TESTOLACTONE-ASSOCIATED HIGH ANDROGEN LEVELS, A PHARMACOLOGICAL EFFECT OR A LABORATORY ARTIFACT

Testolactone, an aromatase inhibitor, blocks conversion of androgens t o estrogens. In familial male precocious puberty, slowing of pubertal progression and growth velocity occurs with testolactone and spironola ctone. Girls with McCune-Albright syndrome, given testolactone, respon d similarly. A a-yr-old female (case 1) on testolactone for non-McCune -Albright gonadotropin independent precocious puberty had marked eleva tions of androstenedione (18 ng/mL, normal: 0.2-3.1) and testosterone (3.6 ng/mL, normal < 0.2) but no virilization. Investigations were und ertaken to determine whether elevations in testosterone and androstene dione were caused by interference in these RIAs. After a single oral d ose of testolactone (5 mg/kg in case 1; 4 mg/kg in case 2, a 3-yr-old boy with familial male precocious puberty; 10 mg/kg in a healthy postm enopausal control), serum testosterone and androstenedione were measur ed serially by RIA for 24 h. Androstenedione went from normal to a mea n peak of 45.4 ng/mL at 1-2 h and returned to baseline by 24 h. Testos terone, undetectable at baseline (case 1 and control) or 1.8 ng/mL (ca se 2) rose to a mean peak of 6.9 ng/mL and returned to baseline by 24 h. Testolactone, in serial dilutions, cross-reacted in the testosteron e assay. Testolactone significantly interferes in these serum RIAs, ma king their use unreliable in follow-up of patients treated with testol actone.