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1.
Medicine (Baltimore) ; 99(2): e18387, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914016

RESUMO

RATIONALE: Congenital adrenal hyperplasia (CAH) is caused by various enzyme deficiencies, among which 21-hydroxylase (21-OH) deficiency accounts for more than 90% of cases. Neonatal screening became mandatory only a few decades ago. Many patients who were born before this went undiagnosed and some of the severely virilized females were raised as men. PATIENT CONCERNS: A 58-year old man with a history of excisional surgery in the external genitalia when he was a toddler presented with three days of dysuria and low abdominal pain. DIAGNOSIS: The patient's laboratory results showed leukocytosis and elevated C-reactive protein (CRP); thus, the physicians decided to perform a computed tomography (CT) scan. The CT demonstrated pelvic inflammatory disease (PID), left adrenal gland myelolipoma, and a mesenteric mass. Meanwhile, we suspected CAH based on the clinical history and assessed the patient's hormone levels. Seventeen-hydroxyprogesterone (17-OH-PG) was markedly elevated and the patient was diagnosed with classic simple virilizing CAH. INTERVENTIONS: Intravenous antibiotics were administered, and positron emission tomography-CT (PET-CT) was performed to evaluate any metastases. OUTCOMES: After 2 weeks of antibiotic treatment, CRP decreased to 0.12 mg/dL and PID was resolved. The patient opted for resection of the female genitalia along with the mesenteric and adrenal gland tumors in the near future, and was safely discharged. LESSONS: The adrenal gland myelolipoma was thought to have developed as a result of a longstanding exposure to adrenocorticotropic hormone. There are controversies regarding the management of female genitalia in CAH patients who identify themselves as men. In this case, the physician and patient decided to remove the female genitalia because the surgery for the mesenteric mass was inevitable and there was a possibility of recurrent PID. To our knowledge, this is the first article to report primary mesenteric tumor in a CAH patient to date. In conclusion, patients who were born before neonatal screening for CAH became the mainstay, who are suspected to have CAH from their history, and present with abdominal pain must be diagnosed by performing an imaging study, testing levels of serum 17-OH-PG, and screening for female genitalia and adrenal gland myelolipoma.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Antibacterianos/administração & dosagem , Genitália Feminina/cirurgia , Doença Inflamatória Pélvica/diagnóstico por imagem , 17-alfa-Hidroxiprogesterona/sangue , Administração Intravenosa , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/patologia , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielolipoma/diagnóstico por imagem , Mielolipoma/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Eur J Endocrinol ; 182(3): K15-K24, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917682

RESUMO

Objective: CYP11A1 mutations cause P450 side-chain cleavage (scc) deficiency, a rare form of congenital adrenal hyperplasia with a wide clinical spectrum. We detail the phenotype and evolution in a male sibship identified by HaloPlex targeted capture array. Family study: The youngest of three brothers from a non-consanguineous Scottish family presented with hyperpigmentation at 3.7 years. Investigation showed grossly impaired glucocorticoid function with ACTH elevation, moderately impaired mineralocorticoid function, and normal external genitalia. The older brothers were found to be pigmented also, with glucocorticoid impairment but normal electrolytes. Linkage studies in 2002 showed that all three brothers had inherited the same critical regions of the maternal X chromosome suggesting an X-linked disorder, but analysis of NR0B1 (DAX-1, adrenal hypoplasia) and ABCD1 (adrenoleukodystrophy) were negative. In 2016, next-generation sequencing revealed compound heterozygosity for the rs6161 variant in CYP11A1 (c.940G>A, p.Glu314Lys), together with a severely disruptive frameshift mutation (c.790_802del, K264Lfs*5). The brothers were stable on hydrocortisone and fludrocortisone replacement, testicular volumes (15-20 mL), and serum testosterone levels (24.7, 33.3, and 27.2 nmol/L) were normal, but FSH (41.2 µ/L) was elevated in the proband. The latter had undergone left orchidectomy for suspected malignancy at the age of 25 years and was attending a fertility clinic for oligospermia. Initial histology was reported as showing nodular Leydig cell hyperplasia. However, histological review using CD56 staining confirmed testicular adrenal rest cell tumour (TART). Conclusion: This kinship with partial P450scc deficiency demonstrates the importance of precise diagnosis in primary adrenal insufficiency to ensure appropriate counselling and management, particularly of TART.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/deficiência , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Tumor de Resto Suprarrenal/genética , Tumor de Resto Suprarrenal/patologia , Tumor de Resto Suprarrenal/cirurgia , Adulto , Pré-Escolar , Progressão da Doença , Diagnóstico Precoce , Família , Mutação da Fase de Leitura , Doenças Genéticas Ligadas ao Cromossomo X/genética , Glucocorticoides/metabolismo , Terapia de Reposição Hormonal , Humanos , Hiperpigmentação/etiologia , Hiperpigmentação/genética , Masculino , Linhagem , Fenótipo , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Resultado do Tratamento
3.
Eur J Endocrinol ; 182(3): C9-C12, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31972544

RESUMO

Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.


Assuntos
Doença de Addison/genética , Hiperplasia Suprarrenal Congênita/genética , Doença de Addison/complicações , Doença de Addison/diagnóstico , Doença de Addison/fisiopatologia , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/fisiopatologia , Doenças do Desenvolvimento Ósseo/etiologia , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/fisiopatologia , Encefalopatias/etiologia , Encefalopatias/genética , Encefalopatias/fisiopatologia , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Transtornos do Desenvolvimento Sexual/etiologia , Transtornos do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/fisiopatologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/fisiopatologia , Humanos , Hipoadrenocorticismo Familiar/complicações , Hipoadrenocorticismo Familiar/diagnóstico , Hipoadrenocorticismo Familiar/genética , Hipoadrenocorticismo Familiar/fisiopatologia , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/fisiopatologia , Técnicas de Diagnóstico Molecular , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/genética , Síndrome Nefrótica/fisiopatologia , Dermatopatias/etiologia , Dermatopatias/genética , Dermatopatias/fisiopatologia
4.
Exp Suppl ; 111: 245-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588535

RESUMO

Congenital adrenal hyperplasia (CAH) is a group of seven autosomal recessively inherited disorders of various enzymes participating in adrenal steroid hormone synthesis. Patients present with various symptoms depending on the nature and severity of the enzymatic block. More than 95% of all CAH patients suffer from 21-hydroxylase deficiency. The genetic background is well characterized for all CAH subtypes. Characterization of their genetic background has provided important pathophysiologic understanding of steroid biosynthesis disorders. Genotyping is important for confirming diagnosis, determining prognostic factors, and for genetic counseling for family planning and may reveal new therapeutic approaches.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Patrimônio Genético , Hiperplasia Suprarrenal Congênita/diagnóstico , Aconselhamento Genético , Humanos
5.
J Ayub Med Coll Abbottabad ; 31(3): 454-458, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535527

RESUMO

The term intersex used in the past has been replaced by "Disorders of Sex Differentiation". In this condition the development of chromosomal, gonadal or anatomical sex is atypical. This problem creates anxiety to the parents and a challenge for attending doctor. The problems faced by the individual are sexual, reproductive, sex of raring, placement in the society and psychological impact. The optimal management of the patient should be individualized by multidisciplinary team. Three cases of Disorders of Sex Differentiation (DSD) are presented with different causes and presentations. Two cases carrying XY karyotype pattern, while one case was of XX. The diagnosis of swyers syndrome, 5 alpha reductase deficiency and congenital adrenal hyperplasia was made on the basis of genital tract development, hormonal analysis and karyotyping. The strange feature which was common in all these cases was the wish of patients as well as family members to adopt sex of raring as male.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Hiperplasia Suprarrenal Congênita/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Disgenesia Gonadal 46 XY/diagnóstico , Hipospadia/diagnóstico , Erros Inatos do Metabolismo de Esteroides/diagnóstico , Adolescente , Hiperplasia Suprarrenal Congênita/terapia , Criança , Transtorno 46,XY do Desenvolvimento Sexual/terapia , Feminino , Disgenesia Gonadal 46 XY/terapia , Humanos , Hipospadia/terapia , Masculino , Erros Inatos do Metabolismo de Esteroides/terapia , Adulto Jovem
6.
BMJ Case Rep ; 12(9)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501175

RESUMO

Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (17OHP). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated 17OHP, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of 17OHP confirmed the underlying presence of non-classic CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Tumor de Células de Sertoli-Leydig/diagnóstico , 17-alfa-Hidroxiprogesterona/metabolismo , Adolescente , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/metabolismo , Feminino , Humanos , Achados Incidentais , Salpingo-Ooforectomia , Tumor de Células de Sertoli-Leydig/complicações , Tumor de Células de Sertoli-Leydig/metabolismo , Tumor de Células de Sertoli-Leydig/patologia , Virilismo/etiologia
7.
J Med Case Rep ; 13(1): 235, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31358067

RESUMO

BACKGROUND: 17α-Hydroxylase deficiency is a recessively inherited autosomal disease caused by mutations in the CYP17A1 gene. It is a rare disease and accounts for approximately 1% of congenital adrenal cortex hyperplasias. Inhibition of 17α-hydroxylase causes low levels of cortisol and high levels of adrenocorticotropic hormone in the blood as well as excessive levels of mineralocorticoids that lead to hypertension and hypokalemia. Usually, the female patients are diagnosed with abnormality of the genitalia or extra genitalia, primary amenorrhea, or hypertension in puberty. We report a case of a 29-year-old woman who had undergone gonadectomy in her childhood due to complete androgen insensitivity syndrome and was diagnosed with 17α-hydroxylase deficiency in adulthood. CASE PRESENTATION: Our patient was a Japanese female diagnosed with androgen insensitivity syndrome, and both gonadectomy and episioplasty were performed at the age of 11 years at the University of Tsukuba Hospital. Thereafter, she was transferred to our hospital at the age of 21 years for vaginoplasty. At the age of 25 years, she presented with hypertension followed by complicated hypokalemia at the age of 28 years. The captopril loading test and adrenocorticotropic hormone loading test of her adrenal steroidogenesis revealed primary aldosteronism. After sufficient genetic counseling, a genetic test was performed that identified her as having CYP17A1 gene mutation. CONCLUSIONS: The differential diagnosis of disorders of sex development can be difficult at a young age without complete expression of the phenotype. However, diagnosis at a later age would change the treatment and prognosis of the disease; therefore, a genetic examination should be considered.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Esteroide 17-alfa-Hidroxilase , Hiperplasia Suprarrenal Congênita/diagnóstico , Castração , Criança , Diagnóstico Tardio , Feminino , Aconselhamento Genético , Humanos , Mutação de Sentido Incorreto
8.
J Steroid Biochem Mol Biol ; 192: 105410, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31201926

RESUMO

CONTEXT: Cushing's syndrome is caused by increased exposure to cortisol. Discrimination of different causes of endogenous hypercortisolism can make a diagnostic dilemma. PATIENTS AND METHODS: In serum samples from patients with Cushing's syndrome (47 with Cushing's disease, 6 with ectopic ACTH-dependent Cushing's syndrome, 16 with adrenal adenoma, 7 bilateral adrenal hyperplasia (BMAH) with overt Cushing's syndrome, 42 controls from the general population) using novel method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) we measured 94 serum steroids to search for steroid fingerprint of each subtype. RESULTS: Patients with Cushing's disease and ectopic ACTH producing tumors showed elevated levels of androgens and their metabolites when compared with healthy controls. Mineralocorticoid precursors were also elevated in ectopic ACTH syndrome. The levels of androgens were decreased in adrenal adenomas and BMAH. ROC analysis showed 100% sensitivity and 93.6% specificity for 11ß-hydroxyepiandrosterone sulfate for discrimination of Cushing's disease from ectopic ACTH secretion. We didn't find any significant (p < 0.05) difference in steroids that would discriminate BMAH from unilateral adenomas causing Cushing's syndrome. CONCLUSION: Various causes of Cushing's syndrome show particular steroid fingerprints that can be used to discriminate and may help to achieve appropriate clinical diagnosis.


Assuntos
Síndrome de ACTH Ectópico/diagnóstico , Adenoma/diagnóstico , Hiperplasia Suprarrenal Congênita/diagnóstico , Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Hidrocortisona/sangue , Esteroides/sangue , Síndrome de ACTH Ectópico/sangue , Adenoma/sangue , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Síndrome de Cushing/sangue , Transtorno 46,XY do Desenvolvimento Sexual/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
J Steroid Biochem Mol Biol ; 192: 105389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31158444

RESUMO

Steroid analysis by LC-MS/MS in daily clinical routine diagnostics requires high-throughput conditions including fast chromatographic separation. Hereby, signal interferences may occur due to limited specificity in complex biologic matrices. During the last three years of routine steroid analysis in our laboratory and roughly 50,000 measurements, about 1% was affected by interferences, mainly serum cortisol (>90%) and dried blood 17α-hydroxyprogesterone (17-OHP). To overcome specificity problems, enhanced chromatography, ionization polarity switching, and detection via two-stage fragmentation (MS3) using a quadrupole linear ion trap were investigated in our study. Signal interferences of serum cortisol were eliminated by applying a protocol for automated method switching without changing the basic high-throughput LC-MS/MS setup. This approach includes negative ionization and extended chromatography from 4 to 6.6 min using the fourfold column length. From 9 samples affected by cortisol interference using the high-throughput method, 8 could be reliably analyzed applying the method switching protocol. Moreover, the applicability of the high-throughput method as second tier analysis in congenital adrenal hyperplasia (CAH) diagnostics from dried blood was verified with 100% diagnostic specificity. In addition, the combination of fast LC and MS3 detection enables specific quantitation of 17-OHP from dried blood spots on a screening time scale. This approach may be an alternative to the newborn screening for CAH by immunoassay due to its higher specificity, reducing the number of false positive results by 90%. In this work we recap experiences from three years of clinical routine steroid analysis via LC-MS/MS and present a unique analytical setup that enables both high-throughput and enhanced resolution analysis of steroid hormones in serum and dried blood.


Assuntos
17-alfa-Hidroxiprogesterona/análise , Hiperplasia Suprarrenal Congênita/diagnóstico , Cromatografia Líquida/métodos , Testes Diagnósticos de Rotina/métodos , Teste em Amostras de Sangue Seco/métodos , Hidrocortisona/sangue , Espectrometria de Massas em Tandem/métodos , 17-alfa-Hidroxiprogesterona/metabolismo , Hiperplasia Suprarrenal Congênita/sangue , Humanos
10.
Zhonghua Nei Ke Za Zhi ; 58(6): 428-434, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159521

RESUMO

Objective: To analyze the clinical features and genotypes of adult patients with simple virilizing form of 21-hydroxylase deficiency (SV 21-OHD). Methods: This is a retrospective study including 33 patients with SV 21-OHD from January 2015 to March 2018 in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine. Results: The diagnostic age of the patients was (26.3±6.5) years old. All patients presented with signs of masculinization, such as short stature (100%), clitoromegaly/microphallus (89.65%, 26/29), undeveloped breasts (82.76%, 24/29), deep voice (55.17%,16/29) and primary amenorrhea (89.65%, 26/29). The serum levels of 17-hydroxyprogesterone (17-OHP), androstenedione (AD) and testosterone were significantly elevated in 90.9%, 93.9% and 91.2% of the patients, respectively. Thirteen types of mutations were identified in CYP21A2 from these patients. Among them, I173N accounted for 40% and I2 G accounted for 18.33%. Four patients were found with multiple mutations in CYP21A2. Conclusions: Short stature, clitoromegaly/microphallus and primary amenorrhea are the most common clinical features in adult patients with SV 21-OHD. Serum levels of 17-OHP and AD are important indices for the diagnosis and monitoring of the patients. I173N and I2 G are the two most prevalent mutations in patients of the present study. Limitation of clinical recognition and delay in treatment contribute to the short stature of the SV 21-OHD patients.


Assuntos
Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 21-Hidroxilase/genética , 17-alfa-Hidroxiprogesterona/sangue , Adulto , Androstenodiona/sangue , China , Feminino , Humanos , Masculino , Estudos Retrospectivos , Testosterona/sangue
11.
J Pak Med Assoc ; 69(5): 711-717, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31105293

RESUMO

Disorders of sex development (DSD) are defined as discrepancy between chromosomal, gonadal and anatomic sex. The basic principles for the management of DSD include a multidisciplinary approach for gender assignment. Clinical assessment includes a detailed history and examination of external genitalia. Most of the disorders with symmetrical gonades indicate hormonal cause while asymmetrical gonades are found in chromosomal DSDs. Karyotyping will indicate a 46XX DSD, 46 XY DSD or mosicism. Internal anatomy is defined by ultrasonography, genitoscopy and laparoscopy. Human chorionic gonadotrophins (hCG) stimulation test is carried out in under-virilised males to see the function of Leydig cells in testes. The Most common cause of 46XX DSD is congenital adrenal hyperplasia (CAH). The decision of gender assignment surgery is to be taken in a multidisciplinary environment and with informed consent of the parents. Most of 46 XX CAH patients, even if markedly virilised, and 46 XY complete androgen insensitivity syndrome are raised as females. Similarly, most of 5-α reductase deficiency and 17-ß hydroxysteroid dehydrogenase deficiency patients are assigned to the male gender. The decision in cases of mixed gondal dysgenesis and ovotesticular DSD is based on the development of external and internal genitalia. Patients with androgen biosynthetic defects, partial androgen insensitivity syndrome are usually assigned to the male gender.


Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , 17-Hidroxiesteroide Desidrogenases/deficiência , Hiperplasia Suprarrenal Congênita/diagnóstico , Síndrome de Resistência a Andrógenos/diagnóstico , Colestenona 5 alfa-Redutase/deficiência , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Feminino , Disgenesia Gonadal/diagnóstico , Ginecomastia/diagnóstico , Humanos , Cariotipagem , Masculino , Erros Inatos do Metabolismo de Esteroides/diagnóstico
12.
Urology ; 130: 132-137, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31071351

RESUMO

OBJECTIVE: To validate a parental assessment of children's external genitalia scale for females (PACE-F) for girls with congenital adrenal hyperplasia (CAH) by adapting the validated adult female genital self-image scale. METHODS: PACE-F was administered to parents of girls (Tanner 1, 2 months-12 years) with and without CAH. Final questions were determined by clinical relevance and psychometric properties (scores: 0-100). A reference range was established using 95% confidence interval among controls. Age-matched controls were compared to girls with CAH (1) <4 years old before and after female genital reconstruction surgery (FGRS), and (2) 4-12-year olds after FGRS. Nonparametric statistics were used. RESULTS: Participants included 56 parents of 41 girls with CAH (median 3.9 years old, 97.6% FGRS) and 139 parents of 130 girls without CAH. Face and content validity was established by families, experts, and factor analysis. Internal consistency was high (Cronbach's alpha: 0.83). Population reference score range was 66.7-100. Ten consecutive girls had pre- and post-FGRS PACE-F scores. All scores improved at 4 months after surgery and all preoperative scores were below reference range and lower than controls (P = .0001). All postoperative scores were within reference range, no different from controls (P = .18). Scores for girls with CAH after FGRS aged 4-12 years were no different from controls (100.0 vs 88.9, P = .77) and 90.0% were in reference range, as expected (P = .99). CONCLUSION: We present a validated instrument for parental assessment of genital appearance in girls with CAH. We demonstrate improved parent-reported appearance after FGRS, with scores similar to age-matched controls.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/cirurgia , Genitália Feminina/patologia , Genitália Feminina/cirurgia , Pais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Autorrelato
13.
J Coll Physicians Surg Pak ; 29(6): S54-S55, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142423

RESUMO

Lipoid congenital adrenal hyperplasia (LCAH) (OMIM No. 201710) is the most severe type of congenital adrenal hyperplasia (CAH). Its clinical presentation includes lethal disturbance of adrenal and gonadal steroid synthesis due to impairment in the conversion of cholesterol to pregnenolone. Infants with this disorder experience salt loss, and glucocorticoid and mineralocorticoid deficiencies. Replacement therapy has enabled long-term survival. Classic LCAH is relatively common in Japan and Korea but extremely rare in Caucasian populations. An XY male 5-year-old child presented at Endocrine Clinic of Armed Forces Institute of Pathology with ambiguous genitalia and hyperpigmentation. He had family history of CAH. His laboratory investigations revealed normal serum cortisol and 17 Hydroxy (17 OH) progesterone levels with high plasma ACTH and renin levels. He had low aldosterone with inadequate response with hCG stimulation test. This is the first case of non-classic LCAH reported in the Pakistani population. Steroidogenic acute regulatory protein (StAR) gene mutations result in LCAH and the condition should be considered in the differential diagnosis of an XY child with primary adrenal insufficiency.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtornos do Desenvolvimento Sexual/genética , Mutação , Fosfoproteínas/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Pré-Escolar , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Humanos , Masculino , Ultrassonografia
14.
J Pediatr Endocrinol Metab ; 32(5): 499-504, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31028712

RESUMO

Background Early diagnosis after newborn screening (NBS) for congenital adrenal hyperplasia (CAH) allows proper treatment, reducing mortality rates and preventing development of hyperandrogenic manifestations and incorrect sex assignment at birth. Despite the high NBS sensitivity to detect CAH classical forms, one of the main issues is identifying asymptomatic children who remained with increased 17-hydroxyprogesterone (17-OHP) levels. In this study, we aimed to contribute to understanding the diagnosis of these children. Methods Children with increased serum 17-OHP levels, and without disease-related clinical features during follow-up, underwent the entire CYP21A2 gene sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis (SALSA MLPA P050B CAH). Patients' genotypes were subsequently sorted as compatible with CAH disease, and children were evaluated to determine the clinical status. Results During the study period, 106,476 newborns underwent CAH NBS. During follow-up, 328 children (0.3%) were identified as having false-positive tests and 295 were discharged after presenting with 17-OHP levels within reference values. Thirty-three remained asymptomatic and with increased serum 17-OHP levels after a mean follow-up of 3.4 years, and were subjected to molecular analysis. Seventeen out of the 33 children carried mutations: seven in the heterozygous state, nine carried non-classical genotypes and the remaining child carried a classical genotype. Conclusions We found a high frequency of non-classical CAH (NCCAH) diagnosis among children with persistent elevation of 17-OHP levels. Our findings support molecular study as decisive for elucidating diagnosis in these asymptomatic children. Molecular analysis as a confirmatory test is relevant to guide their follow-up, allows genetic counseling and avoids over treating NCCAH form.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Biomarcadores/sangue , Mutação , Triagem Neonatal/métodos , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/genética , Estudos Transversais , Diagnóstico Precoce , Feminino , Seguimentos , Genótipo , Humanos , Recém-Nascido , Masculino , Prognóstico
15.
J Pediatr Endocrinol Metab ; 32(3): 259-267, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30817301

RESUMO

Background 11ß-hydroxylase deficiency (11ßOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5-8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11ßOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11ßOHD. Methods Clinical, biochemical and radiological data of patients with 11ßOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11ßOHD were identified (0.1-13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA-CA: 5.5 years, range 1.5-9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11ßOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11ßOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11ßOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 11-beta-Hidroxilase/genética , 17-alfa-Hidroxiprogesterona/sangue , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/genética , Hormônio Adrenocorticotrópico/sangue , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Mutação , Renina/sangue , Estudos Retrospectivos , Avaliação de Sintomas
16.
J Pediatr Endocrinol Metab ; 32(3): 253-258, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30817302

RESUMO

Background A provisionary screening programme for 21-hydroxylase deficiency (21-OHD) was initiated in Beijing in 2014. The aim of this study was to investigate the incidence and the associated clinical characteristics of neonatal congenital adrenal hyperplasia (CAH) in Beijing and to provide evidence-based guidance for its application in CAH screening. Methods Live birth newborns (n=44,360) were screened for CAH in Beijing from July 2014 to April 2018. The levels of 17-hydroxyprogesterone (17-OHP) in the blood were estimated using the time-resolved fluoroimmunoassay. Neonates with a positive result and a level >30 nmol/L of 17-OHP were called for a retest. CAH was diagnosed based on further laboratory findings combined with clinical signs, such as weight loss, feeding difficulties, skin pigmentation, and atypical genitalia. Through a review of medical records, the clinical findings including molecular data were reported. Results Of the 44,360 neonates screened, 280 cases were deemed positive. Of these, 203 neonates were recalled for further tests and six patients (three boys and three girls) were diagnosed with CAH. Five cases of classic salt-wasting and one case of simple virilising 21-OHD were identified. The incidence of CAH in Beijing was 1:7393. The most frequent 21-OHD mutation was c.293-13C/A>G. Conclusions The incidence of CAH in Beijing was higher than the national average. The results support the need for neonatal CAH screening in Beijing. This pilot study demonstrates the clinical characteristics of 21-OHD through newborn screening. Early detection and treatment through neonatal screening may reduce mortality rates and optimise developmental outcomes.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Triagem Neonatal , Hiperplasia Suprarrenal Congênita/sangue , Pequim , Feminino , Humanos , Recém-Nascido , Masculino , Projetos Piloto
17.
J Pediatr Endocrinol Metab ; 32(1): 75-82, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30864373

RESUMO

Background Sex assignment is a major issue in disorders of sexual differentiation (DSD). Not all conditions of DSD have clear recommendations on assignment and timing of surgery. Reports about sex assignment practice and the influence of culture and religion in the Arab region are scarce. Methods A survey questionnaire was distributed to participants in a paediatric endocrinology conference. Four DSD cases were presented. Participants were asked to fill in their answers on sex assignment choice, reasons for the particular assignment, strength of own recommendation and timing of surgery based on their practice. The cases presented were severely virilised XX congenital adrenal hyperplasia (CAH), complete androgen insensitivity syndrome (CAIS), severely undervirilised 5α reductase deficiency (5α RD) and XX ovotesticular case. Results Eighty-five endocrinologists participated in the study. Eighty (97.5%) chose a female sex to assign for the XX CAH. For the CAIS, 64 (78%) chose a female sex. Seventy-one (86.5%) voted for a male sex for the XY case of 5α RD. Forty-seven (57%) and 35 (43%) chose a female and a male sex for the ovotesticular case, respectively. The majority indicated that their advice for sex assignment is based on strong recommendations for the CAH, CAIS and 5α RD patients but they were open to the parents' cultural and religious beliefs in their decision of the assignment for the ovotesticular case. Conclusions Practice in the Arab region appears to be in line with the international guidelines in the majority of DSD sex assignment and timing of surgery issues. However, culture and religious beliefs influence the practice in certain circumstances.


Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Endocrinologistas/psicologia , Genitália/anormalidades , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Diferenciação Sexual , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/psicologia , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/psicologia , Transtornos do Desenvolvimento Sexual/psicologia , Endocrinologistas/normas , Feminino , Humanos , Recém-Nascido , Masculino , Processos de Determinação Sexual , Fatores Sexuais , Inquéritos e Questionários
19.
Exp Clin Endocrinol Diabetes ; 127(2-03): 171-177, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30812049

RESUMO

The introduction of newborn screening programmes in most Western countries for classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) enables timely introduction of life-saving glucocorticoid replacement in affected babies. Early diagnosis and optimised pediatric care not only successfully led to survival but also allow that almost all patients reach adulthood. Cohort studies in adults, however, provided evidence for significant health problems and co-morbidities of adult patients such as life-threatening adrenal crises, cardiovascular and metabolic health problems, fertility problems, benign endocrine tumours, and osteopenia and osteoporosis. This review summarises the current state of knowledge aiming to emphasize the neccessity of primary and secondary prevention of additional long-term health issues as a major task of health professionals in the care of CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/terapia , Hiperplasia Suprarrenal Congênita/prevenção & controle , Adulto , Criança , Humanos , Recém-Nascido
20.
BMJ Case Rep ; 12(2)2019 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739087

RESUMO

Adrenal myelolipomas are relatively rare tumours composed of adipocytes and myeloid cells that arise in response to chronic adrenocorticotropic hormone stimulation. We present the case of bilateral adrenal myelolipomas in a 39-year-old man with untreated congenital adrenal hyperplasia (CAH) presenting with acute adrenal insufficiency and severe virilisation. Phenotypically, he is a man of short stature and has hyperpigmentation of the skin, gingiva and nail beds. Genital examination revealed micropenis and no palpable testes. Laboratory testing was consistent with primary adrenal insufficiency. An abdominal CT showed bilateral adrenal myelolipomas. An MRI of the pelvis revealed female reproductive organs. Chromosome study showed a karyotype of 46,XX. A CYP21A2 gene mutation confirmed diagnosis of CAH with 21-hydroxylase deficiency. The patient was treated with stress dose corticosteroids, subsequently tapered to physiological doses. We review previously reported cases and discussed diagnosis and treatment, including hormonal therapy and psychological approach.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Hiperplasia Suprarrenal Congênita/diagnóstico , Insuficiência Adrenal/diagnóstico , Mielolipoma/diagnóstico por imagem , Corticosteroides/uso terapêutico , Neoplasias das Glândulas Suprarrenais/complicações , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/complicações , Insuficiência Adrenal/sangue , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/etiologia , Adulto , Diagnóstico Tardio , Feminino , Humanos , Imagem por Ressonância Magnética , Mielolipoma/complicações , Tomografia Computadorizada por Raios X , Virilismo/etiologia
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