CYTOGENETIC ANALYSIS OF PATIENTS WITH AMBIGUOUS GENITALIA

Objective: To determine the magnitude and classification of cases of ambiguous genitalia presenting to our setup. Study Design: Cross-sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Aug 2018 to Feb 2019. Methodology: All the patients with ambiguous genitalia referred for cytogenetic analysis, were included in the study. The patients were subjected to a detailed history and physical examination. The record of radiological investigations was were obtained. Cytogenetic analysis was performed using the conventional G-banding technique. Hormonal testing included 17- hydroxyprogesterone (17-OHP) levels was also performed. Results: Fifty-one cases of ambiguous genitalia were studied. The median age was 15 months. Thirty-three patients (64.7%) had a 46XY karyotype, 17 (33.3%) had a 46XX karyotype while 1 (1.9%) had 45X/46, XY mosaic karyotype. Thirty patients (58.8%) were products of consanguineous marriage. Congenital adrenal hyperplasia was diagnosed in 12 cases (70.5%) of 46 XX karyotype and in 3 cases (9%) of 46XY karyotype. Conclusion: Ambiguous genitalia, currently categorized as disorders of sex development, are not uncommon in our populartion. Increased awareness and early diagnosis are crucial to prevent life threatening complications of congenital adrenal hyperplasia, to determine sex of rearing, and to counsel the parents or patients.

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Study on 46 XY Disorders of Sex Development

Journal of Armed Forces Medical College Bangladesh ◽

10.3329/jafmc.v14i2.45893 ◽

2020 ◽

Vol 14 (2) ◽

pp. 134-138

Author(s):

Eva Jesmin ◽

Fauzia Mohsin ◽

Nurun Nahar Fatema Begum

Keyword(s):

Disorders Of Sex Development ◽

Armed Forces ◽

Ambiguous Genitalia ◽

Cross Sectional Study ◽

Correct Identification ◽

Disorders Of Sexual Development ◽

Gender Orientation ◽

Cross Sectional ◽

Early Presentation ◽

Sex Development

Introduction: 46 XY disorders of sexual development (DSD) include a wide sphere of phenotypes which can be ambiguous male genitalia with or without hypospadias, unambiguous female genitalia or dysgenetic gonads or any combination of them. Management of these patients depends on the aetiology, age at presentation, gender orientation and advancement in feminization. Objectives: To assess the clinical, biochemical, radiological and chromosomal profile of the paediatric patients with suspected DSD attending a tertiary level healthcare centre and plan for appropriate management. Materials and Methods: This cross-sectional study was carried out among 30 cases of 46XY DSD attending the paediatric endocrine unit of Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM) General Hospital from May 2016 to April 2017. Clinical, biochemical, radiological and chromosomal evaluations were done to identify the cause of DSD. Results: The mean age of the patients recruited in the study was 3.51 (±5.03) years ranging from 13 days old to 13 years old. Among these 30 patients, the chief complaint was ambiguous genitalia in 29 (96.7%) cases, 1 (3.3%) case with Micropenis and 1 (3.3%) case with absence of development of secondary sexual characteristics. The gender of rearing was male in 23 (76.7%) cases and rest as female. Among the patients 5 (16.67%) patients were diagnosed with PAIS, 5 (16.67%) patients with CAIS, 3 (10%) patients had a deficiency of 5αRD and gonadal dysgenesis was found in 5 (16.67%) patients. The corrective surgery was done in 5(16.67%) patients, 16 (53.3%) patients referred to surgeon for operative treatment and 7(23.3%) patients were prescribed to administer testosterone. Conclusions: The early presentation, correct identification of the cause and initiation of cause-based treatment can abate the physical and psychosocial complications and may support better gender orientation related adjustability. Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 134-138

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SAT-LB050 Congenital Adrenal Hyperplasia Newborn Screening Protocols Differ Widely in the US: A Survey by the Differences/Disorders of Sex Development Translational Research Network (DSD-TRN)

Journal of the Endocrine Society ◽

10.1210/js.2019-sat-lb050 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Phyllis Speiser ◽

Reeti Chawla ◽

Ming Chen ◽

Emmanuele Delot ◽

Alicia Thomas ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Newborn Screening ◽

Translational Research ◽

Disorders Of Sex Development ◽

Research Network ◽

Adrenal Hyperplasia ◽

Sex Development ◽

The Us

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Disorders of sex development

10.1093/med/9780199659579.003.0124 ◽

2017 ◽

Author(s):

David F.M. Thomas

Keyword(s):

Disorders Of Sex Development ◽

Ambiguous Genitalia ◽

Surgical Reconstruction ◽

Adrenal Hyperplasia ◽

Specialist Care ◽

Gender Assignment ◽

Developmental Abnormalities ◽

Sex Development

The aetiology of disorders of sex development (DSD) is multifactorial and includes chromosomal defects, developmental abnormalities of the gonads, and defects of hormonal synthesis and expression. Infants born with ambiguous genitalia require urgent investigation because of the risk of hyponatraemia associated with congenital adrenal hyperplasia (CAH) and to permit an informed decision on gender assignment. CAH is the commonest form of DSD, accounting for around 80% of all infants born with ambiguous genitalia. Despite controversy regarding timing and consent, feminizing genitoplasty in early childhood remains the accepted management for girls with significant clitoromegaly. Surgical reconstruction for 46XY DSD is guided by several factors, notably the size of the phallus and gonadal phenotype. The majority of individuals with disorders of sex development will require ongoing specialist care and long-term multidisciplinary follow-up and support.

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A Multicenter Cross-Sectional Study of Malaysian Females With Congenital Adrenal Hyperplasia: Their Body Image and Their Perspectives on Feminizing Surgery

Journal of Pediatric and Adolescent Gynecology ◽

10.1016/j.jpag.2020.04.008 ◽

2020 ◽

Vol 33 (5) ◽

pp. 477-483

Author(s):

Ani Amelia Zainuddin ◽

Sonia Regina Grover ◽

Chong Hong Soon ◽

Nur Azurah Abdul Ghani ◽

Zaleha Abdullah Mahdy ◽

...

Keyword(s):

Body Image ◽

Congenital Adrenal Hyperplasia ◽

Cross Sectional Study ◽

Sectional Study ◽

Adrenal Hyperplasia ◽

Cross Sectional

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Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a cross-sectional study of factors involved in bone mineral density

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-003-0434-6 ◽

2003 ◽

Vol 21 (6) ◽

pp. 396-401 ◽

Cited By ~ 28

Author(s):

Patr�cia Oliveira de Almeida Freire ◽

Sofia Helena Valente de Lemos-Marini ◽

Andr�a Trevas Maciel-Guerra ◽

Andr� Moreno Morcillo ◽

Maria Tereza Matias Baptista ◽

...

Keyword(s):

Bone Mineral Density ◽

Congenital Adrenal Hyperplasia ◽

Bone Mineral ◽

Cross Sectional Study ◽

Sectional Study ◽

Adrenal Hyperplasia ◽

Mineral Density ◽

Hydroxylase Deficiency ◽

Cross Sectional ◽

21 Hydroxylase Deficiency

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Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Acta Endocrinologica ◽

10.1530/eje-15-0064 ◽

2015 ◽

Vol 173 (6) ◽

pp. 727-737 ◽

Cited By ~ 10

Author(s):

Miguel Debono ◽

Ashwini Mallappa ◽

Verena Gounden ◽

Aikaterini A Nella ◽

Robert F Harrison ◽

...

Keyword(s):

Circadian Rhythms ◽

Congenital Adrenal Hyperplasia ◽

Cross Sectional Study ◽

Adrenal Hyperplasia ◽

Cross Sectional ◽

Dose Administration ◽

Disease Biomarkers ◽

Optimal Monitoring ◽

17 Hydroxyprogesterone ◽

Long Acting

ObjectivesThe treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids.DesignThis was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH.MethodsTwenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated.ResultsA significant rhythm was confirmed for ACTH (r2, 0.95;P<0.001), 17OHP (r2, 0.70;P=0.003), androstenedione (r2, 0.47;P=0.043), androsterone (r2, 0.80;P<0.001), testosterone (r2, 0.47;P=0.042) and progesterone (r2, 0.64;P=0.006). The mean (s.d.)TminAC andTmaxAC for 17OHP and A4were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0–24 hprogesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP.ConclusionIn CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.

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Influence of hormones on the immunotolerogenic molecule HLA-G: a cross-sectional study in patients with congenital adrenal hyperplasia

Acta Endocrinologica ◽

10.1530/eje-19-0379 ◽

2019 ◽

Vol 181 (5) ◽

pp. 481-488 ◽

Cited By ~ 3

Author(s):

Lee S Nguyen ◽

Nathalie Rouas-Freiss ◽

Christian Funck-Brentano ◽

Monique Leban ◽

Edgardo D Carosella ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Critical Role ◽

Renin Angiotensin System ◽

Cross Sectional Study ◽

Healthy Controls ◽

Sectional Study ◽

Adrenal Hyperplasia ◽

Cross Sectional ◽

Adequate Model ◽

Soluble Hla

Background HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. Methods In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. Results Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (β = 0.44 (0.35–1.27) and −0.44 (−0.94, −0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (β = 0.25 (0.04–0.41), P = 0.001) and estradiol (β = −0.22 (−0.57, −0.02), P < 0.001). Conclusion CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.

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Association Between Plasma Renin Activity with Hypertension in Children with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Enzyme Deficiency

10.21203/rs.3.rs-212181/v1 ◽

2021 ◽

Author(s):

Siska Mayasari Lubis ◽

Eka Lakshmi Hidayati ◽

Frida Soesanti ◽

Bambang Tridjaja AAP

Keyword(s):

Plasma Renin Activity ◽

Congenital Adrenal Hyperplasia ◽

Plasma Renin ◽

Cross Sectional Study ◽

Renin Activity ◽

Enzyme Deficiency ◽

Activity Levels ◽

Adrenal Hyperplasia ◽

Cross Sectional ◽

Salt Wasting

Abstract BackgroundHypertension is an uncommon manifestation of congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency (21-OHD CAH). Nevertheless, it is necessary to continuously be aware of hypertension incidence in 21-OHD CAH patients and its possible causes. Conflicting results regarding the role of PRA have been reported. This study aims to evaluate the association between plasma renin activity levels (PRA) with hypertension in 21-OHD CAH children. MethodsWe did an observational analytic study with a cross-sectional study design. The subjects were 21-OHD CAH children, aged >6 months to 18 years, selected by consecutive sampling and then compared between 21-OHD CAH with hypertension and non-hypertension groups. We gathered 40 subjects, 20 subjects in hypertension and 20 subjects in non-hypertension groups.ResultsThere were 16 from 27 (59.3%) and 4 from 13 subjects (30.8%) with hypertension in salt-wasting and simple virilizing type, respectively. There was a significant mean difference in PRA levels between hypertension and non-hypertension groups in salt wasting patients (p=0,016). The risk of hypertension in salt wasting patients with low PRA levels was 1,09 times after controlling for sex, 17-OHP levels, and the last fludrocortisone dose. The last dose of hydrocortisone had a significant relationship with the incidence of hypertension in salt wasting patients. ConclusionsThis study concludes that hypertension in 21-OHD CAH patients during the study period was 32%. The risk of hypertension in salt wasting patients with low PRA levels was 1.09 times after being controlled for sex, 17 OHP level, and the last dose of fludrocortisone.

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FREQUENCY OF CLINICAL FEATURES AND CYTOGENETIC DEFECTS IN DOWN SYNDROME DIAGNOSED AT AFIP

Pakistan Armed Forces Medical Journal ◽

10.51253/pafmj.v71isuppl-1.6196 ◽

2021 ◽

Vol 71 (Suppl-1) ◽

pp. S28-31

Author(s):

Saira Irum ◽

Helen Mary Robert ◽

Asad Mahmood ◽

Rafia Mahmood ◽

Ayesha Khurshid ◽

...

Keyword(s):

Down Syndrome ◽

Clinical Features ◽

Trisomy 21 ◽

Armed Forces ◽

Cross Sectional Study ◽

Banding Technique ◽

Nasal Bridge ◽

Cross Sectional ◽

Cytogenetic Abnormalities ◽

Conventional Cytogenetic Analysis

Objective: To determine the frequency of clinical features and cytogenetic abnormalities in patients of down syndrome and correlation of cytogenetic abnormalities with clinical features. Study Design: Cross sectional study. Place and Duration of Study: Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, from Feb 2017 to Feb 2018. Methodology: Total 163 patients with clinical suspicion of Down syndrome were selected by non-probability convenient sampling and diagnosis was confirmed by conventional cytogenetic analysis using Giemsa trypsin banding technique. Clinical features were assessed and frequency of different cytogenetic abnormalities were noted. Results: Out of total 163 patients, 96 (59%) were male and 67 (41%) were female. Median age of the patients was 11 months. Trisomy 21 was detected in 158 (96.9%), Robertsonian translocation in 4 (2.4%) and mosaicism in 01 (0.6%) patient. The predominant clinical features observed were slaunted with eyes, epicanthic folds, depressed nasal bridge and protruding tongue. Conclusion: Trisomy 21 is the most common cytogenetic abnormality observed in patients of down syndrome.

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