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Endocrine Oct 2018Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about...
PURPOSE
Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about psychological challenges in males remains sparse. The aim of this systematic review was therefore to assess these in males with CAH.
METHODS
We systematically searched the OVID Medline, PsycINFO, CINAHL, and Web of Science databases, for articles published up to April 20, 2018, investigating psychological adjustment in males with CAH.
RESULTS
Eleven studies were included in the review. Three main health domains were identified: psychological and psychiatric health, quality of life (QoL), and self-perceptions of reproductive health. Some studies covered more than one health domain. Seven studies explored psychological adjustment and/or the presence of psychiatric symptoms or disorders. Results indicated that males with CAH had more problems related to internalizing behaviors (negative behaviors directed toward the self) and more negative emotionality compared to reference groups. Six studies examined QoL, five of them reporting reduced QoL compared to reference groups. Three studies explored the impact of fertility and sexual health issues on psychological health with varying results from impaired to normal sexual well-being.
CONCLUSIONS
CAH seems to have an impact on males' psychological health. However, the number of identified studies was limited, included few participants, and revealed divergent findings, demonstrating the need for larger studies and highlighting a number of methodological challenges that should be addressed by future research.
Topics: Adrenal Hyperplasia, Congenital; Emotional Adjustment; Humans; Male; Mental Health; Quality of Life; Self Concept
PubMed: 30128958
DOI: 10.1007/s12020-018-1723-0 -
The Journal of Clinical Endocrinology... May 2018Management of congenital adrenal hyperplasia (CAH) involves suppression of the hypothalamic-pituitary-adrenal axis using supraphysiological doses of exogenous... (Meta-Analysis)
Meta-Analysis
CONTEXT
Management of congenital adrenal hyperplasia (CAH) involves suppression of the hypothalamic-pituitary-adrenal axis using supraphysiological doses of exogenous glucocorticoids. This can pose a challenge, with Cushing syndrome a frequent complication of adequate suppression. Bilateral adrenalectomy, with subsequent replacement of glucocorticoids and mineralocorticoids at physiological doses, has been proposed as an alternative therapeutic strategy.
OBJECTIVE
To review the outcomes after bilateral adrenalectomy for CAH.
DATA SOURCES
A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 January 2018.
STUDY SELECTION
Case reports or case series were included if they reported individual patient data from patients with CAH who had undergone bilateral adrenalectomy.
DATA EXTRACTION
Information regarding the following was extracted: first author, country, sex, age at adrenalectomy, year of adrenalectomy, diagnosis, molecular abnormality, pre- and postoperative biochemistry, pre- and postoperative medications, pre- and postoperative body mass index, indication for adrenalectomy, surgical technique, gross and microscopic adrenal characteristics, follow-up duration, and short- and long-term postoperative outcomes.
DATA SYNTHESIS
We identified 48 cases of bilateral adrenalectomy for CAH, with patients aged from 4 months to 56 years at surgery. The most common indication for surgery was the inability to control hyperandrogenism/virilization and/or Cushing syndrome (n = 30; 62%). Most patients (n = 34; 71%) reported symptomatic improvement postoperatively, with some cases of short-term (n = 5; 10%) and long-term (n = 13; 27%) adverse outcomes.
CONCLUSIONS
Bilateral adrenalectomy for CAH appears to be a reasonable therapeutic option for carefully selected patients who have had unsatisfactory outcomes with conventional medical management.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adrenalectomy; Adult; Child; Child, Preschool; Cushing Syndrome; Female; Fertility; Glucocorticoids; Hormone Replacement Therapy; Humans; Hyperandrogenism; Infant; MEDLINE; Male; Middle Aged; Mineralocorticoids; Postoperative Complications; Pregnancy; Treatment Outcome; Virilism
PubMed: 29554355
DOI: 10.1210/jc.2018-00217 -
Hormone and Metabolic Research =... Dec 2017The aim of this review was to determine the impact of primary aldosteronism on health-related quality of life (HRQoL) and mental health. We performed a systematic... (Review)
Review
The aim of this review was to determine the impact of primary aldosteronism on health-related quality of life (HRQoL) and mental health. We performed a systematic literature search up to July 2017 in six electronic databases. First, we screened the articles derived from this search based on title and abstract. Second, the selected studies were systematically reviewed and checked for our predefined inclusion criteria. The search yielded 753 articles, of which 15 studies met our inclusion criteria. Untreated patients with primary aldosteronism showed an impaired physical and mental HRQoL as compared to the general population. Multiple domains of HRQoL were affected. This applied to patients with both an aldosterone-producing adenoma and bilateral adrenal hyperplasia. Adrenalectomy improves HRQoL. Conflicting results have been reported on the extent of this improvement, the improvement after initiation of medical treatment, and whether there is a difference in HRQoL after both treatments. Similarly, psychopathological symptoms of anxiety, demoralization, stress, depression and nervousness were more frequently reported in untreated patients with primary aldosteronism than in the general population and patients with hypertension. Also an impaired sleep quality has been reported. Improvement of these symptoms was observed after treatment with both adrenalectomy and mineralocorticoid receptor antagonists. This review shows that HRQoL is impaired and psychopathology is more frequently reported in patients with primary aldosteronism. This seems to be at least partly reversible after treatment but the extent of improvement remains unknown. To assess HRQoL in these patients more precisely a primary aldosteronism-specific HRQoL questionnaire is required.
Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Glands; Aldosterone; Health Status; Humans; Hyperaldosteronism; Hyperplasia; Mental Health; Quality of Life
PubMed: 29202493
DOI: 10.1055/s-0043-121706 -
The Lancet. Diabetes & Endocrinology Jan 2018There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is conflicting evidence, relying on heterogeneous studies, as to whether aldosterone excess is responsible for an increased risk of cardiovascular and cerebrovascular complications in patients with primary aldosteronism. We aimed to assess the association between primary aldosteronism and adverse cardiac and cerebrovascular events, target organ damage, diabetes, and metabolic syndrome, compared with the association of essential hypertension and these cardiovascular and end organ events, by integrating results of previous studies.
METHODS
We did a meta-analysis of prospective and retrospective observational studies that compared patients with primary aldosteronism and essential hypertension, to analyse the association between primary aldosteronism and stroke, coronary artery disease (as co-primary endpoints), atrial fibrillation and heart failure, target organ damage, metabolic syndrome, and diabetes (as secondary endpoints). We searched MEDLINE and Cochrane Library for articles published up to Feb 28, 2017, with no start date restriction. Eligible studies compared patients with primary aldosteronism with patients with essential hypertension (as a control group) and reported on the clinical events or endpoints of interest. We also compared primary aldosteronism subtypes, aldosterone-producing adenoma, and bilateral adrenal hyperplasia.
FINDINGS
We identified 31 studies including 3838 patients with primary aldosteronism and 9284 patients with essential hypertension. After a median of 8·8 years (IQR 6·2-10·7) from the diagnosis of hypertension, compared with patients with essential hypertension, patients with primary aldosteronism had an increased risk of stroke (odds ratio [OR] 2·58, 95% CI 1·93-3·45), coronary artery disease (1·77, 1·10-2·83), atrial fibrillation (3·52, 2·06-5·99), and heart failure (2·05, 1·11-3·78). These results were consistent for patients with aldosterone-producing adenoma and bilateral adrenal hyperplasia, with no difference between these subgroups. Similarly, primary aldosteronism increased the risk of diabetes (OR 1·33, 95% CI 1·01-1·74), metabolic syndrome (1·53, 1·22-1·91), and left ventricular hypertrophy (2·29, 1·65-3·17).
INTERPRETATION
Diagnosing primary aldosteronism in the early stages of disease, with early initiation of specific treatment, is important because affected patients display an increased cardiovascular risk compared with patients with essential hypertension.
FUNDING
None.
Topics: Cardiovascular Diseases; Essential Hypertension; Humans; Hyperaldosteronism; Prognosis; Prospective Studies; Retrospective Studies
PubMed: 29129575
DOI: 10.1016/S2213-8587(17)30319-4 -
Gynecologic Oncology Oct 2017Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients.
METHODS
The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users.
RESULTS
Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I=40%).
CONCLUSION
Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions.
Topics: Biomarkers, Tumor; Chemotherapy, Adjuvant; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Hypoglycemic Agents; Metformin; Prospective Studies
PubMed: 28760367
DOI: 10.1016/j.ygyno.2017.07.120 -
Human Reproduction Update Sep 2017Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess.
OBJECTIVE AND RATIONALE
We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of NCAH. A meta-analysis of epidemiological data was also performed.
SEARCH METHODS
Peer-reviewed studies evaluating NCAH published up to October 2016 were reviewed. Multiple databases were searched including MEDLINE, EMBASE, Cochrane, ERIC, EBSCO, dissertation abstracts, and current contents.
OUTCOMES
The worldwide prevalence of NCAH amongst women presenting with signs and symptoms of androgen excess is 4.2% (95% confidence interval: 3.2-5.4%). The clinical consequences of NCAH expand from infancy, i.e. accelerated growth, to adolescence and adulthood, i.e. premature pubarche, cutaneous symptoms and oligo-ovulation in a polycystic ovary syndrome (PCOS)-like clinical picture. The diagnosis of NCAH relies on serum 17-hydroxyprogesterone (17-OHP) concentrations. A basal 17-OHP concentration ≥2 ng/ml (6 nmol/l) should be used for screening if more appropriate in-house cut-off values are not available. Definitive diagnosis requires a 17-OHP concentration ≥10 ng/ml (30 nmol/l), either basally or after cosyntropin-stimulation. Molecular genetic analysis of the CYP21A2 gene, which is responsible for 21-hydroxylase activity, may be used for confirmation purposes and should be offered to all patients with NCAH along with genetic counseling because these patients frequently carry alleles that may result in classic CAH, the more severe form of the disease, in their progeny. Treatment must be individualized. Glucocorticoid replacement therapy may benefit pediatric patients with accelerated growth or advanced bone age or adult women seeking fertility, whereas adequate control of menstrual irregularity, hirsutism and other cutaneous symptoms is best served by the use of oral contraceptive pills and/or anti-androgens. Some women may need ovulation induction or assisted reproductive technology to achieve pregnancy. Patients with NCAH have a higher risk of miscarriage and may benefit from glucocorticoid treatment during pregnancy.
WIDER IMPLICATIONS
Evidence-based diagnostic and treatment strategies are essential for the proper management of women with NCAH, especially considering that these patients may need different therapeutic strategies at different stages during their follow-up and that appropriate genetic counseling may prevent the occurrence of CAH in their children.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androgen Antagonists; Female; Hirsutism; Humans; Infertility, Female; Menstruation Disturbances
PubMed: 28582566
DOI: 10.1093/humupd/dmx014 -
Journal of Pediatric Urology Dec 2016Disorders of sex development (DSD) are a heterogeneous group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex. In addition to impacts... (Review)
Review
INTRODUCTION
Disorders of sex development (DSD) are a heterogeneous group of complex conditions that can affect chromosomal, gonadal, and/or phenotypical sex. In addition to impacts on internal and external genitalia,these conditions can affect fertility potentialto various degrees. In this review we discuss fertility issues including gonadalpreservation and reproductive outcomes based on specific DSD conditions.
METHODS AND MATERIALS
A systematic literature review was performed on Embase, PubMed, and Google Scholar for disordersof sex development and infertility. Original research articles and relevant reviews were examinedand a synopsis of these data was generated for a comprehensive review of fertility potential in disorders of sex development.
RESULTS
While patients with some DSDs may have functioning gonads with viable germ cells but an inability to achieve natural fertility secondary to incongruent internal or external genitalia, other patients may have phenotypically normal genitalia but infertility due to abnormal gonad development. Fertility rates in females with congenital adrenal hyperplasia (CAH) depend on phenotype and are inversely proportionalto the severity of the disease. Men with classic CAH have reduced fertility and due to the presence of testicular adrenal rest tumors and to suppression of the hypothalamic-pituitary-gonadal axis by high systemic levels of androgens. Infertility is seen in complete androgen insensitivity and subfertility is common in partial cases. Fertility is rare in pure or mixed gonadal dysgenesis, ovotesticular disorder, Klinefelter syndrome, and XX males.
CONCLUSION
Fertility potential appears to be the highest in patientswith XX or XY CAH, especially non-classic forms. Advancements in assisted reproduction techniques has in rare cases produced offspring in some diagnoses thought to be universally infertile. Discussion of fertility issues with the patient and family is essential to the optimal treatment of each patient and an important part of the multi-disciplinary approach to evaluating and counseling these families.
Topics: Disorders of Sex Development; Female; Humans; Infertility; Male
PubMed: 27856173
DOI: 10.1016/j.jpurol.2016.09.015 -
Endocrine Practice : Official Journal... Jun 2016Adrenal incidentalomas (AIs) may be due to congenital adrenal hyperplasia (CAH) due to homozygous CYP21A2 mutations, or perhaps from heterozygous carrier status. It is...
OBJECTIVE
Adrenal incidentalomas (AIs) may be due to congenital adrenal hyperplasia (CAH) due to homozygous CYP21A2 mutations, or perhaps from heterozygous carrier status. It is unclear if genetic or biochemical testing of CYP21A2 status in AI is justified, despite its potential for avoiding adrenal crises in those referred for adrenalectomy.
METHODS
We systematically searched PubMed/MEDLINE for articles published up to October 19, 2015 containing all terms associated with adrenal tumors and CAH. Meta-analyses were used to estimate the CAH or carrier prevalence in AI and assess clinical factors that may guide testing.
RESULTS
Thirty-six publications were included. Of AI patients biochemically screened for CAH, 58/990 (5.9%) were diagnosed with CAH. Genetic screening of all AIs revealed only 2/252 (0.8%) with clear CAH. The carrier prevalence was 10.2% (36/352). The rate of 0.8% (8/1,000) genetically confirmed CAH is higher than the 1/15,000 affected by classic CAH or 1/1,000 by nonclassic CAH in the Caucasian population. The rate of heterozygous CYP21A2 mutation frequency is similar to those in reported in population studies. Levels of both basal and stimulated 17-hydroxyprogesterone positively correlated with AI diameter. Although bilateral incidentalomata were frequent in CAH, their presence did not predict CYP21A2 status.
CONCLUSION
The presence of an AI does not increase the probability of detection of CAH or CYP21A2 carrier status to the extent routine genetic testing is justified. Screening with 17-hydroxyprogesterone levels appears to lack specificity in the setting of an AI. CYP21A2 mutation analysis is probably the only reliable method for CAH diagnosis in AIs.
ABBREVIATIONS
ACC = adrenocortical carcinoma ACTH = adrenocorticotropic hormone AI = adrenal incidentaloma CAH = congenital adrenal hyperplasia NCAH = nonclassic congenital adrenal hyperplasia 17OHP = 17-hydroxyprogesterone SV = simple virilizing.
PubMed: 26919651
DOI: 10.4158/EP151085.RA -
The Journal of Clinical Endocrinology... Oct 2013The outcome of bilateral adrenalectomy (BADx) in patients with Cushing's syndrome (CS) is not well characterized. (Review)
Review
BACKGROUND
The outcome of bilateral adrenalectomy (BADx) in patients with Cushing's syndrome (CS) is not well characterized.
METHODS
A literature search was performed with the search terms "bilateral adrenalectomy" or "total adrenalectomy" and "Cushing's" or "Cushing." Immediate and long-term outcomes after BADx in CS were analyzed using descriptive statistics (median [range]).
RESULTS
From 549 screened publications, 37 studies met inclusion criteria (1320 patients, 82% having Cushing's disease [CD], 13% having ectopic CS, and 5% having primary adrenal hyperplasia). Surgical morbidity and mortality of BADx (23 studies, 739 patients) were 18% (6-31) and 3% (0-15), respectively. In patients with CD, surgical mortality was below 1%. Although residual cortisol secretion due to accessory adrenal tissue or adrenal remnants was found in 3-34% (5 studies, 236 patients), less than 2% had a relapse of CS. Symptoms of hypercortisolism (eg, hypertension, obesity, or depression) improved in the majority of the patients after BADx (7 studies, 195 patients). The number of adrenal crises per 100 patient-years was 9.3 (6 studies, 203 patients). Nelson's syndrome occurred in 21% (0-47) of the patients (24 studies, 768 patients). Mortality (23 studies, 690 patients) was 17% (0-88) at a follow-up of 41 months (14-294). Remarkably, 46% of the patients died in the first year after surgery. The median ages at death were 62 years (CD) and 53 years (ectopic CS).
CONCLUSION
BADx is relatively safe and provides adequate success. Excess mortality within the first year after surgery suggests that intensive clinical care for patients after BADx is warranted.
Topics: Adrenalectomy; Cushing Syndrome; Humans; Treatment Outcome
PubMed: 23956347
DOI: 10.1210/jc.2013-1470 -
Advances in Pediatrics 2012Systematic literature review and meta-analysis guided by expert opinion has refined current approaches to the treatment of CAH. The advent of widespread newborn... (Review)
Review
Systematic literature review and meta-analysis guided by expert opinion has refined current approaches to the treatment of CAH. The advent of widespread newborn screening has improved outcomes, with lower morbidities and mortality. Future advances may be recognized in the form of more efficient diagnostic tools, physiologic drug delivery, improved surgical methods, and assisted reproductive technologies.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Child; Humans; Infant; Infant, Newborn; Neonatal Screening; Treatment Outcome
PubMed: 22789582
DOI: 10.1016/j.yapd.2012.04.009