Endocrine findings in male pseudohermaphroditism

Abstract

Recent discoveries in molecular biology have much clarified the regulation and function of steroid converting enzymes. Most progress has been made in the area of cytochromes, which regulate the side chain cleavage of cholesterol (P-450 SCC) and the 17 alpha-hydroxylase- and 17,20-desmolase (or 17,20-lyase) activities (P-450 17 alpha), as well as in 3 beta-hydroxysteroid dehydrogenase. Nevertheless, there are some discrepancies between fundamental knowledge and clinical experience, which are difficult to understand: why is it possible, e.g., that cases with "pure" 17 alpha-hydroxylase or 17,20-desmolase deficiency exist, when there is only one cytochrome regulating both steps? After a brief review of clinical and biochemical findings in the various defects of testosterone biosynthesis, a case is discussed which is of interest in this respect.

Disorders of Sex Development: Classification, Review, and Impact on Fertility

“…However, some mutations selectively impair 17,20-lyase activity, and others that affect cytochrome P450-oxidoreductase and cytochrome b5 cofactor proteins also selectively alter 17,20-lyase activity, leading to a defect in the synthesis of sex steroids that impairs fertility in male and female patients when the deficiency is severe. Zachmann et al [120] described steroid 17,20-desmolase deficiency as a new cause of male Ps or MAD, showing that family members with this disorder can also have ambiguous external genitalia, inguinal or intra-abdominal testicles, and severe hypospadias, with a male-type urethra and the development of male ducts [120][121][122][123]. If the diagnosis is made in infancy, T treatment will result in adequate penis growth and the development of male secondary sexual characteristics [120][121][122][123].…”

“…Zachmann et al [120] described steroid 17,20-desmolase deficiency as a new cause of male Ps or MAD, showing that family members with this disorder can also have ambiguous external genitalia, inguinal or intra-abdominal testicles, and severe hypospadias, with a male-type urethra and the development of male ducts [120][121][122][123]. If the diagnosis is made in infancy, T treatment will result in adequate penis growth and the development of male secondary sexual characteristics [120][121][122][123]. Miller reviewed and updated the syndrome of 17,20-lyase deficiency [124].…”

Perspectives in Pediatric Pathology, Chapter 6. Male Undermasculinization

“…At puberty, patients show complete virilization without gynecomastia; low serum levels of testosterone, androstenedione, DHEA, and estradiol; and high levels of pregnanetriolone (a metabolite of 17-α-hydroxyprogesterone) [60]. Some adult patients with 17,20 desmolase deficiency develop an additional deficiency of 17-α-hydroxylase with hypertension [61,62].…”