What is the diagnosis for an infant presenting with lethargy, low activity, hyperpigmentation of the gums and scrotum, and undescended testes with a normally sized penis?

Diagnosis: Congenital Adrenal Hyperplasia

This infant has congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, presenting as a virilized 46,XX genetic female with life-threatening adrenal crisis. 1

Clinical Reasoning

The constellation of findings is pathognomonic for CAH:

• Bilateral nonpalpable testes with normal-length phallus in a phenotypic male newborn is the classic presentation of a virilized 46,XX infant with CAH 1
• Hyperpigmentation of gums and scrotum indicates elevated ACTH from cortisol deficiency 1
• Lethargy and low activity signal adrenal crisis with cortisol and aldosterone deficiency 1

A phenotypic male newborn with bilateral nonpalpable testes is potentially a genetic female (46,XX) with congenital adrenal hyperplasia until proven otherwise. 2, 1

Why This Is Not Septic Shock

While the infant appears critically ill with lethargy, the specific combination of hyperpigmentation and bilateral nonpalpable gonads points specifically to CAH rather than sepsis 1. However, these infants can present with shock-like symptoms due to electrolyte derangements (hyponatremia and hyperkalemia) from aldosterone deficiency 2, 1.

Critical Management Points

Failure to diagnose congenital adrenal hyperplasia can result in serious harm, as a high proportion of patients are unable to regulate their electrolyte levels and may present with shock, hyponatremia, and hyperkalemia. 2, 1

Immediate Actions Required:

• Immediate pediatric endocrinology consultation is mandatory 1
• Check serum electrolytes (expect hyponatremia and hyperkalemia), glucose (expect hypoglycemia), and 17-hydroxyprogesterone (markedly elevated) 3, 4
• Do not circumcise until disorder of sex development workup is complete 2, 1
• Initiate glucocorticoid and mineralocorticoid replacement therapy emergently 4

Pathophysiology

CAH due to 21-hydroxylase deficiency blocks cortisol and aldosterone synthesis, causing:

• Accumulation of 17-hydroxyprogesterone (diagnostic hallmark) 5, 3
• Shunting of precursors to androgen synthesis pathways 5
• Virilization of 46,XX fetuses in utero, creating ambiguous genitalia that may appear as a phenotypic male with bilateral cryptorchidism 3, 4
• Life-threatening salt-wasting in approximately 75% of classic cases 3

Common Pitfall to Avoid

Never assume bilateral nonpalpable testes in a newborn represents simple cryptorchidism. This presentation demands immediate evaluation for disorder of sex development, particularly CAH, which can be lethal if missed 2, 1.