Diagnosis: Congenital Adrenal Hyperplasia (CAH)
This infant has congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, presenting with salt-wasting adrenal crisis. The combination of lethargy, hyperpigmentation, and bilateral nonpalpable testes in a phenotypic male infant is pathognomonic for a 46,XX genetic female with severe CAH who has been virilized in utero 1.
Critical Clinical Recognition
A phenotypic male newborn with bilateral nonpalpable testes is potentially a genetic female (46,XX) with congenital adrenal hyperplasia until proven otherwise 1. This is a life-threatening emergency requiring immediate specialist consultation.
Key Diagnostic Features Present:
- Lethargy and low activity: Indicates adrenal crisis with cortisol and aldosterone deficiency 1
- Hyperpigmentation of gums and scrotum: Results from compensatory ACTH hypersecretion stimulating melanocytes 2, 3
- Bilateral nonpalpable testes with normal-length phallus: Classic presentation of virilized 46,XX infant with CAH 1
- The "scrotum" is actually fused labia majora, and the "penis" is an enlarged clitoris from prenatal androgen excess 3, 4
Why This is NOT Septic Shock
While septic shock can cause lethargy and hypotension, it does not explain:
- The hyperpigmentation pattern (specific to ACTH excess) 2
- The bilateral nonpalpable gonads in a phenotypic male 1
- The constellation of findings pointing to a disorder of sex development 1
Pathophysiology
CAH due to 21-hydroxylase deficiency causes:
- Cortisol deficiency: Leading to compensatory ACTH elevation and hyperpigmentation 2, 3
- Aldosterone deficiency: Causing salt-wasting crisis with shock, hyponatremia, and hyperkalemia 1, 2
- Androgen excess: Virilizing 46,XX fetuses to appear phenotypically male at birth 3, 5
Immediate Management Required
Failure to diagnose congenital adrenal hyperplasia can result in serious harm, as a high proportion of patients with this condition are unable to regulate their electrolyte levels and may present with shock, hyponatremia and hyperkalemia 1.
Urgent Actions:
- Immediate specialist consultation (pediatric endocrinology) 1
- Obtain serum electrolytes: Expect hyponatremia and hyperkalemia 1, 6
- Measure 17-hydroxyprogesterone (17-OHP): Markedly elevated in CAH 2, 3
- Initiate treatment for adrenal crisis: Glucocorticoid and mineralocorticoid replacement, sodium correction, hyperkalemia management 6, 4
- Karyotype analysis: To confirm 46,XX genotype 1, 4
Critical Pitfall to Avoid
Do NOT circumcise this infant until the workup is complete, even though a completely normal phenotypic penis appears to be present on examination 1. The AUA guidelines explicitly state that newborns with bilateral nonpalpable testes should not be circumcised until after evaluation for disorder of sex development is complete 1.
Prevalence and Screening
The classic form of CAH has a prevalence of approximately 1:12,000 to 1:15,000 births 2. Neonatal screening programs exist specifically to detect this condition before life-threatening adrenal crisis develops 2, 4.