A 9-day-old, term, neonate with normal perinatal history and no risk factors for sepsis presents to the Emergency Department with history of vomiting and lethargy. Mother describes baby as “difficult to arouse for feeds” since a day. On examination, you notice a lethargic baby with cold and mottled peripheries with CRT 3 secs.
Initial blood gas showed –
You suspect Congenital Adrenal Hyperplasia.
Understanding adrenal gland physiology
The adrenal gland has two main regions – the cortex and medulla. The adrenal cortex is split into the zona glomerulosa (outer), zona fasciculata (middle) and the zona reticularis (inner).
They produce mineralocorticoids (mainly aldosterone), glucocorticoids (primarily cortisol) and androgen. The release of these hormones is controlled by the negative feedback loop of the hypothalamic-pituitary axis (HPA).
What is congenital adrenal hyperplasia?
Around 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency.
CLASSICAL congenital adrenal hyperplasia
Salt-wasting 21-hydroxylase deficiency is due to the inheritance of two severe mutations that lead to the loss of function.
The enzyme is needed to convert progesterone and 17OH-progesterone to deoxycorticosterone and deoxycortisol.
21-hydroxylase deficiency halts production of aldosterone and cortisol.
NON-CLASSICAL congenital adrenal hyperplasia
Non-classical CAH presents later, often in adolescence or early adulthood, and is milder. Take a look at the chart to understand how different enzyme deficiencies can affect hormone production.
11-B-hydroxylase is needed to convert deoxycorticosterone and deoxycortisol to aldosterone and cortisol.
In 11 B-hydroxylase deficiency, the pathway is shunted leading to increased levels of DHEA, ACTH, androstenedione and testosterone.
Clinical features of CLASSICAL congenital adrenal hyperplasia
Older children may present with precocious puberty, short stature and fertility issues.
In classic salt-wasting congenital adrenal hyperplasia, young boys tend to present in a shock state that is unresponsive to fluid replacement. They need steroids. The lack of cortisol leads to poor cardiac function and a lack of sensitivity to catecholamines coupled with increased anti-diuretic hormone (ADH) production. Aldosterone deficiency leads to hyponatraemia and hyperkalaemia.
Clinical features of NON-CLASSICAL congenital adrenal hyperplasia
Children with nonclassical CAH tend to have arly puberty and all that that entails:-
- Oily skin or acne
- Rapid growth during adolescence but short adult height
- Irregular periods (in women)
- Fertility problem
Investigations for CAH
You may find raised 17-OH hydroxyprogesterone levels in 21-hydroxylase deficiency and raised 11-deoxycortisol levels in 11 B-hydroxylase deficiency.
Patients should also have an USS to look at the ovaries or testes.
Salt-losing congenital adrenal hyperplasia classically presents with metabolic acidosis, hypoglycaemia, hyponatremia and hyperkalemia.
How is congenital adrenal hyperplasia managed?
Acute management is based on fluid management and the treatment of hypoglycaemia. These patients will require lifelong steroid replacement.
Hydrocortisone is least likely to impair growth but has a shorter duration of action than other steroids – prednisolone or dexamethasone. Let’s consider these three.
- Because of the short half-life of hydrocortisone, it may need to be given thrice daily.
- Prednisolone is around 5 times more potent than hydrocortisone
- Because of its longer duration of action it may be given at night to cover the twilight hours
- Dexamethasone is between 20 – 40 times more potent than hydrocortisone
- With its duration of action of between 24 to 48 hours, dexamethasone is most likely to interfere with growth
We would prescribe fludrocortisone if salt-wasting is a problem. They may require sodium supplements too.
Signs and symptoms of an adrenal crisis
- Weakness or fatigue
- Severe dehydration
- Low blood pressure
- Life-threatening shock
Treatment of an adrenal crisis
1. Check the blood sugar
if the cortisol is low then the sugar is going to be low – an easy fix.
Give an IV bolus of 10% dextrose 2-5 mL/kg and recheck blood glucose level after half an hour
2. Replace the fluids
If the child has moderate to severe hydration, then give them a bolus of 10-20ml/kg of 0.9% sodium chloride. If there is a response to this bolus then you can replace the rest of the deficit and chart some maintenance fluids.
3. Replace the glucocorticoids
When the body is placed under stress, extra cortisol is needed. This is given as either IM or IV hydrocortisone.
It’s worth considering cortisol deficiency in any case of shock that is unresponsive to fluid resuscitation.
Hydrocortisone IM/IV Stat Dose
< 3 years: 25mg (0.5ml of the 2ml vial)
3-12 years: 50mg (1ml of the 2ml vial)
>12 years: 100mg (2ml of the 2ml vial
4. Replace the mineralocorticoids
Nowhere near as important as glucocorticoid replacement, mineralocorticoid replacement with fludrocortisone can wait until the patient can tolerate oral medication.
Give fludrocortisone at maintenance doses of 0.05 – 0.1 mg per day
5. Treat the hyperkalemia
This should get better with fluids and steroids
6. Treat the underlying cause
Look out for any underlying illness or injury that may have kicked things off.
Preventing an adrenal crisis – sick day rules
Patients with CAH are given sick day rules with hydrocortisone dose to be doubled when acutely unwell or in case of surgery or stress, in addition to an extra dose in early hours of the morning.
If the patient cannot tolerate medications orally, is drowsy, or isn’t better after an oral double dose, IM hydrocortisone is given by the parent or ambulance crew if there is difficulty in getting venous access.
Illustrated Textbook of Paediatrics (Tim Lissauer, Graham Clayden)
Images from Wikipedia
Practical Endocrinology and Diabetes in Children (Malcolm D.C. Donaldson, John W.Gregory, Guy Van Vliet, Joseph I.Wolfsdorf)
Core EM – Adrenal Crisis
EM Sim Cases – Congenital Adrenal Hyperplasia and Adrenal Crisis
Pediatric EM Morsels – Congenital Adrenal Hyperplasia