Secondary Biosynthetic Defects in Women with Late-Onset Congenital Adrenal Hyperplasia

Eldar‐Geva, Talia; Hurwitz, Arye; Vecsei, P.; Palti, Z.; Milwidsky, Ariel; Rösler, Ariel

doi:10.1056/nejm199009273231302

Cited by 125 publications

(42 citation statements)

References 33 publications

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“…A combined alteration of 21-hydroxylase and 11b-hydroxylase was observed in 7 cases. Apart from anecdotal records with evidence for an actual deficiency of these two enzymes (42), such findings have already been observed for patients with hyperandrogenism (23,24,43). The increased peak 21-DF levels displayed by 7 patients with high post-stimulation S/F ratios is difficult to reconcile with adrenal steroidogenesis.…”

Section: Figurementioning

confidence: 97%

“…Poststimulated 21-DF levels over 2.2 nmol/l were taken as indicative of 21-hydroxylase impairment (20,21). A post-stimulative S/F ratio above 0.12 was taken as indicative of an altered 11b-hydroxylase activity; this cut-off value was determined from previously published studies (12,(23)(24)(25). Similarly, it was assumed that 17,20-lyase was impaired when the 17-OHG/DHEA ratio and the 17-OHP/D4-A ratio after stimulation were above 3.0 (26)(27)(28)(29)(30).…”

Section: Endocrine Assessmentmentioning

confidence: 99%

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Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

Sadoul

Kezachian²,

Altare³

et al. 1999

European Journal of Endocrinology

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Objective: An increased response of 17-hydroxyprogesterone to ACTH stimulation has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11b-hydroxylase activity. To analyse this question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas. Design and Patients: 17 patients (7 women, 10 men; mean age, 62 Ϯ 12 years) with non-histologically analyzed adrenal incidentalomas were prospectively evaluated. Methods:The following variables were investigated: 24-h urinary methanephrines and free cortisol excretion; plasma levels of ACTH and dehydroepiandrosterone; overnight dexamethasone suppression test; 1-24 ACTH stimulation test with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, D4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol. Results: Discordant features of subclinical hypercorticism were noted in one case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycortisol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively. An increased 11-deoxycortisol/cortisol ratio identified reduced activity of 11b-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunction. Whereas only 2 patients showed no enzyme modification, 9 displayed alterations of at least two pathways. Conclusion: In our hands, a combination of enzyme dysfunction was frequently observed. Shared biochemical mechanisms could explain combined 17,20-lyase and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (particularly when based on peak 21-deoxycortisol) and 11b-hydroxylase is more puzzling.

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Section: Figurementioning

confidence: 97%

Section: Endocrine Assessmentmentioning

confidence: 99%

Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

Sadoul

Kezachian²,

Altare³

et al. 1999

European Journal of Endocrinology

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“…Increased secretion of 17-hydroxyprogesterone after stimulation with ACTHhas been described in 30-71% of adrenal "incidentaloma", suggesting a defect in the 2 1 -hydroxylase gene (7,8). An exaggerated response of 17-hydroxyprogesterone to ACTHmay be due to mild 21-hydroxylase deficiency (9) or may be caused by other abnormalities of steroid biosynthesis in these tumors, such as 1 1(3-hydroxylase deficiency (10). The ratio of 1 1-deoxycortisol to cortisol is higher in 40% of patients with adrenal "incidentalomas", and these patients have increased responses of precursors of the mineralcorticoid and glucocorticoid pathway including 1 7-hydroxyprogesterone after stimulation with ACTH(ll).…”

Section: Discussionmentioning

confidence: 99%

Primary Amenorrhea Accompanied by Adrenal Adenoma: Start of Menarche Soon after Tumor Resection.

et al. 2002

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Wereport a patient with primary amenorrhea accompanied by adrenal adenoma. A 21-year-old womanwas admitted to our hospital because of primary amenorrhea and hyperprogesteronemia without virilization. Venous sampling showedprogesterone overproduction at the left adrenal gland. Computedtomography revealed a 7 cm mass in left adrenal gland. Serum pregnenorone, 17-hydroxypregnenorone, dehydroepiandrosterone, 17-hydroxyprogesterone, deoxycorticosterone, and 1 1-deoxycortisol were elevated. The diagnosis of steroid hormone producing tumorwas made.Following tumor resection, serum progesterone normalized 4 days later, and menarche occurred 51 days after operation. The present case indicated that adrenal functioning tumor should not be overlooked in patients with primary amenorrhea. (Internal Medicine 41: 972-976, 2002)

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“…But, at least to our knowledge, so far no mutation has been identified in the CYPIIB1 gene of individuals with LOCAH due to 11b-OH deficiency. The prevalence of 11b-OH deficiency has been reported to be between 0.8 and 8% in different studies carried out in women with hirsutism or hyperandrogenism (38,39). Carmina (37) recently found that only 0.6% of the hirsute women had LO 11b-OH deficiency.…”

Section: Discussionmentioning

confidence: 99%

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

Şahin¹,

Keleştimur

1997

European Journal of Endocrinology

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Objective: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11b-hydroxylase (11b-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS).Design: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study.Methods: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormonebinding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTHstimulated 17-OHP levels >30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis of 11b-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls.Results: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0:05) and 11-DOC (P < 0:0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency.Conclusions: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11b-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11b-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.

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Secondary Biosynthetic Defects in Women with Late-Onset Congenital Adrenal Hyperplasia

Cited by 125 publications

References 33 publications

Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

Primary Amenorrhea Accompanied by Adrenal Adenoma: Start of Menarche Soon after Tumor Resection.

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

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