Skip to main content
SpringerLink
Log in

17-α-hydroxylase deficiency in three siblings: short- and long-term studies

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

We have studied a family (12 members) with 3 patients (2 adult females and 1 pubertal-aged genotypic male) affected by congenital adrenal hyperplasia due to 17-α-hydroxylase deficiency, all of whom presented as phenotypically female subjects with lack of sexual development and with hypokalemic hypertension. The baseline hormonal pattern revealed low glucocorticoid levels (17-hydroxyprogesterone, plasma and urinary cortisol, cortisol secretion rate), as well as androgen (testosterone and dehydroepiandrosterone sulfate) and estrogen (17-ß-estradiol) levels, since the defect is present at both adrenal and gonadal levels. As a consequence ACTH, LH, and FSH concentrations were high. Otherwise steroids not requiring 17-α-hydroxylation, such as deoxycorticosterone, corticosterone and their 18-hydroxylated compounds, were secreted in excess with the exception of aldosterone whose levels were undetectable; baseline plasma renin activity levels were suppressed. Short-term dexamethasone treatment normalized potassium and reduced blood pressure and the abnormal mineralocorticoid levels. During chronic ACTH suppression with low doses of glucocorticoids (8 years), electrolyte disturbances were corrected, blood pressure was normalized in 2 cases but only reduced in the third; plasma renin activity returned to normal range within four years in all the patients, while urinary aldosterone was normalized only after 8 years of therapy and became partially responsive to posture, ACTH, angiotensin II, and furosemide. The other mineralo-corticoids were reduced but remained above the normal range. The HLA-genotyping in all the family members revealed that the gene responsible for 17-α-hydroxylase deficiency was not linked to the HLA system. Measurement of plasma steroids (deoxycorticosterone, corticosterone, aldosterone) in this family revealed that the heterozygotes were different from the control population only in their ACTH-stimulated corticosterone levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Biglieri E.G., Herron H.A., Brust N. 17-α-hydroxylation in man. J. Clin. Invest. 45: 1946, 1966.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Mills I.H., Wilson R.J., Tait A.D., Cooper H.R. Steroid metabolic studies in a patient with 17-α-hydroxylation deficiency. J.Endocrinol. 38: 19, 1967.

    Google Scholar 

  3. Goldsmith O., Solomon D.H., Horton R. Hypogonadism and mineralocorticoid excess. The 17-hydroxylase deficiency syndrome. N. Engl. J. Med. 277: 673, 1967.

    Article  PubMed  CAS  Google Scholar 

  4. Rovner D.R., Conn J.W., Cohen E.L., Berlinger F.G., Kern D.C. Biglieri’s syndrome: unexplained by 17-α-hydroxylase defect alone. J. Lab. Clin. Med. 72: 1009, 1968.

    Google Scholar 

  5. Mallin S.R. Congenital adrenal hyperplasia secondary to 17-hydroxylase deficiency. Ann. Intern. Med. 49: 1930, 1969.

    Google Scholar 

  6. Linquette M., Dupont A., Rocadot A., Lefebvre J., May J.P., Cappoen J.P. Deficit en 17-hydroxylase. A propos d’une observation. Ann. Endocrinol. 32: 574, 1971.

    Google Scholar 

  7. De Lange W.E., Weeke A., Artz W., Jansen W., Doorenbos H. Primary amenorrhea with hypertension due to 17-hydroxylase deficiency. Acta. Med. Scand. 193: 565, 1973.

    Article  PubMed  Google Scholar 

  8. Rovner D.R., Conn J.W., Cohen E.L., Berlinger F.G., Kern D.C., Gordon D.L. 17-α-hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis. Acta Endocrinol. (Copenh.) 90: 490, 1979.

    CAS  Google Scholar 

  9. Saruta T., Kondo K., Saito I., Nagahomo S., Suzuki H., Konishi K., Matsuki S. Control of aldosterone in 17-α-hydroxylase deficiency. Horm. Res. 13: 98, 1980.

    Article  PubMed  CAS  Google Scholar 

  10. Tvedegaard E., Frederiksen V., Olgaard K., Damkjaer Nielsen M., Starup J. Two cases of 17-α-hydroxylase deficiency. One combined with complete gonadal agenesis. Acta Endocrinol. (Copenh.) 98: 267, 1981.

    CAS  Google Scholar 

  11. D’Armiento M., Reda G., Kater C., Shackleton C.H.L., Biglieri E.G. 17-α-hydroxylase deficiency: mineralocorticoid hormone profiles in an affected family. J. Clin. Endocrinol. Metab. 56: 697, 1983.

    Article  PubMed  Google Scholar 

  12. New M.I. Male pseudohermaphroditism due to 17-α-hydroxylase deficiency. J. Clin. Invest. 49: 1930, 1970.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Mantero F., Busnardo B., Riondel A., Veyrat R., Austoni M. Hypertension arterielle, alcalose hypokaliemique et pseudohermaphrodisme male par deficit en 17-α-hydroxylase. Schweiz. Med. Wochenschr. 101: 38, 1971.

    PubMed  CAS  Google Scholar 

  14. Bricaire H., Luton J.P., Laudat P., Legrand J.P., Turpin G., Corvol P., Lemmer M. A new male pseudohermaphroditism associated with hypertension due to a block of 17-α-hydroxylation. J. Clin. Endocrinol. Metab. 35: 67, 1972.

    Article  PubMed  CAS  Google Scholar 

  15. Hammerstein J., Zielska F., Distler A., Wolff H.P. 17-α-hydroxylase deficiency of the gonads and adrenals in a male pseudohermaphrodite. Acta Endocrinol. (Copenh.) 173 (Suppl.): 76, 1973.

    CAS  Google Scholar 

  16. Alvarez M.N., Coutier M.D., Hayles A.B. Male pseudohermaphroditism due to 17-hydroxylase deficiency in 2 siblings. Pediatr. Res. 7: 325, 1973.

    Google Scholar 

  17. Kershnar A.K., Borut D., Kogut M.D., Biglieri E.G., Schambelan M. Studies in a phenotypic female with 17-a -hydroxylase deficiency. J. Pediatr. 89: 395, 1976.

    Article  PubMed  CAS  Google Scholar 

  18. Tournaire J., Audi Parera L., Loras B., Blum J., Castelnovo P., Forest M.G. Male pseudohermaphroditism with hypertension due to 17-α-hydroxylation deficiency. Clin. Endocrinol. (Oxf.) 5: 53, 1976.

    Article  Google Scholar 

  19. Waldhause W., Herkner K., Novotry P., Bratusch-Marrain P. Combined 17-α- and 18-α-hydroxylase deficiency associated with complete male, pseudohermaphroditism and hypoaldosteronism. J. Clin. Endocrinol. Metab. 46: 236, 1978.

    Article  Google Scholar 

  20. Dupont B., Oberfield S.E., Smithwick E.M., Lee T.D., Levine L.S. Close genetic linkage between HLA and congenital adrenal hyperplasia (21-hydroxylase deficiency) Lancet 2: 1309, 1977.

    Article  PubMed  CAS  Google Scholar 

  21. Terasaky P.I., McClelland J.D. Microdroplet assay to human cytotoxins. Nature 204: 998, 1964.

    Article  Google Scholar 

  22. Boscaro M., Karbowiak I., Mantero F. Urinary free cortisol radioimmunoassay; its application in the diagnosis of adrenal diseases. Ric. Clin. Lab. 8: 169, 1978.

    PubMed  CAS  Google Scholar 

  23. Boscaro M., Armanini D., Mantero F. Indicazioni allo studio della funzione surrenalica mediante misura del tasso di secrezione del cortisolo. Quaderni Sclavo di Diagnostica 12: 39, 1976.

    CAS  Google Scholar 

  24. Carpenè G., Opocher G., Vettoretti A., Rocco S., Scarante M., Mantero F. Impact of high-performance liquid chromatography on the assay of steroid hormones. Ann. N.Y. Acad. Sci., 595: 480, 1990.

    Article  Google Scholar 

  25. Feit J.P., David L., Paticot M.C., Macabeo V., Lebacq E., Francois R. Le deficit en 17-hydroxylase: une cause de croissance et puberté rétardées chez la fille. Arch. Pediatr. 35: 395, 1978.

    CAS  Google Scholar 

  26. Kater G.E., Biglieri E.G., Brust N., Chang B., Hirai J. Zona fasciculata origin of 18-hydroxycorticosterone in the chronically suppressed zona glomerulosa. J. Clin. Endocrinol. Metab. 55: 628, 1982.

    Article  PubMed  CAS  Google Scholar 

  27. Scaroni C., Opocher G., Mantero F. Renin-angiotensin-aldosterone system: a long-term follow-up study in 17-α-hydroxylase deficiency syndrome. bl]ReferencesClin. Exp. Hyper. Tens. A8(4–5): 773, 1986.

    Google Scholar 

  28. Rovner D.R., Conn J.W., Cohen E.L., Berlinger F.G., Kern D.C., Gordon DL. 17-α-hydroxylase deficiency. A combination of hydroxylation defect and reversible blockade in aldosterone biosynthesis. Acta Endocrinol. (Copenh.) 90: 490, 1979.

    CAS  Google Scholar 

  29. Lorenzen F., Pang S., New M.I., Pollack M., Oberfield S., Dupont B., Chow D., Schneider B., Levine L. Studies of C-21 and C-19 steroids and HLA genotyping in siblings and parents of patients with congenital adrenal hypereplasia due to 21 hydroxylase deficiency. J. Clin. Endocrinol. Metab. 50: 572, 1980.

    Article  PubMed  CAS  Google Scholar 

  30. Mantero F., Scaroni C., Venturi-Pasini C., Fagiolo U. No linkage between HLA and congenital adrenal hyperplasia due to 17-hydroxylase deficiency. N. Engl. J. Med. 303: 530, 1980.

    PubMed  CAS  Google Scholar 

  31. White P.C., New M.I., Dupont B.O. Congenital adrenal hyperplasia. N. Engl. J. Med. 316: 1519, 1987.

    Article  PubMed  CAS  Google Scholar 

  32. Mantero F., Scaroni C., Masarotto P., Venturi-Pasini C. HLA and congenital adrenal hyperplasia. Eur. J. Clin. Invest. 11: 20, 1981.

    Google Scholar 

  33. Simpson E.R., Kagimoto M., Mason J.I., Waterman M.R. Regulation of expression of genes encoding steroidogenic enzymes. In: Mantero F., Takeda R., Scoggins B.A., Biglieri E.G., Funder J.W.(Eds.), The Adrenal and hypertension: from Cloning to Clinic. Serono Symposia Publication, vol. 5, Raven Press, 1989, p.15.

Download references

Author information

Authors and Affiliations

  1. Istituto di Semeiotica Medica, University of Padova, Italy

    C. Scaroni, A. Biason, G. Carpenè & G. Opocher

  2. Istituto di Clinica Medica I, University of Catania, Italy

    F. Mantero

Authors
  1. C. Scaroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Biason
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Carpenè
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Opocher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Mantero
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Scaroni, C., Biason, A., Carpenè, G. et al. 17-α-hydroxylase deficiency in three siblings: short- and long-term studies. J Endocrinol Invest 14, 99–108 (1991). https://doi.org/10.1007/BF03350278

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350278

Key-words

Search

Navigation