From the Guidelines
Elevated DHEAS levels require immediate evaluation for potential underlying causes, with a focus on polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), adrenal tumors, and Cushing's syndrome, as these conditions can significantly impact morbidity, mortality, and quality of life. The most recent and highest quality study, 1, recommends using total testosterone (TT), free testosterone (FT), and free androgen index (FAI) as first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. If these tests are not elevated, but clinical suspicion is high, measuring androstenedione (A4) and DHEAS may be considered, noting their poorer specificity.
Key points to consider in the evaluation of elevated DHEAS levels include:
- Confirming the elevation with repeat testing
- Conducting additional hormone tests, including cortisol, ACTH, testosterone, and 17-hydroxyprogesterone
- Imaging studies, such as adrenal CT or MRI, if an adrenal tumor is suspected
- Treatment depends on the underlying cause, with options including lifestyle modifications, metformin, hormonal contraceptives for PCOS, glucocorticoid replacement for CAH, and surgical intervention for adrenal tumors
It's essential to note that mildly elevated DHEAS can occur normally during puberty, pregnancy, and in response to stress. However, the clinical significance of elevated DHEAS relates to its role as a precursor to androgens, which can cause symptoms like hirsutism, acne, and menstrual irregularities in women. Proper diagnosis and management are crucial, as some causes, particularly adrenal tumors, may have serious health implications if left untreated, affecting morbidity, mortality, and quality of life 1.
From the Research
Implications of Elevated DHEAS Levels
Elevated Dehydroepiandrosterone sulfate (DHEAS) levels have been associated with various implications, including:
- Androgen-secreting adrenal cortical adenoma: A DHEAS level over 600 mg/dl indicates a diagnosis of androgen-secreting adrenal cortical adenoma 2
- PCOS: Elevated DHEAS levels are common in women with polycystic ovary syndrome (PCOS), particularly in those with non-classic (B or C) phenotypes 3
- Adrenal hyperandrogenism: Elevated DHEAS levels can indicate adrenal hyperandrogenism, which is more common in patients with non-classic (B and C) phenotypes of PCOS 3
- Generalized higher androgen production: Elevated DHEAS levels are generally part of a generalized higher androgen production in a subgroup of PCOS patients, independently of the finding of anovulatory or ovulatory cycles or of polycystic or normal ovaries 3
Factors Influencing DHEAS Levels
Several factors can influence DHEAS levels, including:
- Age: Serum DHEAS concentrations peak at around age 25 years and then decline steadily over the following decades 4
- Endogenous production: DHEAS is produced by the adrenal glands and can be converted to either androgens or estrogens 4
- Hormone supplementation: Hormone supplementation can change circulating concentrations of DHEAS 4
- Drugs: Many kinds of drugs can change circulating concentrations of DHEAS 4
- Disease states: Many types of disease states can change circulating concentrations of DHEAS 4
- Genetic mutations: Certain genetic mutations, such as a heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene, can affect DHEAS levels 5
Clinical Significance
Elevated DHEAS levels can have clinical significance, including: