An 18-day-old baby boy presented to the Emergency Department (ED) of Yangon Children Hospital (YCH) with a 2-day history of poor feeding and lethargy. On arrival, he was found to have shock which was revived with 0.9% normal saline at ED, YCH and the baby was admitted to Neonatal Intensive Care Unit (NICU), YCH.
Soon after arrival at the NICU, he suffered from generalised tonic fits which was controlled by intravenous Phenobarbitone 20 mg/kg stat and then was put on nasal Continuous Positive Airway Pressure (CPAP) 5 cmH2O with Fraction of Inspired Oxygen (FiO2) of 47%. The baby had marked tachycardia (around 170 to 190/min with occasional ventricular tachycardia/VT). There was no pre-ductal as well as post-ductal saturation difference (saturation 97% with FiO2:47%) and both femoral pulsations were intact. His admission temperature was normal with no toe-core temperature difference.
Initial investigation revealed RBS of 95 mg% with blood results depicting metabolic acidosis with
- Sodium: 105 mmol/l (133-146 mmol/L)
- Potassium: 8.4 mmol/l (3.5-5.5 mmol/L)
- Bicarbonate: 5 mmol/l (19-28 mmol/L)
- Chloride: 85 mmol/l (95-108 mmol/L)
Regarding birth history, he was born at 40 weeks’ gestation by elective caesarean section with no complications. He had good Apgar scores at birth having birth weight of 2.9 kg. His antenatal scans were normal; maternal serology protective and he had no risk factors for sepsis. He was the first child of non-consanguineous Indian parents. He was discharged on day 4 of life. However, the mother noticed on unusual dark complexion of her son since birth. He was normal until day 16 of age and from that time onwards, was noticed to be lethargic with poor sucking and reduced urine output.
On examination (day 18 in YCH),
Marked dark skin complexion of whole-body including genitalia, no other dysmorphic features AF (anterior fontanelle): depressed
Moro’s and sucking reflex could not be assessed as the baby had injection phenobarbitone at that time
- HR: 170-190/min
- ECG: occasional Ventricular Tachycardia
- BP: 79/54 mmHg (MAP: 53 mmHg)
- Heart: no murmur, femoral pulse intact both sides
- Abdomen: soft, no hepatosplenomegaly
- Umbilicus: dry
- Genitalia, dark, penis length ~ 4 cm, bilateral testes (+) and descended
- Urine Output (+) and bowel opened
- Full blood count and C-reactive protein: within normal limit
Fig.1: Neonate having dehydration and dark skin complexion
Fig.2: Hyperpigmented genital area
Treatment with intravenous ampicillin and cefotaxime was commenced for suspected sepsis. However, in view of irrelevant dark complexion, hyponatremia, hyperkalaemia, metabolic acidosis, having shock on day 18 in addition to hyperpigmented genitalia, a probable diagnosis of “congenital adrenal hyperplasia with salt-wasting crisis with arrythmia” was made and urgent treatment had been commenced with injection hydrocortisone 4mg/kg stat and six hourly along with sodium and potassium correction according to the result.
Point-of-care cranial ultrasound and echocardiography were done to rule out cerebral oedema and congenital heart defect and both were normal. Capillary blood gas after an hour of injection hydrocortisone and electrolyte correction showed Na of 122 mmol/l and K of 5.4 mmol/l. Since that time, the baby had been stable in air and oral feeding could be commenced from next day along salt supplementation.
Consultation with paediatric endocrinologist has been done and as per advice, blood for cortisol, ACTH and 17OH progesterone were sent which was returned back as below:
- ACTH: 210 pg/ml (ref: 7.2-63.6 pg/ml)
- Cortisol: 0.7 microgram/dL (ref: 3.7-19.4 microgram/dl)
- 17 OH progesterone: 20 ng/ml (ref :0.03-0.9 ng/ml)
In view of the above results, the diagnosis of Congenital Adrenal Hyperplasia: salt losing type due to 21-hydroxylase deficiency was confirmed. From the 3rd day of admission, injection hydrocortisone had been switched to oral hydrocortisone 10 mg/m2 in 3 divided doses together with oral fludrocortisone 50 microgram per day. He had been on full feeds and off antibiotics on 4th day of admission. Parents had been updated about the disease as well as the importance to stick to the treatment regime for life long and regular follow up.
His glucose and electrolytes have been monitored daily during hospital stay, and they improved to satisfactory levels. He was discharged with oral hydrocortisone, fludrocortisone acetate and salt tablet. Instruction was given to his parents to double the dose of his oral hydrocortisone if the baby has intercurrent illness (e.g., fever, cough, vomiting and diarrhoea).
Differential diagnosis to be considered in this case
In a neonate presenting with lethargy, electrolyte imbalance, shock and arrhythmia, the following differential diagnosis need to be considered in addition to the “congenital adrenal hyperplasia with salt losing crisis”1:
Neonatal sepsis
Signs and symptoms of neonatal sepsis can range from nonspecific symptoms such as irritability, lethargy, poor feeding up to fever, respiratory distress, hypotension and shock. The most common organisms that can cause neonatal sepsis are Group B Streptococcus, Escherichia coli and Listeria monocytogenes. This patient received intravenous cefotaxime and ampicillin to cover for these micro-organisms.
Congenital heart disease
It can present with lethargy, poor feeding, respiratory distress and arrhythmia. Chest X-ray, ECG and echocardiogram should be done to rule out this condition.
Metabolic disorders
Metabolic disorders such as fatty oxidation and urea cycle defects can present with lethargy, poor feeding, electrolyte imbalance and a life-threatening arrhythmia. The presence of urinary ketone can rule out fatty acid oxidation defect and a very high ammonia level supports the diagnosis of urea cycle defect.
Treatment given in this case:
1. Immediate management
a. High flow nasal canula oxygen
b. 9% sodium chloride bolus to treat shock
c. Control of seizures
d. Intravenous antibiotics to cover suspected sepsis
e. Potassium correction (10% calcium gluconate, nebulised salbutamol, sodium bicarbonate, insulin and glucose infusion)
2. Endocrine management
a. Intravenous hydrocortisone (4mg/kg 6 hourly) followed by oral hydrocortisone (100 mg/m2/day in three divided dose)
b. Oral fludrocortisone acetate (50 microgram once daily).
c. Oral salt tablet
d. Written instruction to parents to double the dose of oral hydrocortisone in case the child has intercurrent illness and attend emergency department.
Literature review
Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive disorders due to single gene defects in the various enzymes required for cortisol biosynthesis.
The normal pathway of aldosterone and cortisol production is dependent upon three major enzymes in the adrenal gland. Reduced function of any of them leads to virilization due to failure of feedback inhibition of ACTH secretion from reduced cortisol levels and preservation of the androgen synthetic pathway2.
The most important variant is the one with salt-losing crisis presenting as a medical emergency. These patients cannot synthesise sufficient aldosterone to maintain sodium balance and may develop potentially fatal ‘salt-wasting’ crisis if not treated.
CAH represents a continuous phenotypic spectrum with over 95% of all cases caused by 21-hydroxylase deficiency. Many patients with 21-hydroxylase deficiency have skin pigmentation, virilisation of the external genitalia (females), poor suckling and poor weight gain3. Although females with classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilised external genitalia4, males have no genital ambiguity to alert physicians before the onset of dehydration and shock hence the diagnosis is particularly critical in them5. If CAH is not diagnosed and treated early, neonates are susceptible to sudden death in the first few weeks of life6-8. Diagnosis is made from elevation of plasma 17 alpha-hydroxyprogesterone2.
Treatment requires hydrocortisone at a dose that ensures suppression of ACTH and adrenal androgen production. Adequacy of therapy is monitored by measurement of 17-hydroxyprogesterone profiles and androgen concentrations. In salt-wasting forms, fludrocortisone is also needed. Because of the presence of functional resistance to mineralocorticoid activity in infancy, it is usual to need to administer large doses of sodium chloride during the first year, monitored by measurement of plasma renin activity. Monitoring of growth and pubertal development are the most sensitive markers of adequate treatment; excess height velocity usually indicates excess androgenic activity and undertreatment, whereas excessive glucocorticoid therapy may slow growth. In females, subsequent surgery (feminizing genitoplasty) may be required2.
11β-hydroxylase deficiency is the second most common cause of CAH which is associated with severe virilisation, salt retention and potassium loss and in some instances impaired stress response and hypoglycaemia. This is detected by elevated plasma levels of 11-deoxycortisol2.
There have been some reports of CAH in neonates with salt-losing crisis but without arrhythmia6. This patient presented with hyponatraemia, hyperkalaemia and a life-threatening arrhythmia. A combination of hyperkalaemia and hyponatraemia with metabolic acidosis is suggestive of adrenal insufficiency and treatment with hydrocortisone gives excellent response. An urgent and appropriate management of salt-wasting crisis is very important to prevent fatality. It is important to consider congenital adrenal hyperplasia (CAH) as a differential diagnosis in any neonate who presents with arrhythmia or unresponsive shock1.
References
1. Canlas JF, Ponmani C. 2019. “BMJ Case Rep”;12: e227565. doi:10.1136/bcr-2018- 2275652. Lissauer T, Carroll W. Editors. 2017. “The Science of Paediatrics: MRCPCH Mastercourse,” 1st ed. United Kingdom. Elsevier Health Sciences.
3. Ishii T, Anzo M, Adachi M, et al. Guidelines for diagnosis and treatment of 21-hydroxylase deficiency. Clin Pediatr Endocrinol. 2015;24: 77–105
4. Fleming L, Knafl K, Van Riper M. How the child’s gender matters for families having a child with congenital adrenal hyperplasia. J Fam Nurs. 2017;23: 516–33.
5. Kovács J, Votava F, Heinze G, et al. Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries. J Clin Endocrinol Metab. 2001;86: 2958–64.
6. Rossignol P, Legrand M, Kosiborod M, et al. Emergency management of severe hyperkalemia: Guideline for best practice and opportunities for the future. Pharmacol Res. 2016; 113:585–91.
7. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36: 3246–51.
8. Masilamani K, van der Voort J. The management of acute hyperkalaemia in neonates and children. Arch Dis Child. 2012;97:376–80.
Author Information
Myat Thida Seinn
Senior Consultant Paediatrician,
Neonatal Intensive Care Unit, Yangon Children Hospital
