Endocrine Abstracts (2002) 3 P264

Cortisone reductase (11 beta-hydroxysteroid dehydrogenase type 1) deficiency presenting with features of late onset congenital adrenal hyperplasia

I Laing1, JE Adams2, PJ Wood3, NF Taylor4 & DW Ray5

1Department of Clinical Biochemistry, Manchester Royal Infirmary, Manchester, UK; 2Department of Radiology, University of Manchester, Manchester, UK; 3Regional Endocrine Unit, Southampton General Hospital, Southampton, UK; 4Department of Clinical Biochemistry, King's College Hospital, London, UK; 5Department of Endocrinology, Manchester Royal Infirmary, Manchester, UK.

A South Asian woman aged 44 years presented with longstanding hirsutism. Her periods had always been regular and she had two children. She had been treated with spironolactone and Dianette without clinical benefit and the hirsutism was managed cosmetically. Investigations showed a high serum testosterone of 6.1 nmol/l ( 1-3nmol/l) and androstenedione 25nmol/l (2-10nmol/l). Serum sex hormone binding globulin was elevated at 96 nmol/l (23-85nmol/l), with normal DHEA sulphate, 4.8 umol/l ( 2-12umol/l) and 17-hydroxyprogesterone, 7.5 nmol/l ( 0 -10nmol/l). Urine free cortisol was raised at 385 nmol\/24h ( <300nmol\/24h) and normal on another occasion (185nmol/24h). She responded normally to an overnight dexamethasone suppression test (9 a.m. serum cortisol < 30nmol/l). Midnight serum cortisol was 113nmol/l, and at 9 a.m. 396nmol/l, rising to 1344 nmol/l 30 minutes after 250ug Synacthen i.v. ( normal 500-1250nmol/l). Basal 17-hydroxy progesterone was 10nmol/l rising to 50nmol\/l after Synacthen (normal <20nmol\/l). Adrenal CT showed bilaterally enlarged adrenals suggesting congenital adrenal hyperplasia. However, a urine steroid profile showed greatly exaggerated total cortisol metabolites with a markedly elevated ratio of tetrahydrocortisone to tetrahydrocortisol confirming a diagnosis of cortisone reductase deficiency. Following dexamethasone suppression (4x500ug/day) both serum testosterone and androstendione normalised and she had a subnormal serum cortisol response to both a 25mg oral cortisone acetate bolus and a 10mg oral cortisol bolus. The second phase half-life of administered cortisol was reduced at 1.3h ( normal 1.7-3.5h), confirming accelerated cortisol catabolism. These results further support a functional deficit in cortisone reductase. Although rare, this abnormality is well described and is difficult to distinguish clinically or biochemically from late onset congenital adrenal hyperplasia or polycystic ovary syndrome. As with previous cases the urine steroid profile is diagnostic.

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