Clinical manifestations and hormonal profile of two women with Cushing's disease and mild deficiency of 21-hydroxylase.
The development of Cushing's disease among patients with deficiency of 21-hydroxylase has not been observed to date. The clinical manifestations and the hormonal profile of this exceptional association are herein described through the study of two cases. The first one was a 39-yr-old woman who had undergone non-curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12 yr before. She showed hypertension, central obesity, severe hirsutism, alopecia and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin-induced hypoglycemia and dexamethasone suppression tests) revealed the qualitative disturbances that characterize Cushing's disease. Serum concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone were clearly increased. Reexamination of the tissue samples from previous surgery confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene analysis found the splicing 655G mutation at intron 2 and the V281L mutation at exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary ACTH-dependent Cushing's syndrome according to unequivocal clinical and laboratory findings. However, hirsutism was particularly severe and both serum androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote for a large conversion of CYP21 gene. In these cases, the clinical and biochemical expression of Cushing's syndrome was determined by the different severity of 21-hydroxylase deficiency and the subsequent residual ability of adrenal cortex to synthesize cortisol.
Boronat
M
M
Section of Endocrinology and Nutrition, Hospital Universitario Insular, Las Palmas de Gran Canaria Spain. mboronat@ctv.es
Carrillo
A
A
Ojeda
A
A
Estrada
J
J
Ezquieta
B
B
Marín
F
F
Nóvoa
F J
FJ
D000236:Adenoma / Q000473:pathology*; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000505:Alopecia / Q000209:etiology; D005260:Female; D006628:Hirsutism / Q000209:etiology; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006973:Hypertension / Q000209:etiology; D009765:Obesity / Q000209:etiology; D047748:Pituitary ACTH Hypersecretion / Q000150:complications* / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000473:pathology*
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
N Engl J Med. 1997 Jan 16;336(3):172-7
8988897
J Clin Endocrinol Metab. 1992 Mar;74(3):685-9
1311000
Horm Metab Res. 2001 Oct;33(10):596-601
11607879
Ann N Y Acad Sci. 1985;458:277-87
3879126
Clin Endocrinol (Oxf). 1996 Aug;45(2):147-56
8881446
World J Surg. 1995 Jan-Feb;19(1):150-3
7740803
Clin Endocrinol (Oxf). 2000 Oct;53(4):493-500
11012575
Clin Radiol. 1986 Mar;37(2):155-60
3698500
J Clin Endocrinol Metab. 2001 Dec;86(12):5695-9
11739423
Arch Dis Child. 1981 Mar;56(3):208-13
7212759
Acta Endocrinol (Copenh). 1982 Mar;99(3):357-63
6280426
Am J Obstet Gynecol. 2000 Dec;183(6):1468-74
11120512
Biochem Mol Med. 1997 Dec;62(2):151-8
9441866
Endocr Rev. 2000 Jun;21(3):245-91
10857554
Hum Genet. 1995 Aug;96(2):198-204
7635470
AJNR Am J Neuroradiol. 2000 Apr;21(4):690-6
10782779
Surg Neurol. 1992 Jun;37(6):441-7
1317610
Clin Endocrinol (Oxf). 1998 Jan;48(1):45-51
9509067