11beta-hydroxysteroid dehydrogenase type 1 deficiency ('apparent cortisone reductase deficiency') in a 6-year-old boy.
OBJECTIVE
We present the 1st case of prepubertal hyperandrogenism because of a defect in the conversion of cortisone (E) to cortisol (F) by hepatic 11beta-hydroxysteroid dehydrogenase type 1.


RESULTS
Clinical and anthropometric data were obtained. Serum androgens and gonadotropins with luteinizing hormone releasing hormone stimulation test, dexamethasone suppression test, and corticotropin-releasing hormone stimulation test were evaluated. Adrenal imaging and urinary steroid profiling by gas chromatography/mass spectrometry were employed. A 6.9-year-old boy presented with precocious pubarche, height (+2.6 SD), accelerated bone age (11.5 years), and Tanner stage 2 pubic hair and genitalia. Serum androgen levels were elevated and dexamethasone suppressible. Serum F was normal, but the E concentration was increased. Central precocious puberty and congenital adrenal hyperplasia were excluded. The excretion of androgen metabolites was moderately increased, but a highly increased tetrahydrocortisone (THE) and a diminished tetrahydrocortisol (THF + allo-THF) excretion was found with a [THF + allo-THF/ THE] ratio of 0.032 (normal controls 1.05 +/- 0.17). The corticotropin-releasing hormone stimulation test showed an exaggerated adrenocorticotropic hormone response, suggesting a relative deficiency of F. Two months of hydrocortisone treatment (17.5 mg daily) failed to suppress androgens adequately. Treatment with dexamethasone (0.375 mg/daily) resulted in androgen suppression.


CONCLUSIONS
In the case of precocious pubarche and accelerated growth, the diagnosis of 11beta-hydroxysteroid dehydrogenase type 1 deficiency ('apparent cortisone reductase deficiency') should be considered. The diagnosis is based on determinations of urinary steroid metabolites.
Małunowicz
Ewa M
EM
Department of Laboratory Diagnostics, The Children's Memorial Health Institute, Warsaw, Poland. ewamalun@poczta.onet.pl
Romer
Tomasz E
TE
Urban
Maria
M
Bossowski
Artur
A
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000365:Age Determination by Skeleton; D002648:Child; D003349:Cortisone Reductase / Q000172:deficiency*; D003907:Dexamethasone / Q000627:therapeutic use; D003937:Diagnosis, Differential; D005938:Glucocorticoids / Q000627:therapeutic use; D006130:Growth Disorders / Q000209:etiology; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D017588:Hyperandrogenism / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis; D011629:Puberty, Precocious / Q000209:etiology
D005938:Glucocorticoids; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D003349:Cortisone Reductase