Documented Cases of ACC with Isolated DHEA-S Elevation in Men
The medical literature contains extremely few documented cases of adrenocortical carcinoma presenting with isolated DHEA-S elevation and no other hormonal abnormalities—this presentation is exceedingly rare and poorly characterized in men specifically.
Epidemiological Context
ACC itself is already an exceptionally rare malignancy with an incidence of only 0.5-2 cases per million people annually 1. The disease shows a female predominance (ratio 1.5:1), making male cases inherently less common 1.
Hormonal Presentation Patterns
The typical hormonal profile of ACC differs substantially from isolated DHEA-S elevation:
Most ACCs produce multiple hormones simultaneously rather than isolated elevations 2, 1. The guidelines emphasize comprehensive steroid work-ups precisely because ACC characteristically shows abnormalities across multiple steroid pathways including glucocorticoids, sex steroids, and precursor steroids 2, 1.
Isolated DHEA-S secretion by adrenal neoplasms is described as "exceedingly rare" even when considering both benign and malignant tumors 3. One 2020 case report specifically highlights a purely DHEA-S secreting adrenal neoplasm as exceptional enough to warrant publication 3.
Clinical Reality
The specific scenario you describe—a man with ACC presenting subtly with moderate DHEA-S elevation alone—represents such an unusual constellation that exact case numbers are not documented in the available literature. The guidelines from ESMO-EURACAN 2 and earlier ESMO guidelines 1 do not address this specific presentation pattern, suggesting it falls outside typical clinical experience.
Key Clinical Pitfalls
- Subtle presentations with isolated hormonal abnormalities may delay diagnosis, as the proportion of incidentally discovered ACC is increasing 1.
- In men, even moderate DHEA-S elevation may not produce obvious clinical signs, unlike in women where virilization symptoms would be more apparent.
- The absence of cortisol excess or other hormonal abnormalities does not exclude ACC—approximately 15% of ACC cases are diagnosed incidentally without obvious hormonal excess 4.
Diagnostic Approach When Suspecting ACC
When evaluating an adrenal mass in a man with isolated DHEA-S elevation:
- Measure the complete steroid panel including 17-OH-progesterone, androstenedione, testosterone, and 17-beta-estradiol 1.
- Assess for subtle glucocorticoid excess with dexamethasone suppression testing, urinary free cortisol, and ACTH 1.
- Obtain high-quality cross-sectional imaging (CT or MRI) looking for malignant features: size >4 cm, irregular margins, inhomogeneous appearance, Hounsfield units >10 on unenhanced CT 2, 1.
- Consider 24-hour urine steroid metabolite examination, which can reveal patterns of immature steroidogenesis characteristic of ACC 1.
The rarity of this presentation means clinicians must maintain high suspicion for ACC in any adrenal mass regardless of hormonal pattern, as relying on "typical" presentations will miss atypical cases.