Adult Congenital Adrenal Hyperplasia Research Articles

SAT303 High Frequency Of Stress Dose Adjustment And Adrenal Crisis In Adult Patients With Congenital Adrenal Hyperplasia

Abstract Disclosure: L. Tschaidse: None. S. Wimmer: None. M. Auer: None. C. Lottspeich: None. H.F. Nowotny: None. I. Dubinski: None. H. Schmidt: None. M. Quinkler: None. N. Reisch: None. Background: Due to impaired cortisol synthesis, patients with congenital adrenal hyperplasia (CAH) require lifelong glucocorticoid replacement therapy, including stress dose adjustment, to prevent life-threatening adrenal crises (AC). Previous studies indicate a high incidence of AC in patients with CAH but also inadequate stress dose adjustment. The aim of this study was to prospectively investigate the incidence of AC, the frequency and details of stress dose adjustment as well as knowledge of the disease in adult patients with CAH. Methods: A total of 162 adult CAH patients with CAH were enrolled in this prospective, multi-centre study. Data was collected using a patient diary with the following aspects being assessed: frequency, cause, duration and dosage of dose adjustments and the occurrence of AC. In case of AC, additional medical records were reviewed and patient interviews were conducted. Additionally, it was assessed if current sick day rules of the German Society of Endocrinology (DGE) were followed adequately. Knowledge of disease was assessed using the CAH Knowledge Assessment Questionnaire (CAHKAQ) in the German version. Results: We found an AC incidence of 8.4 per 100 patient years in 145 patients. 29 patients were subsequently excluded from further analysis due to habitual dose adjustments. Of 116 patients, 77.6% reported at least one dose adjustment with a total of195.4 dose adjustments per 100 patient years. There were no significant differences of median frequency in dose adjustments between male and female patients (2.0 (5.0) vs 3.0 (6.0), p = .829) or salt-wasting and simple-virilizing patients (2.0 (5.0) vs 3.5 (8.3), p =.111). The causes for dose adjustment were mental distress (23.8%), strenuous physical activity (14.6%), flu-like symptoms (12.7%), gastrointestinal symptoms (10.1%), medical procedures (9.1%), fever (8.6%), discomfort (6.8%), pain or trauma (6.3%), unspecific physical symptoms (5.5%) and other forms of infection (2.6%). According to the DGE recommendations, in 24.1% of cases, dose adjustment was unnecessary and in 33.9% of cases, the dosage of adjustment was incorrect. A total of 34.8% of dose adjustments were performed according to sick day rule recommendations of the DGE. There was a significant positive correlation of the frequency of dose adjustments and the incidence of AC (r =.24, p = .011) and CAHKAQ Score (r =.23, p = .014). Conclusion: Adult patients with CAH show a high incidence of AC and stress dose adjustments. Compared to the retrospective AC incidence in the same cohort, we found an even higher AC incidence in this prospective study. The majority of stress dose adjustments were not in accordance to the recommendations of the DGE. These findings suggest the need for structured and repeated education of patients and their caregivers to avoid unnecessary dose adjustments while preventing AC, with particular focus on the timing of transition. Presentation: Saturday, June 17, 2023

ODP028 Association Between Serum Steroid Profile and Metabolic Risks in Adults with Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Abstract Objective In adult patients with congenital adrenal hyperplasia (CAH), long-term health outcomes, including metabolic and cardiovascular health, are a priority for the management of CAH. The enzyme 21-hydroxylase deficiency, which accounts for a majority of CAH, leads to a large perturbation in serum steroid profile under glucocorticoid replacement therapy. Serum levels of several adrenal steroids, including 17-hydroxyprogesterone and androstenedione, are associated with disease severity and sexual dysfunction of CAH patients. However, the association between the serum steroid profiles with metabolic risk in CAH patients is not elucidated yet. We aimed to investigate the serum steroid profile of adult CAH patients using liquid chromatography-mass spectrometry (LC-MS) and their association with metabolic risk. Methods Adult patients with classic CAH due to 21-hydroxylase deficiency were included in this study (36 females and 27 males). A multi-steroid panel composed of 25 steroids and their metabolites was applied to morning serum samples of study subjects using LC-MS. An unsupervised clustering algorithm was applied to the serum steroid panel to discover any unique pattern which divides CAH subjects into clusters. The association between serum steroid profiles and clinical characteristics, including age, sex, body mass index (BMI), subtypes (simple virilizing and salt wasting), glucocorticoid dose, and the presence of hypertension, diabetes mellitus (DM), and metabolic syndrome (MetS) was analyzed. The discriminatory power of each steroid or a combination of steroids was estimated using the area under the curve of receiver operating characteristics (AUROC) for metabolic diseases. Results Fifteen steroids including pregnenolone sulfate, 17α-hydroxyprogesterone, cortisol, cortisone, 21-deoxycortisol, 20α-dihydrocortisol, 20α-dihydrocortisone, α-cortolone, β-cortolone, tetrahydrocortisone, dehydroepiandrosterone sulfate, testosterone, androstenedione, 11β-hydroxytestosterone, and 11β-hydroxyandrostenedione were successfully quantified in all subjects. The median age of subjects was 28 years (interquartile range: 25-35). The prevalence of DM, hypertension, and MetS was 3.2% (2/63), 15.8% (10/63), and 28.6% (18/63), respectively. The subjects were divided into two clusters based on the pattern of serum steroid profile using unsupervised hierarchical clustering. The prevalence of MetS was significantly different between the two clusters (cluster 1, 37.8% [17/45] vs. cluster 2, 5.6% [1/18], P = 0. 011). The prevalence of HTN was numerically higher in cluster 1 than cluster 2 (20. 0% [9/45] vs. 5.6% [1/18], P = 0.257). Other clinical characteristics, including age, sex, BMI, subtypes, and glucocorticoid dose, were not different between the two clusters. Among fifteen steroids, the level of tetrahydrocortisone showed the highest discriminatory power for MetS (AUROC 0.795, 95% confidence interval: 0.675-0.914). The multivariate logistic regression model of all 15 steroids showed AUROC of 0.832 (95% CI: 0.732-0.933) for MetS. Conclusion The serum steroid profiles of CAH patients were significantly associated with the presence of MetS. This suggests that serum steroid signatures can guide the optimal management of adult CAH patients to minimize the risk of MetS. Presentation: No date and time listed

The burden of illness associated with adolescent and adult congenital adrenal hyperplasia: results of a structured literature review

The burden of illness associated with adolescent and adult congenital adrenal hyperplasia: results of a structured literature review

The Burden of Illness of Congenital Adrenal Hyperplasia (CAH) in Adults: Results: of a Structured Literature Review

Objectives: Congenital adrenal hyperplasia (CAH) is a group of rare autosomal-recessive disorders that arise from genetic deficiencies in key enzymes involved in cortisol synthesis. The burden of CAH has never been comprehensively reviewed; this literature review was conducted to summarise the existing burden of illness evidence available for these patients. Methods: A structured, comprehensive literature review was conducted to identify articles describing the burden and treatment landscape of CAH. Literature databases (MEDLINE, Embase, the Cochrane Library and EconLit), websites and conference proceedings were searched. Searches were performed in 2016 and updated in June 2020; eligible articles presented evidence for patients with CAH or paediatric patients with adrenal insufficiency (AI), for ≥1 topic of interest (epidemiology; natural history; clinical characteristics; humanistic, caregiver and economic burden; treatment options; or clinical guidelines). The evidence presented here focusses on the humanistic and economic burden of CAH in adults. Results: A total of 3,711 citations were identified and 336 were included; 84 references reported humanistic or economic burden data relevant to adult patients with CAH. 51 publications were identified reporting patient symptoms, comorbidities and cardiometabolic risk factors; 38 reporting on the impact of CAH on health-related quality of life (HRQL); 5 reporting patient views and 2 reporting economic burden associated with CAH. Compared to the general population, adult patients with CAH were found to be significantly shorter, have poorer bone health, increased levels of obesity, impaired male and female fertility, higher blood pressure and cholesterol levels, have more psychiatric and neurological disorders and have poorer cognitive performance. Adult patients with CAH were also found to have greater insulin resistance and higher levels of type 2 diabetes (T2D). CAH patients are also at risk of adrenal crisis, which contributes to excess mortality. The reported HRQL in adults with CAH varies, with increased impairment observed in more severe forms of CAH, and challenges due to living with a chronic disease impacting HRQL varying according to sex. “Sick day rules” where patients need to double or triple treatment doses, have a significant impact on patients’ HRQL and also have an impact on patients’ resource use, with a UK study reporting that CAH patients will implement these rules 171 times over their lifetime, and be hospitalised for adrenal crises on 11 occasions. CAH was also found to have a significant economic impact, with significantly higher annual healthcare costs compared to matched controls (p=0.007 for patients aged 18–40 years; p<0.001 for patients aged ≥40 years). Conclusions: This comprehensive review highlights that CAH in adults is associated with a significant humanistic and economic burden.

Dose Escalating and Bioavailability Phase 1 Studies Assessing Safety and Tolerability and Pharmacokinetics of Tildacerfont, a Small-Molecule CRF1 Receptor Antagonist

Background: Tildacerfont (SPR001; LY2371712), a second generation, potent, selective, nonsteroidal, oral small-molecule antagonist of corticotropin-releasing factor type-1 (CRF1) receptors in the pituitary gland, is in late stage development as a potential treatment for adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). We report the results of 3 randomized Phase 1 studies of safety, tolerability, and pharmacokinetics (PK) of tildacerfont in healthy adults and compare the relative bioavailability of 2 tildacerfont formulations. Methods: Two Phase 1 studies were double-blind, placebo-controlled and evaluated escalating doses (2–800 mg QD) as single doses (SAD; n=18) and 50-200mg as multiple doses (MAD; n=47). The studies also included pilot food effect and drug-drug interaction sub studies, respectively. A randomized, balanced, open-label, crossover study (n=42) examined the relative bioavailability (BA) of single oral doses of 2 tildacerfont formulations, 200 mg powder-in-capsule (PIC) compared to 200 mg low-drug load tablet. Results: In the SAD and MAD studies, the most common, non-procedural adverse events were headache and cough. In the BA study, the most common, non-procedural adverse events were constipation and headache. There were no study drug-related serious adverse events (SAEs) in any study. In the SAD and MAD (PIC formulation), tildacerfont concentrations declined in a multi-exponential manner with Cmax occurring moderately late, ~5 hours post dose, and a high degree of variability was observed in AUC and Cmax (CV range: 54–122%). A food effect was observed in the SAD. Fourteen days of dosing achieved near steady state exposure with an AUC accumulation ratio of 2.51 to 3.65 in the MAD study. Midazolam, a sensitive probe substrate for CYP3A4 exhibited ~2-fold increase in AUC and a 1.8 increase in Cmax when co-administered with tildacerfont suggesting moderate CYP3A4 inhibition. The tablet formulation reduced the variability (AUC and Cmax CV range: 69–72%) compared to the PIC formulation resulting in a more predictable pharmacokinetic profile. The half-life of the tablet was ~60 hrs. Bioequivalence in AUC was established with the tablet and PIC formulations (fed state) with Cmax ~20% higher for tablet than PIC due to a reduction in and more consistent Tmax, median [range], from 6 [4.5, 24] hours to 3 [2, 6] hours. Conclusions: These results suggest that tildacerfont is safe and generally well-tolerated in healthy adults and suitable for further study in patients with CAH. The tablet formulation provided a more consistent pharmacokinetic profile with reduced variability in all parameters and is being evaluated in late stage studies of tildacerfont in adult CAH.

Giant bilateral adrenal lipoma in a patient with congenital adrenal hyperplasia.

SummaryApart from adrenal myelolipomas, adrenal lipomatous tumors are rare and only seldom described in the literature. We present the case of a 50-year-old man, with a classical form of congenital adrenal hyperplasia (CAH), which was well treated with prednisolone and fludrocortisone. The patient presented with pollakisuria and shortness of breath while bending over. On MRI, fat-equivalent masses were found in the abdomen (14 × 19 × 11 cm on the right side and 10 × 11 × 6 cm on the left side). The right adrenal mass was resected during open laparotomy and the pathohistological examination revealed the diagnosis of an adrenal lipoma. Symptoms were subdued totally postoperatively. This is the first report of a bilateral adrenal lipoma in a patient with CAH that we are aware of.Learning pointsMacronodular hyperplasia is common in patients with congenital adrenal hyperplasia (CAH).Solitary adrenal tumors appear in approximately 10% of adult CAH patients and are often benign myelolipomas.The Endocrine Society Clinical Practice Guideline does not recommend routine adrenal imaging in adult CAH patients.Adrenal imaging should be performed in CAH patients with clinical signs for an adrenal or abdominal mass.Adrenal lipoma is rare and histopathological examinations should rule out a differentiated liposarcoma.

Singularities of the undertreatment of congenital adrenal hyperplasia in adults

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia.

Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd-LIFE study.

In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoids used as well as sex hormone secretion during puberty have important actions on bone mineral density (BMD) in adulthood. To evaluate BMD in adult CAH patients depending on current glucocorticoid therapy and on androgen levels in adulthood and at age 16years. We included 244 CAH patients from the dsd-LIFE cohort (women n=147, men n=97; salt-wasting n=148, simple-virilizing n=71, nonclassical n=25) in which BMD and bloods were available. Clinical and hormonal data at age 16years were retrieved from patients' files. Simple-virilizing women showed lower BMD compared to salt-wasting women at trochanter (0.65±0.12 vs 0.75±0.15g/cm2 ; P<.050), whole femur T-score (-0.87±1.08 vs -0.16±1.24; P<.05) and lumbar T-score (-0.81±1.34 vs 0.09±1.3; P<.050). Fracture prevalence did not differ significantly between the CAH groups. Prednisolone vs. hydrocortisone only therapy caused worse trochanter Z-score (-1.38±1.46 vs -0.47±1.16; P<.050). In women lumbar spine, BMD correlated negatively with hydrocortisone-equivalent dose per body surface (r2 =0.695, P<.001). Furthermore, BMI at age 16years correlated positively with lumbar spine T-score (r2 =0.439, P=.003) and BMD (r2 =0.420, P=.002) in women. The androstenedione/testosterone ratio at age 16years correlated positively with lumbar spine Z-score in women (r2 =0.284, P=.024) and trochanter Z-score in men (r2 =0.600, P=.025). Higher glucocorticoid doses seemed to cause lower BMD especially in women. Prednisolone appeared to have more detrimental effects on BMD than hydrocortisone. Higher glucocorticoid doses (lower androstenedione/testosterone ratio) during adolescence may cause lower BMD in adulthood.

Effect of androgen excess and glucocorticoid exposure on metabolic risk profiles in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Data on cardiovascular morbidity in adults with congenital adrenal hyperplasia (CAH) is sparse. We therefore aimed to determine the role of androgen control and glucocorticoid therapy on metabolic health. For that purpose, we included 90 patients (N = 39 men, N = 51 women) with classic CAH due to 21-hydroxylase deficiency (N = 61 salt wasting, N = 29 simple virilizing) and an equal number of controls matched for age, sex, BMI and smoking-habits. We could show that there was no difference in intima-media-thickness between patients and controls and only one patient fulfilled all criteria of the metabolic syndrome. CAH men presented with an increased relative body fat mass in comparison to controls (25.6 % vs. 22.1 %; p = 0.011) while this was not true for CAH women. Body fat was lower in those taking hydrocortisone instead of synthetic glucocorticoids (B = -3.27; p = 0.048). While arterial hypertension was rare, 54 % of patients had an impaired systolic drop at night or were classified as non-dippers (17 %). Impaired dipping was not associated with evening glucocorticoid and fludrocortisone intake but mediated by sodium levels. Insulin resistance was more common in CAH women (B = 1.689; p = 0.036) and in those with poor androgen control (B = 0.823; p = 0.046). In summary, we could show that good cardiovascular health outcome in adult CAH patients can be achieved. Hydrocortisone is superior in terms of body composition. It is yet unclear how non-dipping will translate into cardiovascular morbidity in the long-term.

Impact of Long-Term Dexamethasone Therapy on the Metabolic Profile of Patients With 21-Hydroxylase Deficiency.

ContextNo consensus has been reached regarding the glucocorticoid (GC) to use for congenital adrenal hyperplasia (CAH) during adulthood. Dexamethasone (DEX), because of its longer half-life, could improve compliance; however, no data are available regarding the long-term effects of DEX therapy.ObjectiveTo analyze the metabolic effect of DEX therapy for adults with CAH.DesignRetrospective analysis of a CAH cohort receiving DEX therapy.SettingMedical School Hospital, São Paulo University, Brazil.ParticipantsSixty patients with well-controlled classic CAH (41 women; 30 with salt-wasting) receiving DEX after achievement of final height.InterventionsNone.Main Outcome MeasuresClinical, laboratory, and metabolic data were compared immediately before DEX and at the last evaluation.ResultsThe mean age at the last evaluation was 31.9 ± 9.6 years, and the duration of DEX therapy was 11.5 ± 4.9 years. The mean DEX dose was 0.18 ± 0.07 mg/m2/d. The body mass index SD score (1.6 ± 1.6 vs 1.5 ± 1.5 mg/m2; P = 0.65) and obesity prevalence (27% vs 27%) did not differ between evaluations. However, the waist/height ratio (WtHR) had increased from 0.54 ± 0.08 to 0.56 ± 0.1 (P = 0.001). An increase in the homeostatic model assessment for insulin resistance index (2.5 ± 1.3 vs 2.8 ± 1.7; P = 0.03) was observed and positively correlated with the WtHR (r = 0.54). The prevalence of metabolic syndrome (7% vs 10%; P = 0.7) and hypertension (15% vs 13.3%; P = 0.8) did not differ significantly between the two evaluations.ConclusionsLong-term and low-dose DEX therapy did not lead to increases in obesity or metabolic syndrome, although it was associated with an increased WtHR and greater homeostatic model assessment for insulin resistance observed with chronic use of GCs. DEX appears to be an acceptable option to treat adult CAH.

Early central blood pressure elevation in adult patients with 21-hydroxylase deficiency.

Controversial data exist on cardiovascular damages in patients with congenital adrenal hyperplasia (CAH). To assess blood pressure and early cardiovascular damages on a large cohort of adult CAH patients and control individuals. Case-control study. Referral Center for Rare Disease, Pitié Salpêtrière Hospital, Paris, France. Fifty-eight women and 26 men with CAH diagnosed in childhood and 85 controls matched-paired for sex, age and smoking status were prospectively included. Measurement of large arteries and microcirculatory anatomical and functional indices as well as hormonal status and cardiovascular risk factors evaluation. The primary objective was to compare carotid intima-media thickness (cIMT) in CAH patients and controls. The secondary objectives were to compare blood pressure (BP), radial augmentation index (rAI), central BP, carotid-femoral pulse wave velocity (PWV), skin microcirculation indices and inflammation parameters in CAH patients and controls. Although PWV and cIMT were identical in patients and controls, higher rAI (64.6 ± 1.7 vs. 59.9 ± 1.6%, P = 0.02) and higher central SBP (101.8 ± 1.5 vs. 95.1 ± 1.5 mmHg, P < 0.001) were observed in CAH patients. Regarding microcirculatory indices, there was a higher functional resting capacity and a lower anatomical capillary density in CAH patients. In multivariate analysis, we found an independant association between CAH and central SBP elevation. We found an early rise in central SBP in CAH patients whereas sublinical arterial damages markers were normal. Our study suggest that vascular damages and increased cardiovascular risk could be mainly BP-driven.

ЧИ Є ВРОДЖЕНА ГІПЕРПЛАЗІЯ НАДНИРНИКІВ ЧЕРЕЗ 21-ГИДРОКСИЛАЗНУ НЕДОСТАТНІСТЬ ОМАНЛИВОГО ЗАХВОРЮВАННЯ? УПРАВЛІННЯ ТА ДИФЕРЕНЦІЮВАННЯ СИНДРОМУ У ДОРОСЛИХ

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase defi ciency is one of the most common autosomal recessive hereditary diseases. The lack of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH). Moreover the impairment of cortisol synthesis results in adrenal hyperplasia and excessive androgen synthesis. Congenital adrenal hyperplasia is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase defi ciency. The clinical manifestations of congenital adrenal hyperplasia in adults result from adrenocortical insuffi ciency, hyperandrogenism, and the adverse effects of glucocorticosteroids, which are used for the treatment of the syndrome. Non-classic congenital adrenal hyperplasia may sometimes be asymptomatic. Patients with classic congenital adrenal experience a wide variety of symptoms, including obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. The symptoms are more often seen in patients suffering from congenital adrenal hyperplasia syndrome than in the general population. Long-term glucocorticosteroid treatment is also a known risk factor for many diseases, for instance osteoporosis. Patients with congenital adrenal hyperplasia require constant monitoring of biochemical parameters (17a-hydroxyprogesterone [17-OHP] and androstenedione), clinical parameters (Body Mass Index, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. Appropriate treatment of congenital adrenal hyperplasia is extremely important. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females. Furthermore it is key to reduce the adverse effects of medicaments used for therapy of the CAH syndrome. Patients with classic congenital adrenal hyperplasia require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic congenital adrenal hyperplasia require monitoring; treatment is not always necessary. Medical care for patients suffering from congenital adrenal hyperplasia should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.

A model for measuring the health burden of classic congenital adrenal hyperplasia in adults.

Patients with classic congenital adrenal hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. The model, built in Excel, comprises subdomains addressing the health consequences of CAH and synthesises evidence from clinical and epidemiological studies on health outcomes. The model estimates that adults with classic CAH will implement 'sick day rules' (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime and attend hospital for adrenal crisis on 11 occasions. In a population of 1000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. Patients with CAH may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in patients with CAH compared to the general population, leading on average to an additional 0·8 fractures per patient with CAH over their lifetime. The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.

Experience in optimizing fertility outcomes in men with congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

Men with congenital adrenal hyperplasia (CAH) have impaired fertility. We aimed to assess fertility outcomes and the importance of hypogonadotropic hypogonadism, testicular failure and the presence of testicular adrenal rest tumours (TART). Retrospective analysis of men attending an adult CAH clinic in a tertiary centre. Fifty men with CAH due to 21 hydroxylase deficiency were identified of whom 35 were salt wasting and 15 were non-salt-wasting. Review of fertility history and parameters including luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, 17-hydroxyprogesterone (17-OHP), semen analysis and the presence of testicular adrenal rest tissue (TART) on ultrasound. TART were detected by ultrasound in 21 (47%), and their presence was associated with an elevated FSH (P = 0·01). Severe oligospermia was present in 11 of 23 (48%), and this was associated with an elevated FSH (P = 0·02), suppressed LH (P < 0·01) and TART (P = 0·03) when compared to those with a sperm count >5 × 10(6) per ml. Of those that desired fertility, 10 of 17 (59%) required treatment intensification and four underwent in vitro fertilization. Intensification resulted in a rise in median LH (0·6-4·3 IU/l; P = 0·01). Live birth rate was 15 of 17 (88%) with a median (range) time to conception of 8 (0-38) months. Suppressed LH is a marker for subfertility and is often reversible. Testicular failure is closely associated with TART formation. If TART are detected, sperm cryopreservation should be offered given the risk of progression to irreversible testicular failure. Male fertility in CAH can be improved by intensified treatment and assisted reproductive technology.

An Unusual Case of Triazophos Poisoning Presenting with New-Onset Refractory Status Epilepticus.

Background:There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids.Objective:We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range.Subjects and Methods:Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison.Results:The BMD at hip (0.85 ± 0.02 g/cm2) in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029). BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH.Conclusion:Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

Imaging features of poorly controlled congenital adrenal hyperplasia in adults.

Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the effects of cortisol precursor excess on various target organs. We present a spectrum of imaging findings encountered in adult patients with poorly treated CAH, with an emphasis on radiological features and their clinical relevance.

Determining clinical and biological indicators for health outcomes in adult patients with childhood onset of congenital adrenal hyperplasia

Adverse outcomes in adult congenital adrenal hyperplasia (CAH) patients are frequent. The determinants of them have not yet been established. To establish the prevalence of adverse outcomes and to find determining factors for each of them. Cross-sectional monocentric study of 104 patients with childhood onset of CAH (71 women, 33 men). Analysis established first the determinants of clinical, hormonal, genetic variables and second a composite criterion for some of the outcomes and determinants. BMI was above 25 kg/m(2) in 44% of the cohort, adrenal hyperplasia and/or nodules were present in 45% of the patients, and irregular menstrual cycles and hyperandrogenism were found in 50 and 35% of the women respectively. In univariate analysis, the determinants of these outcomes were all linked to disease control, especially 17-hydroxyprogesterone (17OHP) and androstenedione concentrations. Low weight was a determinant of abnormal bone mineral density (BMD) (60% of the cohort). Multivariate analysis confirmed these data. A classic form (CF) of CAH was a determinant of testicular adrenal rest tumors (TARTs) (36% of the men). Total cumulative glucocorticoid dose was a determinant of BMI and TART, whereas fludrocortisone dose was a determinant of TART (P=0.03). In men, the composite criterion was associated with androstenedione concentration and CF. In women, the composite criterion was associated with total testosterone concentration. The present study confirms the high prevalence of adverse outcomes in CAH patients. These are, most often, related to disease control. The impaired health status of adults with CAH could therefore be improved through the modification of treatment.

An unusual case of triazophos poisoning presenting with New-Onset refractory status epilepticus

Background: There is equipoise regarding the status of bone mineral density (BMD) in patients with congenital adrenal hyperplasia (CAH), where patients need to be on long-term low-dose steroids. Objective: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. Subjects and Methods: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years) underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. Results: The BMD at hip (0.85 ± 0.02 g/cm2) in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029). BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057). The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range). There was no history of fractures in CAH. Conclusion: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

Quality of life, social situation, and sexual satisfaction, in adult males with congenital adrenal hyperplasia

To determine quality of life (QoL) in adult males with congenital adrenal hyperplasia (CAH). CAH males with 21-hydroxylase deficiency (n = 30), 19-67 years old, were compared with controls (n = 32). QoL was assessed using questionnaires on general living conditions and sexual issues, and the psychological well-being index (PGWB) form. Fewer CAH males than controls were students (3 vs. 25 %, P = 0.028) and more had blue-collar work (57 vs. 33 %, P = 0.023). Patients were less interested in sports (47 vs. 72 %, P = 0.034) and art/literature/film (10 vs. 47 %, P = 0.004). PGWB total score was 82.7 ± 13.7 versus 87.0 ± 11.1 (P = NS), but hydrocortisone/cortisone acetate treated scored lower than controls and prednisolone treated. Glucocorticoid over-treated had lower QoL than those with poor control (PGWB total score 77.1 ± 13.5 vs. 92.4 ± 11.1, P = 0.026) and controls (P = 0.025). Total PGWB score was positively correlated with adrenal androgens and steroid precursors. Subscale scores indicated that patients with late diagnosis were more depressive (12.1 ± 2.8 vs. 13.9 ± 1.4, P = 0.011) and had a lower self-control (11.3 ± 3.6 vs. 13.1 ± 1.0, P = 0.019) compared with controls. Sexual satisfaction was similar in spite of more patients being sexually inactive (27 vs. 6 %, P = 0.040). Adult CAH males differed from controls with respect to type of occupation and spare time interests but had similar QoL despite being less sexually active. Optimizing glucocorticoid therapy might further improve QoL. Some disadvantages found in patients diagnosed late will hopefully not be seen in patients diagnosed by neonatal screening, but this has yet to be studied.