title: Testolactone-associated high androgen levels, a pharmacologic effect or a laboratory artifact?
abstract: Testolactone, an aromatase inhibitor, blocks conversion of androgens to estrogens. In familial male precocious puberty, slowing of pubertal progression and growth velocity occurs with testolactone and spironolactone. Girls with McCune-Albright syndrome, given testolactone, respond similarly. A 2-yr-old female (case 1) on testolactone for non-McCune-Albright gonadotropin independent precocious puberty had marked elevations of androstenedione (18 ng/mL, normal: 0.2-3.1) and testosterone (3.6 ng/mL, normal < 0.2) but no virilization. Investigations were undertaken to determine whether elevations in testosterone and androstenedione were caused by interference in these RIAs. After a single oral dose 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 postmenopausal control), serum testosterone and androstenedione were measured serially by RIA for 24 h. Androstenedione went from normal to a mean peak of 45.4 ng/mL at 1-2 h and returned to baseline by 24 h. Testosterone, undetectable at baseline (case 1 and control) or 1.8 ng/mL (case 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 testosterone assay. Testolactone significantly interferes in these serum RIAs, making their use unreliable in follow-up of patients treated with testolactone.
authors.affiliation: Department of Pediatrics, IWK Grace Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: E A
authors.initials: EA
authors.lastname: Cummings
authors.forename: S R
authors.initials: SR
authors.lastname: Salisbury
authors.forename: M L
authors.initials: ML
authors.lastname: Givner
authors.forename: R S
authors.initials: RS
authors.lastname: Rittmaster
mesh_terms: D000735:Androstenedione / Q000097:blood*; D016477:Artifacts; D002675:Child, Preschool; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D011629:Puberty, Precocious / Q000097:blood* / Q000188:drug therapy*; D011863:Radioimmunoassay; D012016:Reference Values; D013738:Testolactone / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
chemical_list: D013739:Testosterone; D000735:Androstenedione; D013738:Testolactone