Dehydroepiandrosterone (DHEA) is a steroid hormone produced by the adrenal glands, the small endocrine organs located above the kidneys. It functions as a precursor, meaning the body converts it into more potent sex hormones, primarily testosterone and estrogen. DHEA-sulfate (DHEA-S) is the sulfated, and more stable, form of DHEA that circulates at much higher concentrations in the bloodstream. Because of its stability, a blood test measuring DHEA-S is the standard method used to assess the body’s overall production of this hormone. When a patient’s DHEA-S level is found to be high, it signals an overproduction of adrenal androgens.
The Function of DHEA and Associated Symptoms
DHEA functions as a precursor, and its significance lies in its conversion to sex steroids in peripheral tissues. The adrenal glands produce almost all of the circulating DHEA-S, making the measurement a reliable indicator of adrenal androgen output. This hormone is particularly relevant to the development of secondary sex characteristics, which is why symptoms of excess are most evident in women and children.
The physical signs that prompt testing are generally related to the masculinizing effects of the downstream androgens. In women, this often manifests as hirsutism (the growth of coarse, dark hair in a male-like pattern, such as on the upper lip, chin, and chest). Other common symptoms include persistent acne, male-pattern baldness (androgenic alopecia), and menstrual irregularities. In severe cases, high DHEA-S can cause virilization, resulting in a deepening of the voice or enlargement of the clitoris.
Primary Causes: Adrenal Gland Dysfunction
The most significant causes of a high DHEA-S level originate in the adrenal glands. These conditions are typically divided into two major pathological categories: genetic defects and tumors.
Congenital Adrenal Hyperplasia (CAH) is a group of inherited disorders where a specific enzyme needed for cortisol production is deficient, most commonly 21-hydroxylase. When cortisol synthesis fails, the pituitary gland overproduces Adrenocorticotropic Hormone (ACTH) to stimulate the adrenal glands. This constant stimulation causes the adrenal gland to hypertrophy (grow excessively) and shunts precursor hormones into the alternative pathway that produces androgens, including DHEA-S. Patients with CAH, especially the non-classic form presenting later in life, can exhibit DHEA-S levels five to ten times higher than the upper limit of the normal range.
Adrenal tumors represent the other major adrenal cause of DHEA-S overproduction, and these can be either benign or malignant. Benign tumors (adenomas) may secrete DHEA-S, but the highest, most concerning levels are often associated with the aggressive cancer called Adrenocortical Carcinoma (ACC). Levels of DHEA-S that exceed 600 micrograms per deciliter or are more than five times the upper limit of the normal range strongly suggest the presence of an androgen-secreting tumor, especially ACC. These tumors produce DHEA-S autonomously, independent of the normal feedback regulation by the pituitary gland.
Secondary and External Factors Elevating DHEA
While adrenal pathology causes the most pronounced elevations, other conditions and external factors can also lead to high DHEA-S levels. Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is often associated with hyperandrogenism. In women with PCOS, roughly 20 to 30 percent will have an elevated DHEA-S level, reflecting an exaggerated adrenal androgen response to ACTH, although the primary source of androgen excess in this condition is usually the ovary.
Another common cause is the use of exogenous DHEA supplements, which are available over the counter and often marketed for anti-aging or performance enhancement. Taking DHEA supplements bypasses the body’s natural regulatory systems and directly increases circulating DHEA. This artificially elevated DHEA is quickly converted by the liver into DHEA-S, leading to a measured increase that reflects the supplement intake rather than an underlying medical condition.
Rarely, tumors originating outside of the adrenal gland can secrete DHEA. Specific types of ovarian masses, such as Steroid Cell Tumors, can be a source of DHEA. Ovarian-based androgen excess is more often characterized by a significantly elevated testosterone level with a DHEA-S level that is only mildly or moderately increased.
How Doctors Investigate High DHEA Levels
The diagnostic process for high DHEA levels focuses on differentiating between the adrenal and ovarian sources of the excess. After confirming an elevated DHEA-S level, physicians order additional hormone tests to narrow the possibilities. One important secondary test is the measurement of 17-hydroxyprogesterone (17-OHP), which is a key precursor that builds up significantly in patients with the most common form of CAH.
Measuring other sex hormones, particularly total and free testosterone, helps to distinguish between adrenal and ovarian origins. A profoundly elevated DHEA-S level (e.g., above 600 micrograms per deciliter) is highly suspicious for an adrenal tumor, whereas a very high testosterone level with a near-normal DHEA-S level points more strongly toward an ovarian tumor.
Imaging studies are a crucial next step. A CT or MRI scan of the adrenal glands is essential to look for any masses and rule out a tumor or carcinoma. If the hormone profile suggests an ovarian source, a pelvic ultrasound is performed to check for ovarian tumors or the characteristic polycystic morphology seen in PCOS. The ultimate management depends entirely on the diagnosed cause, ranging from steroid replacement therapy for CAH to surgical removal for tumors or lifestyle and medical management for PCOS.