A 4-week-old male infant is brought to the pediatric clinic for evaluation of poor feeding and lethargy. The parents report vomiting and weight loss. Laboratory results show hyponatremia (Na+ 128 mEq/L) and hyperkalemia (K+ 6.2 mEq/L). Which assessment finding would be most indicative of congenital adrenal hyperplasia (CAH)?
1Elevated 17-hydroxyprogesterone levels✓ 정답
2Decreased cortisol levels only
3Elevated growth hormone levels
4Decreased thyroid-stimulating hormone levels
해설
Elevated 17-hydroxyprogesterone is the most specific diagnostic finding for CAH, reflecting enzyme deficiency. Other options are not indicative of CAH in this context.
The infant in this scenario presents with a classic triad of poor feeding, lethargy, and vomiting, accompanied by significant laboratory abnormalities: hyponatremia (Na+ 128 mEq/L) and hyperkalemia (K+ 6.2 mEq/L). This electrolyte pattern is the hallmark of a salt-wasting crisis, a life-threatening manifestation of adrenal insufficiency. In the context of a 4-week-old infant, the primary condition that must be ruled out is Congenital Adrenal Hyperplasia (CAH).
The Pathophysiology of CAH and the Rationale for the Correct Answer
CAH is a group of autosomal recessive disorders caused by defects in enzymes responsible for cortisol synthesis in the adrenal cortex [3]. The most common form is 21-hydroxylase deficiency. This enzymatic block prevents the effective production of cortisol and, in the salt-wasting form, aldosterone. The lack of cortisol removes the negative feedback loop on the pituitary gland, leading to an overproduction of adrenocorticotropic hormone (ACTH). ACTH relentlessly stimulates the adrenal cortex, causing hyperplasia and a buildup of steroid precursors upstream of the blocked enzyme. The key precursor that accumulates in 21-hydroxylase deficiency is 17-hydroxyprogesterone (17-OHP).
Therefore, an elevated 17-OHP level is the most specific biochemical marker for the most common form of CAH and is the cornerstone of diagnosis. This is why newborn screening programs, as highlighted in the literature, measure 17-OHP levels to detect affected infants before a life-threatening crisis occurs [4]. The case of the infant presenting with sudden cardiac arrest due to an adrenal crisis from a rarer enzyme deficiency, 3β-hydroxysteroid dehydrogenase (3β-HSD2) deficiency, also underscores the critical nature of identifying CAH, even though the specific steroid profile would differ [1]. The principle remains that a salt-wasting crisis in a young infant points directly to an inborn error of adrenal steroidogenesis until proven otherwise.
Analysis of Incorrect Options
Option 2: Decreased cortisol levels only. While cortisol is indeed low in CAH, this finding is not specific. An isolated low cortisol level could be due to a variety of other conditions, including primary adrenal insufficiency from other causes, secondary adrenal insufficiency due to pituitary dysfunction, or even a lab artifact. Furthermore, the diagnosis of CAH hinges on demonstrating the accumulation of precursor hormones (like 17-OHP) that occurs as a consequence of the enzyme block, not just the deficiency of the end-product. In a salt-wasting crisis, the more immediately life-threatening issue is the mineralocorticoid deficiency leading to the electrolyte imbalance.
Option 3: Elevated growth hormone levels. Growth hormone is produced by the anterior pituitary and is not directly involved in the adrenal steroidogenesis pathway. CAH is a defect confined to the adrenal cortex's enzymatic machinery for producing cortisol, aldosterone, and androgens [3]. There is no pathophysiological link between an enzyme deficiency in the adrenal gland and a primary elevation in growth hormone.
Option 4: Decreased thyroid-stimulating hormone levels. TSH is a pituitary hormone that regulates the thyroid gland and is entirely separate from the hypothalamic-pituitary-adrenal (HPA) axis. CAH does not directly cause a decrease in TSH. While critically ill infants can sometimes exhibit alterations in thyroid function tests as part of a non-thyroidal illness syndrome, a decreased TSH is not a diagnostic indicator for CAH.
Clinical and Diagnostic Correlation
The urgency in this clinical picture cannot be overstated. The case report of an infant with a delayed presentation of salt-wasting CAH who experienced a sudden cardiac arrest serves as a stark reminder that these patients can deteriorate rapidly [1]. The initial well-being of an infant does not rule out CAH, as decompensation can be triggered by the stress of an illness or progressively worsen over the first few weeks of life. The report of four consecutive false-negative newborn screens in a patient with classical CAH further complicates the picture, emphasizing that clinical suspicion must override a negative screening test when symptoms are present [4]. In such cases, the definitive diagnostic step is to measure serum 17-OHP, which will be markedly elevated, confirming the diagnosis and allowing for the immediate initiation of life-saving glucocorticoid and mineralocorticoid replacement therapy. Advanced techniques like liquid chromatography-tandem mass spectrometry (LC-MS/MS) can provide a more comprehensive steroid profile to differentiate between various forms of CAH, but the initial critical finding is the elevated 17-OHP [3].
References (research sources)
[1]
A Delayed Presentation of Salt-Wasting Congenital Adrenal Hyperplasia Due to 3β-Hydroxysteroid Dehydrogenase Deficiency in an Infant: A Case Report.Case reportGhareeb BM, Shakeeb FN, Busehail M, Alarrayedh M. (2026) · DOI: 10.7759/cureus.108805
[3]
Steroid profiling in congenital adrenal hyperplasia: comparing immunoassays and LC-MS/MS accuracy.Research articleTaba-Tabai S, Ozsu E, Cetin SK, Siklar Z, Dogan O, Aycan Z, Berberoglu M. (2026) · DOI: 10.1515/jpem-2025-0538
[4]
Four Consecutive False Negative Newborn Screens in a Patient with Classical Congenital Adrenal Hyperplasia: A Case ReportCase reportRizzuto P, Gangat M, Khattab A, Marshall I. (2026) · DOI: 10.4274/jcrpe.galenos.2025.2024-10-16
Clinical Practice Guide: Suspected Congenital Adrenal Hyperplasia
Critical Assessment
Recognize the Salt-Wasting Crisis: Poor feeding, vomiting, lethargy, and weight loss in a neonate with hyponatremia (Na+ < 130 mEq/L) and hyperkalemia (K+ > 5.5 mEq/L) requires immediate evaluation for CAH.
Monitor for Shock: Assess for hypotension, tachycardia, and prolonged capillary refill. These infants can rapidly progress to hypovolemic shock.
Check for Ambiguous Genitalia: Females with classic 21-hydroxylase deficiency are often virilized at birth; males may appear normal, making biochemical screening essential.
Diagnostic Workup
First-Line Lab: Serum 17-hydroxyprogesterone (17-OHP) is the key diagnostic marker. Levels are markedly elevated in classic 21-hydroxylase deficiency.
Confirmatory Tests: Send cortisol, ACTH, aldosterone, and plasma renin activity. Expect low cortisol/aldosterone, high ACTH, and high renin.
Newborn Screening: If not already resulted, obtain the state newborn screen, which measures 17-OHP on a dried blood spot.
Emergency Management Priorities
Stabilize ABCs: Secure IV access and administer a 20 mL/kg normal saline bolus for signs of shock.
Correct Hypoglycemia: Check bedside glucose; administer dextrose if needed, as adrenal insufficiency impairs gluconeogenesis.
Administer Glucocorticoids: Do not delay treatment while awaiting labs. Hydrocortisone is the standard of care, given as a stress-dose IV bolus (typically 25 mg for an infant).
Manage Hyperkalemia: If ECG changes are present or K+ is severely elevated, initiate standard hyperkalemia protocols (calcium gluconate, insulin/glucose, sodium bicarbonate).
Nursing Considerations & Family Support
Strict I/O and Daily Weights: Monitor fluid balance closely during the acute phase.
Medication Education: Teach parents that lifelong steroid replacement is required, with stress-dosing for illness or injury.
Medical Alert Identification: Emphasize the need for a medical alert bracelet indicating adrenal insufficiency.
Genetic Counseling: Refer the family for counseling, as CAH is an autosomal recessive condition.
Congenital Adrenal Hyperplasia (CAH) — A group of autosomal recessive disorders characterized by enzyme deficiencies in cortisol synthesis, most commonly 21-hydroxylase deficiency, leading to adrenal insufficiency and androgen excess.
17-Hydroxyprogesterone (17-OHP) — A steroid precursor that accumulates due to 21-hydroxylase deficiency; elevated serum levels are the primary diagnostic marker for classic CAH.
Salt-Wasting Crisis — A life-threatening manifestation of adrenal insufficiency in CAH characterized by hyponatremia, hyperkalemia, dehydration, and shock due to aldosterone deficiency.
21-Hydroxylase Deficiency — The most common enzymatic defect causing CAH, impairing the conversion of 17-hydroxyprogesterone to 11-deoxycortisol, reducing cortisol and aldosterone production.