Clinical Manifestations of Elevated 17-Hydroxyprogesterone (17-OHP)
Elevated 17-OHP is primarily a biochemical marker rather than a cause of direct symptoms; the clinical manifestations result from the underlying condition causing the elevation—most commonly congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency—which presents with androgen excess and adrenal insufficiency.
Primary Clinical Presentations by Age and Sex
Newborns and Infants
- Virilization in 46,XX infants (girls): Ambiguous genitalia or disordered sexual development present at birth due to prenatal androgen excess 1, 2
- Salt-wasting adrenal crisis: Life-threatening hyponatremia, hyperkalemia, and dehydration occurring within days to weeks of life in both sexes when aldosterone production is compromised 1, 2, 3
- Delayed diagnosis in 46,XY infants (boys): Normal-appearing external genitalia at birth can mask the diagnosis until salt-wasting crisis develops 2
Children and Adolescents
- Precocious puberty: Early development of secondary sexual characteristics due to excess androgens 2
- Accelerated growth velocity with advanced bone age, ultimately leading to short adult stature 2
- Acne: Severe or treatment-resistant acne, particularly in adolescents 2
Adolescents and Adults (Non-Classical CAH)
- Hirsutism: Excess terminal hair growth in androgen-dependent areas, affecting up to 9% of women with androgen excess depending on ethnic background 2
- Menstrual irregularities: Oligomenorrhea or amenorrhea in females 4, 2
- Subfertility: Reduced fertility in both sexes 2
- Acne vulgaris: Persistent or severe acne that may prompt endocrine evaluation 4
Diagnostic Context and Screening Indications
When to Measure 17-OHP
- Bilateral adrenal incidentalomas: Screen with 17-OHP to exclude CAH as the etiology; normal or low levels effectively rule out CAH 4, 5
- Severe or refractory acne with hyperandrogenism: Consider screening when prolonged amenorrhea or other signs of androgen excess are present 4
- Newborn screening: Universal screening detects elevated 17-OHP, though false positives are common in premature infants, stressed neonates, and other forms of CAH 1, 3
Important Diagnostic Pitfalls
- Transitory elevation in newborns: 17-OHP can be falsely elevated in premature infants, during the first 24 hours of life, and in term infants with physiologic stress from unrelated diseases 1, 3
- Other enzyme deficiencies: Elevated 17-OHP can occur in 11β-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and P450 oxidoreductase deficiency, not just 21-hydroxylase deficiency 1, 6
- Vanishing 17-OHP: In rare cases of complete adrenal cortex failure (potentially from autoimmune adrenalitis), 17-OHP levels may become immeasurable despite proven CAH 7
Optimal Testing Strategy
- Timing: Obtain morning samples before hydrocortisone administration when levels are highest and best reflect hypothalamic-pituitary-adrenal axis activity 5
- ACTH stimulation test: If basal 17-OHP is normal but clinical suspicion remains high, stimulated levels typically exceed 30 nmol/L in non-classical CAH 2
- Consider 21-deoxycortisol: This is a more specific marker for 21-hydroxylase deficiency than 17-OHP, as it is not elevated in premature infants or other forms of CAH 1, 6
Associated Laboratory Findings
- Hyponatremia and hyperkalemia: Present in salt-wasting forms, distinguishing true 21-hydroxylase deficiency from transitory elevation 3
- Elevated ACTH: Reflects inadequate cortisol synthesis 2, 7
- Elevated androgens: Including testosterone and DHEA-sulfate in the context of androgen excess symptoms 4, 8