Evaluation of the therapeutic effects of AGA drugs by measuring finasteride, dutasteride, and dihydrotestosterone in hair.

BACKGROUND: Androgenetic alopecia (AGA) is treated by 5α-reductase inhibitors (5ARI) such as finasteride and dutasteride, which are widely used as therapeutic agents. However, their pharmacokinetics in target organs (scalp and hair follicles) have not yet been investigated. PURPOSE: To confirm the effective action of finasteride and dutasteride in the hair follicle tissues, we developed a method to measure these concentrations in hair. RESULTS: Compared to the non-detection (N.D.) group, the dihydrotestosterone (DHT) concentrations decreased significantly in both the finasteride and dutasteride groups. The dutasteride group showed significantly lower DHT concentrations among all groups. CONCLUSIONS: Measurement of finasteride, dutasteride, and DHT concentrations in hair would aid in evaluating the drug pharmacokinetics and its therapeutic effects on AGA patients.

18-Oxocortisol Synthesis in Aldosterone-Producing Adrenocortical Adenoma and Significance of KCNJ5 Mutation Status.

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11ß-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.