Adrenal Hyperplasia Research Articles

Diurnal 11-ketotestosterone and 17-hydroxyprogesterone saliva profiles in paediatric classical congenital adrenal hyperplasia.

The most suitable biochemical markers for therapy adjustment in patients with congenital adrenal hyperplasia are controversial. 11-Oxygenated androgens are a promising new approach. The objective of this study was to investigate the diurnal rhythm of 11-ketotestosterone in children and adolescents in saliva and to correlate it with salivary 17-hydroxyprogesterone. Fifty-one samples of steroid day-profiles from 17 patients were additionally analysed for 11-ketotestosterone, retrospectively. All patients were treated in our university outpatient clinic for paediatric endocrinology between 2020 and 2022. Steroid day-profiles of 17 patients could be examined. The cohort showed a balanced sex ratio. The median age was 13 years. The measurements for 17-hydroxyprogesterone were carried out during routine care by immunoassay. The measurements of 11-ketotestosterone were performed from frozen saliva samples using an implemented in-house protocol for liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most important outcome were the absolute values for 11-ketotestosterone, their diurnal rhythmicity and the correlation with 17-hydroxyprogesterone. Both steroids show a circadian diurnal rhythm. 17-hydroxyprogesterone and 11-ketotestosterone correlate significantly. 11-Ketotestosterone showed a positive correlation with BMI at all times of the day. 11-Ketotestosterone shows circadian rhythmicity in our cohort and correlates with 17-hydroxyprogesterone. These findings serve as an important basis for prospective research into 11-oxygenated androgens as therapeutic markers in paediatrics. However, 11-ketotestosterone appears to be very dependent on BMI.

Female virilization related to congenital adrenal hyperplasia and psychological distress

Introduction In females, congenital adrenal hyperplasia (CAH), a spectrum of inherited genetic conditions related to the disruption of adrenal steroidogenesis, is among the most common conditions leading to inappropriate virilization. For adolescent and adult women, progression of hirsutism may have many psychological concerns.Objectives To explore the psychological distress of a young Tunisian woman who sought medical help and psychological support at a late stage, after suffering from genital ambiguity and severe virilization.MethodsHarboring phenotypic male transformation at puberty, our patient attended genetic counselling for cytogenetics assessment. Clinical, biological, psychological and genetic explorations were thus carried out.Results A 17-year-old female was born from first-degree consanguineous parents, and had healthy siblings (a sister and three brothers). After a single menstrual episode at puberty, she developed amenorrhea and an unexpected progressive virilization, including hirsutism with an inappropriate beard that she had to shave every day and a male voice. Clinical examination revealed a male morphotype with an enlarged clitoris that resemble a penis, male-type pubic hair, underdeveloped of breasts, abnormal cutaneous hyperpigmentation, and a short stature. Pelvic ultrasound revealed a small uterus, but with no visualized gonads. Genetic exploration showed a female 46,XX karyotype and the absence of Y chromosome sequences. Diagnosis of a non-classic CAH was confirmed. Psychological assessment found that the psychological development of the sexual identity corresponded to the assignment of the female sex. A severe psychological suffering due to the non-acceptance of her virile appearance impaired the quality of her daily personal and social life. Stigmata of a depressive syndrome were also revealed.ConclusionsParticular attention to the psychological assessment of patients with CAH is recommended, as changes in physical appearance have a detrimental impact on psychological and mental well-being.Disclosure of InterestNone Declared

A Comparative Study of Fresh versus Frozen Embryo Transfer and their Outcomes in Patients with Polycystic Ovarian Syndrome

Background: In in vitro fertilization (IVF)/assisted reproductive technology, fresh embryo transfer is generally preferred over frozen embryo transfer (FET). Still, some research shows that FET could increase the childbirth rate which reduces the amount of ovarian hyperstimulation syndrome (OHSS) and pregnancy problems in females with polycystic ovarian syndrome (PCOS). There is a high risk of aberrant pregnancies, incorrect placentation, and other issues when a fresh embryo is transferred. They are more likely to get OHSS. Fresh embryo transfer reduces the chances to get pregnant as the stimulatory effect will be there for long time, and the endometrium is less receptive for the embryos and vice versa in the case of FET. For IVF, the transfer of fresh embryos is typically preferred over the transfer of frozen embryos. However, some research suggests that the transfer of frozen embryos may increase the live birth rate and decrease the rates of OHSS and pregnancy complications in women with polycystic ovary syndrome. One of the most prevalent endocrine illnesses in women of reproductive age is PCOS. Chronic anovulation, hyperandrogenemia, and clinical signs of hyperandrogenism are hallmarks of polycystic ovary syndrome in the absence of additional diseases such as congenital adrenal hyperplasia, androgen-producing tumors, or Cushing syndrome. Despite the fact that some patients are discovered to be clomiphene citrate (CC) resistant, CC is still the first line of treatment for anovulatory infertility caused by PCOS. Numerous treatments, such as the usage of metformin, ovarian drilling, and gonadotropin therapy, may be taken into consideration in these people. Materials and Methods: Fifty women in all ranging in age from 25 to 45 participated in the study. Half of the study participants are from Wardha, and the other half are from rural areas close to Wardha. Participants were chosen from patients who sought medical attention for issues relating to infertility. We have taken consent from all the patients with the mutual understanding that their medical is being used for a comparative study. All the patients in our study are subjected to IVF following embryo transfer. We have taken n = 50 in which all the patients are PCOS patients with AMH noticeably higher than others. Out of them, we have taken 25 patients who are allocated for fresh Day 5 transfer and 25 of them are allocated for Day 5 FET. We have collected data for a total of 50 patients and compared the β-human chorionic gonadotropin values whether it is positive or negative in each case. We have done a comparative study by comparing the results of patients undergoing fresh versus FET with their ages ranging from 25 to 45 years. Results: The data of fresh Day 5 embryo and frozen Day 5 transfer and their outcome were noted. We concluded that FET has good results compared to fresh embryo transfer.

Androgenetic Alopecia: update on Etiology, Pathophysiology, Diagnosis and Treatment

Alopecia means loss of hair. Androgenetic alopecia (AGA) now called as patterned hair loss (male pattern hair loss; MPHL, female pattern hair loss; FPHL) is caused by androgens in a predisposed individual. It is modulated by factors like age, sex, genes, smoking, and alcohol. If untreated this leads to psychological problems like stress, anxiety, depression and decrease self-confidence which affect quality of life. A thorough clinical examination and a certain hormonal estimation could reveal levels of androgens, hyperandrogenism, adrenal hyperplasia, (PCOS) polycystic ovarian syndrome, and ovarian/adrenal tumors. A simple Trichoscopy could show the typical picture of hair miniaturization commonly seen in this condition. Finally, a biopsy of the scalp could help in clinching conclusive diagnosis. Out of the many treatments at our disposal, the non-pharmacologic methods like temporary camouflage techniques, synthetic hair wigs, hair-thickening fibers, hair weaving, pigmented powders are useful. Semi-permanent options like scalp micro-pigmentation (thorough tattooing) are useful to enhance appearances. Presently the United States Food and Drug Administration (USFDA) approved pharmacologic treatments are Minoxidil and Finasteride. The non-USFDA approved methods of treatments like various surgical procedures {[hair transplantation]: follicular unit transplantation (FUT), follicular unit extraction (FUE), microneedling, light therapy, indigenous medicines, Platelet-Rich Plasma (PRP)}, and various loco-regional hair care practices are in vogue. The outcome of this review is to offer the latest update and insights into the newer novel therapies in patterned hair loss. Also, the patients could enhance their knowledge about the condition, the benefits and prognosis of each treatment.

Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

PurposeTo investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.MethodsThis study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.ResultsThe incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0–25.1) ng/mL; T1: 7.1 (1.8–19.9) ng/mL; T2: 5.9 (2.0–20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3–2.5) ng/mL; T1: 0.3 (0.3–1.1) ng/mL; T2: 0.5 (0.3–1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.Conclusionsour data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.

Discovery of CRN04894: A Novel Potent Selective MC2R Antagonist.

A novel class of nonpeptide melanocortin type 2 receptor (MC2R) antagonists was discovered through modification of known nonpeptide MC4R ligands. Structure-activity relationship (SAR) studies led to the discovery of 17h (CRN04894), a highly potent and subtype-selective first-in-class MC2R antagonist, which demonstrated remarkable efficacy in a rat model of adrenocorticotrophic hormone (ACTH)-stimulated corticosterone secretion. Oral administration of 17h suppressed ACTH-stimulated corticosterone secretion in a dose-dependent manner at doses ≥3 mg/kg. With its satisfactory pharmaceutical properties, 17h was advanced to Phase 1 human clinical trials in healthy volunteers with the goal of moving into patient trials to evaluate CRN04894 for the treatment of ACTH-dependent diseases, including congenital adrenal hyperplasia (CAH) and Cushing's disease (CD).

Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.org/) was established to enable insights into CAH management and outcomes, yet its global adoption by endocrine centres remains unclear. We sought (1) to assess current practices amongst clinicians managing patients with CAH in the United Kingdom and Ireland, with a focus on choice of glucocorticoid, monitoring practices and screening for associated co-morbidities, and (2) to assess use of the I-CAH registry. We designed and distributed an anonymised online survey disseminated to members of the Society for Endocrinology and Irish Endocrine Society to capture management practices in the care of patients with CAH. Marked variability was found in CAH management, with differences between general endocrinology and subspecialist settings, particularly in glucocorticoid use, biochemical monitoring and comorbidity screening, with significant disparities in reproductive health monitoring, notably in testicular adrenal rest tumours (TARTs) screening (p = .002), sperm banking (p = .0004) and partner testing for CAH (p < .0001). Adoption of the I-CAH registry was universally low. Differences in current management of CAH continue to exist. It appears crucial to objectify if different approaches result in different long-term outcomes. New studies such as CaHASE2, incorporating standardised minimum datasets including replacement therapies and monitoring strategies as well as longitudinal data collection, are now needed to define best-practice and standardise care.

Parental concerns about genital differences in children with congenital adrenal hyperplasia persist regardless of the selected intervention.

Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency (21HD) can affect the in utero development of the genital anatomy of people with the 46XX karyotype. Health professionals engage parents in decision-making regarding managing genitals with this difference, including genital surgery options and patient communication. We sought to investigate parental communication with their daughters regarding clitoral size variation related to neonatal CAH. Semistructured in-person interviews of 24 parents of chromosomal XX children with clitoral size variation attributable to a neonatal CAH diagnosis comprised 3 management categories: (1) clitoral reduction surgery (RS) (7 parents, 9 children), (2) clitoral concealment surgery (CS) (8 parents, 8 children), and no surgery on or around the clitoris (NS) (9 parents, 7 children). Four representative themes, Obvious Choice, Still Different, Parental Burden, and Ignorance Is Bliss, were common across all 3 treatment groups. For most parents, none of the 3 options of genital appearance alteration via clitoral reduction, clitoral concealment surgery, or avoidance of clitoral surgery ameliorated concerns, with most parents expressing an aversion to educating their child on the topic of genital differences, past treatment, or future function. Reliance on surgical treatment pathways to manage this psychosocial concern is ineffective in alleviating parental uncertainty without the application of psychosocial interventions. This was a qualitative study but was limited to parents of children with a specific genital difference, without direct exploration of parental values regarding the clitoris or the application of adequate psychosocial care. Healthcare services must have an impact on parental ability to engage in essential communication with their children in cases such as clitoral size variation related to neonatal CAH. Improved communication skills allow parents to engage in more genuine decision-making and adapt to enduring genital reality, including possible future sexual challenges for their adult child, without resorting to burdensome strategies focused on attempts to perpetuate a benevolent ignorance.

Analysis of the CYP21A2 gene pathogenic variants in CAH patients from Surgut using next-generation sequencing (NGS)

Background21-hydroxylase deficiency is present in 90–95% of cases of congenital adrenal hyperplasia (CAH). Eleven major pathogenic variants account for 93% of all identified variants in the CYP21A2 gene in various clinical forms of the disease. Each population has its own range of significant pathogenic variants. We aimed to study the frequency of pathogenic variants in the CYP21A2 gene using NGS technology and real-time PCR in Surgut patients with different clinical forms of CAH. NGS was performed on 70 patients with salt-wasting and non-classical clinical forms of 21-hydroxylase deficiency, verified by direct Sanger sequencing and PCR–RFLP analysis.ResultsEleven different pathogenic variants were found in 68.57% (48/70) of patients. Among 92.86% (13/14) of patients with salt-wasting CAH, variants were found to be homozygous, with CYP21A2 gene deletion as the most frequent mutation (46.4% or 13/28 alleles). In the group with non-classical CAH, pathogenic variants were identified only in 60.71% (34/56) of patients. V282L was discovered to be the most common variant in heterozygous carriers (45.45%, 15/33). NGS method identified 2 variants that were not determined by the standard method for major mutations detection: p.C170* and p.W22X, accounting for 3% of all known pathogenic variants.ConclusionOur data make it possible to clarify the specific spectrum of CYP21A2 gene pathogenic variants in CAH patients from Surgut. The NGS method allows for the identification of rare pathogenic variants (3%) in the CYP21A2 gene that are not included in the conventional PCR–RFLP analysis.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

National Service Evaluation of the Quality of Care for Children and Young People with Congenital Adrenal Hyperplasia in the UK: Survey Responses from Patients and Clinicians

Plain Language SummaryCongenital adrenal hyperplasia (CAH) is a lifelong condition where the body does not produce enough steroids, and thus patients need to take daily steroid replacement. There are differences of opinion in how CAH is treated, and we aimed to find out about these differences in the UK. We surveyed children and young people living with CAH, their parents or carers, and doctors and nurses who look after them throughout the UK. We received 152 responses from carers, 43 from patients, and 34 from clinicians from a total of 33 different clinics. Overall satisfaction with services was high, although, while 94% of clinicians said they provided formal training to families with CAH, over 80% of both patients and carers said that they had not attended what they considered formal training. Most patients and carers said that they would like to engage with further training. Clinicians said they wanted better access to other support for patients, including psychologists. Treatment of CAH was generally in keeping with international guidelines. New methods of monitoring, such as dripping blood onto a card instead of attending hospital for a formal blood test, are increasing with two-thirds of clinicians reporting this method being used. In conclusion, there is good satisfaction with care provision among patients and carers with CAH in the UK. However, there are opportunities for increasing psychological support and family education about the condition to further improve the lives of those living with this disease.

AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia, however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct in vivo gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalised, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

Ovarian reserve and fertility parameters in post-pubertal females with congenital adrenal hyperplasia: a case-control study.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired activity of the enzyme required for cortisol and aldosterone production, resulting in increased adrenal androgen synthesis. Factors affecting fertility in CAH patients include ambiguous genitalia and their complications, excessive androgen secretion, adrenal progesterone hypersecretion, and various psychosocial factors. Serum anti-Müllerian hormone (AMH) level is used to assess ovarian reserve in women. A few data on serum AMH levels in CAH patients are available in the literature. The aim of the study was to evaluate ovarian reserve in a group of post-menarche females diagnosed with CAH by measuring serum AMH level and assessing the number of antral follicles sonographically. A case-control study was conducted on 17 post-pubertal CAH females and 17 age-matched healthy female controls; the mean age of the patient group was 15.09±3.55 years ranging from 11 to 24 years, while the mean age of the control group was 16.04±3.72 years ranging from 12 to 25 years, the mean post-menarchal age of the patients group was 3.29±1.37 years ranging from 1 to 6 years while the mean post-menarchal age of the control group was 4.13±1.62 years ranging from 1 to 9 years. The degree of hirsutism was compared between the two groups according to the modified Ferriman-Gallwey score, clitoral length was assessed using a digital caliber. Serum levels of adrenal androgens in addition to basal levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and serum AMH were measured in both groups. Patients had smaller uterine volumes, and smaller ovarian volumes but a comparable number of antral follicles and comparable serum AMH levels relative to controls. Good compliance with treatment in patients with CAH results in good hormonal control, low risk of PCOS, good fertility parameters, and a good ovarian reserve.

Cardiovascular risk in women with nonclassical congenital adrenal hyperplasia.

The outcomes related to cardiovascular risk (CVR) in patients with nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids (GCs) or oral contraceptive pills. to analyze CVR by markers of atherosclerosis in females with nonclassical form according to therapeutic options. a cross-sectional study at a tertiary center. Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into: G1 (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day); G2 (n = 19) with oral contraceptive pills; and G3 (30 matched controls). CVR was analyzed through serum lipids, HOMA-IR, inflammatory cytokines levels and quantitative image evaluations (pulse wave velocity-PWV, endothelial function by flow mediated dilatation-FMD, carotid intima media thickness-CIMT and visceral fat-VAT by abdominal tomography. There were no statistically significant differences in BMI, HOMA-IR, HDL-cholesterol, or triglyceride levels among groups (p > 0.05). Serum interleukin-6 levels ​​were higher in G1 than in G2 (p = 0.048), and interleukin-8 levels were higher in G1 than in G2/3 (p = 0.008). There were no statistically significant differences in VAT, PWV, FMD or CIMT among groups (p > 0.05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes. Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and 8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up.

Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

A Rare Case of Co-occurrence of Multiple Endocrine Neoplasia Syndrome and Congenital Adrenal Hyperplasia

Multiple endocrine neoplasia type 1 (MEN1) and congenital adrenal hyperplasia (CAH) are rare monogenic hereditary endocrinopathies with a prevalence of 1–9 cases per 100,000 and 9–15 cases per 100,000, respectively. MEN1 is characterized by the development of multiple endocrine and nonendocrine organ tumors, including parathyroid, pituitary, and duodenopancreatic neuroendocrine tumors (NETs), which constitute the classical triad of the disease. CAH is associated with genetic defects in enzymes and transport proteins involved in the synthesis of adrenal cortical steroid hormones. Overall, cases of the combination of two hereditary diseases in one patient are extremely rare. In this article, we describe a clinical case of the combination of MEN-1 with all three classical components and CAH, which, taking into account the low prevalence of both diseases, represents scientific interest. To date, only one similar case has been described in the literature. In addition, the paper discusses the pathogenetically determined combination of CAH and Ehlers-Danlos syndrome, known as the CAH-X syndrome.

Outcomes of one-stage feminizing genitoplasty in children with congenital adrenal hyperplasia and severe virilization

PurposeTo present our surgical experience and outcomes in congenital adrenal hyperplasia (CAH) patients with severe virilization using a combined technique of total urogenital mobilization (TUM) and a modified pull-through vaginoplasty to perform a safe and effective one-stage feminizing genital reconstruction for these children.MethodsFourteen CAH patients with severe virilization, defined by a Prader IV and V rating of the external genitalia, underwent TUM followed by a limited vaginal pull-through procedure from June 2016 to December 2020. Postoperative anatomical and cosmetic outcomes, and urinary continence, were evaluated.ResultsOut of the 14 cases in this study, 8 were classified as prader IV and 6 as Prader V. The median age at surgery was 11 months (range 6–36 months), and the mean urethral length was 1.4 cm (range 1.2–1.8 cm). The median follow-up period was 4 years. Our cosmetic outcomes were good in 11 (78.5%), satisfactory in 2, and poor in one case. All patients achieved age-appropriate toilet training without urinary incontinence.ConclusionAdopting our surgical approach of TUM with modified pull-through vaginoplasty has simplified feminizing surgical reconstruction in CAH cases with severe genital atypia and a very high vaginal confluence with short urethral length, yielding adequate introitus with good anatomical and cosmetic appearance and adequate urinary continence outcomes.

Prenatal diagnosis and in utero treatment of congenital adrenal hyperplasia: An up-to-date comprehensive review.

Congenital adrenal hyperplasia (CAH) is a term that encompasses a wide range of conditions that affect the adrenals. Diagnosis and treatment before birth are important as irreparable birth defects can be avoided, decreasing the need for surgical intervention later in life, especially regarding genitalia anomalies. Although early implementation of dexamethasone in the prenatal treatment of CAH has been controversial, there is recent evidence that this treatment can reduce long-term complications.

High carrier frequency of CYP21A2 gene mutations in Southern India - underscoring the need for genetic testing in Congenital Adrenal Hyperplasia.

Congenital Adrenal Hyperplasia (CAH) is one of the highly prevalent autosomal recessive endocrine disorders. The majority of CAH cases result from mutations in the CYP21A2 gene, leading to 21-hydroxylase deficiency. However, with the pseudogene-associated challenges in CYP21A2 gene analysis, routine genetic diagnostics and carrier screening in CAH are not a part of the first-tier investigations in a clinical setting. Furthermore, there is a lack of data on the carrier frequency for 21-OH deficiency. Therefore, this study is aimed at investigating the carrier frequency of common pseudogene derived CYP21A2 mutations in Southern India. Recently, a cost-effective Allele-specific PCR based genotyping for CYP21A2 hotspot mutations has been demonstrated to be a highly specific and sensitive assay at the authors' center. Leveraging this approach, a total of 1034 healthy individuals from South India underwent screening to identify the carrier frequency of nine hotspot mutations in the CYP21A2 gene. In this study, it was observed that 9.76% of the subjects were carriers for one or more of the nine different CYP21A2 mutations. Among the carriers, the most common was the large 30 kb deletion, followed by II72N, E6 CLUS, and I2G mutations. We have identified a high prevalence of CYP21A2 mutation carriers in Southern India. These findings emphasize the importance of implementing and expanding cost-effective genetic diagnostics and carrier screening throughout India. Such initiatives would play a crucial role in managing the disease burden, enabling early intervention, and establishing guidelines for CAH newborn genetic screening in the country. This study represents the first carrier screening data on CYP21A2 hotspot mutations from India and is the largest study conducted till date in this context.