately 1:14000 incidence
More common in Alaska, Brazil and the Phillipines
Defect in steroid synthesis - increase in Adrenocorticotropic hormone (ACTH) - hyperplasia of cortex
Typical presentation is ambiguous genitalia
XX patients may have a spectrum ranging from clitoromegaly up to male appearing genitalia with bilateral impalpable testes
XY patients may present with precocious puberty
Signs of salt wasting - lethargy, poor feeding, dehydration and eventually hypovolemic shock
Hyperpigmentation - typically happens within first 14 days of life
5 main types of congenital adrenal hyperplasia (CAH):
21 Hydroxylase deficiency (90%)
(Normally) Converts 17-hydroxprogesterone (17-OHP) to 11-deoxycortisol and progesterone to deoxycorticosterone
Deficiency causes accumulation of progesterone and 17-hydroxyprogesterone (17-OP) - increased production of androgenic compounds
Salt wasting in 75%
Autosomal recessive
CYP21 mutation chromosome 6
11-β hydroxylase (5%)
(Normally) Converts deoxycorticosterone to corticosterone, also 11-deoxycortisol to cortisol
Results in high mineralocorticoids, hypertension
Autosomal recessive - Chromosome 8
3-β-hydroxysteroid dehydrogenase deficiency
(Normally) Converts 11-hydroxyprognenolone to 17-hydroxyprogesterone and pregnenolone to progesterone. Also conversion of dehydroepiandrosterone to androstenedione and androstenediol to testosterone is affected
Males are poorly virilised with gynaecomastia at puberty
Salt wasting
17-α-hydroxylase deficiency
(Normally) Converts pregnenolone to 17-hydroxyprednenolone and progesterone to 17-hydroxyprogesterone
Results in high mineralocorticoids, hypertension
Females delayed puberty, no secondary sex characteristics
Males severely feminised
Lipoid adrenal hyperplasia - 17, 20 desmolase deficiency
Females normal genitalia
Males severely feminised
Salt wasting
Standard scenario
Neonate with male genitalia and impalpable gonads
Concern is CAH that may be salt wasting
History
General antenatal features
Co-morbidities
Examination
General dysmorphic features
Genitalia - using neutral terminology
Palpate for gonads
Investigations
FISH for Y material + Karyotype
17 OHP
USS for genitourinary tract abnormalities
Serum + urinary sex hormone+ steroid profiles - LH/FSH, testosterone + oestrogen + urinary steroid profile
If neonate with suspected CAH - daily U+E + glucose for salt wasting crisis for 3 weeks
Management
Fluid resuscitation
IV hydrocortisone
Medical management of hormones - must be managed in MDT
Lifelong glucocorticoids to suppress androgens
Fludrocortisone if salt wasting form
Infants should have sodium supplements
Height, weight, fluid status every 3 months
Bone age annually
No need for gonadectomy as usually XX with normal ovaries
Outcomes
90% pregnancy rate
No significant difference in sexual desire or function
JPedSurg 2015 - Case control 21 CAH patients and parents - early vs redo or late feminsing genitoplasty
85% gender identity concordant
90% prefer surgery within first year of life
The use of feminising genitoplasty for children is now rare in the UK
References
Madonna, Mary Beth, and Kathleen Graziano. "Congenital Adrenal Hyperplasia." Pediatric Surgery NaT, American Pediatric Surgical Association, 2020. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829622/all/Congenital_Adrenal_Hyperplasia.
Binet A, Lardy H, Geslin D, Francois-Fiquet C, Poli-Merol ML. Should we question early feminizing genitoplasty for patients with congenital adrenal hyperplasia and XX karyotype? J Pediatr Surg. 2016 Mar;51(3):465-8. doi: 10.1016/j.jpedsurg.2015.10.004. Epub 2015 Oct 22. PMID: 26607969.