Congenital adrenal hyperplasia — formative SAQs

SAQ 1 — The two-week-old vomiting boy (20 marks, ~15 minutes)

A term male infant, genitally normal at birth, passed his newborn bloodspot screen. He presents at day 14 with three days of poor feeding and vomiting, and is now lethargic and mottled. Weight is down 12 percent from birth. Sodium 122 mmol per litre, potassium 6.8 mmol per litre, glucose 1.9 mmol per litre, capillary pH 7.24 with a base excess of minus 10. [8]

Questions

1. Give the most likely diagnosis, the single most important immediate drug, and its dose and route. (5 marks) [4]
2. Outline the first-hour resuscitation and investigation bundle, and state why the definitive test does not delay treatment. (5 marks) [4]
3. Explain why the diagnosis was missed despite a passed newborn screen, and what that implies for the threshold to investigate a vomiting neonate. (4 marks) [8]
4. Describe the lifelong replacement regimen and the stress-dose plan you will give the family. (6 marks) [1]

Model answer (must-hit)

1. This is classic salt-wasting 21-hydroxylase deficiency until proven otherwise. A genitally normal male neonate who salt-wastes at one to three weeks — with hyponatraemia, hyperkalaemia, hypoglycaemia and acidosis — is the classic missed presentation. The immediate drug is hydrocortisone intravenously: 25 mg stat, then 50 to 100 mg per square metre per day. [4]
2. Resuscitate on three tracks: 10 to 20 mL per kg isotonic saline repeated to restore perfusion; hydrocortisone as above; treat the hypoglycaemia with intravenous dextrose and cover sepsis with cultures and empiric antibiotics. Send serum 17-hydroxyprogesterone, ACTH, plasma renin, aldosterone and androgens, a karyotype and a pelvic ultrasound, and CYP21A2 molecular testing. The definitive biochemistry confirms the diagnosis but does not treat the shock, so hydrocortisone is given empirically before the results return. [4]
3. The newborn 17-hydroxyprogesterone screen is sensitive but imperfect: it misses a minority of classic cases, over-represented by simple-virilising disease and infants whose salt-wasting declares after the screen. A passed screen never lowers the threshold to send a serum 17-hydroxyprogesterone in any vomiting or collapsing neonate. [8]
4. Start oral hydrocortisone 10 to 15 mg per square metre per day in three divided doses, add fludrocortisone 0.05 to 0.2 mg per day, and supplement oral sodium at 2 to 3 mmol per kg per day in infancy. Build a stress-dose plan: two to three times the hydrocortisone dose for illness, and a parent-held intramuscular hydrocortisone injection for vomiting or collapse, with a MedicAlert identifier and a school care plan. [1]

SAQ 2 — The virilised 46,XX newborn (20 marks, ~15 minutes)

A term newborn is noted at the routine examination to have clitoromegaly, posterior labial fusion and a single perineal opening. No gonad is palpable in the labioscrotal folds. Pelvic ultrasound confirms a uterus. [10]

Questions

1. Give the most likely diagnosis and the key clinical finding that supports it over a 46,XY disorder. (4 marks) [10]
2. Outline the confirmatory biochemical and genetic work-up and interpret the expected results. (5 marks) [9]
3. Explain why this infant is at risk of salt-wasting even if she currently looks well, and what you would do to detect it. (4 marks) [1]
4. Describe the counselling and the multidisciplinary approach to sex-of-rearing and genitoplasty. (7 marks) [10]

Model answer (must-hit)

1. The most likely diagnosis is virilising congenital adrenal hyperplasia (21-hydroxylase deficiency). The decisive findings are a 46,XX virilised phenotype with a uterus and no palpable gonad — a palpable gonad would mean testicular tissue and shift the work-up toward a 46,XY disorder. The commonest cause of 46,XX disorder of sex development is CAH. [10]
2. Send serum 17-hydroxyprogesterone (markedly elevated in classic 21-OHD), ACTH (elevated), plasma renin (high) and aldosterone (low in the salt-wasting form), and androstenedione and testosterone (elevated). Confirm the chromosomal sex with a karyotype or SNP array and the gonadal anatomy with ultrasound, then send CYP21A2 molecular testing, which defines the genotype and correlates well with phenotype and informs sibling and prenatal counselling. [9]
3. Most 46,XX infants with classic 21-OHD have the salt-wasting form, and they can decompensate once maternal cortisol and aldosterone clear at one to three weeks even if well at birth. Monitor weight, feeding, electrolytes and blood pressure, and treat empirically with hydrocortisone and fludrocortisone once confirmed, with a clear safety-net and return pathway. [1]
4. Sex-of-rearing is female and concordant with the chromosomal and gonadal sex (46,XX, ovaries, uterus). Genitoplasty timing is now a shared decision with the family, often deferred, led by a multidisciplinary disorders-of-sex-development team — paediatric endocrinology, urology, gynaecology, psychology, ethics and nursing. The counselling is honest, non-stigmatising, and acknowledges that the decision about surgery can wait. [10]