Normal and elevated 3 alpha-androstanediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels.

Abstract

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confounding effect of ovarian T on hirsutism.

Two different pathogenetic mechanisms may play a role in acne and in hirsutism

“…This confirms results obtained previously by us (Toscano, 1986) and by other authors (Paulson et a]., 1986). The findings of increased values of 3Ad and 3AG and their correlation with hirsutism degree in hirsute patients are in disagreement with some results in the literature (Scanlon et al, 1988, Thompson et al, 1990, Pang et al, 1992, which showed normal values of 3AG and a lack of correlation between 3AG plasma values and hirsutism score at least in patients with hyperandrogenism of ovarian origin. The absence of any selection in our hirsute patients as far as the source of hyperandrogenism is concerned, may explain the difference.…”

5α-Androstane-3α, 17β-diol and 5α-androstane-3α, 17β-diolglucuronide in plasma of normal children, adults and patients with idiopathic hirsutism: a mass spectrometric study

“…ADG was hydrolyzed enzymatically and the AD released was quantified consecutively by RIA. Most of the values that have been reported so far for adults (5,(19)(20)(21)(22)(23) are in good agreement with our data. Beside reports of slightly increased, i.e.…”

“…While some studies could confirm these findings (19,33), discordant results have mean¬ while been published, too, showing considerable over¬ lap or lack of differentiation between ADG levels in normal women and hirsute patients (9,22,23,25,32). …”

Carriers for type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) deficiency can only be identified by HSD3B2 genotype study and not by hormone test

“…All males were healthy, had a history of normal male sexual maturation and were on no medication for several months prior to the ACTH stimulation test. These normal adult females and males were included in part in the previous report of analysis of normal reference hormonal data (Pang et al ., 1992; Lutfallah et al ., 2002).…”

“…Blood samples were obtained before and 60 min after administering a synthetic ACTH (Cortrosyn, Ben Venue Laboratories, Inc, Bedford, OH, USA), 250 µg intravenously by a bolus. Serum Δ5‐17P, 17‐OHP, F, dehydroepiandrosterone (DHEA) and Δ4‐A levels were determined by a reported and validated radioimmunoassay following a celite chromatographic purification (Pang et al ., 1992; Sakkal‐Alkaddour et al ., 1998; Lutfallah et al ., 2002). The inter‐ and intra‐assay variations of these assays were 10–15% and 5–10%, respectively.…”