beta-HSD Deficiency Research Articles

Adrenal steroidogenic function in a black and Hispanic population with precocious pubarche.

Adrenal steroidogenic function was evaluated in 34 children with precocious pubarche (PP; onset of pubic hair, less than 8 yr in girls and less than 9 yr in boys). The adrenal steroid response to an iv bolus of ACTH-(1-24) in the patients (aged 9 months to 9 7/12 yr) was compared to that in 16 normal controls (prepubertal, n = 9; Tanner stage II pubic hair, n = 7). The patient population consisted of 20 Hispanics (17 from the Dominican Republic), 13 black Americans, and 1 black Haitian. All patients had normal stimulated levels of 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (compound S), and desoxycorticosterone, thereby ruling out 21-hydroxylase deficiency and 11 beta-hydroxylase deficiency, respectively. To evaluate for the presence of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency, the patients were classified on the basis of their 60-min delta 5-17-hydroxypregnenolone/17-OHP (delta 5-17P/17-OHP) ratio [PP1 (n = 13), less than or equal to 2 SD of Tanner I controls; PP2 (n = 17), greater than 2 SD above Tanner I controls and less than or equal to 2 SD Tanner II controls; and PP3 (n = 4), greater than 2 SD above Tanner II controls; 2.1 +/- 1.0, 6.1 +/- 1.7, and 16.1 +/- 3.3 for PP1, PP2, and PP3, respectively. delta 5-17P/17-OHP for PP1 vs. PP2, PP2 vs. PP3, and PP1 vs. PP3 were significantly different (P less than 0.05) by analysis of variance and multiple comparison testing using the Student-Newman-Keuls procedure. The four patients in PP3 were considered to have a possible nonclassical 3 beta-HSD deficiency. This diagnosis was supported by the fact that these patients had the greatest increment in delta 5-17P and dehydroepiandrosterone (DHEA) levels as well as the highest stimulated delta 5-17P/cortisol (delta 5-17P/F) ratio among the patient groups. In contrast to the ACTH-stimulated androgens there were no differences in the baseline delta 5-17P/170HP or androgens among the patient groups. Additionally, the 60-min delta 5-17P/17-OHP within the patient groups was highly correlated with the 60 min-values for delta 5-17P, DHEA, DHEA/delta 4-androstendione, and delta 5-17P/F. In the children with PP the mean bone age/chronological age (BA/CA) was 1.27 +/- .27, the mean BA/height age (BA/HA) was 1.09 +/- 0.25, and the mean HA/CA was 1.18 +/- 0.17. No differences were noted between the patient population groups in mean BA/CA, mean BA/HA, or mean HA/CA.(ABSTRACT TRUNCATED AT 400 WORDS)

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: gender reassignment in early infancy.

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency has a high prevalence within the Arab population of the Gaza strip and is characterised by marked virilization at puberty, leading in many cases to the spontaneous adoption of a male gender role. As a result of this, parents of 7 affected male infants (aged 1-10 months) born with female phenotype requested early gender reassignment. Diagnosis was suspected in 5 on the basis of a positive family history, but confirmed in all cases by the finding of low to normal testosterone levels (30-184 ng/dl) with high delta 4-androstenedione levels (188-808 ng/dl), after hCG. Treatment with im testosterone oenanthate (25-50 mg/dose) was given in one to three 3-months courses and penile size was increased into the normal range without evoking a significant increase in height velocity or skeletal maturation. Five patients underwent the first stage of male genitoplasty between 2 and 3 years of age. This consisted of bilateral orchidopexy, chordee release and penile lengthening - yielding finally an anatomically normal-sized and shaped penis. Androgen responsive male pseudohermaphroditism due to 17 beta-HSD deficiency or a similar defect and diagnosed in infancy should be treated as soon as possible with systemic testosterone before considering any sex change, and in preparation for male genitoplasty. Early gender reassignment according to genetic and gonadal sex is probably the management of choice for these cases since this may result in a normal adjustment to the male gender role, particularly after puberty.

Apparent Mineralocorticoid Excess Causing Hypertension and Hypokalemia in Children

Cortisol 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was observed in four patients with apparent mineralocorticoid excess. The 11 beta-HSD deficiency was demonstrated by a markedly decreased urinary tetrahydrocortisone/tetrahydrocortisol (THE/THF) ratio (less than 1 in normal children) during infusion of ACTH and administration of hydrocortisone. We propose that in these patients the 11 beta-HSD deficiency impairs the metabolism of cortisol to cortisone, resulting in a prolonged cortisol half-life, suppression of ACTH, and normal serum cortisol. The 11 beta-HSD deficiency protects the patient from adrenal insufficiency despite the low cortisol secretion; the prolonged half-life of cortisol may contribute to the hypertension and hyporeninemia observed in this disorder. Continuous intravenous hydrocortisone administration resulted in increased blood pressure and decreased serum potassium. Addition of spironolactone during continued administration of 20 mg per day of hydrocortisone resulted in a decrease in blood pressure and a rise in serum potassium. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid. These findings may account for this syndrome of apparent mineralocorticoid excess.