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Partial 17, 20-desmolase and 17α-hydroxylase deficiencies in a 16-year-old boy

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Abstract

Thirteen plasma steroids as well as ACTH, LH and FSH were measured by specific RIAs under basal and dynamic conditions in a 16-year-old boy (normal external genitalia, 46, XY karyotype) who presented slowness and unachievement of pubertal development. On the Δ4-pathway: basal levels of testosterone and dihydrotestosterone were low — with a normal ratio-, Δ4-androstenedione and 11β-hydroxyandrostenedione were in the low normal range. Meanwhile, 17α-hydroxyprogesterone and progesterone levels were markedly elevated. On the Δ5-pathway: dehydroepiandrosterone was extremely low while 17α-hydroxypregnenolone and pregnenolone were almost normal; dehydroepiandrosterone sulfate was subnormal while pregnenolone sulfate was normal. Cortisol, aldsoterone were normal while ACTH was moderately increased. Basal and responsive levels of LH and FSH were markedly increased. ACTH stimulation induced asubnormal rise of Cortisol and 11 β-hydroxyandrostenedione, a low or absent rise of dehydroepiandrosterone, 17α-hydroxypregnenolone, androstenedione and 17α-hydroxyprogesterone contrasting with a marked rise of pregnenolone and progesterone. After hCG stimulation, responses were low for testosterone, extremely high for 17α-hydroxyprogesterone with a normalisation of the 17α-hydroxyprogesterone/progesterone ratio. Fluoxymesterone dramatically reduced the pathologically high basal levels of progesterone and 17α-hydroxyprogesterone. Dexamethasone induced only a minute decrease in the A4-progestagens, a marked decrease in pregnenolone, with a more than 80% reduction of 17α-hydroxypregnenolone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and androstenedione. These data suggest a defect involving the cytochrome P450 common to both 17α-hydroxylase and 17,20-desmolase activities. In the testis, the alteration is already present in basal state and mainly expressed in its 17,20-desmolase activity whereas in the adrenal, it is only expressed in its 17a-hydroxylase component. The different behavior of adrenals and testes regarding this common defect is probably due to local factors affecting specifically the tissue expression of the enzyme.

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Authors and Affiliations

  1. Department of Medical Chemistry, Free University of Brussels, Belgium

    D. Bosson M.D., M. Toppet & J. R. M. Franckson

  2. Department of Pediatrics, Saint-Pierre Hospital, Free University of Brussels, Belgium

    R. Wolter

  3. Unité de Recherches Endocriniennes et Métaboliques chez l’Enfant, INSERM U. 34, Hôpital Debrousse, 69322, Lyon, France

    E. de Peretti & M. G. Forest

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  1. D. Bosson M.D.
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Bosson, D., Wolter, R., Toppet, M. et al. Partial 17, 20-desmolase and 17α-hydroxylase deficiencies in a 16-year-old boy. J Endocrinol Invest 11, 527–533 (1988). https://doi.org/10.1007/BF03350177

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