Endocrine Abstracts

Background: Three 5α-reductase (5α-R1-3) isoenzymes are described. In humans, 5α-R2 deficiency (5α-R2D) causes pseudohermaphroditism and 5α-R3 neurological defects. The role of 5α-R1 is not clear. Urine steroid profiling (USP) by GC–MS can compare 5α-reduction activity based on excretion of 5α- and 5β-reduced metabolite ratios. Finasteride predominantly inhibits 5α-R2. USP in these patients shows concordance with 5α-R...

CYP17A1 is a key enzyme of human steroidogenesis, which is unique in that it catalyses two reactions, 17-hydroxylase activity and 17,20 lyase activity. 17-hydroxylase deficiency, a variant of congenital adrenal hyperplasia, results in hypertension and mild glucocorticoid deficiency. Loss of 17,20 lyase activity results in sex steroid deficiency, presenting with undervirilisation in boys (46, XY DSD) and lack of pubertal development in girls. Here we present the cases of two si...

The human CYP17A1 enzyme exerts two activities, 17a-hydroxylase and 17,20 lyase, catalysing key steps in human adrenal steroid biosynthesis. An in frame deletion of 3 bp in exon 1 of the CYP17A1 gene, resulting in the loss of phenylalanine in position 53 (F53del), is one of the first CYP17A1 mutations described (JBC 1989, 264:18076). Reported patients have invariably presented with severe hypokalaemic hypertension, reflecting 17α-hydoxylase deficiency, and s...

Introduction: In total of 5α-reductase 2 is vital in sexual development of male foetus; its deficiency causes impaired virilisation due to defective conversion of testosterone to dihydrotestosterone and is an important cause of Disorders of Sexual Development (DSD). We report 3 cases of severe primary acquired auto-immune hypothyroidism, which show a similar picture of 5α-reductase deficiency (5ARD) on urine steroid profile (USP) and reversible following adequate thy...

The adrenal cortex is the primary site of steroid synthesis, producing glucocorticoids under the control of the hypothalamic–pituitary axis and mineralocorticoids under the control of the renin–angiotensin system.Adrenal insufficiency, which can be life threatening, is cause by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. No drug suitably mimics the diurnal pattern of corti...

Background: 5α-Reductase type 2 deficiency (5ARD) is caused by mutations in the SRD5A2 gene. Inadequate masculinisation in XY individuals results from failure to convert testosterone (T) to dihydrotestosterone (DHT), a potent androgen. A decreased serum T:DHT ratio is frequently taken to identify 5ARD, but requires hCG stimulation for prepubertal patients; findings are not always supported by genotyping. Urine steroid profiling (USP) by GC-MS is established as showing sig...

Objective: Mitotane (o,p’DDD) is an effective adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC). Suppression of cortisol biosynthesis, including inhibition of 11β-hydroxylation, has been described. Decreased cortisol bioavailability is indicated by increased dose requirement for hydrocortisone replacement during mitotane treatment. Urinary excretion of common cortisol metabolites (CM) has been reported to be normal but with increase of 6&#946...

Mitotane (o,p’DDD) is an effective oral adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC). Inhibition of cortisol biosynthesis has been described. Cortisol metabolic clearance rate is unchanged, but decreased cortisol biovailability is indicated by increased dose requirement for hydrocortisone replacement during mitotane treatment. Urinary excretion of common cortisol metabolites (CM) has been reported to be normal but with increase of 6β-hyd...

Background: Virilising congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, and 90–95% of CAH cases are caused by 21-hydroxylase deficiency. Associated inefficient cortisol synthesis results in increased CRH and ACTH levels, leading to production of excess sex hormone precursors. These are further metabolized to active androgens and to a lesser extent oestrogens. We recently reported that one of these androgens, DHEA-S or its metabolites sig...

Pituitary patients with different aetiologies of hypopituitarism exhibit differing phenotypes despite optimal replacement therapy. We hypothesised that differential regulation of the isoenzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which mediates the autocrine conversion of cortisone to cortisol in adipose tissues and liver may play a role.We prospectively studied 11β-HSD1 activity through analysis of 24 h urine cortisol/cortisone ...