Why Test 17-Hydroxyprogesterone (17-OHP)?
17-hydroxyprogesterone testing is primarily indicated to diagnose congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and should be specifically ordered when evaluating bilateral adrenal incidentalomas, newborn screening abnormalities, or clinical signs of androgen excess and virilization. 1
Primary Diagnostic Indications
Bilateral Adrenal Incidentalomas
- When bilateral adrenal masses are discovered incidentally on imaging, 17-OHP levels must be collected to rule out congenital adrenal hyperplasia. 1, 2
- This is a critical screening step before considering any intervention, as CAH can present with bilateral adrenal enlargement in adults who were previously undiagnosed 1
Suspected Adrenocortical Carcinoma or Virilization
- In cases of suspected adrenocortical carcinoma (ACC) or when clinical signs of virilization are present, serum testing for excess androgens should be performed, which includes 17-OHP along with DHEAS, testosterone, 17β-estradiol, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1
- ACC is responsible for more than half of androgen hypersecretion cases 1
Newborn Screening and Pediatric Diagnosis
- Elevated 17-OHP in newborn screening is the primary marker for detecting classical CAH, which typically presents with virilization in girls at birth and potential salt-wasting crisis in both sexes within days if aldosterone production is compromised 3, 4
- Diagnosis can be delayed in boys who lack obvious virilization, making screening critical 3
Clinical Context and Interpretation
Classical vs. Non-Classical CAH
- Classical CAH: Greatly elevated 17-OHP levels (often >1000 nmol/L) with virilization at birth or salt-wasting in early infancy 3
- Non-classical CAH (NC-CAH): Moderately raised or even normal basal 17-OHP concentrations, but if clinical suspicion is high and basal levels are normal, an ACTH stimulation test will show 17-OHP concentrations typically >30 nmol/L above normal response 3
- NC-CAH prevalence in women with androgen excess can reach up to 9% depending on ethnic background and genotype 3
Clinical Presentations Warranting Testing
- Precocious puberty 3
- Acne and hirsutism 3
- Subfertility 3
- Androgen excess in females (more commonly detected clinically than in males) 3
Monitoring Treatment in Established CAH
Role in Treatment Adjustment
- Once CAH is diagnosed, 17-OHP serves as a monitoring marker, though opinions differ on whether 17-OHP or androstenedione is superior for monitoring treatment 3
- Morning 17-OHP concentrations (before hydrocortisone administration) correlate strongly with androstenedione levels (r = 0.81) and reflect adequacy of adrenal suppression 5
- 17-OHP demonstrates marked circadian variation with peak values between 0400-0900 hours, requiring strategic timing of glucocorticoid dosing 5, 6
Practical Monitoring Approach
- Home monitoring using dried filter paper blood samples is reliable and practical for assessing adrenal steroid activity, with results correlating well with venous samples (r = 0.98) 7
- Blood sampling at different times provides insights into patterns of 17-OHP secretion and identifies periods of inadequate adrenal suppression 7
Important Caveats
Differential Diagnosis
- Elevated 17-OHP is not exclusively diagnostic of 21-hydroxylase deficiency; other rare enzyme defects (such as 3β-hydroxysteroid dehydrogenase deficiency) can also cause elevated levels 4
- Physical examination findings must guide interpretation—absence of virilization in a female infant with elevated 17-OHP should prompt consideration of alternative diagnoses 4