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Developmental abnormalities of the genitalia: intersex, hypospadias, and cryptorchidism
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
11β-hydroxylase deficiency: <5% of CAHNot salt wasting (i.e. no mineralocorticoid deficiency)Presentation: hypertension, hyperpigmentation, virilization (and precocious puberty in males)Diagnosis: will have elevated serum levels of 11-deoxycortisol and 11-deoxycorticosterone.
Menstrual Effects on Neuroendocrine Measures
Published in Diana L. Taylor, Nancy F. Woods, Menstruation, Health, and Illness, 2019
Daniel J. Cardona, Rajiv Tandon, Roger F. Haskett, John F. Greden
Hypothalamo-Pituitary-Adrenal (HPA) Axis Plasma ACTH levels reach a peak around the time of ovulation and a trough during menstruation (Gennazini, 1975; Gennazini et al., 1975; Burns, 1975). As mentioned, beta-endorphin levels follow a similar pattern, indicating that the activity of proopiomelanocortin (POMC, the precursor molecule of both ACTH and beta-endorphin; Roberts & Herbert, 1977) is highest in the periovulatory phase and lowest around menstruation. Plasma cortisol levels may show an identical pattern (Gennazini et al., 1975; Tam et al., 1985), with levels rising throughout the follicular phase and falling throughout the luteal phase. Collins, Eneroth, and Langdren (1985) observed higher baseline urinary cortisol levels in the ovulatory phase as compared to the follicular and luteal phases, although this pattern was reversed following stress. Plasma aldosterone and 11-deoxycorticosterone show a similar pattern, although their levels peak somewhat later in the luteal phase (Parker, Winkel, Rush, Porter, & MacDonald, 1981; Schwartz & Abraham, 1975).
Introduction to Human Cytochrome P450 Superfamily
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
CYP11B2 (also known as aldosterone synthase, previously known as corticosterone methyloxidase) has 503 amino acids with a molecular weight of 57.6 kDa. It is responsible for the three-step conversion from 11-deoxycorticosterone to aldosterone. The enzyme catalyzes the conversion of the 11(3-hydroxylation of 11-deoxycorticosterone followed by 18-hydroxylation and two-electron oxidation of the 18-alcohol to an aldehyde. CYP11B2 is expressed in the adrenal cortex (zona glomerulosa). It is also a mitochondrial CYP as other CYP11 family. Regulation of CYP11B2 can be overlapped with CYP11B1, which involves CRE/Ad1 element and ARF-1. However, SF1 does not involve the regulating process.
A novel homozygous CYP17A1 mutation causes partial 17 α-hydroxylase/17,20-lyase deficiency in 46,XX: a case report and literature review
Published in Blood Pressure, 2023
Heye Chen, Yingting Chen, Hongxian Mao, Huaying Huang, Xueyong Lou
17 α-Hydroxylase/17,20-lyase deficiency (17-OHD) is an extremely rare autosomal recessive disorder caused by mutations in the CYP17A1 gene, which encodes the P450c17 enzyme. This enzyme plays a critical role in the production of both glucocorticoids and sex steroids, specifically by regulating the activities of 17 α-hydroxylase and 17,20-lyase, respectively [1,2]. The deficiency of 17 α-hydroxylase and 17,20-lyase has a significant impact on the patient’s health. The 17-hydroxylase deficiency results in decreased cortisol levels, which compensatively stimulates the secretion of adrenocorticotropic hormone (ACTH). It also increases the production of mineralocorticoid precursors, corticosterone, and 11-deoxycorticosterone (DOC), ultimately resulting in hypertension and hypokalaemia. In contrast, the 17,20-lyase deficiency leads to decreased sex steroid production, which compensatively stimulates Follicle-Stimulating Hormone (FSH) and luteinizing hormone (LH), resulting in primary amenorrhoea and a lack of secondary sex characteristics [3]. Overall, patients with 17-OHD typically present with hypertension, hypokalaemia, primary amenorrhoea, and a lack of secondary sex characteristics.
Moyamoya syndrome in a male pseudohermaphrodite patient with congenital adrenal hyperplasia – a rare association. Case report and review of literature
Published in British Journal of Neurosurgery, 2023
Remesh Chirayil Vasudevan, Reshma Vachali Madayi, Rohit Ravindranath Nambiar
CAH is a rare disorder that results from defective biosynthesis of steroid hormones in the adrenal cortex. CAH with 17 alpha-hydroxylase and 11 beta-hydroxylase deficiencies is associated with hypertension. Pathogenesis of CAH is due to various genetic mutations in the enzymes involved in steroid synthesis. As a result, cortisol production is reduced and the negative feedback control on adrenocorticotropic hormone (ACTH) is lost. Elevated ACTH level results in overproduction and accumulation of steroids precursors prior to the enzyme defect.6 There is hyperplasia of adrenal cortex. The clinical features depend on the level of enzyme defect. Patients with ambiguous genitalia, hypogonadism, hypertension and associated hypokalemia should be evaluated for possible CAH. In CAH due to 17 alpha-hydroxylase deficiency, both adrenal and gonadal steroid hormones production will be impaired. In male patients, lack of testosterone will impair Wolffian duct development. They will have gonads but no internal genitalia.7 High 11 deoxycorticosterone levels will cause sodium retention, potassium loss and hypertension due to potent mineralocorticoid action.
Osilodrostat for the treatment of Cushing’s disease
Published in Expert Opinion on Pharmacotherapy, 2021
The 22-week LINC2 study included two cohorts; the continuation cohort were 4 of the 12 LINC1 patients who re-enrolled and had a UFC >ULN after being taken off osilodrostat therapy for 15–19 months. The expansion cohort included 15 new patients who had a UFC > 1.5× ULN. After a washout and screening period for both groups, LINC1 patients continued treatment for 22 weeks on the dose that they tolerated in LINC1 with dosing adjustments made if needed. The expansion titration mirrored the LINC1 protocol. After two patients discontinued treatment, 15 patients (88.2%) had normal UFC levels by week 22 in the per protocol analysis, with 15 (78.9%) in the intention-to-treat analysis. Other hormonal changes were similar to those observed in LINC1. Morning serum and salivary cortisol decreased to normal levels while late-night salivary cortisol changes were variable, and levels remained above normal during treatment. ACTH levels increased fourfold at week 22. Overall mean baseline 11-deoxycortisol and 11-deoxycorticosterone levels increased during treatment. Overall mean aldosterone and renin levels decreased. Mean testosterone levels in 9 (75%) females increased to greater than ULN at week 22. Of note, two patients (10.5%) had not undergone prior surgery for management of CD [10].