11beta-hydroxysteroid dehydrogenase type 1 deficiency ('apparent cortisone reductase deficiency') in a 6-year-old boy

• Published in: Hormone research Vol. 59; no. 4; p. 205
• Main Authors: Małunowicz, Ewa M, Romer, Tomasz E, Urban, Maria, Bossowski, Artur
• Format: Journal Article
• Language: English
• Published: Switzerland 2003
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Age Determination by Skeleton; Child; Cortisone Reductase - deficiency; Dexamethasone - therapeutic use; Diagnosis, Differential; Glucocorticoids - therapeutic use; Growth Disorders - etiology; Humans; Hydroxysteroid Dehydrogenases - deficiency; Hyperandrogenism - drug therapy; Hyperandrogenism - etiology; Male; Metabolism, Inborn Errors - complications; Metabolism, Inborn Errors - diagnosis; Puberty, Precocious - etiology
• ISSN: 0301-0163

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.
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.
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.