Impact of transition on quality of life in patients with congenital adrenal hyperplasia diagnosed during childhood.
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ABSTRACT:
SUBMITTER: Bachelot A
PROVIDER: S-EPMC5551429 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:ContextQuality of life (QoL) has been variously reported as normal or impaired in adults with congenital adrenal hyperplasia (CAH). To explore the reasons for this discrepancy we investigated the relationship between QoL, glucocorticoid treatment and other health outcomes in CAH adults.MethodsCross-sectional analysis of 151 adults with 21-hydroxylase deficiency aged 18-69 years in whom QoL (assessed using the Short Form Health Survey), glucocorticoid regimen, anthropometric and metabolic measures were recorded. Relationships were examined between QoL, type of glucocorticoid (hydrocortisone, prednisolone and dexamethasone) and dose of glucocorticoid expressed as prednisolone dose equivalent (PreDEq). QoL was expressed as z-scores calculated from matched controls (14,430 subjects from UK population). Principal components analysis (PCA) was undertaken to identify clusters of associated clinical and biochemical features and the principal component (PC) scores used in regression analysis as predictor of QoL.ResultsQoL scores were associated with type of glucocorticoid treatment for vitality (P=0.002) and mental health (P=0.011), with higher z-scores indicating better QoL in patients on hydrocortisone monotherapy (P<0.05). QoL did not relate to PreDEq or mutation severity. PCA identified three PCs (PC1, disease control; PC2, adiposity and insulin resistance and PC3, blood pressure and mutations) that explained 61% of the variance in observed variables. Stepwise multiple regression analysis demonstrated that PC2, reflecting adiposity and insulin resistance (waist circumference, serum triglycerides, homeostasis model assessment of insulin resistance and HDL-cholesterol), related to QoL scores, specifically impaired physical functioning, bodily pain, general health, Physical Component Summary Score (P<0.001) and vitality (P=0.002).ConclusionsIncreased adiposity, insulin resistance and use of prednisolone or dexamethasone are associated with impaired QoL in adults with CAH. Intervention trials are required to establish whether choice of glucocorticoid treatment and/or weight loss can improve QoL in CAH adults.
| S-EPMC3650754 | biostudies-literature
Project description:Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroid biosynthesis, leading to hypocortisolism, hypoaldosteronism, and hyperandrogenism. Impaired quality of life (QoL) has been demonstrated in women with CAH, but data on men with CAH are scarce. We hypothesized that disease severity and poor treatment control are inversely associated with QoL. In this study, 109 men (16-68 years) with 21OHD were included. The WHOQOL-BREF questionnaire was used to measure self-reported QoL domain scores on a 0-100 scale, where higher scores reflect better QoL. QoL domain scores were compared to published data on healthy and chronically ill reference populations from France, Germany, the Netherlands, and the United Kingdom. Differences in QoL scores among groups of disease severity and treatment control were tested within the study population. Overall, the men with CAH in this study appeared to rate their QoL as good. Median domain scores were 78.6 (IQR: 67.9-85.7) for physical health, 79.2 (IQR: 66.7-87.5) for psychological health, 75.0 (IQR: 58.3-83.3) for social relationships, and 81.3 (IQR: 71.9-90.6) for environment. In general, these scores were similar to WHOQOL-BREF domain scores in healthy references and higher compared to chronically ill reference populations. The domain scores did not differ among genotype groups, but patients with undertreatment or increased 17-hydroxyprogestrone concentrations scored higher on several QoL domains (p<0.05). Patients treated with dexamethasone or prednisone scored higher on the physical health, psychological health, and social relationships domains, but not on the environmental domain. In conclusion, QoL domain scores appeared to be comparable to healthy reference populations and higher compared to patients with a chronic illness. QoL was not influenced by genotype, but undertreatment and use of dexamethasone or prednisone were associated with higher QoL.
| S-EPMC8018222 | biostudies-literature
Project description:Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the deficiency of one of four steroidogenic enzymes involved in cortisol biosynthesis or in the electron donor enzyme P450 oxidoreductase (POR) that serves as electron donor to steroidogenic cytochrome P450 (CYP) type II enzymes. The biochemical and clinical phenotype depends on the specific enzymatic defect and the impairment of specific enzyme activity. Defects of steroid 21-hydroxylase (CYP21A2) and 11beta-hydroxylase (CYP11B1) only affect adrenal steroidogenesis, whereas 17alpha-hydroxylase (CYP17A1) and 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency also impact on gonadal steroid biosynthesis. Inactivating POR gene mutations are the cause of CAH manifesting with apparent combined CYP17A1-CYP21A2 deficiency. P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant: skeletal malformations and severe genital ambiguity in both sexes.
| S-EPMC5576025 | biostudies-literature
Project description:We report on a patient with genetically confirmed adrenal hypoplasia congenita (AHC) whose presentation and laboratory abnormalities were consistent with the more common condition, congenital adrenal hyperplasia (CAH). The patient presented with failure to thrive and salt wasting. General appearance showed marked hyperpigmentation and normal male genitalia. He displayed mildly elevated 17-hydroxyprogesterone and markedly elevated 11-deoxycortisol levels at baseline and with ACTH stimulation testing. Results were consistent with 11 β -hydroxylase deficiency. He required glucocorticoids and high doses of mineralocorticoids. The marked elevation in 11-deoxycortisol directed our clinical reasoning away from a hypoplastic condition and towards a hyperplasic adrenal condition. Sequencing of the DAX1 gene (named for dosage-sensitive sex reversal (DSS) locus and the AHC locus on the X chromosome) revealed a missense mutation. A review of the literature revealed that elevated 11-deoxycortisol levels have been noted in kindreds with DAX1 mutations, but only when measured very early in life. A mouse model has recently been described that displays elevated 11-deoxycorticosterone levels and evidence for hyperplasia of the zona glomerulosa of the adrenal gland. We conclude that DAX1 testing may be considered in patients with laboratory evidence of 11 β -hydroxylase deficiency, especially in those with severe salt wasting.
| S-EPMC3583052 | biostudies-literature
Project description:Purpose of reviewAlthough the basic treatment of congenital adrenal hyperplasia (CAH) is well established, there are active clinical research projects to more closely mimic the normal diurnal rhythm of cortisol secretion and to reduce total glucocorticoid doses to minimize adverse metabolic effects.Recent findingsWe review clinical studies on CAH treatment published in the last 18 months or currently underway according to ClinicalTrials.gov listings. These can be grouped into several broad themes: alternative dosing forms of hydrocortisone with altered pharmacokinetics or easier dose titration; corticotropin-releasing hormone receptor antagonists that reduce corticotropin (ACTH) secretion and thereby reduce adrenal androgen secretion; androgen biosynthesis inhibitors; a first clinical trial of a gene therapy vector.SummaryAlternative dosing forms of hydrocortisone are, or will shortly be, marketed, but cost may be a barrier to utilization, at least in the US market. Trials of corticotropin releasing hormone receptor antagonists and androgen biosynthesis inhibitors are currently underway. The author believes that trials of gene therapy for CAH are premature.
| S-EPMC9302862 | biostudies-literature
Project description:OBJECTIVE:Adrenonodular hyperplasia and tumour formation are potential long-term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH. DESIGN:This was a cross-sectional study of 88 patients (mean age 29.2 ± 13 years, 47 females) with classic CAH seen in a tertiary referral centre. METHODS:CT imaging, performed at study entry or when reaching adulthood, was used to create 3-dimensional volumetric models. Clinical, genetic and hormonal evaluations were collected and correlated with adrenal morphology and tumour formation. RESULTS:Over one-third of the cohort was obese. 53% had elevated 17-OH-progesterone or androstenedione; and 60% had adrenal hyperplasia. Tumours included 11 myelolipomas, 8 benign adrenocortical adenomas, 1 pheochromocytoma and 50% of men had testicular adrenal rest tissue. CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than those with morphologically normal adrenals (P = 0.03). Variables that positively correlated with adrenal volume included hypogonadal/oligomenorrhoeic status, hypertension, androstenedione, aldosterone, and triglyceride levels, and in women, low HDL and insulin resistance. Elevated aldosterone was observed in a subset of patients with simple virilizing CAH. CONCLUSIONS:Adrenocortical hyperplasia is associated with a number of comorbidities, especially hypogonadism. Aldosterone production associated with adrenal enlargement may play a role in the development of metabolic risk factors. Further studies are needed to assess the long-term impact of the excess adrenal steroid milieu associated with adrenal enlargement to develop improved management strategies for CAH.
| S-EPMC6635023 | biostudies-literature
Project description:ContextStandard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes.ObjectiveWe investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control.MethodsA 6-month, randomized, phase 3 study was conducted of MR-HC vs standard glucocorticoid, followed by a single-arm MR-HC extension study. Primary outcomes were change in 24-hour SD score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase 3, and efficacy, safety and tolerability of MR-HC for the extension study.ResultsThe phase 3 study recruited 122 adult CAH patients. Although the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P = .007) and 12 (P = .019) weeks, and between 07:00h to 15:00h (P = .044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (< 1200 ng/dL) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P = .002), and 80% for MR-HC at 18 months' extension. The median daily hydrocortisone dose was 25 mg at baseline, at 6 months 31 mg for standard therapy, and 30 mg for MR-HC, and after 18 months 20 mg MR-HC. Three adrenal crises occurred in phase 3, none on MR-HC and 4 in the extension study. MR-HC resulted in patient-reported benefit including menses restoration in 8 patients (1 on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy).ConclusionMR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.
| S-EPMC8063257 | biostudies-literature
Project description:Congenital adrenal hyperplasia has traditionally been treated with daily oral doses of glucocorticoids and mineralocorticoid supplements. Such therapy does not precisely replicate the adrenal cortex's circadian pattern. As a consequence, patients are intermittently overtreated or undertreated leading to growth suppression in children, excess weight gain and altered metabolism. Several new treatments are on the horizon. This article will summarize some new potential therapies as adjuncts to, or replacement for, standard therapy.
| S-EPMC6446492 | biostudies-literature
Project description:Adrenal insufficiency (AI) is a severe endocrine disorder characterized by insufficient glucocorticoid (GC) and/or mineralocorticoid (MC) secretion by the adrenal glands, due to impaired adrenal function (primary adrenal insufficiency, PAI) or to insufficient adrenal stimulation by pituitary ACTH (secondary adrenal insufficiency, SAI) or tertiary adrenal insufficiency due to hypothalamic dysfunction. In this review, we describe rare genetic causes of PAI with isolated GC or combined GC and MC deficiencies and we also describe rare syndromes of isolated MC deficiency. In children, the most frequent cause of PAI is congenital adrenal hyperplasia (CAH), a group of adrenal disorders related to steroidogenic enzyme deficiencies, which will not be included in this review. Less frequently, several rare diseases can cause PAI, either affecting exclusively the adrenal glands or with systemic involvement. The diagnosis of these diseases is often challenging, due to the heterogeneity of their clinical presentation and to their rarity. Therefore, the current review aims to provide an overview on these rare genetic forms of paediatric PAI, offering a review of genetic and clinical features and a summary of diagnostic and therapeutic approaches, promoting awareness among practitioners, and favoring early diagnosis and optimal clinical management in suspect cases.
| S-EPMC10023752 | biostudies-literature
Project description:Congenital adrenal hyperplasias (CAH) are a group of autosomal recessive defects in cortisol biosynthesis. Substantial progress has been made since the description of the first report, 150 years ago. This article reviews some of the recent advances in the genetics, diagnosis and treatment of CAH. In addition, we underline the aspects where further progress is required, including, among others, better diagnostic modalities for the mild phenotype and for some of the rare forms of disease, elucidation of epigenetic factors that lead to different phenotypes in patients with identical genotype and expending on treatment options for controlling the adrenal androgen excess.
| S-EPMC4568140 | biostudies-literature