The Prevalence of 21-Hydroxylase Deficiency in Adrenal Incidentalomas - Hormonal and Mutation Screening

Abstract

The aim of the present study was to evaluate and compare the response of 17 OHP to ACTH stimulation in patients with various types of adrenal incidentalomas and to examine the occurence of germline CYP21 mutation in these patients.

Subjects and Methods: 40 patients (27 females, 13 males) with unilateral and bilateral masses were screened for five most common mutations of the CYP21 in peripheral blood DNA samples. A hormonal evaluation, i.e. baseline plasma values of 17OHP, DHEAS as well as plasma 17OHP and DHEA after ACTH stimulation, was performed in all patients.

21 of them had unilateral adrenal adenoma, 13 patients had adrenal hyperplasia (six of them unilateral) and 6 patients had CT characteristics of other tumors (myelolipomas, cysts, adrenocortical carcinoma).

Results: There were no significant differences in plasma 17OHP, DHEAS and plasma cortisol between all three groups. Stimulated plasma values of DHEA and 17OHP after ACTH administration were significantly higher in patients with adenomas (p<0.05 and p<0.01) and with hyperplasia (p<0.05 and p<0.05) compared with those with other tumors.

An exaggerated response of 17 OHP was found in 5 (12%) patients. However, mutation screening in peripheral blood samples revealed no CYP21 mutation in all examined groups.

Summary: Although 12% of patients with adrenal incidentalomas had an exaggerated response of 17 OHP after ACTH administration indicating a possible 21-hydroxylase deficiency, these findings are not associated with CYP21 mutation estimated in peripheral blood samples. There was found no germline CYP21 mutation in all patients with various adrenal incidentalomas.

adrenal incidentalomas - 21-hydroxylase deficiency - 17-OH progesterone

References

• 1 Abecassis M, MacLoughlin MJ, Langer B, Kudlow JE. Serendipitous adrenal masses. Prevalence, significance and management.  Am J Surg. 1985;  149 783-788
• 2 Avivi I, Pollack S, Gideoni O, Linn S, Blumenfeld Z. Overdiagnosis of 21 hydroxylase late onset congenital adrenal hyperplasia: correlation of corticotropin test and human leukocyte antigen typing.  Fertil Steril. 1996;  66 557-563
• 3 Azziz R, Dewailly D, Owerbach D. Clinical review 56. Nonclassic adrenal hyperplasia: Current concepts.  J Clin Endocrinol Metab. 1994;  78 810-815
• 4 Bernini GP, Argenio GF, Vivaldi MS, Moretti A, Miccoli P, Iaconi P, Magagna A, Salvetti A. Utility of plasma dehydroepiandrosterone sulphate determination in adrenal incidentalomas.  J Endocrinol Invest. 1998;  21 365-371
• 5 Beuschlein F, Schulze E, Moro P, Gensheimer HP, Maser-Gluth C, Allolio B, Reincke M. Steroid 21-hydroxylase mutation and 21-hydroxylase mRNA expression in human adrenocortical tumor.  J Clin Endocrinol Metab. 1998;  83 2585-2588
• 6 Devenyi I. Possibility of normokaliemic primary aldosteronism as reflected in the frequency of adrenal cortical adenomas.  J Clin Pathol. 1967;  20 49-51
• 7 Jaresch S, Kornely E, Kley HK, Schlaghecke R. Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia.  J Clin Endocrinol Metab. 1992;  74 685-690
• 8 Hedeland H, Ostberg G, Hokfelt B. One the prevalence of adrenocortical adenomas in an autopsy material in relation to hypertension and diabetes.  Acta Med Scand. 1968;  184 211-214
• 9 Mancini T, Kola B, Mantero F, Arnaldi G. Functional and nonfunctional adrenocortical tumors demonstrate a high responsiveness to low-dose adrenocorticotropin.  J Clin Endocrinol Metab. 2003;  88 1994-1998
• 10 Mantero F, Arnaldi G. Investigation protocol: adrenal enlargement.  Clin Endocrinol (Oxf). 1999;  50 141-146
• 11 Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. A survey on Adrenal Icidentaloma in Italy.  J Clin Endocrinol Metab. 2000;  85 637-644
• 12 Oriola J, Plensa I, Machuca I, Pavia C, Rivera-Fillat F. Rapid screening method for detecting mutations in the 21-hydroxylase gene.  Clin Chem. 1997;  43 557-561
• 13 Pang S. The molecular and clinical spectrum of 3beta-hydroxysteroid dehydrogenase deficiency disorder.  Trends Endocrinol Metab. 1998;  9 82-86
• 14 Patócs A, Tóth M, Barta C, Sasvári-Székely M, Varga I, Szucs N, Jakab C, Gláz E, Rácz K. Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency in patients with unilateral and bilateral adrenal incidentalomas.  Eur J Endocrinol. 2002;  147 349-355
• 15 Reincke M, Peter M, Sippel WG, Allollio B. Impairment of 11-beta-hydroxylase but not 21 hydroxylase in adrenal „incidentaloma”.  Eur J Endocrinol. 1997;  136 196-200
• 16 Rossi R, Tauchmannova L, Luciano A, Di Martino M, Battista C, Viscovo L del, Nuzzo V, Lombardi G. Subclinical CushingŽs syndrome in patients with adrenal incidentaloma. Clinical and biochemical features.  J Clin Endocrinol Metab. 2000;  85 1440-1448
• 17 Wedell A, Luthman H. Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations.  Hum Mol Genet. 1993;  2 499-504

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