Stikkelbroeck et al. (2001) investigated the prevalence of testicular tumors in 17 adolescent and adult male patients with CAH aged 16 to 40 years. In 16 of 17 patients, one or more testicular tumors ranging in maximal length from to cm were found on ultrasonography. In 6 patients, the testicular tumors were palpable. Undertreatment, defined as the presence of a salivary androstenedione level above the upper reference morning level, was found in 5 of 17 patients at the time of investigation. The other 12 patients were treated adequately or even overtreated at the time of investigation. Nevertheless, 11 of these 12 patients showed testicular tumors on ultrasonography. Tumor size was significantly larger in patients who were heterozygous or homozygous for deletion or conversion of the CYP21 gene than in patients who did not have this genotype. Impairment of Leydig cell function as manifested by decreased plasma levels of testosterone was found in 6 of 17 patients. Semen analysis in 11 patients revealed azoospermia in 3 patients and poor semen quality in 4 patients. The authors concluded that, when carefully sought for, testicular adrenal rest tumors are frequently present in adolescent and adult males with CAH and are often accompanied by impaired spermatogenesis and Leydig cell failure.
Interpretation: A rise from the baseline of at least 7 μg/dL to 10 μg/dL of cortisol, reaching at least 18 μg/dL at 60 minutes post stimulation effectively rules out primary adrenal insufficiency and suggests that adrenal suppression is minimal. A blunted or absent response suggests some level of secondary adrenal insufficiency (cortical atrophy or significant suppression.) If a subnormal response is obtained with an elevated baseline ACTH level, the patient has primary adrenal insufficiency or a form of ACTH unresponsiveness. A subnormal response with a low baseline ACTH level suggests CRF (corticotrophin releasing factor) and/or ACTH deficiency of hypothalamic and/or pituitary origin. Prior administration of estrogens, spironolactone, cortisone, and hydrocortisone (cortisol) can all interfere with the ACTH stimulation test by causing abnormally high baseline cortisol levels.
AB - We have previously reported the purification of a phosphoprotein (p43) intermediary in steroid synthesis from adrenal zona fasciculata [Paz C., Dada, ., Cornejo Maciel, ., Mele, ., Cymeryng, ., Neuman, I., Mendez, ., Finkielstein, ., Solano, ., Park, M., Fischer, ., Towbin, H., Scartazzini, R. and Podesta, . (1994) Eur. J. Biochem. 224, 709-716]. Here, we describe the cloning and sequencing of a cDNA encoding p43 as well as the hormonal regulation of the p43 transcript. The protein resulted homologous to a very recently described mitochondrial peroxisome-proliferator-induced very-long-chain acyl-CoA thioesterase (MTE-I). The deduced amino acid sequence of the protein shows consensus sites for phosphorylation by different protein kinases, and a lipase serine motif. Antibodies raised against a synthetic peptide that includes the lipase serine motif and against the N-terminal region of p43 block the action of the protein. The transcript of p43 was detected in ovary of pseudopregnant rats, rat adrenal zona fasciculata and glomerulosa, mouse Leydig tumor cell line (MA-10), rat brain and human placenta. Inhibition of adrenocorticotropin hormone (ACTH) release and steroid synthesis by by dexamethasone produced a dose-dependent decrease in the abundance of the adrenal transcript. The transcript was induced by in vivo stimulation of the adrenals with ACTH. The effect bad a rapid onset (5 min), reached maximal stimulation (62%) at 15 min, and returned to basal levels at 30 min. The effect of ACTH on the p43 transcript was inhibited by actinomycin D and enhanced by cycloheximide. Our results provide the first evidence linking acyl-CoA thioesterases with very-long-chain specificities, and a protein intermediary in steroid synthesis, thereby supporting a regulatory role for acyl-CoA thioesterases in steroidogenic tissues.