Table 31.1 Medications Associated with Hirsutism determination of androgen conjugates to assess hirsute patients is not recommended, because hirsutism itself is an excellent bioassay of free testosterone action on the hair follicle and because these androgen conjugates arise from adrenal precursors and are likely markers of adrenal and not ovarian steroid production (8).
In the zona reticularis layer of the adrenal cortex, DHEAS is generated by SULT2A1 (9). This layer of the adrenal cortex is thought to be the primary source of serum DHEAS. DHEAS levels decline as a person ages and the reticularis layer diminishes in size. In most laboratories, the upper limit of a DHEAS level is 350 μg/dL (9.5 nmol/L). A random sample is sufficient because the level of variation is minimized as a result of the long half-life characteristic of sulfated steroids. DHEAS is used as a screen for androgen-secreting adrenocortical tumors; however, moderate elevations are a common finding in the presence of PCOS, obesity, and stress, which reduces specificity (10).
A study of women with androgen-secreting adrenocortical tumors (ACT-AS) (N = 44), compared to women with nontumor androgen excess (NTAE) (N = 102), sheds additional light on the choice of hormones used to screen for an adrenocortical tumor. In the study, the demographics and the prevalence of hirsutism, acne, oligomenorrhea and amenorrhea were not different in each group. Free testosterone (free T) was the most commonly elevated androgen in ACT-AS (94%), followed by androstenedione (A) (90%), DHEAS (82%), and total testosterone (total T) (76%),
Table 31.2 Normal Values for Serum Androgensa
Free testosterone (calculated) 0.6–6.8 pg/mL
Percentage free testosterone 0.4–2.4%
Bioavailable testosterone 1.6–19.1 ng/dL
Albumin 3,300–4,800 mg/dL
SHBG, sex hormone–binding globulin. aNormal values may vary among different laboratories. Free testosterone is calculated using measurements for total testosterone and sex hormone–binding globulin, whereas bioavailable testosterone is calculated using measured total testosterone, sex hormone–binding globulin, and albumin. Calculated values for free and bioavailable testosterone compare well with equilibrium dialysis methods of measuring unbound testosterone when albumin levels are normal. Bioavailable testosterone includes free plus very weakly bound (non-SHBG, nonalbumin) testosterone. Bioavailable testosterone is the most accurate assessment of bioactive testosterone in the serum without performing equilibrium dialysis.
Table 31.3 Sensitivity and Specificity of Basal Hormone Levels in the Evaluation of Female Patients with Androgen-secreting Adrenocortical Tumors (ACT-AS) and Nontumor Causes of Androgen Excess (NTAE)
Thresholds were selected using Youden’s index, as described in the methods. a CI: 95% confidence intervals. (Reprinted with permission from d’Alva CB, Abiven-Lepage G, Viallon V, et al. Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess. Eur J Endocrinol 2008;159:641–647.