Adrenal Androgens Production
The adrenal glands primarily produce dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, and 11β-hydroxyandrostenedione (11OHA4) as their main androgens. 1, 2
Primary Adrenal Androgens
The zona reticularis of the adrenal cortex is the specific anatomical site responsible for androgen synthesis 2, 3. The key androgens produced include:
- DHEA - The most abundant circulating hormone in the human body, though biologically inactive until converted peripherally 2, 4
- DHEAS - The sulfated form of DHEA, representing the most reliable measure of adrenal androgen production 1, 2
- Androstenedione - A direct precursor of testosterone that can be produced in peripheral tissues from DHEA 1
- 11β-hydroxyandrostenedione (11OHA4) - The second most abundant unconjugated androgen produced by human adrenals after DHEA 4
Emerging Understanding of 11-Oxygenated Androgens
Recent evidence has identified a class of adrenal-derived androgens termed "11-oxyandrogens" that share an oxygen atom on carbon 11 4. These include:
- 11-ketotestosterone - A downstream metabolite of 11OHA4 produced mostly in peripheral tissues, with potency equivalent to testosterone 4
- 11-ketodihydrotestosterone - The 5α-reduced product of 11-ketotestosterone, with potency equivalent to dihydrotestosterone 4
These 11-oxyandrogens have emerged as major components in disorders of androgen excess and, unlike traditional androgens, do not demonstrate age-dependent decline 4.
Clinical Relevance in Adrenal Insufficiency
In primary adrenal insufficiency (PAI), patients become deficient in all adrenal androgen secretion, particularly affecting female patients who lack gonadal androgen production 1. When monitoring adrenal androgen replacement:
- DHEAS, androstenedione, and testosterone levels should be measured in the morning prior to DHEA ingestion and maintained in the normal range 1
- DHEA replacement (10-50 mg, typically 25 mg daily) can be offered to female patients with persistent lack of libido or low energy despite optimized glucocorticoid and mineralocorticoid replacement 1
Regulation of Adrenal Androgen Production
ACTH is the major regulator of adrenal androgen secretion 5. However, production is also influenced by:
- Gonadal sex steroids, insulin, growth hormone, and prolactin 5
- The sympathoadrenal and immunoadrenal systems 5
- Key enzymes including cytochrome b5, DHEA sulfotransferase, and 3β-hydroxysteroid dehydrogenase 2
Diagnostic Testing for Androgen Excess
When evaluating suspected adrenal androgen excess or virilization, testing should include 1:
- DHEAS and testosterone as primary markers 1
- Extended panel for suspected adrenocortical carcinoma: 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol 1
Higher androgen levels suggest greater disease burden, particularly in adrenocortical carcinoma where androgen hypersecretion occurs in more than half of cases 1.