Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

PubMed Central

Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

2014-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia.

PubMed

Deshpande, Saurabh S; Shetty, Devdas; Saifi, Shenaz

2017-01-01

Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of.

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia

PubMed Central

Shetty, Devdas; Saifi, Shenaz

2017-01-01

Summary Background Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. Case Report We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Conclusions Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of. PMID:29662583

Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations.

PubMed

Stoupa, Athanasia; Chaabane, Rim; Guériouz, Manelle; Raynaud-Ravni, Catherine; Nitschke, Patrick; Bole-Feyset, Christine; Mnif, Mouna; Ammar Keskes, Leila; Hachicha, Mongia; Belguith, Neila; Polak, Michel; Carré, Aurore

2018-05-23

Primary congenital hypothyroidism (CH) affects about 1:3000 newborns worldwide and is mainly caused by defects in thyroid gland development (thyroid dysgenesis, TD) or hormone synthesis. A genetic cause is identified in less than 10% of TD patients. Our aim was to identify novel candidate genes in patients with TD using next-generation sequencing tools. We used whole exome sequencing (WES) to study two families, a consanguineous Tunisian family (one child with severe thyroid hypoplasia) and a French family (two newborn siblings, with a thyroid in situ that was not enlarged on ultrasound at diagnosis). Variants in candidate genes were filtered according to type of variation, frequency in public and in-house databases, in silico prediction tools, and inheritance mode. We unexpectedly identified three different variants of the thyroid peroxidase (TPO) gene. A homozygous missense mutation (c.875C>T, p.S292F) was found in the Tunisian patient with severe thyroid hypoplasia. The two French siblings were compound heterozygotes (c.387delC/c.2578G>A, p.N129Kfs*80/p.G860R) for TPO mutations. All three mutations have been previously described in patients with goitrous CH. In our patients treatment was initiated immediately after diagnosis and the effect, if any, of TSH stimulation of these thyroids remains unclear. We report the first cases of thyroid hypoplasia at diagnosis during neonatal period in patients with CH and TPO mutations. These cases highlight the importance of screening for TPO mutations not only in goitrous CH, but also in thyroids of normal or small size, and they broaden the clinical spectrum of described phenotypes.

Mistaken gender identity in non-classical congenital adrenal hyperplasia.

PubMed

Kukreti, Prerna; Kandpal, Manish; Jiloha, R C

2014-04-01

Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder.

Diagnosis and management of classical congenital adrenal hyperplasia.

PubMed

Marumudi, Eunice; Khadgawat, Rajesh; Surana, Vineet; Shabir, Iram; Joseph, Angela; Ammini, Ariachery C

2013-08-01

Congenital adrenal hyperplasia (CAH) is among the most common genetic disorders. Deficiency of adrenal steroid 21-hydroxylase deficiency due to mutations in the CYP21A2 gene accounts for about 95% cases of CAH. This disorder manifests with androgen excess with or without salt wasting. It also is a potentially life threatening disorder; neonatal screening with 17-hydroxyprogesterone measurement can diagnose the condition in asymptomatic children. Carefully monitored therapy with glucocorticoid and mineralocorticoid supplementation will ensure optimal growth and development for children with CAH. Genital surgery may be required for girls with CAH. Continued care is required for individuals with CAH as adults to prevent long-term adverse consequences of the disease, including infertility, metabolic syndrome and osteoporosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Parental management of adrenal crisis in children with congenital adrenal hyperplasia

PubMed Central

Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

2018-01-01

Purpose Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydro-cortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents’ perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents’ perceived management ability and the impact CAH has on the family. Methods In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents’ experiences in managing crises. Results There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Practice

Parental management of adrenal crisis in children with congenital adrenal hyperplasia.

PubMed

Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

2017-10-01

Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydrocortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents' perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents' perceived management ability and the impact CAH has on the family. In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents' experiences in managing crises. There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Provider support is needed for these parents

Mistaken gender identity in non-classical congenital adrenal hyperplasia

PubMed Central

Kukreti, Prerna; Kandpal, Manish; Jiloha, R. C.

2014-01-01

Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder. PMID:24891708

Congenital Adrenal Hyperplasia: Unresolved Issues.

PubMed

Yau, Mabel; Khattab, Ahmed; Poppas, Dix; Ghizzoni, Lucia; New, Maria

2016-01-01

Congenital adrenal hyperplasia (CAH) describes a family of disorders that comes from enzymatic deficiencies in cortisol production, with 21-hydroxylase deficiency causing ∼90% of cases. Distinction is made between the severe classical form and milder nonclassical form of CAH. Molecular genetic analysis is used to confirm the hormonal diagnosis. A high rate of genotype-phenotype disconcordance has been found in 21-hydroxylase deficiency. The goal of treatment is to replace with synthetic glucocorticoids and mineralocorticoids and suppress adrenal androgen production. The treatment of patients affected with nonclassical CAH, particularly males, remains controversial. Variable synthetic glucocorticoids are used and new modes of glucocorticoid delivery are under investigation. To improve height, growth hormone and other adjuvant therapies are employed. Long-term outcomes of genital surgery using modern techniques in females affected with classical CAH continue to be investigated. Prenatal treatment with dexamethasone is available to avoid ambiguous genitalia in these females. Although studies have shown its safety to mother and fetus, prenatal treatment is still regarded as experimental. Currently, prenatal diagnosis of CAH can only be obtained through invasive methods. Recently, the detection of cell-free fetal DNA in maternal plasma has made it possible to make this diagnosis earlier and noninvasively. © 2016 S. Karger AG, Basel.

Dual-Hit Hypothesis Explains Pulmonary Hypoplasia in the Nitrofen Model of Congenital Diaphragmatic Hernia

PubMed Central

Keijzer, Richard; Liu, Jason; Deimling, Julie; Tibboel, Dick; Post, Martin

2000-01-01

Pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains a major therapeutic problem. Moreover, the pathogenesis of pulmonary hypoplasia in case of CDH is controversial. In particular, little is known about early lung development in this anomaly. To investigate lung development separate from diaphragm development we used an in vitro modification of the 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) animal model for CDH. This enabled us to investigate the direct effects of Nitrofen on early lung development and branching morphogenesis in an organotypic explant system without the influence of impaired diaphragm development. Epithelial cell differentiation of the lung explants was assessed using surfactant protein-C and Clara cell secretory protein-10 mRNA expression as markers. Furthermore, cell proliferation and apoptosis were investigated. Our results indicate that Nitrofen negatively influences branching morphogenesis of the lung. Initial lung anlage formation is not affected. In addition, epithelial cell differentiation and cell proliferation are attenuated in lungs exposed to Nitrofen. These data indicate that Nitrofen interferes with early lung development before and separate from (aberrant) diaphragm development. Therefore, we postulate the dual-hit hypothesis, which explains pulmonary hypoplasia in CDH by two insults, one affecting both lungs before diaphragm development and one affecting the ipsilateral lung after defective diaphragm development. PMID:10751355

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia.

PubMed

Mahood, Thomas H; Johar, Dina R; Iwasiow, Barbara M; Xu, Wayne; Keijzer, Richard

2016-05-01

We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects. Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico. Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofen-induced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K, TGF-β, and cell cycle kinases. Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.

Early diagnosis of salt-losing congenital adrenal hyperplasia in a newborn boy.

PubMed Central

Hughes, I. A.; Winter, J. S.

1977-01-01

Assays of serum 17-hydroxyprogesterone concentration may be relied upon to establish a diagnosis of congenital adrenal hyperplasia within a few hours of birth. In a male infant the concentration of 17-hydroxyprogesterone was increased in cord serum and remained elevated until glucocorticoid therapy was started on the 5th day of life. Plasma renin activity was increased only slightly in the first few days, but a striking increase on day 5, along with a gradual increase in the serum potassium concentration, confirmed that the infant had the salt-losing form of congenital adrenal hyperplasia. It was not possible to demonstrate an increased concentration of 17-hydroxyprogesterone, in amniotic fluid obtained at 30 weeks' gestation, presumably because of interference in this assay by cross-reacting steroids. Studies of the mother's serum concentration of 17-hydroxyprogesterone and cortisol during delivery did not disclose any deviation from normal. PMID:890632

Clinical and molecular profile of newborns with confirmed or suspicious congenital adrenal hyperplasia detected after a public screening program implementation.

PubMed

Kopacek, Cristiane; Prado, Mayara J; da Silva, Claudia M D; de Castro, Simone M; Beltrão, Luciana A; Vargas, Paula R; Grandi, Tarciana; Rossetti, Maria L R; Spritzer, Poli Mara

2018-04-30

To describe the results obtained in a neonatal screening program after its implementation and to assess the clinical and molecular profiles of confirmed and suspicious congenital adrenal hyperplasia cases. A cross-sectional study was conducted. Newborns with suspected disease due to high 17-hydroxyprogesterone levels and adjusted for birth weight were selected. Classical congenital adrenal hyperplasia (salt-wasting and simple virilizing forms) was diagnosed by an increase in 17-hydroxyprogesterone levels as confirmed in the retest, clinical evaluation, and genotype determined by SNaPshot and multiplex ligation-dependent probe amplification. After 24 months, 15 classic congenital adrenal hyperplasia cases were diagnosed in a total of 217,965 newborns, with an estimated incidence of 1:14,531. From 132 patients, seven non-classical and 14 heterozygous patients were screened for CYP21A2 mutations, and 96 patients presented false positives with wild type CYP21A2. On retest, increased 17-hydroxyprogesterone levels were found in classical congenital adrenal hyperplasia patients and showed significant correlation with genotype-related classical genital adrenal hyperplasia. The most frequent mutations were IVS2-13A/C>G followed by gene deletion or rearrangement events in the classical form. In non-classical and heterozygous diseases, p.Val282Leu was the most common mutation. The results underscore the effectiveness of congenital adrenal hyperplasia neonatal screening in the public health system and indicate that the adopted strategy was appropriate. The second sample collection along with genotyping of suspected cases helped to properly diagnose both severe and milder cases and delineate them from false positive patients. Copyright © 2018. Published by Elsevier Editora Ltda.

Changing perspectives in screening for congenital hypothyroidism and congenital adrenal hyperplasia.

PubMed

Mitchell, Marvin L; Hsu, Ho-Wen; Sahai, Inderneel

2014-02-01

The purpose of this review is to summarize recent information that has had a significant impact on the laboratory diagnosis and clinical management of newborns with congenital hypothyroidism and congenital adrenal hyperplasia (CAH). An approximate doubling of the incidence rate of congenital hypothyroidism in many parts of the world has been attributed to increased detection of infants with mild disease, delayed thyroid stimulating hormone elevations and demographic changes. A substantial number of children with modest thyroid stimulating hormone elevations on screening have permanent disease. Circulating levels of thyroxine may vary among hypothyroid children who are given identical dosages of medication. Treated infants should be monitored every 1-2 months during the first year of life. Although, generic and brand name thyroxine preparations may not be bioequivalent, children can be well controlled on generic formulations.Enzyme linked immunoassay assay for 17-hydroxyprogesterone is associated with a high rate of false positive specimens. In attempts to minimize this problem, some programs have resorted to two-tier screening of the initial specimen with steroid profiling as the second tier. Several programs are routinely testing second specimens in an effort to reduce the incidence of missed CAH cases. This review explains the uptick in incidence rate of congenital hypothyroidism and underscores issues in management that can affect developmental outcome. One specimen two-tier testing for CAH resulted in an increased false negative rate without significantly reducing the false positive rate. The benefit of collecting second specimens for CAH screening is problematic. Optimal treatment of CAH continues to pose a challenge.

Magnetic Resonance Imaging of the Vocal Folds in Women with Congenital Adrenal Hyperplasia and Virilized Voices

ERIC Educational Resources Information Center

Nygren, Ulrika; Isberg, Bengt; Arver, Stefan; Hertegård, Stellan; Södersten, Maria; Nordenskjöld, Agneta

2016-01-01

Purpose: Women with congenital adrenal hyperplasia (CAH) may develop a virilized voice due to late diagnosis or suboptimal suppression of adrenal androgens. Changes in the vocal folds due to virilization have not been studied in vivo. The purpose was to investigate if the thyroarytenoid (TA) muscle is affected by virilization and correlate…

Feminising genitoplasty: one-stage genital reconstruction in congenital adrenal hyperplasia: 30 years' experience.

PubMed

Roll, M F; Kneppo, C; Roth, H; Bettendorf, M; Waag, K-L; Holland-Cunz, S

2006-10-01

The study objective is to evaluate the results of our surgical technique for children with congenital adrenal hyperplasia and ambiguous genitalia at the University Hospital of Heidelberg, Department of Paediatric Surgery. The records of 19 patients with congenital adrenal hyperplasia treated between 1972 and 2004 were reviewed with respect to age at surgery, operative procedures and outcome. We describe the recession clitoroplasty technique currently used in our hospital and highlight the importance of short and long-term follow-up results with respect to appearance, position and size of the clitoris and quality of the vagina. One-stage recession clitoroplasty and vaginoplasty gives very satisfactory cosmetic and functional results, with few complications and a reduced need for secondary surgical interventions. The results of this study support the assumption that total correction can be achieved through a single-stage operation, performed in infancy.

Congenital adrenal hyperplasia with localized aggressive periodontitis and amelogenesis imperfecta.

PubMed

Ajlan, Sumaiah Abdulbaqi

2015-11-01

Congenital adrenal hyperplasia (CAH) is an inherited medical condition that implies defects in steroid biosynthesis. The dental findings of a female patient with CAH are reported. The patient suffered from severe periodontal tissue destruction, obvious enamel defects, as well as some occlusal problems. The management approach is presented and the possibility of interrelation of her dental findings with her medical condition is discussed. © 2015 Japanese Teratology Society.

p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia

PubMed Central

Park, Hye Won; Kwak, Byung Ok; Kim, Gu-Hwan; Yoo, Han-Wook

2013-01-01

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia which is caused by mutations in the steroidogenic acute regulatory protein (StAR). The mutations in StAR gene resulted in failure of the transport cholesterol into mitochondria for steroidogenesis in the adrenal gland. Twin sisters (A, B) with normal 46, XX were born at 36+2 gestational week, premature to nonrelated parents. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium. Laboratory finding revealed normal 17-hydroxyprogesterone level, elevated adrenocorticotropin hormone (A, 4,379.2 pg/mL; B, 11,616.1 pg/mL), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng mL/hr). However, the level of plasma cortisol before treatment was low (1.5 µg/dL) in patient B but normal (8.71 µg/dL) in patient A. Among them, only patient A was presented with adrenal insufficiency symptoms which was suggestive of CLAH and prompted us to order a gene analysis in both twin. The results of gene analysis of StAR in twin revealed same heterozygous conditions for c.544C>T (Arg182Cys) in exon 5 and c.722C>T (Gln258*) in exon 7. We report the first case on the mutation of p.R182C in exon 5 of the StAR gene in Korea. PMID:24904850

Should male gender assignment be considered in the markedly virilized patient With 46,XX and congenital adrenal hyperplasia?

PubMed

Lee, Peter A; Houk, Christopher P; Husmann, Douglas A

2010-10-01

We assess the outcome in 46,XX men with congenital adrenal hyperplasia who were born with Prader 4 or 5 genitalia and assigned male gender at birth. After receiving institutional review board approval and subject consent we reviewed the medical records of 12 men 35 to 69 years old with 46,XX congenital adrenal hyperplasia, of whom 6 completed social and gender issue questionnaires. All subjects were assigned male gender at birth, were diagnosed with virilizing congenital adrenal hyperplasia at age greater than 3 years and indicated a male gender identity with sexual orientation to females. Ten of the 12 subjects had always lived as male and 2 who were reassigned to female gender in childhood subsequently self-reassigned as male. Nine of the 12 men had long-term female partners, including 7 married 12 years or more. The 3 subjects without a long-term female partner included 1 priest, 1 who was reassigned female gender, married, divorced and self-reassigned as male, and 1 with a girlfriend and sexual activity. All except the priest and the subject who was previously married when female indicated a strong libido and frequent orgasmic sexual activity. Responses to self-esteem, masculinity, body image, social adjustment and symptom questionnaires suggested adjustments related to the extent of familial and social support. Outcome data on severely masculinized 46,XX patients with congenital adrenal hyperplasia who were assigned male gender at birth indicate male gender identity in adulthood with satisfactory male sexual function in those retaining male genitalia. In men who completed questionnaires results were poorer in those lacking familial/social support. Male gender of rearing may be a viable option for parents whose children are born with congenital adrenal hyperplasia, a 46,XX karyotype and male genitalia, although positive parental and other support, and counseling are needed for adjustment. Copyright © 2010 American Urological Association Education and Research

Adrenal rest tissue in gonads of patients with classical congenital adrenal hyperplasia: multicenter study of 45 French male patients.

PubMed

Pierre, Peggy; Despert, François; Tranquart, François; Coutant, Régis; Tardy, Véronique; Kerlan, Véronique; Sonnet, Emmanuel; Baron, Sabine; Lorcy, Yannick; Emy, Philippe; Delavierre, Dominique; Monceaux, Françoise; Morel, Yves; Lecomte, Pierre

2012-12-01

Several cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue. Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared. TART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART. Due to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Congenital diaphragmatic hernia: antenatal prognostic factors. Does cardiac ventricular disproportion in utero predict outcome and pulmonary hypoplasia?

PubMed

Thébaud, B; Azancot, A; de Lagausie, P; Vuillard, E; Ferkadji, L; Benali, K; Beaufils, F

1997-10-01

Despite regular progress in neonatal intensive care, congenital diaphragmatic hernia (CDH) diagnosed antenatally is still associated with up to 80% mortality. It is impossible to predict which fetus with CDH will survive or not. To identify reliable antenatal predictors of outcome and of pulmonary hypoplasia (PH) in fetuses with CDH. Retrospective study. Paediatric intensive care unit of a university children's hospital. Antenatal parameters and presence of left ventricular hypoplasia in utero were compared retrospectively to outcome and to presence of PH in 32 consecutive newborn infants with antenatally diagnosed CDH. Antenatal parameters included: gestational age at diagnosis, herniated organs, associated malformations and presence of polyhydramnios. Size of the cardiac ventricles, the aorta (Ao) and the pulmonary artery (PA) were obtained by fetal echocardiography, from which we calculated a cardioventricular index (left ventricle/right ventricle, LV/RV) and a cardiovascular index (Ao/PA). Delivery was planned in order to provide ventilatory and hemodynamic management. In case of death, PH was assessed according to the following criteria: the lung weight/body weight index and the radial alveolar count. For statistical comparisons, patients were separated into two groups: the hypoplasia group (H) and the non-hypoplasia group (NH). Thirty-two pregnancies were delivered. Twenty-six newborns died (81%), 6 survived (19%). When comparing non-survivors to survivors, predictors of poor outcome were: mean gestational age at diagnosis (23 vs 28 weeks, p = 0.002), intrathoracic stomach (20 vs 1 s, p = 0.01) and associated malformations (6 vs 0). Cardiac ventricular disproportion, expressed by the LV/RV ratio, appeared to correlate well with a poor outcome (0.63 in non-survivors vs 0.93 in survivors, p = 0.03) and with PH (0.63 in the H group vs 0.95 in the NH group, p = 0.03). Our study confirmed the factors for a poor prognosis associated with CDH previously described in

Nasomaxillary hypoplasia with a congenitally missing tooth treated with LeFort II osteotomy, autotransplantation, and nickel-titanium alloy wire.

PubMed

Ishida, Takayoshi; Ikemoto, Shigehiro; Ono, Takashi

2015-09-01

In some skeletal Class III adult patients with nasomaxillary hypoplasia, the LeFort I osteotomy provides insufficient correction. This case report describes a 20-year-old woman with a combination of nasomaxillary hypoplasia and a protrusive mandible with a congenitally missing mandibular second premolar. We performed a LeFort II osteotomy for maxillary advancement. Autotransplantation of a tooth was also performed; the donor tooth was used to replace the missing permanent tooth. To increase the chance of success, we applied light continuous force with an improved superelastic nickel-titanium alloy wire technique before extraction and after transplantation. The patient's profile and malocclusion were corrected, and the autotransplanted tooth functioned well. The postero-occlusal relationships were improved, and ideal overbite and overjet relationships were achieved. The methods used in this case represent a remarkable treatment. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia.

PubMed

Khoshgoo, Naghmeh; Kholdebarin, Ramin; Pereira-Terra, Patricia; Mahood, Thomas H; Falk, Landon; Day, Chelsea A; Iwasiow, Barbara M; Zhu, Fuqin; Mulhall, Drew; Fraser, Carly; Correia-Pinto, Jorge; Keijzer, Richard

2017-11-13

We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy. We profiled miR-200b expression during nitrofen-induced PH using RT-qPCR and in situ hybridization in the nitrofen rat model of PH and CDH. The effects of nitrofen on downstream miR-200b targets were studied in bronchial lung epithelial cells using a SMAD luciferase assay, Western blotting and Immunohistochemistry. We evaluated miR-200b as a lung growth promoting therapy ex vivo and in vivo using lung explant culture and transplacental prenatal therapy in the nitrofen rat model. We show that late lung hypoplasia in CDH is associated with (compensatory) upregulation of miR-200b in less hypoplastic lungs. Increasing miR-200b abundance with mimics early after nitrofen treatment decreases SMAD-driven TGF-β signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH. Our data indicate that miR-200b improves PH and decreases the incidence of CDH. Future studies will further exploit this newly discovered prenatal therapy for lung hypoplasia and CDH.

Staged transcatheter treatment of portal hypoplasia and congenital portosystemic shunts in children.

PubMed

Bruckheimer, Elchanan; Dagan, Tamir; Atar, Eli; Schwartz, Michael; Kachko, Ludmila; Superina, Riccardo; Amir, Gabriel; Shapiro, Rivka; Birk, Einat

2013-12-01

Congenital portosystemic shunts (CPSS) with portal venous hypoplasia cause hyperammonemia. Acute shunt closure results in portal hypertension. A transcatheter method of staged shunt reduction to afford growth of portal vessels followed by shunt closure is reported. Pressure measurements and angiography in the CPSS or superior mesenteric artery (SMA) during temporary occlusion of the shunt were performed. If vessels were diminutive and the pressure was above 18 mmHg, a staged approach was performed, which included implantation of a tailored reducing stent to reduce shunt diameter by ~50 %. Recatheterization was performed approximately 3 months later. If the portal pressure was below 18 mmHg and vessels had developed, the shunt was closed with a device. Six patients (5 boys, 1 girl) with a median age of 3.3 (range 0.5-13) years had CPSS portal venous hypoplasia and hyperammonemia. Five patients underwent staged closure. One patient tolerated acute closure. One patient required surgical shunt banding because a reducing stent could not be positioned. At median follow-up of 3.8 (range 2.2-8.4) years, a total of 21 procedures (20 transcatheter, 1 surgical) were performed. In all patients, the shunt was closed with a significant reduction in portal pressure (27.7 ± 11.3 to 10.8 ± 1.8 mmHg; p = 0.016), significant growth of the portal vessels (0.8 ± 0.5 to 4.0 ± 2.4 mm; p = 0.037), and normalization of ammonia levels (202.1 ± 53.6 to 65.7 ± 9.6 μmol/L; p = 0.002) with no complications. Staged CPSS closure is effective in causing portal vessel growth and treating hyperammonemia.

Unusual congenital pulmonary anomaly with presumed left lung hypoplasia in a young dog.

PubMed

Lee, C M; Kim, J H; Kang, M H; Eom, K D; Park, H M

2014-05-01

A seven-month-old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors' knowledge, this case represents the first report of such a pulmonary anomaly in a dog. © 2014 British Small Animal Veterinary Association.

Fetal endocrine therapy for congenital adrenal hyperplasia should not be done.

PubMed

Miller, Walter L

2015-06-01

Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus remains a controversial experimental treatment. Review of data from animal experimentation and human trials indicates that dexamethasone cannot be considered safe for the fetus. In animals, prenatal dexamethasone decreases birth weight, affects renal, pancreatic beta cell and brain development, increases anxiety and predisposes to adult hypertension and hyperglycemia. In human studies, prenatal dexamethasone is associated with orofacial clefts, decreased birth weight, poorer verbal working memory, and poorer self-perception of scholastic and social competence. Numerous medical societies have cautioned that prenatal treatment of adrenal hyperplasia with dexamethasone is not appropriate for routine clinical practice and should only be done in Institutional Review Board approved, prospective clinical research settings with written informed consent. The data indicate that this treatment is inconsistent with the classic medical ethical maxim to 'first do no harm'. Copyright © 2015 Elsevier Ltd. All rights reserved.

HYDROCORTISONE THERAPY AND GROWTH TRAJECTORY IN CHILDREN WITH CLASSICAL CONGENITAL ADRENAL HYPERPLASIA.

PubMed

Bizzarri, Carla; Improda, Nicola; Maggioli, Chiara; Capalbo, Donatella; Roma, Silvia; Porzio, Ottavia; Salerno, Mariacarolina; Cappa, Marco

2017-05-01

Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations. Height velocity, pubertal growth spurt, and final height were evaluated as outcomes. Final height standard deviation score (SDS) was lower than target height SDS (-0.74 ± 1.1 versus -0.31 ± 1.01; P<.001). Target-adjusted final height SDS was -0.44 ± 1.8 in males and -0.13 ± 1.1 in females (P = .001). Total pubertal growth was 21.9 ± 7.3 cm in males and 19.2 ± 8.2 cm in females (P = .19). Hydrocortisone dose increased and height-velocity SDS decreased during puberty. At multivariable analysis, height-velocity SDS was adversely affected by hydrocortisone dose (P = .038) and directly related to adrenocorticotropic hormone (ACTH) levels (P = .023). Target-adjusted final-height SDS was adversely affected by hydrocortisone dose (P<.001) and positively related to mineralocorticoid therapy (P = .001) and ACTH levels (P = .02). Total pubertal growth (cm) was positively related to ACTH levels (P = .01). Height outcome of CAH patients is now better than previously reported. During puberty, the lowest effective dose of hydrocortisone should be used to optimize pubertal growth spurt and final height. 17-OHP = 17-alpha-hydroxyprogesterone ACTH = adrenocorticotropic hormone BMI = body mass index CAH = congenital adrenal hyperplasia GH = growth hormone HPA = hypothalamus-pituitary-adrenal PRA = plasma renin activity SDS = standard deviation score SV = simple virilizing SW = salt-wasting.

Congenital Adrenal Hyperplasia in an Elite Female Soccer Player; What Sports Medicine Clinicians Should Know about This?

PubMed

Angoorani, Hooman; Haratian, Zohreh; Halabchi, Farzin

2012-09-01

Congenital Adrenal Hyperplasia (CAH) refers to a group of congenital conditions characterized by disordered cortisol synthesis. The correlation between CAH and sports performance has been less studied before and there is very limited information regarding the impacts of this congenital disease on sports performance. Probably, there are some limitations for patients who suffer from CAH in sports, but at the same time, they may enjoy some advantage due to the probable effect of endogenous hyperandrogenism on their exercise performance. The case is a 14 - year old girl with male phenotype who is a known case of congenital adrenal hyperplasia. She plays in the women's national soccer team of under 16. She has been in the first division league of indoor soccer for 4 years and was also selected in the preparation training camp of women's football team for Singapore's youth Olympic Games. Her illness and dependence on corticosteroid have caused some concerns for her participation in the international competitions of women. However, following consultations with the Therapeutic Use Exemption (TUE) Committee of games organization, she received TUE to use corticosteroid only within the games period. Despite all her problems, she is now playing in the Second Division League of indoor soccer. A female adolescent with CAH may compete at the high level of outdoor and indoor soccer. However, there are many questions regarding the advantages and disadvantages of this congenital disorder and its treatment on sports related issues.

Staged Transcatheter Treatment of Portal Hypoplasia and Congenital Portosystemic Shunts in Children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruckheimer, Elchanan, E-mail: elchananb@bezeqint.net; Dagan, Tamir; Atar, Eli

2013-12-15

Purpose: Congenital portosystemic shunts (CPSS) with portal venous hypoplasia cause hyperammonemia. Acute shunt closure results in portal hypertension. A transcatheter method of staged shunt reduction to afford growth of portal vessels followed by shunt closure is reported. Methods: Pressure measurements and angiography in the CPSS or superior mesenteric artery (SMA) during temporary occlusion of the shunt were performed. If vessels were diminutive and the pressure was above 18 mmHg, a staged approach was performed, which included implantation of a tailored reducing stent to reduce shunt diameter by {approx}50 %. Recatheterization was performed approximately 3 months later. If the portal pressuremore » was below 18 mmHg and vessels had developed, the shunt was closed with a device. Results: Six patients (5 boys, 1 girl) with a median age of 3.3 (range 0.5-13) years had CPSS portal venous hypoplasia and hyperammonemia. Five patients underwent staged closure. One patient tolerated acute closure. One patient required surgical shunt banding because a reducing stent could not be positioned. At median follow-up of 3.8 (range 2.2-8.4) years, a total of 21 procedures (20 transcatheter, 1 surgical) were performed. In all patients, the shunt was closed with a significant reduction in portal pressure (27.7 {+-} 11.3 to 10.8 {+-} 1.8 mmHg; p = 0.016), significant growth of the portal vessels (0.8 {+-} 0.5 to 4.0 {+-} 2.4 mm; p = 0.037), and normalization of ammonia levels (202.1 {+-} 53.6 to 65.7 {+-} 9.6 {mu}mol/L; p = 0.002) with no complications. Conclusion: Staged CPSS closure is effective in causing portal vessel growth and treating hyperammonemia.« less

EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Congenital left-sided heart obstruction

PubMed Central

Carr, Michelle; Curtis, Stephanie; Marek, Jan

2018-01-01

Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation. PMID:29681546

Antenatal Saireito (TJ-114) Can Improve Pulmonary Hypoplasia and Pulmonary Vascular Remodeling in Nitrofen-Induced Congenital Diaphragmatic Hernia.

PubMed

Hirako, Shima; Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Mano, Yukio; Nakano, Tomoko; Imai, Kenji; Li, Hua; Toyokuni, Shinya; Kikkawa, Fumitaka

2016-09-01

Congenital diaphragmatic hernia (CDH) can induce lung hypoplasia and pulmonary hypertension and is associated with high mortality. The purpose of this study is to examine the efficacy and safety of antenatal Saireito (TJ-114), a traditional Japanese herbal medicine, in a rat CDH model. Sprague-Dawley rats were exposed to an herbicide (nitrofen, 100 mg) on embryonic day 9 (E9) to induce CDH, and antenatal Saireito (2000 mg/kg/day) was orally administered from E10 to E20. On E21, fetuses were delivered. Antenatal Saireito significantly decreased the incidence of CDH (p < 0.01), increased lung volume (p < 0.01), improved alveolarization and pulmonary artery remodeling using histological analysis, and improved respiratory function using gasometric analysis (pH; p < 0.05, and PCO2 ; p < 0.01). In addition, antenatal Saireito significantly decreased endothelin-1 and endothelin receptor A expression in the pulmonary arteries. Taken together, our results demonstrated that antenatal Saireito can improve fetal pulmonary hypoplasia and pulmonary vascular remodeling and, as a result, can improve respiratory function in a rat CDH model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Abnormal platelet-derived growth factor signaling accounting for lung hypoplasia in experimental congenital diaphragmatic hernia.

PubMed

Dingemann, Jens; Doi, Takashi; Ruttenstock, Elke; Puri, Prem

2010-10-01

The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is not fully understood. Platelet-derived growth factor A (PDGFA) and platelet-derived growth factor receptor α (PDGFRα) play a crucial role in lung development. It has been reported that PDGF induces H(2)O(2)-production and that oxidative stress may be an important mechanism for the impaired lung development in the nitrofen rat model. We hypothesized that pulmonary expression of PDGFA and PDGFRα is altered in the nitrofen induced CDH model. Pregnant rats received 100 mg nitrofen or vehicle on gestational day 9 (D9) and were sacrificed on D15, D18 or D21. RNA was extracted from fetal left lungs and mRNA levels of PDGFA and PDGFRα were determined using real-time polymerase chain reaction. Immunohistochemistry for protein expression of PDGFA and PDGFRα was performed. Pulmonary H(2)O(2) was measured colorimetrically. mRNA levels of PDGFRα at D15 (4.50 ± 0.87) and PDGFA at D18 (2.90 ± 1.38) were increased in the nitrofen group (P < .05). Immunohistochemistry revealed increased pulmonary expression of PDGFRα and PDGFA. H(2)O(2) content was significantly higher in the nitrofen group. Increased expression of PDGFA and PDGFRα suggests that pulmonary hypoplasia in the nitrofen CDH model may be owing to PDGF-induced oxidative stress during lung development. Copyright © 2010 Elsevier Inc. All rights reserved.

[Diffuse hypertrichosis revealing non-classical congenital adrenal hyperplasia].

PubMed

Berthin, C; Sibilia, P; Martins-Hericher, J; Donzeau, A; Martin, L

2018-04-01

Non-classical congenital adrenal hyperplasia (NC-CAH) is a recessive autosomal disease caused by a deficiency of adrenal steroidogenesis enzymes. It must be distinguished from classical CAH, either simple virilising or salt-wasting, diagnosed during the neonatal period and responsible for potentially lethal disorders of sexual differentiation. NC-CAH presents a simpler and less specific clinical picture. Herein, we present two cases comprising twin girls consulting for diffuse hypertrichosis. Two 5-year-old twin girls were seen at our consultation for increased pilosity on all four limbs, but with no facial pilosity or synophrys, as well as comedones on the chin. Their height and weight and psychomotor development was normal, with no signs of precocious puberty and no clitoral hypertrophy. Levels of 17OH-P and SDHA were high, while FSH and LH were low and IGF1 and TSH were normal. Analysis of gene CYP21 associated with NC-CAH showed mutations p.V281L and IVS2-13A/C>G. Mutation p.V281L was present in the heterozygous state in the older sister and the father, together with moderate hyperpilosity but without hirsutism or acne. No mutations were found in the mother, indicating either de novo appearance of mutation IVS2-13A/C>G in the twins or germline mosaicism in the mother. We diagnosed NC-CAH as the cause of diffuse hypertrichosis in these twins. This disease is not rare, with a prevalence of 1/1000 to 1500 among peoples of European descent. It is often diagnosed late since routine neonatal screening is not performed. In some cases, NC-CAH remains asymptomatic. The appearance of pubic hair at around 5 to 7 years is the initial reason for consultation, particularly with a dermatologist. Hyperandrogenism varies, involving hirsutism, acne, fertility disorders and premature ageing of bone. Cortisol and aldosterone levels are generally normal. The risk of acute adrenal insufficiency is extremely low. Differential diagnosis concerns ovarian or adrenal tumors and

Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.

PubMed

Bizzarri, Carla; Olivini, Nicole; Pedicelli, Stefania; Marini, Romana; Giannone, Germana; Cambiaso, Paola; Cappa, Marco

2016-08-02

Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine. A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission. Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3β-Hydroxysteroid dehydrogenase (3βHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified. Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants

Antenatal vitamin A administration attenuates lung hypoplasia by interfering with early instead of late determinants of lung underdevelopment in congenital diaphragmatic hernia.

PubMed

Baptista, Maria J; Melo-Rocha, Gustavo; Pedrosa, Carla; Gonzaga, Sílvia; Teles, Antónia; Estevão-Costa, José; Areias, José C; Flake, Alan W; Leite-Moreira, Adelino F; Correia-Pinto, Jorge

2005-04-01

Early and late lung underdevelopment in congenital diaphragmatic hernia (CDH) is likely caused by nonmechanical (directly mediated by nitrofen) and mechanical (mediated by thoracic herniation) factors, respectively. The authors investigated if vitamin A enhances lung growth because of effects on both early and late determinants of lung hypoplasia. Twenty-seven pregnant Wistar rats were exposed on embryonic day (E)9.5 to 100 mg of nitrofen or just olive oil. From nitrofen-exposed pregnant rats, 12 were treated at day 9.5 or 18.5 with 15,000 IU of vitamin A. Lungs were harvested at E18, E20, and E22, weighed, and analyzed for DNA and protein contents. Left and/or right lung hypoplasia was estimated by assessment of the ratios of lung to body weight and left to right lung weight. Fetuses were assigned to 5 experimental groups: baseline (exposed neither to nitrofen nor vitamin A), nitrofen (exposed to nitrofen without CDH), CDH (exposed to nitrofen with CDH), nitr+vitA (exposed to nitrofen without CDH and treated with vitamin A), and CDH+vitA (exposed to nitrofen with CDH and treated with vitamin A). Incidence of hernia was significantly reduced in fetuses treated with vitamin A. When vitamin A was administered at E9.5, the authors observed similar effect on lung hypoplasia measured through ratio of lung to body weight at E18 in the nitrofen and CDH groups (nitrofen 1.92% +/- 0.05%, CDH 1.92% +/- 0.04%), whereas lung hypoplasia was attenuated relative to baseline (2.45% +/- 0.05%) in 5% and 4% in nitrofen (nitr+vitA 2.05% +/- 0.03%) and CDH (CDH+vitA 2.08% +/- 0.04%) groups, respectively. At E20, lung hypoplasia was increased in CDH compared with nitrofen groups (nitrofen 2.52% +/- 0.1%, CDH 2.39% +/- 0.05%), whereas vitamin A attenuated lung hypoplasia, in relation to baseline (3.20% +/- 0.07%), 14% in both nitrofen-exposed groups (nitr+vitA 2.96% +/- 0.03%, CDH+vitA 2.83% +/- 0.03%). At E22, lung hypoplasia was significantly higher in CDH group than nitrofen group

[Pulmonary hypoplasia: An analysis of cases over a 20-year period].

PubMed

Delgado-Peña, Yanny Paola; Torrent-Vernetta, Alba; Sacoto, Gabriela; de Mir-Messa, Inés; Rovira-Amigo, Sandra; Gartner, Silvia; Moreno-Galdó, Antonio; Molino-Gahete, José Andrés; Castillo-Salinas, Felíx

2016-08-01

Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Growth in disorders of adrenal hyperfunction.

PubMed

Magiakou, Maria Alexandra

2004-08-01

This article reviews how growth is affected in disorders of adrenal hyperfunction. Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Adrenal androgens, when in excess, lead to advanced linear growth and skeletal maturation, and prolonged hypercortisolemia leads to the suppression of growth hormone (GH) secretion and inhibition of somatomedin C and other growth factor effects on their target tissues. In virilizing adrenal tumors height is increased at diagnosis, but after surgical cure the final height is usually in the normal range. In congenital adrenal hyperplasia height is usually compromised by advanced skeletal maturation or by suppressed growth, particularly in the first years of life, due to excess glucocorticoid treatment. The final height is reduced in both clinical forms (salt wasting and simple virilizing) and sexes in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Growth impairment is also the hallmark of Cushing syndrome of whatever etiology when it occurs in children and growing adolescents, and the final height of these patients, even after surgical cure, remains compromised. This is apparently due to direct or indirect growth impairment by the hypercortisolism during the disease, followed by inadequate catch-up growth. Although it seems that GH treatment might be beneficial for improving final height both in patients with congenital adrenal hyperplasia who have poor height predictions and in patients with Cushing disease and GH deficiency, a larger number of studies is needed to confirm this suggestion.

[Class I HLA antigens in children from families with congenital adrenal hyperplasia].

PubMed

Turowska-Heydel, D; Pietrzyk, J J; Turowski, G

1995-02-01

Congenital adrenal hyperplasia (CAH) is a syndrome of adrenal steroid metabolism errors with an autosomal inheritance model. The most common metabolic defect is 21-hydroxylase deficiency. It has been demonstrated that 21-hydroxylase genes are in close association with HLA antigens. I HLA antigens were typed in a group of 32 families of children with CAH-type 21-hydroxylase deficiency with salt loss. The antigen frequencies were determined and compared to those of the control population. The studies revealed that two HLA antigens determined by the B Locus, i.e. HLA-B47 and HLA-B61, showed a highly significant frequency (chi 2 corresponding to 404,5259 and 23,7808, respectively). The calculated relative risk and etiologic fraction values were extremely high, distinguishing the population of patients and their parents. The RR value among patients was 427.1 for HLA-B47 and 7.8 for HLA-B61 antigen. Studies on the correlation between HLA and CAH indicate an association with HLA-B47 and HLA-B61 antigens.

Management issues of congenital adrenal hyperplasia during the transition from pediatric to adult care.

PubMed

Choi, Jin-Ho; Yoo, Han-Wook

2017-02-01

Steroid 21-hydroxylase deficiency is the most prevalent form of congenital adrenal hyperplasia (CAH), accounting for approximately 95% of cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, tumor, osteoporosis, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and health-care providers. Psychosocial issues frequently affect adherence to glucocorticoid treatment. Therefore, the safe transition of adolescents to adult care requires regular follow-up of patients by a multidisciplinary team including pediatric and adult endocrinologists. The major goals for management of adults with 21-hydroxylase deficiency are to minimize the long-term complications of glucocorticoid therapy, reduce hyperandrogenism, prevent adrenal or testicular adrenal rest tumors, maintain fertility, and improve quality of life. Optimized medical or surgical treatment strategies should be developed through coordinated care, both during transition periods and throughout patients' lifetimes. This review will summarize current knowledge on the management of adults with CAH, and suggested appropriate approaches to the transition from pediatric to adult care.

Are all pulmonary hypoplasias the same? A comparison of pulmonary outcomes in neonates with congenital diaphragmatic hernia, omphalocele and congenital lung malformation.

PubMed

Akinkuotu, Adesola C; Sheikh, Fariha; Cass, Darrell L; Zamora, Irving J; Lee, Timothy C; Cassady, Christopher I; Mehollin-Ray, Amy R; Williams, Jennifer L; Ruano, Rodrigo; Welty, Stephen E; Olutoye, Oluyinka O

2015-01-01

Patients with congenital diaphragmatic hernias (CDH), omphaloceles, and congenital lung malformations (CLM) may have pulmonary hypoplasia and experience respiratory insufficiency. We hypothesize that given equivalent lung volumes, the degree of respiratory insufficiency will be comparable regardless of the etiology. Records of all fetuses with CDH, omphalocele, and CLM between January 2000 and June 2013 were reviewed. MRI-based observed-to-expected total fetal lung volumes (O/E-TFLV) were calculated. An analysis of outcomes in patients with O/E-TFLV between 40% and 60%, the most inclusive range, was performed. 285 patients were evaluated (161, CDH; 24, omphalocele; 100, CLM). Fetuses with CDH had the smallest mean O/E-TFLV. CDH patients were intubated for longer and had a higher incidence of pulmonary hypertension. Fifty-six patients with the three diagnoses had an O/E-TFLV of 40%-60%. The need for ECMO, supplemental oxygen at 30days of life, and 6-month mortality were similar among groups. CDH patients had a significantly longer duration of intubation and higher incidence of pulmonary hypertension than the other two diagnoses. Given equivalent lung volumes (40%-60% of expected), CDH patients require more pulmonary support initially than omphalocele and CLM patients. In addition to lung volumes, disease-specific factors, such as pulmonary hypertension in CDH, also contribute to pulmonary morbidity and overall outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

PubMed

Khattab, Ahmed; Yuen, Tony; Sun, Li; Yau, Mabel; Barhan, Ariella; Zaidi, Mone; Lo, Y M Dennis; New, Maria I

2016-01-01

A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. © 2016 S. Karger AG, Basel.

Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry.

PubMed

Rossi, Claudia; Calton, Lisa; Brown, Heather A; Gillingwater, Scott; Wallace, A Michael; Petrucci, Francesca; Ciavardelli, Domenico; Urbani, Andrea; Sacchetta, Paolo; Morris, Michael

2011-04-01

The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤ 6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.

Testicular Fibrous Hypoplasia in Cynomolgus Monkeys ( Macaca fascicularis): An Incidental, Congenital Lesion.

PubMed

Pereira Bacares, Marcia E; Vemireddi, Vimala; Creasy, Dianne

2017-06-01

Testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. A retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred Asian and 90 Mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. The incidence of the lesion increased markedly over time. No cases occurred between 1999 and 2004. Between 2005 and 2009, the incidence ranged between 8.1% and 11.0% of the monkeys examined and then rose to 26.1% in 2010 and 30.9% in 2011. Overall, the lesion was identified in 10.94% of Asian monkeys with the highest incidence in animals originating from China and Vietnam; severity ranged from minimal to severe and it occurred unilaterally (38.5%) and bilaterally (61.5%). In Mauritian monkeys, the lesion was predominantly minimal in severity, bilateral in distribution, and affected 6.6% of the animals examined. The lesion occurred regardless of sexual maturation status but when present in mature monkeys was often associated with cystic tubular atrophy of the seminiferous epithelium. Based on the morphological characteristics of the lesion and the unilateral/bilateral distribution, the lesion is considered to be a congenital or developmental abnormality.

[Recommendations for the diagnosis and treatment of classic forms of 21-hydroxylase-deficient congenital adrenal hyperplasia].

PubMed

Rodríguez, Amparo; Ezquieta, Begoña; Labarta, José Igancio; Clemente, María; Espino, Rafael; Rodriguez, Amaia; Escribano, Aranzazu

2017-08-01

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Cortisol and aldosterone synthesis are impaired in the classic forms (adrenal insufficiency and salt-wasting crisis). Females affected are virilised at birth, and are at risk for genital ambiguity. In this article we give recommendations for an early as possible diagnosis and an appropriate and individualised treatment. A patient and family genetic study is essential for the diagnosis of the patient, and allows genetic counselling, as well as a prenatal diagnosis and treatment for future pregnancy. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Psychological evaluation of treated females with virilizing congenital adrenal hyperplasia.

PubMed

Hurtig, A L; Radhakrishnan, J; Reyes, H M; Rosenthal, I M

1983-12-01

The psychological development of females with congenital adrenal hyperplasia (CAH) has been previously studied by Money, et al, who found that psychological development of sex identity was consistent with sex assignment despite virilizing adrenal hormones and abnormal external genitalia requiring surgical correction. In this study, using a variety of psychological tests, we assessed the sex-dimorphic behavior, body image, cognitive functioning, and sex-role identity of nine patients ranging in age from 13 to 21, all treated with glucocorticoids and surgical correction. Four of the nine showed moderate virilization despite treatment. Psychological measures included the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Bem Sex-Role Inventory, the Draw-A-Person (DAP) and an interview with patient and family. Results indicate that patients fall within the normal expectable range for this developmental period in visual-spatial and verbal cognitive functioning, in sex-role identity, and in social interpersonal early behaviors. In two areas of functioning these patients demonstrated some variance from the norms, specifically in sexual identity and early activity levels. This suggests that sexual identity and physical activity are most prone to hormonal and psychological impact but that cognition and sex-role identity are not affected. Future studies of this sample will look at personality dimensions such as ego functioning, defense and affect to consider the impact of body image concerns and conflicts.

[Fetal magnetic resonance imaging evaluation of congenital diaphragmatic hernia].

PubMed

Sebastià, C; Garcia, R; Gomez, O; Paño, B; Nicolau, C

2014-01-01

A diaphragmatic hernia is defined as the protrusion of abdominal viscera into the thoracic cavity through a normal or pathological orifice. The herniated viscera compress the lungs, resulting in pulmonary hypoplasia and secondary pulmonary hypertension, which are the leading causes of neonatal death in patients with congenital diaphragmatic hernia. Congenital diaphragmatic hernia is diagnosed by sonography in routine prenatal screening. Although magnetic resonance imaging is fundamentally used to determine whether the liver is located within the abdomen or has herniated into the thorax, it also can provide useful information about other herniated structures and the degree of pulmonary hypoplasia. The aim of this article is to review the fetal magnetic resonance findings for congenital diaphragmatic hernia and the signs that enable us to establish the neonatal prognosis when evaluating pulmonary hypoplasia. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Congenital Adrenal Hyperplasia: Review from a Surgeon’s Perspective in the Beginning of the Twenty-First Century

PubMed Central

Piaggio, Lisandro Ariel

2013-01-01

Congenital adrenal hyperplasia (CAH) most commonly due to 21-hydroxylase deficiency is the most common type of disorder of sex development. This review will focus on CAH addressing historical and current surgical techniques with their anatomical foundations, with special attention to long-term results and outcomes on sexual function, patient satisfaction, patient attitude toward surgery, and ongoing controversies in management of these patients. PMID:24400298

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

PubMed

Nella, Aikaterini A; Mallappa, Ashwini; Perritt, Ashley F; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J; Merke, Deborah P

2016-12-01

Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.

Woman with virilizing congenital adrenal hyperplasia and Leydig cell tumor of the ovary.

PubMed

Fernández-García Salazar, Rosario; Muñoz-Darias, Carmen; Haro-Mora, Juan Jesús; Almaraz, M Cruz; Audí, Laura; Martínez-Tudela, Juana; Yahyaoui, Raquel; Esteva, Isabel

2014-08-01

We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH.

Prenatal Androgens and Gender-Typed Behavior: A Study of Girls with Mild and Severe Forms of Congenital Adrenal Hyperplasia.

ERIC Educational Resources Information Center

Servin, Anna; Nordenstrom, Anna; Larsson, Agne; Bohlin, Gunilla

2003-01-01

Examined gender-typed behavior and interests in 2- to 10-year-old girls with congenital adrenal hyperplasia (CAH) and in unaffected girls matched for age. Found that, compared with unaffected girls, girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and…

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia

PubMed Central

Mallappa, Ashwini; Perritt, Ashley F.; Gounden, Verena; Kumar, Parag; Sinaii, Ninet; Daley, Lori-Ann; Ling, Alexander; Liu, Chia-Ying; Soldin, Steven J.; Merke, Deborah P.

2016-01-01

Context: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTH-driven adrenal androgen overproduction. Objective: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI) and evaluate the safety and efficacy of CSHI in patients with difficult-to-treat CAH. Design: Eight adult patients with classic CAH participated in a single-center open-label phase I–II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. Main Outcome Measures: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP) ≤1200 ng/dL was measured. Results: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improved HRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. Conclusions: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study. PMID:27680873

Does the serum uric acid level have any relation to arterial stiffness or blood pressure in adults with congenital renal agenesis and/or hypoplasia?

PubMed

Yazici, Raziye; Guney, İbrahim; Altintepe, Lutfullah; Yazici, Mehmet

2017-01-01

The relationship between serum uric acid and arterial stiffness or blood pressure is not clear. The serum uric acid level and its association with cardiovascular risk is not well known in patients with reduced renal mass. We aimed to investigate the relation between serum uric acid levels and arterial stiffness and also blood pressure in patients with congenital renal agenesis and/or hypoplasia. In this single center, cross-sectional study, a total of 55 patients (39 (% 70.9) with unilateral small kidney and 16 (%29.1) with renal agenesis) were included. The median age was 35 (21-50) years. The study population was divided into tertiles of serum uric acid (according to 2.40-3.96, 3.97-5.10, and 5.11-9.80 mg/dl cut-off values of serum uric acid levels). Official and 24-h ambulatory non-invasive blood pressures of all patients were measured. The arterial stiffness was assessed by pulse wave velocity (PWV). PWV values were increased from first to third tertile (5.5 ± 0.6, 5.7 ± 0.8, 6.1 ± 0.7, respectively), but this gradual increase between tertiles did not reach significance. Linear regression analyses showed a positive correlation between serum uric acid levels and PWV (β = 0.40, p = 0.010), but no correlation was found between uric acid and daytime systolic blood pressure (β = 0.24, p = 0.345). In congenital renal agenesis/hypoplasia, the serum uric acid level was positively correlated with arterial stiffness, but there was no correlation with blood pressure.

Prenatal Hormones and Postnatal Socialization by Parents as Determinants of Male-Typical Toy Play in Girls With Congenital Adrenal Hyperplasia

ERIC Educational Resources Information Center

Pasterski, Vickie L.; Geffner, Mitchell E.; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

2005-01-01

Toy choices of 3- to 10-year-old children with congenital adrenal hyperplasia (CAH) and of their unaffected siblings were assessed. Also assessed was parental encouragement of sex-typed toy play. Girls with CAH displayed more male-typical toy choices than did their unaffected sisters, whereas boys with and without CAH did not differ. Mothers and…

Diagnosis and clinical characteristics of congenital anosmia: case series report.

PubMed

Qu, Qiuyi; Liu, Jianfeng; Ni, Daofeng; Zhang, Qiuhang; Yang, Dazhang; Wang, Naya; Wu, Xueyan; Han, Honglei

2010-12-01

congenital anosmia is extremely rare and tends to present late. We report on a series of patients with congenital anosmia to analyze its clinical characteristics and present illustrative cases. retrospective chart review. tertiary care centre. thirty-five patients with congenital anosmia were reviewed. A thorough medical history taking, physical examination, and nasal endoscopy were performed in all patients. T&T olfactory testing (n = 33), olfactory event-related potentials (OERPs) (n = 33), and sinonasal computed tomography (CT) (n = 35) were carried out. Magnetic resonance images (MRIs) of the olfactory pathway (n = 34) were available. Serum sex hormones were tested (n = 33). physical examination, olfactory testing, MRI of the olfactory pathway, and serum sex hormones. twenty cases were isolated congenital anosmia (ICA). Fifteen cases were congenital anosmia with other anomalies, including 12 cases with Kallmann syndrome (KS), two with CHARGE syndrome, and one with hypoplasia of the nasal cavity and nasal sinus. T&T olfactory testing indicated anosmia (n = 33). No OERP was obtained (n = 33). CT scans indicated three abnormal patients, including two with unilateral choanal atresia and one with hypoplasia of the nasal cavity and sinus. MRI demonstrated aplasia or hypoplasia of the olfactory bulbs, tracts, and olfactory sulci (n = 34). Serum sex hormones were low in 12 patients with KS. early diagnosis of congenital anosmia on the basis of olfactory symptoms is difficult. MRI of the olfactory pathway plays an important role in anatomic location. ICA is the most common congenital anosmia. KS is the primary presentation of congenital anosmia with other anomalies.

Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

PubMed

Pina, Christian; Khattab, Ahmed; Katzman, Philip; Bruckner, Lauren; Andolina, Jeffrey; New, Maria; Yau, Mabel

2015-05-01

A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

Congenital hypoplasia of the cerebellum: developmental causes and behavioral consequences

PubMed Central

Basson, M. Albert; Wingate, Richard J.

2013-01-01

Over the last 60 years, the spotlight of research has periodically returned to the cerebellum as new techniques and insights have emerged. Because of its simple homogeneous structure, limited diversity of cell types and characteristic behavioral pathologies, the cerebellum is a natural home for studies of cell specification, patterning, and neuronal migration. However, recent evidence has extended the traditional range of perceived cerebellar function to include modulation of cognitive processes and implicated cerebellar hypoplasia and Purkinje neuron hypo-cellularity with autistic spectrum disorder. In the light of this emerging frontier, we review the key stages and genetic mechanisms behind cerebellum development. In particular, we discuss the role of the midbrain hindbrain isthmic organizer in the development of the cerebellar vermis and the specification and differentiation of Purkinje cells and granule neurons. These developmental processes are then considered in relation to recent insights into selected human developmental cerebellar defects: Joubert syndrome, Dandy–Walker malformation, and pontocerebellar hypoplasia. Finally, we review current research that opens up the possibility of using the mouse as a genetic model to study the role of the cerebellum in cognitive function. PMID:24027500

Reconstructive surgery for females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a review from the Prince of Wales Hospital.

PubMed

Houben, C H; Tsui, S Y; Mou, J W; Chan, K W; Tam, Y H; Lee, K H

2014-12-01

To present the results of feminising genitoplasty done in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Case series. A tertiary referral centre in Hong Kong. Female patients with congenital adrenal hyperplasia undergoing corrective surgery for virilisation between 1993 and 2012. The operative result was judged with a scoring system (1-3) for four areas: appearance of clitoris, labia and vagina, plus requirement for revision surgery. A total of 23 female patients with congenital adrenal hyperplasia with a median age of 17.5 (range, 1.5-33.8) years were identified. Of these individuals, 17 presented in the neonatal period and early infancy, of which four had an additional salt-losing crisis. Six patients-including four migrants from mainland China-were late presenters at a median age of 2 (range, 0.5-14) years. Twenty-two patients had corrective surgery at a median age of 2 (range, 1-14) years. Clitoral reduction was performed in all, and further surgery in 21 patients. The additional surgery was flap vaginoplasty in 10 patients, a modified Passerini procedure in six, and a labial reconstruction in five; one patient with prominent clitoris was for observation only. Minor revision surgery (eg mucosal trimming) was required in three patients; a revision vaginoplasty was done in one individual. Of the 23 patients, 18 (78%) with a median age of 20 (range, 9.3-33.8) years participated in the outcome evaluation: a 'good' outcome (4 points) was seen in 12 patients and a 'satisfactory' (5-9 points) result in five patients. Nearly three quarters of our cohort (n=17) presented with classic virilising form of 21-hydroxylase deficiency. Only four (25%) patients experienced a salt-losing crisis. Female gender assignment at birth was maintained for all individuals in this group. 'Good' and 'satisfactory' outcomes of surgery were reported in nearly all participants.

Genotype-Phenotype Correlation in 153 Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Analysis of the United Kingdom Congenital Adrenal Hyperplasia Adult Study Executive (CaHASE) Cohort

PubMed Central

Krone, Nils; Rose, Ian T.; Willis, Debbie S.; Hodson, James; Wild, Sarah H.; Doherty, Emma J.; Hahner, Stefanie; Parajes, Silvia; Stimson, Roland H.; Han, Thang S.; Carroll, Paul V.; Conway, Gerry S.; Walker, Brian R.; MacDonald, Fiona; Arlt, Wiebke

2013-01-01

Context: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. Objective: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. Research Design and Methods: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. Results: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. Conclusions: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is

Growth and development in children with classic congenital adrenal hyperplasia.

PubMed

Bonfig, Walter

2017-02-01

Final height outcome in classic congenital adrenal hyperplasia (CAH) has been of interest for many years. With analysis of growth patterns and used glucocorticoid regimens, enhanced treatment strategies have been developed and are still under development. Most of the current reports on final height outcome are confirmative of previous results. Final height data is still reported in cohorts that were diagnosed clinically and not by newborn screening. Clinical diagnosis of CAH leads to delayed diagnosis especially of simple virilizing CAH with significantly advanced bone age resulting in early pubertal development and reduced final height. In contrast salt-wasting CAH is diagnosed at an earlier stage in most cases resulting in better final height outcome in some cohorts. Nevertheless, final height outcome in patients with CAH treated with glucocorticoids is lower than the population norm and also at the lower end of genetic potential. Achievement of regular adult height is still a challenge with conventional glucocorticoid treatment in patients with CAH, which is why new hydrocortisone formulations and new treatment options for CAH are underway.

[Prevalence of selected congenital anomalies in the Czech Republic: renal and cardiac anomalies and congenital chromosomal aberrations].

PubMed

Šípek, Antonín; Gregor, Vladimír; Horáček, Jiří; Šípek, Antonín; Langhammer, Pavel

2013-09-01

Analysis of the prevalence rates of selected diagnoses of congenital anomalies in the Czech Republic in 1994-2009. Retrospective epidemiological analysis of postnatal and total (including prenatally diagnosed cases) prevalence of congenital anomalies from the database of the National Registry of Congenital Anomalies of the Czech Republic. Data from the National Registry of Congenital Anomalies (NRCA) maintained by the Institute of Health Information and Statistics of the Czech Republic (IHIS CR) were used. Data on congenital anomalies in general and selected types of congenital anomalies were analyzed for the entire Czech Republic from 1994-2009. Additional data on prenatally diagnosed anomalies were obtained from medical genetics centres in the Czech Republic thanks to voluntary cooperation. This study analyzed postnatal and overall prevalence of congenital anomalies, with the latter including results of positive prenatal diagnosis. More detailed analysis was carried out for the following diagnoses: cystic kidney disease, renal agenesis/hypoplasia, tetralogy of Fallot, large vessel transposition, left heart hypoplasia, aortic coarctation, Down syndrome, Edward syndrome, and Patau syndrome. Cystic kidney disease showed a significant increase in 1999 and 2000, mainly due to postnatally diagnosed cases. This can be explained, on the one hand, by the modification made to the reporting of congenital anomalies in the Czech Republic and, on the other hand, by an earlier and more complete detection of postnatal cases. Since 2000, there has been a significant increase in reported cystic kidney disease as a result of postnatal kidney screening. In 1994-1999, the prevalence rates of this diagnosis ranged from 1.7 to 3.1 per 10,000 live births. Similar trend is seen in the prevalence of renal agenesis/hypoplasia. In the monitored period, prenatally diagnosed cases showed a slight increase while postnatally diagnosed cases showed a considerable rise. In 1994-1999, the

[Evaluation of the diagnostic usefulness for ultrasonographic and echocardiographic lethal markers in fetal pulmonary hypoplasia. Analysis of 11 cases].

PubMed

Kieszek, S; Kaczmarek, P; Czichos, E; Respondek, M

1996-07-01

Results of ultrasonographic and echocardiographic studies of 11 fetuses were analysed retrospectively in relation to their pulmonary hypoplasia. Congenital malformations, quality of hydramnios and echocardiographical measurements of fetal chest were estimated. The best symptoms of pulmonary hypoplasia were: oligo/ahydramnios, absence of fetal breathing movements and malformations in fetal chest cavity (diaphragmatic hernia, cardiomegaly, hydrothorax). Systemic malformations were present in each case. The measurements such as CC, CA, HA, (CA-HA) x 100/CA were not accurate enough and we did not find any statistical differences between the control and the studied group. Finding several factors predisposing to lung hypoplasia means that its lethal form may be present in fetus.

News about the genetics of congenital primary adrenal insufficiency.

PubMed

Roucher-Boulez, Florence; Mallet-Motak, Delphine; Tardy-Guidollet, Véronique; Menassa, Rita; Goursaud, Claire; Plotton, Ingrid; Morel, Yves

2018-04-13

Primary adrenal insufficiency (PAI) is characterized by impaired production of steroid hormones due to an adrenal cortex defect. This condition incurs a risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relating to oxidative stress have opened the way to research on genes unrelated to the adrenal gland. Identification of causal mutations in a gene responsible for PAI allows genetic counseling, guidance of follow-up and prevention of complications. This is particularly true for stress oxidative anomalies, as extra-adrenal manifestations may occur due to the sensitivity to oxidative stress of other organs such as the heart, thyroid, liver, kidney and pancreas. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Gender reversal in 46XX congenital virilizing adrenal hyperplasia.

PubMed

Sripathi, V; Ahmed, S; Sakati, N; al-Ashwal, A

1997-05-01

To review the results of gender reversal in six patients with 46XX congenital virilizing adrenal hyperplasia (CVAH). Fifty-one patients with 46XX CVAH were seen in an 8 year period; 45 were managed by conventional feminizing genitoplasty, but six underwent gender reversal and were managed as males. The clinical decision for gender reversal was made after appropriate counselling and was based primarily on parental choice, this being influenced significantly by a delayed diagnosis in four patients. Surgical management consisted of gonadectomy, excision of Müllerian structures and staged hypospadias repair/ chordee correction in four patients, and circumcision in two completely masculinized children. All six boys are well adjusted to their gender of rearing, with ages ranging from 3 years to 16.5 years (mean 8.5) at the time of review. Two children have normal penises and four have a satisfactory result after two-stage repair of hypospadias/chordee. Most patients with 46XX CVAH are preferably raised as females and require a feminizing genitoplasty. However, the clinical decision may be influenced by many factors, including delay in diagnosis, social bias and the premium on male rearing in certain communities. When male rearing is chosen, early gonadectomy and excision of Müllerian structures, together with staged hypospadias repair, gives satisfactory results.

Lipoid congenital adrenal hyperplasia due to STAR mutations in a Caucasian patient.

PubMed

Kaur, Jasmeet; Casas, Luis; Bose, Himangshu S

2016-01-01

Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions. STAR mutations cause lipoid CAH.This is a pure population from a caucasian family.Mutation ablated STAR activity.The mutation resulted in loosely folded conformation of STAR.

Identification of five novel STAR variants in ten Chinese patients with congenital lipoid adrenal hyperplasia.

PubMed

Huang, Zhuo; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Zhang, Huiwen; Yu, Yongguo; Liang, Lili; Gong, Zhuwen; Gu, Xuefan

2016-04-01

Congenital lipoid adrenal hyperplasia (CLAH) is a rare autosomal recessive disorder caused by defective synthesis of all steroids. This disorder is characterized by 46,XY sex reversal, skin hyperpigmentation, early-onset adrenal crisis and enlarged adrenal with fatty accumulation. CLAH is caused by mutations in the STAR gene. The clinical features and STAR gene mutation spectrum of a large cohort of Chinese patients with CLAH were not reported previously. We performed clinical retrospective review and genetic analysis of the STAR gene in ten unrelated Chinese phenotypic female patients who were clinically diagnosed with CLAH and followed up in our hospital from 2006 to 2015. All ten patients, including two 46,XY females and eight 46,XX females, presented skin hyperpigmentation and early salt-wasting episode, and showed normal growth and development after steroid replacement treatment. Totally 20 mutant alleles containing 11 different STAR gene mutations were identified in these ten patients, including five novel variants (two missense and three null variants), all predicted to be pathogenic in bioinformatics analysis, and six mutations described in previous literature. Among these 11 mutations, a reported mutation c.772C>T and a novel variant c.707_708delinsCTT were most frequent, accounting for 35% and 15% of the total mutant alleles, respectively. This is the first report of a large Chinese cohort with CLAH, presenting the mutation spectrum of the STAR gene and two possible founder mutations in the Chinese population, which may contribute to better genetic counseling and prenatal diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia.

PubMed

Makanga, Martine; Maruyama, Hidekazu; Dewachter, Celine; Da Costa, Agnès Mendes; Hupkens, Emeline; de Medina, Geoffrey; Naeije, Robert; Dewachter, Laurence

2015-04-01

Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of antenatal simvastatin was compared with antenatal sildenafil, which has already been shown to improve pathological features of PPHN in nitrofen-induced CDH. On embryonic day (E) 9.5, nitrofen or vehicle was administered to pregnant Sprague-Dawley rats. On E11, nitrofen-treated rats were randomly assigned to antenatal simvastatin (20 mg·kg(-1)·day(-1) orally), antenatal sildenafil (100 mg·kg(-1)·day(-1) orally), or placebo administration from E11 to E21. On E21, fetuses were delivered by cesarean section, killed, and checked for left-sided CDH. Lung tissue was then harvested for further pathobiological evaluation. In nitrofen-induced CDH, simvastatin failed to reduce the incidence of nitrofen-induced CDH in the offspring and to increase the body weight, but improved the lung-to-body weight ratio and lung parenchyma structure. Antenatal simvastatin restored the pulmonary vessel density and external diameter, and reduced the pulmonary arteriolar remodeling compared with nitrofen-induced CDH. This was associated with decreased lung expression of endothelin precursor, endothelin type A and B receptors, endothelial and inducible nitric oxide synthase, together with restored lung activation of apoptotic processes mainly in the epithelium. Antenatal simvastatin presented similar effects as antenatal therapy with sildenafil on nitrofen-induced CDH. Antenatal simvastatin improves pathological features of lung hypoplasia and PPHN in experimental nitrofen-induced CDH. Copyright © 2015 the American Physiological Society.

Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia

PubMed Central

Makanga, Martine; Maruyama, Hidekazu; Dewachter, Celine; Da Costa, Agnès Mendes; Hupkens, Emeline; de Medina, Geoffrey; Naeije, Robert

2015-01-01

Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of antenatal simvastatin was compared with antenatal sildenafil, which has already been shown to improve pathological features of PPHN in nitrofen-induced CDH. On embryonic day (E) 9.5, nitrofen or vehicle was administered to pregnant Sprague-Dawley rats. On E11, nitrofen-treated rats were randomly assigned to antenatal simvastatin (20 mg·kg−1·day−1 orally), antenatal sildenafil (100 mg·kg−1·day−1 orally), or placebo administration from E11 to E21. On E21, fetuses were delivered by cesarean section, killed, and checked for left-sided CDH. Lung tissue was then harvested for further pathobiological evaluation. In nitrofen-induced CDH, simvastatin failed to reduce the incidence of nitrofen-induced CDH in the offspring and to increase the body weight, but improved the lung-to-body weight ratio and lung parenchyma structure. Antenatal simvastatin restored the pulmonary vessel density and external diameter, and reduced the pulmonary arteriolar remodeling compared with nitrofen-induced CDH. This was associated with decreased lung expression of endothelin precursor, endothelin type A and B receptors, endothelial and inducible nitric oxide synthase, together with restored lung activation of apoptotic processes mainly in the epithelium. Antenatal simvastatin presented similar effects as antenatal therapy with sildenafil on nitrofen-induced CDH. Antenatal simvastatin improves pathological features of lung hypoplasia and PPHN in experimental nitrofen-induced CDH. PMID:25617377

Correction of axial deformity during lengthening in fibular hypoplasia: Hexapodal versus monorail external fixation.

PubMed

Chalopin, A; Geffroy, L; Pesenti, S; Hamel, A; Launay, F

2017-09-01

Childhood fibular hypoplasia is a rare pathology which may or may not involve limb-length discrepancy and axial deformity in one or more dimensions. The objective of the present study was to compare the quality of the axial correction achieved in lengthening procedures by hexapodal versus monorail external fixators. The hypothesis was that the hexapodal fixator provides more precise correction. A retrospective multicenter study included 52 children with fibular hypoplasia. Seventy-two tibias were analyzed, in 2 groups: 52 using a hexapodal fixator, and 20 using a monorail fixator. Mean age was 10.2 years. Mean lengthening was 5.7cm. Deformities were analyzed and measured in 3 dimensions and classified in 4 preoperative types and 4 post-lengthening types according to residual deformity. Complete correction was achieved in 26 tibias in the hexapodal group (50%) and 2 tibias in the monorail group (10%). Mean post-correction mechanical axis deviation was smaller in the hexapodal group: 12.83mm, versus 14.29mm in the monorail group. Mean post-correction mechanical lateral distal femoral angle was 87.5° in the hexapodal group, versus 84.3° in the monorail group (P=0.002), and mean mechanical medial proximal tibial angle 86.9° versus 89.5°, respectively (P=0.015). No previous studies focused on this congenital pathology in lengthening and axial correction programs for childhood lower-limb deformity. The present study found the hexapodal fixator to be more effective in conserving or restoring mechanical axes during progressive bone lengthening for fibular hypoplasia. The hexapodal fixator met the requirements of limb-length equalization in childhood congenital lower-limb hypoplasia, providing better axial correction than the monorail fixator. IV. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Morphometric study of the avian adrenal gland.

PubMed Central

Aire, T A

1980-01-01

The interrenal and medullary cords as well as the blood vessels and connective tissue proportions in the adrenal glands of the male Nigerian fowl (Gallus domesticus) and guinea-fowl (Numida meleagris) were studied by microstereological techniques. Laying domestic fowl of the Rhode Island Red breed were entirely defeathered and maintained in a hot, humid pen for a period of three months, after which the adrenal glands were also studied microstereologically. Interrenal cord width was also measured in all the birds studied. The interrenal cords of the subscapular zone were consistently wider than those cords in the inner zone of the adrenal glands. This clearly suggested morphological zoning. The proportion of interrenal tissue was significantly greater in the guinea-fowl than in the Nigerian fowl, but the medullary tissue and the blood vessels and connective tissue were not significantly different. Interrenal hypoplasia or medullary hyperplasia occurred in the defeathered Rhode Island Red fowl as compared to the control birds of the same breed and sex. The significance of these findings is discussed. PMID:7440402

MANAGEMENT OF ENDOCRINE DISEASE: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: update on the management of adult patients and prenatal treatment.

PubMed

Bachelot, Anne; Grouthier, Virginie; Courtillot, Carine; Dulon, Jérôme; Touraine, Philippe

2017-04-01

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by cortisol and in some cases aldosterone deficiency associated with androgen excess. Goals of treatment are to replace deficient hormones and control androgen excess, while avoiding the adverse effects of exogenous glucocorticoid. Over the last 5 years, cohorts of adults with CAH due to 21-hydroxylase deficiency from Europe and the United States have been described, allowing us to have a better knowledge of long-term complications of the disease and its treatment. Patients with CAH have increased mortality, morbidity and risk for infertility and metabolic disorders. These comorbidities are due in part to the drawbacks of the currently available glucocorticoid therapy. Consequently, novel therapies are being developed and studied in an attempt to improve patient outcomes. New management strategies in the care of pregnancies at risk for congenital adrenal hyperplasia using fetal sex determination and dexamethasone have also been described, but remain a subject of debate. We focused the present overview on the data published in the last 5 years, concentrating on studies dealing with cardiovascular risk, fertility, treatment and prenatal management in adults with classic CAH to provide the reader with an updated review on this rapidly evolving field of knowledge. © 2017 European Society of Endocrinology.

Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.

PubMed

Idkowiak, Jan; O'Riordan, Stephen; Reisch, Nicole; Malunowicz, Ewa M; Collins, Felicity; Kerstens, Michiel N; Köhler, Birgit; Graul-Neumann, Luitgard Margarete; Szarras-Czapnik, Maria; Dattani, Mehul; Silink, Martin; Shackleton, Cedric H L; Maiter, Dominique; Krone, Nils; Arlt, Wiebke

2011-03-01

P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR.

Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy.

PubMed

Abe, Yuichi; Sakai, Tetsuro; Okumura, Akihisa; Akaboshi, Shinjiro; Fukuda, Mitsumasa; Haginoya, Kazuhiro; Hamano, Shin-Ichiro; Hirano, Kouichi; Kikuchi, Kenjiro; Kubota, Masaya; Lee, Sooyoung; Maegaki, Yoshihiro; Sanefuji, Masafumi; Shimozato, Sachiko; Suzuki, Motomasa; Suzuki, Yasuhiro; Takahashi, Mitsugi; Watanabe, Kenji; Mizuguchi, Masashi; Yamanouchi, Hideo

2016-08-01

This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Gender Identity in Patients with Congenital Adrenal Hyperplasia.

PubMed

Razzaghy-Azar, Maryam; Karimi, Sakineh; Shirazi, Elham

2017-07-01

Sex assignment in infancy for patients with disorder of sex development (DSD) is a challenging problem. Some of the patients with congenital adrenal hyperplasia (CAH) have DSD that may affect their gender identity. The study aimed to assess gender identity in patients with CAH. In this study, 52 patients with CAH, including 22 prepubertal children and 30 adolescents and adults, were assessed using two separate gender identity questionnaires for children and adults based on the criteria of diagnostic and statistical manual of mental disorders, 5th edition. In the children group, compatibility was seen between gender identity and rearing gender. In the adult group, there were three cases of mismatching between gender identity and sex assignment composed of two females with poor control and one male with good control with 21-hydroxylase deficiency (21-OHD). Three girls with 11-hydroxylase deficiency (11-OHD) were reared as boy. Two of them with late diagnosis at 5 and 6 years of age had pseudoprecocious puberty. Parents and children did not accept to change the gender. One of them is 36 years old now, is depressed and unsatisfied with her gender, another girl is still child and has male sexual identity. One girl with 11-OHD and early diagnosis at birth with Prader 5 virilization but with good hormonal control was changed to female gender at 12 years of age when female sexual characteristics appeared; she is 34-years-old now, married, and with two children, and she is satisfied with her gender. In patients with CAH, gender identity disorder is a rare finding. Hormonal control, social, familial, and religious beliefs have impacts on gender identity of these patients.

[Congenital adrenal hyperplasia due to lack of 17α-hydroxylase: a report of a new mutation in the gene CYP17A1].

PubMed

Perales Martínez, J I; Pina Marqués, B; de Arriba Muñoz, A; Mayayo Dehesa, E; Labarta Aizpún, J I; Loidi Fernández, L

2015-01-01

P450c17 enzyme catalyses two different reactions: the 17α-hydroxylation of progesterone and pregnenolone, and segmenting the carbon 17-20 binding from the 17,20lyase producing adrenal androgens. This enzyme is coded by the CYP17A1 gene. The case is presented of a 14 year old patient with delayed pubertal development and a high blood pressure for height and age. 46,XX karyotype. Hormonal studies highlighted hypergonadotropic hypogonadism, adrenal insufficiency and mineralocorticoid excess. Subsequent genetic studies showed a homozygous mutation in the CYP17A1 gene (c.753+G>A), not previously described, which is responsible for the pathophysiology of 17α-hydroxylase deficiency. This entity is a rare form of congenital adrenal hyperplasia. The disease often goes unnoticed until adolescence or early adult life, and should be suspected in 46,XY individuals with ambiguous genitalia or 46,XX with delayed puberty associated with hypertension and/or hypokalaemia. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

A de novo X;8 translocation creates a PTK2-THOC2 gene fusion with THOC2 expression knockdown in a patient with psychomotor retardation and congenital cerebellar hypoplasia

PubMed Central

Di Gregorio, Eleonora; Bianchi, Federico T.; Schiavi, Alfonso; Chiotto, Alessandra M.A.; Rolando, Marco; di Cantogno, Ludovica Verdun; Grosso, Enrico; Cavalieri, Simona; Calcia, Alessandro; Lacerenza, Daniela; Zuffardi, Orsetta; Retta, Saverio Francesco; Stevanin, Giovanni; Marelli, Cecilia; Durr, Alexandra; Forlani, Sylvie; Chelly, Jamel; Montarolo, Francesca; Tempia, Filippo; Beggs, Hilary E.; Reed, Robin; Squadrone, Stefania; Abete, Maria C.; Brussino, Alessandro; Ventura, Natascia; Di Cunto, Ferdinando; Brusco, Alfredo

2014-01-01

We identified a balanced de novo translocation involving chromosomes Xq25 and 8q24 in an eight year-old girl with a non-progressive form of congenital ataxia, cognitive impairment and cerebellar hypoplasia. Breakpoint definition showed that the promoter of the Protein Tyrosine Kinase 2 (PTK2, also known as Focal Adhesion Kinase, FAK) gene on chromosome 8q24.3 is translocated 2 kb upstream of the THO complex subunit 2 (THOC2) gene on chromosome Xq25. PTK2 is a well-known non-receptor tyrosine kinase whereas THOC2 encodes a component of the evolutionarily conserved multiprotein THO complex, involved in mRNA export from nucleus. The translocation generated a sterile fusion transcript under the control of the PTK2 promoter, affecting expression of both PTK2 and THOC2 genes. PTK2 is involved in cell adhesion and, in neurons, plays a role in axonal guidance, and neurite growth and attraction. However, PTK2 haploinsufficiency alone is unlikely to be associated with human disease. Therefore, we studied the role of THOC2 in the CNS using three models: 1) THOC2 ortholog knockout in C. elegans which produced functional defects in specific sensory neurons; 2) Thoc2 knockdown in primary rat hippocampal neurons which increased neurite extension; 3) Thoc2 knockdown in neuronal stem cells (LC1) which increased their in vitro growth rate without modifying apoptosis levels. We suggest that THOC2 can play specific roles in neuronal cells and, possibly in combination with PTK2 reduction, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia. PMID:23749989

Recommendations for Treatment of Nonclassic Congenital Adrenal Hyperplasia (NCCAH): an Update

PubMed Central

Trapp, Christine M.; Oberfield, Sharon E.

2013-01-01

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000–1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20–50% of 21-hydroxylase enzyme activity (vs. 0–5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000–1:2000 births (0.1–0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1–2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. and other alternatives, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome

Transition of Care from Childhood to Adulthood: Congenital Adrenal Hyperplasia.

PubMed

Bachelot, Anne

2018-01-01

Deficiency of the 21-hydroxylase enzyme is the most common form of congenital adrenal hyperplasia (CAH), accounting for more than 95% of the cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, impaired bone mineral density, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and practitioners. In adulthood, the aims of the medical treatment are to substitute cortisol and, when necessary, aldosterone deficiency, to ensure normal fertility, and to avoid the long-term consequences of glucocorticoid use on bone, metabolism, and cardiovascular risk. Recent data suggest that poor health status is likely to begin in adolescence and persist into adulthood, highlighting the importance of this time period in a patient's endocrine care. During transition from pediatric to adult specific care, a shift in treatment goals is thus needed. Successful transition from pediatric to adult health care requires a regular follow-up of patients by a multidisciplinary team including pediatric endocrinologists, urologists, gynecologists, psychiatrists, and adult endocrinologists. All of this could be included in a specific therapeutic education program regarding transition and/or CAH. © 2018 S. Karger AG, Basel.

Stigma Associated with Classical Congenital Adrenal Hyperplasia in Women's Sexual Lives.

PubMed

Meyer-Bahlburg, Heino F L; Khuri, Jananne; Reyes-Portillo, Jazmin; Ehrhardt, Anke A; New, Maria I

2018-05-01

The risk of intersex-related stigma often serves as social indication for "corrective" genital surgery, but has not been comprehensively documented. In preparation for the development of an intersex-specific stigma assessment tool, this qualitative project aimed to explore stigma in girls and women with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. As part of a comprehensive follow-up project, 62 adult women with classical CAH (age range 18-51 years) took part in an open-ended retrospective interview focusing on the impact of CAH and its treatment on various aspects of girls' and women's lives. Deductive qualitative content analysis (Patton, 2014) of de-identified transcripts involved categorization of three types of stigma: experienced, anticipated, and internalized. Two-fifths of the participants reported CAH-related stigma in romantic/sexual situations. Stigma enactment by romantic partners occurred in reaction to both genital and non-genital sex-atypical features of CAH and sometimes included explicit questioning of the women's true gender. Stigma anticipation by the women and their related avoidance of nudity, genital exposure, and romantic involvement altogether were frequent. Internalization of stigma occurred as well. In conclusion, the data suggest that many women with CAH experience, anticipate, and/or internalize intersex-related stigma in the context of their romantic/sexual lives.

Motor development in individuals with congenital adrenal hyperplasia: strength, targeting, and fine motor skill.

PubMed

Collaer, Marcia L; Brook, Charles G D; Conway, Gerard S; Hindmarsh, Peter C; Hines, Melissa

2009-02-01

This study investigated early androgen influence on the development of human motor and visuomotor characteristics. Participants, ages 12-45 years, were individuals with congenital adrenal hyperplasia (CAH), a disorder causing increased adrenal androgen production before birth (40 females, 29 males) and their unaffected relatives (29 females, 30 males). We investigated grip strength and visuomotor targeting tasks on which males generally outperform females, and fine motor pegboard tasks on which females generally outperform males. Physical characteristics (height and weight) were measured to explore whether body parameters could explain differences in motor skills. Females with CAH were stronger and showed better targeting than unaffected females and showed reduced fine visuomotor skill on one pegboard measure, with no difference on the other. Males with CAH were weaker than unaffected males in grip strength but did not differ on the targeting or pegboard measures. Correction for body size could not explain the findings for females, but suggests that the reduced strength of males with CAH may relate to their smaller stature. Further, the targeting advantage in females with CAH persisted following adjustment for their greater strength. Results in females support the hypothesis that androgen may masculinize, or promote, certain motor characteristics at which males excel, and contribute to defeminization of certain fine motor characteristics at which females excel. Thus, these data suggest that organizational effects of androgens on behavior during prenatal life may extend to motor characteristics and may contribute to general sex differences in motor-related behaviors; however, alternative explanations based on activational influences of androgen or altered experiential factors cannot be excluded without further study.

Gender Identity in Patients with Congenital Adrenal Hyperplasia

PubMed Central

Razzaghy-Azar, Maryam; Karimi, Sakineh; Shirazi, Elham

2017-01-01

Background Sex assignment in infancy for patients with disorder of sex development (DSD) is a challenging problem. Some of the patients with congenital adrenal hyperplasia (CAH) have DSD that may affect their gender identity. Objectives The study aimed to assess gender identity in patients with CAH. Methods In this study, 52 patients with CAH, including 22 prepubertal children and 30 adolescents and adults, were assessed using two separate gender identity questionnaires for children and adults based on the criteria of diagnostic and statistical manual of mental disorders, 5th edition. Results In the children group, compatibility was seen between gender identity and rearing gender. In the adult group, there were three cases of mismatching between gender identity and sex assignment composed of two females with poor control and one male with good control with 21-hydroxylase deficiency (21-OHD). Three girls with 11-hydroxylase deficiency (11-OHD) were reared as boy. Two of them with late diagnosis at 5 and 6 years of age had pseudoprecocious puberty. Parents and children did not accept to change the gender. One of them is 36 years old now, is depressed and unsatisfied with her gender, another girl is still child and has male sexual identity. One girl with 11-OHD and early diagnosis at birth with Prader 5 virilization but with good hormonal control was changed to female gender at 12 years of age when female sexual characteristics appeared; she is 34-years-old now, married, and with two children, and she is satisfied with her gender. Conclusions In patients with CAH, gender identity disorder is a rare finding. Hormonal control, social, familial, and religious beliefs have impacts on gender identity of these patients. PMID:29201068

Genetics Home Reference: cartilage-hair hypoplasia

MedlinePlus

... Twitter Home Health Conditions Cartilage-hair hypoplasia Cartilage-hair hypoplasia Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Cartilage-hair hypoplasia is a disorder of bone growth characterized ...

Congenital adrenal hyperplasia: as viewed by parents of affected children in India--a pilot study.

PubMed

Bhakhri, Bhanu Kiran; Jain, Vandana

2011-01-01

A spectrum of myths and misconceptions about congenital adrenal hyperplasia (CAH) is prevalent among the parents of affected children in India. The perceptions of parents may affect several aspects of these children's management, and to explore these perceptions we carried out a cross-sectional questionnaire-based descriptive study during May 2010. Twenty-eight individuals (17 males and 11 females), parents of 22 affected children aged < 5 years, completed the questionnaire. Their responses showed the prevalence among the parents of misconceptions about CAH. These misconceptions were resulting in potentially harmful practices, and in addition there was immense societal pressure on the families as a result of ignorance and myths about the disorder. There is a need for regular CAH education and interaction programs to provide an acceptable platform for the parents and patients, where their concerns can be expressed and shared and their requirements addressed appropriately by a multidisciplinary team.

Neuroimaging findings of congenital Zika virus infection: a pictorial essay.

PubMed

Zare Mehrjardi, Mohammad; Poretti, Andrea; Huisman, Thierry A G M; Werner, Heron; Keshavarz, Elham; Araujo Júnior, Edward

2017-03-01

Zika virus (ZIKV) is a mosquito-borne arbovirus from the Flaviviridae family. It had caused several epidemics since its discovery in 1947, but there was no significant attention to this virus until the recent outbreak in Brazil in 2015. The main concern is the causal relationship between prenatal ZIKV infection and congenital microcephaly, which has been confirmed recently. Moreover, ZIKV may cause other central nervous system abnormalities such as brain parenchymal atrophy with secondary ventriculomegaly, intracranial calcification, malformations of cortical development (such as polymicrogyria, and lissencephaly-pachygyria), agenesis/hypoplasia of the corpus callosum, cerebellar and brainstem hypoplasia, sensorineural hearing-loss, and ocular abnormalities as well as arthrogryposis in the infected fetuses. Postnatal (acquired) ZIKV infection usually has an asymptomatic or mildly symptomatic course, while prenatal (congenital) ZIKV infection has a more severe course and may cause severe brain anomalies that are described as congenital Zika syndrome. In this pictorial essay, we aim to illustrate the prenatal and postnatal neuroimaging findings that may be seen in fetuses and neonates with congenital Zika syndrome, and will discuss possible radiological differential diagnoses. A detailed knowledge of these findings is paramount for an early correct diagnosis, prognosis determination, and counseling of the affected children and families.

Comparison of Adrenal Suppression between Etomidate and Dexmedetomidine in Children with Congenital Heart Disease.

PubMed

Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

2015-05-29

The aim of this study was to compare plasma cortisol concentration during anesthesia of children with congenital heart disease who received dexmedetomidine (DEX) with those who received etomidate (ETO). We recruited 99 ASA physical status II-III pediatric patients scheduled for congenital heart disease (CHD) corrective surgery and divided into them into 3 groups. Group DEX received an infusion of DEX intravenously with a bolus dose of 0.5 µg·kg-1 within 10 min during anesthesia induction, followed by a maintenance dose of DEX 0.5 µg·kg-1·h-1. Group ETO received ETO intravenously with a bolus dose of 0.3 mg·kg-1 without a maintenance dose. Group CON received routine anesthetics as controls. The preset timepoints were: before anesthesia induction (T0), at the end of induction (T1), 30 min after anesthesia induction (T2), at the time of aortic and inferior vena catheterization (T3), and at 180 min (T4) and 24 h (T5) after anesthesia induction. The cortisol concentration decreased gradually after anesthesia induction in all groups, and returned to baseline values after 24 h. The cortisol concentration was significantly lower in Group ETO children than in Group DEX or group CON at T4. The plasma concentrations of cortisol decreased in CHD children after the operation, but returned to baseline after 24 h of anesthesia induction. The adrenal cortex function inhibition induced by ETO in CHD children is longer and more serious than that induced by DEX (if any) during the preoperative period.

A previously undescribed syndrome combining fibular agenesis/hypoplasia, oligodactylous clubfeet, anonychia/ungual hypoplasia, and other defects.

PubMed

Santos, Silvana C; Pardono, Eliete; Ferreira da Costa, Maria Ione; de Melo, Aurea Nogueira; Graciani, Zodja; de Albuquerque e Souza, Alessandra Cavalcanti; Lezirovitz, Karina; Thiele-Aguiar, Renata Soares; Mingroni-Netto, Regina Célia; Opitz, John M; Kok, Fernando; Otto, Paulo A

2008-12-15

We describe an apparently new genetic syndrome in six members of a family living in a remote area in Northeastern Brazil. This syndrome comprises: short stature due to a marked decrease in the length of the lower limbs (predominantly mesomelic with fibular agenesis/marked hypoplasia), grossly malformed/deformed clubfeet with severe oligodactyly, upper limbs with acromial dimples and variable motion limitation of the forearms and/or hands, severe nail hypoplasia/anonychia sometimes associated with mild brachydactyly and occasionally with pre-axial polydactyly. This syndrome is apparently distinct from the syndrome of brachydactyly-ectrodactyly with fibular aplasia or hypoplasia (OMIM 113310), the syndrome of fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly (OMIM 228930), and from other previously described conditions exhibiting fibular agenesis/hypoplasia. Copyright (c) 2008 Wiley-Liss, Inc.

Neuropsychological assessment in prepubertal patients with congenital adrenal hyperplasia: preliminary study.

PubMed

Somajni, F; Sovera, V; Albizzati, A; Russo, G; Peroni, P; Seragni, G; Lenti, C

2011-02-01

Individuals with congenital adrenal hyperplasia (CAH) provide a test population for the theory that elevated testosterone levels alter pre-/perinatal brain development. Seven prepuberal girls with CAH and seven matched controls has been submitted to a neuropsychological evaluation. We measured abilities where gender differences repeatedly has been observed or that had earlier shown differences between CAH subjects and controls. The following cognitive functions were tested: general intelligence, attention, verbal and non-verbal abilities, cerebral dominance for verbal and non-verbal material, frontal functions, peripheral dominance and motor fluency. Since several animal studies shown hippocampal morphological changes induced by prolonged hydrocortisone exposure, we also investigated memory functions. No differences were recorded between two groups on those abilities that are not sexually dimorphic. The mean general intelligence level of the patients was significantly lower than the controls', in agreement with previous studies. The verbal and non-verbal tasks revealed an age-related male-like pattern (i.e., verbal disadvantage) and an inversion of the hemispheric dominances. The latter observation was supported by a right-to-left shift of the peripheral dominances. The patients memory performances were all inferior to the controls'. The results are discussed in the light of possible hormonal influences. Our main findings support the hypothesis that elevated pre-/perinatal androgen exposure can influence some cognitive pattern of specific sexual dimorphic abilities in prepubertal subjects.

Neonatal Bartter Syndrome in association with congenital adrenal hyperplasia in a neonate - a rare combination.

PubMed

Hussain, Shabbir

2016-05-01

Neonatal Bartter syndrome (NBS) is an autosomal recessive renal tubulopathy characterized by hypokalaemic, hypochloraemic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninaemia and hyperaldosteronaemia but normotension. Congenital adrenal hyperplasia (CAH), another autosomal recessive condition, may present in the neonatal period with vomiting, hypovolaemia, failure to gain weight or ambiguous genitalia. We report a case of NBS and CAH combination in a neonate. A male neonate born at term was admitted with history of recurrent vomiting and dehydration episodes. Investigations revealed electrolytes imbalance, metabolic alkalosis, raised aldosterone and renin levels suggestive of NBS. He was treated successfully and discharged. He was re-admitted with the same symptoms. Further evaluation confirmed the presence of CAH as well. We report this case because of the rarity of this combination (NBS plus CAH) and to the best of our knowledge this is the first such case report from Pakistan.

Congenital diaphragmatic disease: An unusual presentation in adulthood. Case report.

PubMed

Gurrado, Angela; Isernia, Roberta Maria; De Luca, Alessandro; Ferraro, Valentina; Virgintino, Daniela; Napoli, Anna; Cavallaro, Giuseppe; Maiorano, Eugenio; Pezzolla, Angela; Testini, Mario

2018-05-07

Congenital diaphragmatic disease is a quite common condition that usually occurs in the neonatal period, and the diagnosis of congenital diaphragmatic disease in adulthood is rare. A 64-years-old Caucasian woman was admitted in emergency at our Department, due to a bowel obstruction and dyspnea. A CT-scan showed a diaphragmatic herniation in the left area, with malposition of dilated transverse and descending colon in the chest. An emergency laparatomy was performed, showing a toxic megacolon, in the absence of a true diaphragmatic hernia, and a left diaphragm and left liver hypoplasia. An intraoperative bronchoscopy revealed concomitant hypoplasia of the left lung. A subtotal colectomy with ileo-rectal anastomosis was performed. The postoperative course was uneventful. Histological examination demonstrated hyperplasia of the muscularis mucosae of the colon and cytoplasmic vacuolization of the Auerbach plexus ganglia. The karyotype genetic analysis excluded concomitant microdeletion or duplication syndromes. To our knowledge, this seems to be the first reported case of toxic megacolon in a patient with congenital hypoplasia of the left bronchial-lung system, of the left liver, and of the left diaphragm. The correct development of the diaphragm is essential for the neighboring organs. The observed clinical pattern could be related to a partial modification of neural crest cell detachment or migration, which could be responsible for bowel and diaphragm defects, even though it was not included in typical neural crest cell syndromes. Further researches should be performed in order to define the sporadic or syndromic source of these multiorgan defects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Congenital absence of dermatoglyphs.

PubMed

Límová, M; Blacker, K L; LeBoit, P E

1993-08-01

Congenital absence or unusual patterns of human dermatoglyphs (fingerprints) occur in several syndromes that are rare and poorly understood. The abnormalities of dermatoglyphs fall into four categories: complete absence, ridge hypoplasia, ridge dissociation, and ridges-off-the-end. Complete congenital absence of ridges is an exceedingly rare syndrome that consists of neonatal blisters and milia, adult traumatic blistering and fissuring, absence of sweating, contracture of digits, and absence of dermatoglyphs on the hands and feet. The syndrome is inherited in an autosomal dominant pattern, and only two kindreds have been described in the literature. We describe a newly identified patient and kindred with findings similar to the previously reported cases and review the clinical and histopathologic findings of this syndrome.

Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohr, E.; Leder, L.D.

1987-01-01

Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

Incidence of Fanconi anemia in children with congenital thumb anomalies referred for diepoxybutane testing.

PubMed

Webb, Michelle L; Rosen, Heather; Taghinia, Amir; McCarty, Erika R; Cerrato, Felecia; Upton, Joseph; Labow, Brian I

2011-06-01

Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive. We queried our database for patients who presented with congenital thumb anomalies and who underwent diepoxybutane (DEB) testing for FA between 1999 and 2008 at Children's Hospital Boston and the Dana-Farber Cancer Institute. During this time period, 543 congenital thumb anomaly patients (235 with thumb hypoplasia) presented to our institution. A total of 81 patients with thumb abnormalities underwent DEB testing. Six patients (7% of those tested; 1% of the total; 3% of thumb hypoplasia patients) had a positive DEB test consistent with the diagnosis of FA; all had other non-upper-extremity anomalies associated with FA. Of 6 FA patients, 5 had bilateral involvement; all had some degree of thumb hypoplasia (3 also had radial dysplasia). Mean age at testing was 2.6 years (SD 4.3). Most of the patients tested had multiple physical anomalies (n = 66). The anomaly distribution was: thumb hypoplasia and radial dysplasia (n = 29), thumb hypoplasia (n = 26), radial polydactyly (n = 12), radial polydactyly and radial dysplasia (n = 1), and proximally placed thumb and radial dysplasia (n = 1). Twelve patients had other thumb anomalies. Although the incidence of FA in patients with thumb anomalies may be low, patients with thumb hypoplasia and other physical findings associated with FA, specifically café au lait spots and short stature, appear to have an increased risk of FA. Because hand surgeons see these patients early in life, they have the

Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

PubMed

Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P

2002-05-01

Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients

STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal hyperplasia: insights from a novel splice mutation and review of reported cases.

PubMed

Camats, Núria; Pandey, Amit V; Fernández-Cancio, Mónica; Fernández, Juan M; Ortega, Ana M; Udhane, Sameer; Andaluz, Pilar; Audí, Laura; Flück, Christa E

2014-02-01

The steroidogenic acute regulatory protein (StAR) transports cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY disorder of sex development (DSD) and failure of pubertal development. Partial loss of StAR activity may cause adrenal insufficiency only. A newborn girl was admitted for mild dehydration, hyponatremia, hyperkalemia and hypoglycaemia and had normal external female genitalia without hyperpigmentation. Plasma cortisol, 17OH-progesterone, DHEA-S, androstendione and aldosterone were low, while ACTH and plasma renin activity were elevated, consistent with the diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and cytogenetics revealed a 46,XX karyotype. She was treated with fluids, hydrocortisone and fludrocortisone. Genetic studies revealed a novel homozygous STAR mutation in the 3' acceptor splice site of intron 4, c.466-1G>A (IVS4-1G>A). To test whether this mutation would affect splicing, we performed a minigene experiment with a plasmid construct containing wild-type or mutant StAR gDNA of exons-introns 4-6 in COS-1 cells. The splicing was assessed on total RNA using RT-PCR for STAR cDNAs. The mutant STAR minigene skipped exon 5 completely and changed the reading frame. Thus, it is predicted to produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis revealed that this mutant protein lacks wild-type exons 5-7 which are essential for StAR-cholesterol interaction. STAR c.466-1A skips exon 5 and causes a dramatic change in the C-terminal sequence of the protein, which is essential for StAR-cholesterol interaction. This splicing mutation is a loss-of-function mutation explaining the severe phenotype of our patient. Thus far, all reported splicing mutations of STAR cause a severe impairment of protein function and phenotype. �

Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE).

PubMed

Han, T S; Conway, G S; Willis, D S; Krone, N; Rees, D A; Stimson, R H; Arlt, W; Walker, B R; Ross, R J

2014-08-01

Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes. This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height. FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P < .05) and in moderately affected genotype group B women than either more severely affected groups null and A (P < .01) or the mildest group C (P < .001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life. Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

The Recalled Childhood Gender Questionnaire-Revised: a psychometric analysis in a sample of women with congenital adrenal hyperplasia.

PubMed

Meyer-Bahlburg, Heino F L; Dolezal, Curtis; Zucker, Kenneth J; Kessler, Suzanna J; Schober, Justine M; New, Maria I

2006-11-01

We administered the 18-item Recalled Childhood Gender Questionnaire-Revised (RCGQ-R), female version, to 147 adult women with congenital adrenal hyperplasia (CAH) representing three different degrees of prenatal androgenization due to 21-hydroxylase deficiency and to non-CAH controls. A principal components analysis generated three components accounting for 46%, 9%, and 6% of the variance, respectively. Corresponding unit-weighted scales (high scores = feminine) were labeled Gender Role (13 items; Cronbach alpha = .91), Physical Activity (3 items; alpha = .64), and Cross-Gender Desire (2 items; alpha = .47). Discriminant validity was demonstrated in terms of highly significant comparisons across the four groups. We conclude that the first 2 RCGQ-R scales show good psychometric qualities, but that the third scale needs to be further evaluated in a sample that includes women with gender identity disorder.

Foveal hemorrhage in an eye with foveal hypoplasia associated with albinism.

PubMed

Masuda, Naonori; Hasegawa, Taiji; Yamashita, Mariko; Ogata, Nahoko

2014-01-01

Oculocutaneous albinism is a group of congenital disorders caused by alterations of melanin biosynthesis. We report our findings in a patient with oculocutaneous albinism who presented with foveal hypoplasia and a foveal hemorrhage. A 48-year-old man noted a dark spot in the middle of the visual field of his right eye. He had depigmented skin, white hair, white eyebrows, and white cilia. He also had horizontal nystagmus and depigmented irides. His best-corrected visual acuity was 2/100 with -14.0 diopters in the right eye and 3/100 with -5.0 diopters in the left eye. Ophthalmoscopy showed diffuse depigmentation in both eyes and a foveal hemorrhage in the right eye. Optical coherence tomography showed the absence of a foveal pit in both eyes and a subretinal hyperreflective lesion corresponding to the foveal hemorrhage in the right eye. Fluorescein angiography showed that the retinal and choroidal vessels were relatively hypofluorescent because of the lack of a blocking effect of the pigments in the retinal pigment epithelium. Fluorescein angiography and indocyanine green angiography did not show any evidence of choroidal neovascularization in either eye. The foveal hemorrhage in the right eye spontaneously regressed and finally resolved at 3 months after onset. At the final examination, the patient reported that his vision had recovered. A foveal hemorrhage is a rare condition in an eye with foveal hypoplasia associated with albinism. The hemorrhage may be related to high myopia and also to the hypoplasia of the fovea associated with albinism.

Unusual Congenital Aortic Anomaly with Rare Common Celiamesenteric Trunk Variation: MR Angiography and Digital Substraction Angiography Findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tosun, Ozgur; Sanlidilek, Umman; Cetin, Huseyin

2007-09-15

Magnetic resonance angiography and digital substraction angiography (DSA) findings in a case with a rare congenital thoracoabdominal aortic hypoplasia and common celiamesenteric trunk variation with occlusion of infrarenal abdominal aorta are described here. To our knowledge, this aortic anomaly has not been previously described in the English literature. DSA is the optimum imaging modality for determination of aortic hypoplasia, associated vascular malformations, collateral vessels, and direction of flow within vessels.

Posterior communicating artery hypoplasia as a risk factor for acute ischemic stroke in the absence of carotid artery occlusion.

PubMed

Chuang, Yu-Ming; Liu, Chih-Yang; Pan, Po-Jung; Lin, Ching-Po

2008-12-01

Posterior communicating artery (PCoA) hypoplasia is a fetal variant of the Circle of Willis. According to angiograms and autopsy reports, this congenital variation is found in 6-21% of the general population. PCoA hypoplasia only becomes a risk factor for ischemic stroke in the presence of ipsilateral internal carotid artery (ICA) occlusion. The aim of our study was to determine the role of PCoA hypoplasia in acute ischemic stroke in the absence of ICA occlusion. We examined 310 acute ischemic stroke patients (mean age+/-standard deviation; 68.9+/-15.6 years). Cerebral magnetic resonance angiography was performed within 72 hours of ischemic stroke onset. For comparison, a risk factor-matched control group was recruited. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors. The overall incidence of PCoA hypoplasia in our experimental group was 19.35% (n=60), which was significantly higher than in the control group (8.20%, n=22, p=0.036, OR, 3.21; 95% CI, 1.43-9.62). The most common ischemic event was ipsilateral thalamic lacunar infarctions with or without occipital lobe involvement. Based on our results, PCoA hypoplasia appears to be a contributor to the risk of ischemic stroke, even in the absence of ICA occlusion. This risk is especially pronounced for strokes involving arteries that penetrate the thalamus.

Newborn screening for congenital adrenal hyperplasia in Cuba: six years of experience.

PubMed

González, Ernesto Carlos; Carvajal, Frank; Frómeta, Amarilys; Arteaga, Ana Luisa; Castells, Elisa María; Espinosa, Tania; Coto, Remigio; Pérez, Pedro Lucio; Tejeda, Yileidis; Del Río, Lesley; Segura, Mary Triny; Almenares, Pedro; Robaina, René; Fernández, José Luis

2013-06-05

Since 2005, a newborn screening program for congenital adrenal hyperplasia (CAH) by measuring 17-alpha-hydroxyprogesterone (17OHP) in dried blood spots was introduced in Cuba. The hormone was measured by the 17OHP Neonatal UMELISA method, in samples collected on the 5th day as average. Confirmatory test was performed to those neonates with 17OHP values above 55 nmol/l. Some perinatal factors that can influence on 17OHP levels were studied. From January 2005 to December 2010, 621,303 newborns were screened and 39 CAH cases were detected. Coverage of the program reached 98%. The incidence of CAH in Cuba was 1:15,931, similar to that reported by other programs. A recall for suspected CAH was performed in 10,799 cases (1.74%). Therapy in classical CAH patients was started at the mean age of 22 days. 17OHP levels were significantly higher in newborns with lower birth-weight (BW) and/or gestational age (GA). In addition, 17OHP values were affected by the gender, twin status or mode of delivery. In Cuba, the nationwide newborn screening program has allowed the early detection of CAH. The use of an optimized cut-off level for BW or GA could lead to a reduction in the percentage of recalled babies. Copyright © 2013 Elsevier B.V. All rights reserved.

Pilot proficiency testing study for second tier congenital adrenal hyperplasia newborn screening.

PubMed

De Jesús, Víctor R; Simms, David A; Schiffer, Jarad; Kennedy, Meredith; Mei, Joanne V; Hannon, W Harry

2010-11-11

Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. The Newborn Screening Quality Assurance Program (NSQAP) initiated a pilot, dried-blood spot (DBS)-based proficiency testing program designed to investigate materials and laboratory performance for second tier CAH screening by tandem mass spectrometry (MS/MS). The ratio of 17-α-hydroxyprogesterone (17-OHP), androstenedione (4-AD) and cortisol is used as an indicator of CAH in laboratory protocols for second tier analysis of DBS specimens. DBS prepared by NSQAP contained a range of steroid concentrations resulting in different clinical ratios. Laboratories received blind-coded DBS specimens and reported results to NSQAP for evaluation. Quantitative values reported by participants for 17-OHP, 4-AD, and cortisol, reflected small differences in their analytical methods. Average quantitative values for 17-OHP increased from 81% to 107% recovery over the 3.5-year period; cortisol recoveries increased from 61.9% to 89.5%; and 4-AD recoveries decreased from 184% to 68%. Laboratory participation in the CAH second tier proficiency testing program has resulted in improved analyte recoveries and enhanced sample preparation methodologies. NSQAP services for the second tier CAH analysis in DBS demonstrate the need for surveillance to ensure harmonization and continuous improvements, and to achieve sustained high-performance of newborn screening laboratories worldwide. Published by Elsevier B.V.

Fetal adrenal gland enlargement - prenatal and postnatal management.

PubMed

Lackova, Eliska; Cunderlik, Anton; Ticha, Lubica; Gabor, Maria

2017-11-01

The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date

Congenital malformations of human dermatoglyphs

PubMed Central

David, T. J.

1973-01-01

A classification for congenital malformations of dermatoglyphs is presented, dividing them into ridge aplasia, ridge hypoplasia, ridge dissociation, ridges-off-the-end, and a combination of the last two. The medical and genetic significance of these are considered in the light both of previous published cases and of new material. Malformations of dermatoglyphs are important as physical signs in paediatric diagnosis. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7 PMID:4693462

Use of intraoperative mesenteric portovenography in congenital portosystemic shunt surgery.

PubMed

White, Robert N; Macdonald, Nicholas J; Burton, Carolyn A

2003-01-01

A retrospective study of the use of intraoperative mesenteric portovenography (IOMP) in the surgical management of congenital portosystemic shunts in 100 dogs and cats was performed. Each portovenogram was scored using a subjective visual analogue scale (VAS) and was assessed for the presence of portal atresia or hypoplasia. VAS scores and portal hypoplasia assessments were obtained for portovenogram images obtained for each animal both before shunt manipulation (preligation) and following the temporary, complete ligation of the vessel (postligation). In each patient, surgical records were reviewed to ascertain the degree of shunt attenuation that was achieved at surgery. Hepatic portal vasculature was significantly different on postligation compared with preligation IOMP. Sixty-two percent of animals had apparent portal hypoplasia or atresia on their preligation IOMP. The majority of these (81%) had an improvement in portal vasculature on postligation IOMP. It was concluded that both preligation and postligation IOMP provided valuable information regarding the morphology of congenital portosystemic shunts. An accurate assessment of an animal's portal vasculature could only be made following the interpretation of a postligation portovenogram, and these findings significantly influenced the surgical management of the patient. Although individuals with high postligation VAS scores were more likely to achieve full shunt attenuation at surgery, there was no quantifiable relationship between IOMP findings and the degree of shunt attenuation achieved.

[Congenital broncho-biliary fistula: a case report].

PubMed

Pérez, Cinthia G; Reusmann, Aixa

2016-10-01

Congenital tracheo-or-bronchobiliary fistula or congenital he-patopulmonary fistula is a rare malformation with high morbidity and mortality if the diagnosis is not made early. The tracheo-or-bronchobiliary fistula is a communication between the respiratory (trachea or bronchus) and biliary tract. To date, only 35 cases have been published worldwide. We report a case of a neonate with right pneumonia and bilious fluid in the endotracheal tube. Diagnosis was made using bronchoscopy with fluoroscopy. Videothoracoscopy was used to remove the bronchobiliary fistula. Subsequently, a left he-patectomy with Roux-en-Y biliary-digestive anastomosis was performed as bile ductus hypoplasia was present. Sociedad Argentina de Pediatría.

Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia.

PubMed

Zurita-Cruz, Jessie Nallely; Villasís-Keever, Miguel Ángel; Damasio-Santana, Leticia; Manuel-Apolinar, Leticia; Ferrusca-Ceja, Rosalba; Nishimura-Meguro, Elisa; Rivera-Hernández, Aleida de J; Garrido-Magaña, Eulalia

2018-01-01

In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight. Copyright: © 2018 SecretarÍa de Salud.

Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia.

PubMed

Chen, Wuyan; Perritt, Ashley F; Morissette, Rachel; Dreiling, Jennifer L; Bohn, Markus-Frederik; Mallappa, Ashwini; Xu, Zhi; Quezado, Martha; Merke, Deborah P

2016-09-01

Some variants that cause autosomal-recessive congenital adrenal hyperplasia (CAH) also cause hypermobility type Ehlers-Danlos syndrome (EDS) due to the monoallelic presence of a chimera disrupting two flanking genes: CYP21A2, encoding 21-hydroxylase, necessary for cortisol and aldosterone biosynthesis, and TNXB, encoding tenascin-X, an extracellular matrix protein. Two types of CAH tenascin-X (CAH-X) chimeras have been described with a total deletion of CYP21A2 and characteristic TNXB variants. CAH-X CH-1 has a TNXB exon 35 120-bp deletion resulting in haploinsufficiency, and CAH-X CH-2 has a TNXB exon 40 c.12174C>G (p.Cys4058Trp) variant resulting in a dominant-negative effect. We present here three patients with biallelic CAH-X and identify a novel dominant-negative chimera termed CAH-X CH-3. Compared with monoallelic CAH-X, biallelic CAH-X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin-X function and computational data linking the type of TNXB variant to disease severity. © 2016 WILEY PERIODICALS, INC.

Genetics Home Reference: Leydig cell hypoplasia

MedlinePlus

... Twitter Home Health Conditions Leydig cell hypoplasia Leydig cell hypoplasia Printable PDF Open All Close All Enable ... consumer genetic testing? What are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Congenital basis of posterior fossa anomalies

PubMed Central

Cotes, Claudia; Bonfante, Eliana; Lazor, Jillian; Jadhav, Siddharth; Caldas, Maria; Swischuk, Leonard

2015-01-01

The classification of posterior fossa congenital anomalies has been a controversial topic. Advances in genetics and imaging have allowed a better understanding of the embryologic development of these abnormalities. A new classification schema correlates the embryologic, morphologic, and genetic bases of these anomalies in order to better distinguish and describe them. Although they provide a better understanding of the clinical aspects and genetics of these disorders, it is crucial for the radiologist to be able to diagnose the congenital posterior fossa anomalies based on their morphology, since neuroimaging is usually the initial step when these disorders are suspected. We divide the most common posterior fossa congenital anomalies into two groups: 1) hindbrain malformations, including diseases with cerebellar or vermian agenesis, aplasia or hypoplasia and cystic posterior fossa anomalies; and 2) cranial vault malformations. In addition, we will review the embryologic development of the posterior fossa and, from the perspective of embryonic development, will describe the imaging appearance of congenital posterior fossa anomalies. Knowledge of the developmental bases of these malformations facilitates detection of the morphological changes identified on imaging, allowing accurate differentiation and diagnosis of congenital posterior fossa anomalies. PMID:26246090

Postmortem Findings for 7 Neonates with Congenital Zika Virus Infection.

PubMed

Sousa, Anastácio Q; Cavalcante, Diane I M; Franco, Luciano M; Araújo, Fernanda M C; Sousa, Emília T; Valença-Junior, José Telmo; Rolim, Dionne B; Melo, Maria E L; Sindeaux, Pedro D T; Araújo, Marialva T F; Pearson, Richard D; Wilson, Mary E; Pompeu, Margarida M L

2017-07-01

Postmortem examination of 7 neonates with congenital Zika virus infection in Brazil revealed microcephaly, ventriculomegaly, dystrophic calcifications, and severe cortical neuronal depletion in all and arthrogryposis in 6. Other findings were leptomeningeal and brain parenchymal inflammation and pulmonary hypoplasia and lymphocytic infiltration in liver and lungs. Findings confirmed virus neurotropism and multiple organ infection.

Gender role across development in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PubMed

Long, Dominique N; Wisniewski, Amy B; Migeon, Claude J

2004-10-01

This study evaluated the degree of femininity and masculinity at different developmental stages in a group of adult women, some of whom were exposed to elevated prenatal adrenal androgens as a result of congenital adrenal hyperplasia (CAH) due to 21 hydroxylase (21-OH) deficiency. Women who had presented to the Johns Hopkins Hospital Pediatric Endocrine Clinic for treatment of CAH due to 21-OH deficiency were included. The control group consisted of sisters of CAH participants and women referred for evaluation of polycystic ovary syndrome. Study participants were given a questionnaire asking them to indicate their degree of masculinity and femininity during childhood, adolescence, and adulthood. In addition, participants were asked questions related to their play behavior during childhood, including playmate preferences, toy preferences, and admiration of male or female characters during fantasy play. Across participant groups, self-reported femininity decreased in a dose response manner, according to prenatal androgen exposure. For all groups, femininity increased through developmental stages. Women with salt-losing CAH remained less feminine than controls into adulthood. Conversely, self-reported masculinity increased in a dose-response manner, according to prenatal androgen exposure, across participant groups. Women with CAH showed a decrease in masculinity across developmental stages, such that by adulthood, there were no significant differences in masculinity between controls and the women with CAH. Women with salt-losing CAH were more likely to recall preferences for boy playmates, male-typical toys, and admiration for male characters during childhood than other study participants. Our data support the effect of both prenatal androgen exposure and socialization on gender role behavior in adult women with CAH due to 21-OH deficiency.

Genetics Home Reference: focal dermal hypoplasia

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... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: description of a new mutation, R384X.

PubMed

Matallana-Rhoades, Audrey Mary; Corredor-Castro, Juan David; Bonilla-Escobar, Francisco Javier; Mecias-Cruz, Bony Valentina; Mejia de Beldjena, Liliana

2016-09-30

It is presented the phenotype of a new compound heterozygous mutation of the genes R384X and Q356X encoding the enzyme of 11-beta-hydroxylase. Severe virilization, peripheral hypertension, and early puberty. Managed with hormone replacement therapy (corticosteroid) and antihypertensive therapy (beta-blocker), resulting in the control of physical changes and levels of arterial tension. According to the phenotypic characteristics of the patient, it is inferred that the R384X mutation carries an additional burden on the Q356X mutation, with the latter previously described as a cause of 11-beta-hydroxylase deficiency. The description of a new genotype, as in this case, expands the understanding of the hereditary burden and deciphers the various factors that lead to this pathology as well as the other forms of congenital adrenal hyperplasia (CAH), presenting with a broad spectrum of clinical presentations. This study highlights the importance of a complete description of the patient's CAH genetic profile as well as their parents' genetic profile.

Malformations associated with congenital diaphragmatic hernia: Impact on survival.

PubMed

Bojanić, Katarina; Pritišanac, Ena; Luetić, Tomislav; Vuković, Jurica; Sprung, Juraj; Weingarten, Toby N; Schroeder, Darrell R; Grizelj, Ruža

2015-11-01

Congenital diaphragmatic hernia (CDH) is associated with high mortality. Survival is influenced by the extent of pulmonary hypoplasia and additional congenital defects. The purpose of this study was to assess the association of congenital anomalies and admission capillary carbon dioxide levels (PcCO2), as a measure of extent of pulmonary hypoplasia, on survival in neonates with CDH. This is a retrospective review of neonates with CDH admitted to a tertiary neonatal intensive care unit between 1990 and 2014. Logistic regression was used to assess whether hospital survival was associated with admission PcCO2 or associated anomalies (isolated CDH, CDH with cardiovascular anomalies, and CDH with noncardiac anomalies). The probabilities of survival (POS) score, based on birth weight and 5-min Apgar as defined by the Congenital Diaphragmatic Hernia Study Group were included as a covariate. Of 97 patients, 55 had additional malformations (cardiovascular n=12, noncardiac anomalies n=43). POS was lower in CDH with other anomalies compared to isolated CDH. Survival rate was 61.9%, 53.5% and 41.7% in isolated CDH, CDH with noncardiac anomalies and CDH with cardiovascular anomalies, respectively. After adjusting for POS score the likelihood of survival in CDH groups with additional anomalies was similar to isolated CDH (OR 0.95, 95% CI 0.22-4.15, and 1.10, 0.39-3.08, for CDH with and without cardiovascular anomalies, respectively). After adjusting for POS score, lower PcCO2 levels (OR=1.25 per 5mmHg decrease, P=0.003) were associated with better survival. Neonates with CDH have a high prevalence of congenital malformations. However, after adjusting for POS score the presence of additional anomalies was not associated with survival. The POS score and admission PcCO2 were important prognosticating factors for survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Poland syndrome a rare congenital anomaly.

PubMed

Ibrahim, Aliyu; Ramatu, Abdallah; Helen, Akhiwu

2013-07-01

Poland syndrome is a rare congenital anomaly classically consisting of unilateral hypoplasia of the sternocostal head of the pectoralis major muscle and ipsilateral brachysyndactyly. It was first described by Alfred Poland in 1840 and may occur with different gravity. Our patient is an eight-year-old Nigerian girl with left-sided anterior chest wall defect with no detectable structural heart abnormality but presented with repeated episodes of syncopal attacks following minor trauma to the anterior chest wall.

Congenital adrenal hyperplasia: problems with developmental anomalies of the external genitalia and sex assignment.

PubMed

Al-Maghribi, Hussein

2007-09-01

A retrospective study was performed on all patients with congenital adrenal hyperplasia (CAH) who were followed up at the King Hussein Medical Center (KHMC), Amman, Jordan, during the period from January 1996 to June 2006. The aim was to evaluate the clinical features, special problems, and corrective interventions for these patients. The records of 73 children (39 were genetic females and 34 were genetic males) with CAH were reviewed in the study. The age of the patients at last follow-up was between five months and 18 years. Diagnostic criteria for CAH were typical clinical features of the illness (salt loss, dehydration, virilization, macrogenitosomia, ambiguous genitalia, and accelerated growth) and typical hormonal abnormalities (decreased serum cortisol and elevated serum 17-hydroxyprogesterone). There were 62 patients with classical presentation; among them, salt-wasting (SW) form was seen in 41 patients (66%). There were 5 patients with the nonclassic form, while 6 others had cryptic presentation. Seven patients (9%) had hypertension, mostly due to salt-retaining CAH. Among the 39 females with CAH, 27 had developed mental anomalies of the external genitalia; 20 of them underwent surgical interventions of their external genitalia. Fourteen genetically female patients were wrongly diagnosed as 'male sex' at birth due to severe virilization. Seven of them were reassigned 'female sex' socially, legally, and surgically; the parents of one of them (a four-year-old girl) wanted the surgical intervention postponed for two to three years. Hysterectomy and gonadectomy were carried out for 6 of the other 7 patients who chose to keep the male gender. Our study indicates that newborns with developmental anomalies of the external genitalia should be diagnosed as early as possible so that medical, psychological, and social complications are minimized. A neonatal screening program for such a disorder can identify infants at risk for the development of life

The pulmonary mesenchymal tissue layer is defective in an in vitro recombinant model of nitrofen-induced lung hypoplasia.

PubMed

van Loenhout, Rhiannon B; Tseu, Irene; Fox, Emily K; Huang, Zhen; Tibboel, Dick; Post, Martin; Keijzer, Richard

2012-01-01

Despite modern treatments, congenital diaphragmatic hernia (CDH) remains associated with variable survival and significant morbidity. The associated pulmonary hypoplasia is a major determinant of outcome. To develop better treatments, improved comprehension of the pathogenesis of lung hypoplasia is warranted. We developed an in vitro cell recombinant model to mimic pulmonary hypoplasia and specifically to investigate epithelial-mesenchymal interactions and to decipher which tissue layer is primarily defective in nitrofen-induced CDH-associated lung hypoplasia. Epithelial cells (E) and fibroblasts (F) were isolated from E19 control ((C)) and nitrofen-induced hypoplastic rat lungs ((N)). Cells were recombined and cultured as either homotypic [(F(C))(E(C)) and (F(N))(E(N))] or heterotypic [(F(C))(E(N)) and (F(N))(E(C))] recombinants. Recombinants containing F(N) fibroblasts had a thickened fibroblast tissue layer and there were fewer organized alveolar-like epithelial structures compared with those in control (F(C))(E(C)) recombinants. These F(N) recombinants exhibited a decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 positive cells. Cell proliferation was arrested in recombinants containing F(N) fibroblasts, which also exhibited increased p27(Kip1) and p57(Kip2) expression. In conclusion, fibroblasts, and not epithelial cells, appear to be the defective cell type in nitrofen-induced hypoplastic lungs due to a decreased ability to undergo apoptosis and maintain overall proliferation. This may explain the characteristic pulmonary interstitial thickening and hypoplasia observed in both nitrofen-induced hypoplastic lungs as well as human hypoplastic CDH lungs. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

PubMed

Kashyap, Raghava

2018-01-01

Testicular adrenal rest tumors (TARTs) are secondary to hypertrophy of adrenal rest cells in the rete testis in settings of hypersecretion of androgens. We present a case of congenital adrenal hyperplasia with TART with clues to the diagnosis on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). To the best of our knowledge, this is the first reported case on the role of 18 F-FDG PET/CT in TART.

[Congenital mydriasis as an initial sign of septo-optic dysplasia].

PubMed

Carrascosa-Romero, M C; Ruiz-Cano, R; Martínez-López, F; Alfaro-Ponce, B; Pérez-Pardo, A

2013-10-01

Septo-optic dysplasia (SOD)[MIM182230] consisting of a heterogeneous and uncommon condition characterised by the classictriad: optic nerve hypoplasia, abnormalities of pituitary hormone, and defects of thebrain midline (including agenesis of the septum pellucidum and/or the corpus callosum; ithas also been described associated cortical malformations, it was referred to as SOD plus syndrome).We report the first known case in which the initial diagnostic sign of SOD was a bilateralmydriasis as a manifestation ofhypoplasia of both optic nerves, pituitary hypoplasia andcerebral dysgenesis with neuronal migration disorder.We discuss thedifferential diagnosis of congenital mydriasis. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics

PubMed Central

Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

2017-01-01

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3′-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3′-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH. PMID:28401898

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.

PubMed

Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

2017-06-01

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.

A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, L.; Sakkal-Alkaddour, S.; Chang, Ying T.

1996-01-01

We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD genemore » region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3{beta}-HSD deficiency in the child caused by the compound heterozygous type II 3{beta}-HSD gene mutation. Both codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3{beta}-HSD protein, thereby causing salt-wasting 3{beta}-HSD deficiency in the patient. 21 refs., 2 figs., 1 tab.« less

Prenatal hormones and postnatal socialization by parents as determinants of male-typical toy play in girls with congenital adrenal hyperplasia.

PubMed

Pasterski, Vickie L; Geffner, Mitchell E; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

2005-01-01

Toy choices of 3- to 10-year-old children with congenital adrenal hyperplasia (CAH) and of their unaffected siblings were assessed. Also assessed was parental encouragement of sex-typed toy play. Girls with CAH displayed more male-typical toy choices than did their unaffected sisters, whereas boys with and without CAH did not differ. Mothers and fathers encouraged sex-typical toy play in children with and without CAH. However, girls with CAH received more positive feedback for play with girls' toys than did unaffected girls. Data show that increased male-typical toy play by girls with CAH cannot be explained by parental encouragement of male-typical toy play. Although parents encourage sex-appropriate behavior, their encouragement appears to be insufficient to override the interest of girls with CAH in cross-sexed toys.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

PubMed

Khattab, Ahmed; Haider, Shozeb; Kumar, Ameet; Dhawan, Samarth; Alam, Dauood; Romero, Raquel; Burns, James; Li, Di; Estatico, Jessica; Rahi, Simran; Fatima, Saleel; Alzahrani, Ali; Hafez, Mona; Musa, Noha; Razzghy Azar, Maryam; Khaloul, Najoua; Gribaa, Moez; Saad, Ali; Charfeddine, Ilhem Ben; Bilharinho de Mendonça, Berenice; Belgorosky, Alicia; Dumic, Katja; Dumic, Miroslav; Aisenberg, Javier; Kandemir, Nurgun; Alikasifoglu, Ayfer; Ozon, Alev; Gonc, Nazli; Cheng, Tina; Kuhnle-Krahl, Ursula; Cappa, Marco; Holterhus, Paul-Martin; Nour, Munier A; Pacaud, Daniele; Holtzman, Assaf; Li, Sun; Zaidi, Mone; Yuen, Tony; New, Maria I

2017-03-07

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1 , a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

Congenital diaphragmatic hernias: from genes to mechanisms to therapies

PubMed Central

McCulley, David J.; Shen, Yufeng; Wynn, Julia; Shang, Linshan; Bogenschutz, Eric; Sun, Xin

2017-01-01

ABSTRACT Congenital diaphragmatic hernias (CDHs) and structural anomalies of the diaphragm are a common class of congenital birth defects that are associated with significant morbidity and mortality due to associated pulmonary hypoplasia, pulmonary hypertension and heart failure. In ∼30% of CDH patients, genomic analyses have identified a range of genetic defects, including chromosomal anomalies, copy number variants and sequence variants. The affected genes identified in CDH patients include transcription factors, such as GATA4, ZFPM2, NR2F2 and WT1, and signaling pathway components, including members of the retinoic acid pathway. Mutations in these genes affect diaphragm development and can have pleiotropic effects on pulmonary and cardiac development. New therapies, including fetal endoscopic tracheal occlusion and prenatal transplacental fetal treatments, aim to normalize lung development and pulmonary vascular tone to prevent and treat lung hypoplasia and pulmonary hypertension, respectively. Studies of the association between particular genetic mutations and clinical outcomes should allow us to better understand the origin of this birth defect and to improve our ability to predict and identify patients most likely to benefit from specialized treatment strategies. PMID:28768736

A three-year follow-up of congenital adrenal hyperplasia newborn screening.

PubMed

Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

2014-01-01

congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

The use of computer-aided design/manufacturing (CAD/CAM) technology to aid in the reconstruction of congenitally deficient pediatric mandibles: A case series.

PubMed

Gougoutas, Alexander J; Bastidas, Nicholas; Bartlett, Scott P; Jackson, Oksana

2015-12-01

Microvascular reconstruction of the pediatric mandible, particularly when necessitated by severe, congenital hypoplasia, presents a formidable challenge. Complex cases, however, may be simplified by computer-aided design/computer-aided manufacturing (CAD/CAM) assisted surgical planning. This series represents the senior authors' preliminary experiences with CAD/CAM assisted, microvascular reconstruction of the pediatric mandible. Presented are two patients with hemifacial/bifacial microsomia, both with profound mandibular hypoplasia, who underwent CAD/CAM assisted reconstruction of their mandibles with vascularized fibula flaps. Surgical techniques, CAD/CAM routines employed, complications, and long-term outcomes are reported. Successful mandibular reconstructions were achieved in both patients with centralization of their native mandibles and augmentation of deficient mandibular subunits. No long-term complications were observed. CAD/CAM technology can be utilized in pediatric mandibular reconstruction, and is particularly beneficial in cases of profound, congenital hypoplasia requiring extensive, multi-planar, bony reconstructions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.

PubMed

Raisingani, Manish; Contreras, Maria F; Prasad, Kris; Pappas, John G; Kluge, Michelle L; Shah, Bina; David, Raphael

2016-07-01

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

PubMed

Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

1983-04-01

glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.

Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia.

PubMed

Berenbaum, Sheri A; Bailey, J Michael

2003-03-01

To address questions about sex assignment in children with ambiguous genitalia, we studied gender identity in girls with congenital adrenal hyperplasia (CAH) in relation to characteristics of the disease and treatment, particularly genital appearance and surgery. A 9-item gender identity interview was administered to 43 girls with classical CAH ranging in age from 3-18 yr, 7 tomboys, and 29 sister control girls. Groups were compared on total score and on individual items. Results showed that, on the total gender identity score, 88% of girls with CAH had scores overlapping those of control girls, but the average score was intermediate between control girls and tomboys. On individual items of gender identity (discomfort as a girl, wish to be a boy), girls with CAH were similar to control girls. Gender identity in girls with CAH was not related to degree of genital virilization or age at which genital reconstructive surgery was done. Thus, moderate androgen excess early in development appears to produce a small increase in the risk of atypical gender identity, but this risk cannot be predicted from genital virilization.

Prenatal androgens and gender-typed behavior: a study of girls with mild and severe forms of congenital adrenal hyperplasia.

PubMed

Servin, Anna; Nordenström, Anna; Larsson, Agne; Bohlin, Gunilla

2003-05-01

Gender-typed behaviors and interests were investigated in 26 girls, aged 2-10 years, affected with congenital adrenal hyperplasia (CAH) and in 26 unaffected girls matched for age. Girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and to wish for masculine careers. Parents of girls with CAH rated their daughters' behaviors as more boylike than did parents of unaffected girls. A relation was found between disease severity and behavior indicating that more severely affected CAH girls were more interested in masculine toys and careers. No parental influence could be demonstrated on play behavior, nor did the comparison of parents' ratings of wished for behavior versus perceived behavior in their daughters indicate an effect of parental expectations. The results are interpreted as supporting a biological contribution to differences in play behavior between girls with and without CAH.

Downregulation of insulin-like growth factor binding protein 3 and 5 in nitrofen-induced pulmonary hypoplasia.

PubMed

Ruttenstock, Elke; Doi, Takashi; Dingemann, Jens; Puri, Prem

2010-01-01

The high mortality in congenital diaphragmatic hernia (CDH) is mainly attributed to pulmonary hypoplasia. Recent studies suggest that retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The insulin-like growth factor (IGF) system plays a crucial role in fetal lung development by interaction of IGFBP-3 and IGFBP-5 with RSP. We hypothesized that pulmonary IGFBP-3 and IGFBP-5 gene expression levels are downregulated in the nitrofen-induced pulmonary hypoplasia. Pregnant rats were exposed to either olive oil or 100 mg nitrofen on day 9.5 (D9.5) of gestation. Fetal lungs were harvested on D18 and D21 and divided into control and nitrofen groups. IGFBP-3 and IGFBP-5 pulmonary gene and protein expression were determined using real-time RT-PCR and immunohistochemistry. Relative levels of IGFBP-3 mRNA were significantly decreased in the nitrofen group (8.00 +/- 14.44) in D21 compared to controls (14.81 +/- 16.11; p < 0.05). Expression levels of IGFBP-5 mRNA were also significantly decreased in nitrofen group (10.66 +/- 4.83) on D18 compared to controls (17.92 +/- 4.77). Immunohistochemistry showed decreased IGFBP-3 expression on D21 and decreased IGFBP-5 immunoreactivity on D18 in hypoplastic lungs compared to controls. Downregulation of IGFBP-3 and IGFBP-5 gene expression may cause pulmonary hypoplasia in the nitrofen-induced CDH model by interfering with retinoid signaling pathway.

[Congenital anomalies of poor prognosis. Genetics Consensus Committee].

PubMed

Pardo Vargas, Rosa A; Aracena, Mariana; Aravena, Teresa; Cares, Carolina; Cortés, Fanny; Faundes, Víctor; Mellado, Cecilia; Passalacqua, Cristóbal; Sanz, Patricia; Castillo Taucher, Silvia

The Genetic Branch of the Chilean Society of Paediatrics, given the draft Law governing the decriminalisation of abortion on three grounds, focusing on the second ground, which considers the "embryo or foetus suffering from a congenital structural anomaly or a genetic disorder incompatible with life outside the womb", met to discuss the scientific evidence according to which congenital anomalies (CA) may be included in this draft law. Experts in clinical genetics focused on 10 CA, reviewed the literature evidence, and met to discuss it. It was agreed not to use the term "incompatible with life outside the womb", as there are exceptions and longer survivals, and change to "congenital anomaly of poor prognosis (CAPP)". Ten CA were evaluated: serious defects of neural tube closure: anencephaly, iniencephaly and craniorachischisis, pulmonary hypoplasia, acardiac foetus, ectopia cordis, non-mosaic triploidy, "limb body wall" complex, "body stalk" anomaly, trisomy 13, trisomy 18, and bilateral renal agenesis. Findings on the prevalence, natural history, prenatal diagnostic methods, survival, and reported cases of prolonged survival were analysed. Post-natal survival, existence of treatments, and outcomes, as well as natural history without intervention, were taken into account in classifying a CA as a CAPP. A CAPP would be: anencephaly, severe pulmonary hypoplasia, acardiac foetus, cervical ectopia cordis, non-mosaic triploidy, limb body wall complex, body stalk anomaly, non-mosaic trisomy 13, non-mosaic trisomy 18, and bilateral renal agenesis. For their diagnosis, it is required that all pregnant women have access to assessments by foetal anatomy ultrasound and occasionally MRI, and cytogenetic and molecular testing. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Maxillary hypoplasia in the cleft patient: contribution of orthodontic dental space closure to orthognathic surgery.

PubMed

Lee, Justine C; Slack, Ginger C; Walker, Ryann; Graves, Lindsay; Yen, Sandra; Woo, Jessica; Ambaram, Rishal; Martz, Martin G; Kawamoto, Henry K; Bradley, James P

2014-02-01

Cleft lip and palate surgery in the developing child is known to be associated with maxillary hypoplasia. However, the effects of nonsurgical manipulations on maxillary growth have not been well investigated. The authors present the contribution of orthodontic dental space closure with canine substitution to maxillary hypoplasia and the need for orthognathic surgery. Cleft lip/palate and cleft palate patients older than 15 years of age were reviewed for dental anomalies, orthodontic canine substitution, and Le Fort I advancement. Skeletal relationships of the maxilla to the skull base (SNA), mandible (ANB), and facial height were determined on lateral cephalograms. Logistic regression analyses were performed to estimate odds ratios. Ninety-five patients were reviewed (mean age, 18.1 years). In 65 patients with congenitally missing teeth, 55 percent with patent dental spaces required Le Fort I advancement. In contrast, 89 percent who underwent canine substitution required Le Fort I advancement (p = 0.004). Canine substitution is associated with a statistically significant increase in maxillary retrognathia when compared with dental space preservation on lateral cephalograms (mean SNA, 75.2 and 79.0, respectively; p = 0.006). Adjusting for missing dentition, logistic regression analyses demonstrated that canine substitution is an independent predictor for orthognathic surgery (OR, 6.47) and maxillary retrusion defined by SNA < 78 (OR, 8.100). The coordination of orthodontia and surgery is essential to cleft care. The authors report a strong association between orthodontic cleft closure using canine substitution with maxillary hypoplasia and subsequent Le Fort I advancement, and suggest systematic criteria for management of cleft-related dental agenesis. Therapeutic, III.

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

PubMed Central

Auchus, Richard J.; Witchel, Selma Feldman; Leight, Kelly R.; Aisenberg, Javier; Azziz, Ricardo; Bachega, Tânia A.; Baker, Linda A.; Baratz, Arlene B.; Baskin, Laurence S.; Berenbaum, Sheri A.; Breault, David T.; Cerame, Barbara I.; Conway, Gerard S.; Eugster, Erica A.; Fracassa, Stephanie; Gearhart, John P.; Geffner, Mitchell E.; Harris, Katharine B.; Hurwitz, Richard S.; Katz, Aviva L.; Kalro, Brinda N.; Lee, Peter A.; Alger Lin, Gretchen; Loechner, Karen J.; Marshall, Ian; Merke, Deborah P.; Migeon, Claude J.; Miller, Walter L.; Nenadovich, Tamara L.; Oberfield, Sharon E.; Pass, Kenneth A.; Poppas, Dix P.; Lloyd-Puryear, Michele A.; Quigley, Charmian A.; Riepe, Felix G.; Rink, Richard C.; Rivkees, Scott A.; Sandberg, David E.; Schaeffer, Traci L.; Schlussel, Richard N.; Schneck, Francis X.; Seely, Ellen W.; Snyder, Diane; Speiser, Phyllis W.; Therrell, Bradford L.; VanRyzin, Carol; Vogiatzi, Maria G.; Wajnrajch, Michael P.; White, Perrin C.; Zuckerman, Alan E.

2010-01-01

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH. PMID:21274448

Orthognathic Surgery and Rhinoplasty to Address Nasomaxillary Hypoplasia.

PubMed

Veeramani, Anamika; Sawh, Raj; Steinbacher, Derek M

2017-11-01

The treatment of nasomaxillary hypoplasia is challenging. The phenotype of Binder "syndrome" includes the following: midfacial hypoplasia, class III malocclusion, small or absent anterior nasal spine, flattened nose, horizontal nostrils, short columella, acute nasolabial angle, and a flat frontonasal angle. A staged approach is used, with orthognathic surgery to achieve vertical maxillary length and sagittal advancement, followed by rhinoplasty aimed to increase nasal tip projection, rotation, and columellar length. This article details the diagnosis and treatment of nasomaxillary hypoplasia, demonstrating the senior author's (D.M.S.) preferred approach and technical steps. Therapeutic, V.

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Gender of rearing and psychosocial aspect in 46 XX congenital adrenal hyperplasia

PubMed Central

Gangaher, Arushi; Jyotsna, Viveka P.; Chauhan, Vasundhera; John, Jomimol; Mehta, Manju

2016-01-01

Background: In congenital adrenal hyperplasia (CAH) with ambiguous genitalia, assigning gender of rearing can be complex, especially If genitalia is highly virilized. Apart from karyotype, prenatal androgen exposure, patient's gender orientation, sociocultural, and parental influences play a role. The aim of this study was to assess gender dysphoria and psychosocial issues in patients of CAH raised as males and females. Materials and Methods: This is a cross-sectional study that includes patients (old and new) with CAH who were treated by us in the last 6 months. A semi-structured interview proforma was used to elicit history and psychosocial background of the patients. The clinical and biochemical details were noted. For psychological analysis, patients were screened for gender dysphoria using Parent Report Gender Identity Questionnaire for children <12 years and Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. Results: We analyzed 22 46 XX CAH patients among which, 3 were reared as males and 19 as females. Among the 19 patients reared as females, 17 patients showed no gender dysphoria. Two patients revealed gender dysphoria as indicated by their marginally low scores on the gender dysphoria assessment. However, in view of current literature and the age groups of the patients, behavior of the 6-year-old patient can be best understood as being tomboyish. Gender dysphoria in the 22-year-old can be explained by the dominance of psychosocial factors and not hormones alone. Among the three patients reared as males, two prepubertal were satisfied with their male gender identity. The third patient, aged 32 years, had gender dysphoria when reared as a male that resolved when gender was reassigned as female and feminizing surgery was done. Conclusion: Gender assignment in 46 XX CAH is guided by factors such as degree of virilization of genitalia, gender orientation, patient involvement, sociocultural, and parental influences. PMID:27867895

Gender of rearing and psychosocial aspect in 46 XX congenital adrenal hyperplasia.

PubMed

Gangaher, Arushi; Jyotsna, Viveka P; Chauhan, Vasundhera; John, Jomimol; Mehta, Manju

2016-01-01

In congenital adrenal hyperplasia (CAH) with ambiguous genitalia, assigning gender of rearing can be complex, especially If genitalia is highly virilized. Apart from karyotype, prenatal androgen exposure, patient's gender orientation, sociocultural, and parental influences play a role. The aim of this study was to assess gender dysphoria and psychosocial issues in patients of CAH raised as males and females. This is a cross-sectional study that includes patients (old and new) with CAH who were treated by us in the last 6 months. A semi-structured interview proforma was used to elicit history and psychosocial background of the patients. The clinical and biochemical details were noted. For psychological analysis, patients were screened for gender dysphoria using Parent Report Gender Identity Questionnaire for children <12 years and Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. We analyzed 22 46 XX CAH patients among which, 3 were reared as males and 19 as females. Among the 19 patients reared as females, 17 patients showed no gender dysphoria. Two patients revealed gender dysphoria as indicated by their marginally low scores on the gender dysphoria assessment. However, in view of current literature and the age groups of the patients, behavior of the 6-year-old patient can be best understood as being tomboyish. Gender dysphoria in the 22-year-old can be explained by the dominance of psychosocial factors and not hormones alone. Among the three patients reared as males, two prepubertal were satisfied with their male gender identity. The third patient, aged 32 years, had gender dysphoria when reared as a male that resolved when gender was reassigned as female and feminizing surgery was done. Gender assignment in 46 XX CAH is guided by factors such as degree of virilization of genitalia, gender orientation, patient involvement, sociocultural, and parental influences.

Congenital adrenal hyperplasia clinical characteristics and genotype in newborn, childhood and adolescence.

PubMed

Pasqualini, Titania; Alonso, Guillermo; Tomasini, Rosangela; Galich, Ana Maria; Buzzalino, Noemi; Fernandez, Cecilia; Minutolo, Carolina; Alba, Liliana; Dain, Liliana

2007-01-01

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a disorder which can adopt three clinical expressions: two classical forms -salt-wasting (SW), with residual enzymatic activity (EA) < or = 1% and simple virilizing (SV), with EA 1-2%- and a mild late onset or nonclassical (NC) form, with EA 10-60%. Our objective is to describe clinical characteristics, growth, and bone mass in a group of patients affected by 21-hydroxylase deficiency. Besides, molecular genetics studies were performed in patients, and also when available in their parents and siblings. Nine patients with neonatal diagnosis and 8 with pre or postpubertal diagnosis were studied. Analyses of 10-point mutations in the CYP21A2 gene were performed. We found that all the patients with the classical expression, except one with a de novo mutation R356W in one allele, were fully genotyped with predictive < 2% EA mutations. Signs of hyperandrogenism were present in 5/6 NC patients; one was diagnosed by searching for mutations in asymptomatic siblings. All the NC patients were compound heterozygotes carrying V281L mutation in one allele and a predictive low EA in the other, except for one not yet determined. In patients with neonatal diagnosis, mean height was low at one year of age, though it showed a significant increase before the onset of puberty. We conclude that neonatal diagnosis of classical CAH allows an adequate follow up enhancing growth. Molecular analyses of all members of an affected family may disclose asymptomatic patients. The presence of de novo mutations, as well as, the presence of mutations with low predicted EA in NC patients reinforces the importance of genotyping for appropriate genetic counseling. In fully genotyped NC patients, the lowest value of ACTH-stimulated 17OHP was 14 ng/ml. Lower cut-off values might overestimate the diagnosis of the NC form.

Fryns anophthalmia-plus syndrome with hypoplastic adrenal glands.

PubMed

Ozalp, O; Ozcimen, E E; Yilmaz, Z; Yanik, F; Sahin, F I

2008-01-01

We report a family with two consequent sibs with anophthalmia and cleft lip and palate. A 27 year old woman married to her first cousin was counseled for anophthalmia and cleft lip and palate detected during routine fetal ultrasonographic examination on the 23rd week of the pregnancy. Her obstetric history revealed a healthy girl aged 7 years and a boy with anophthalmia and cleft lip and palate who lived for 20 days in the neonatal intensive care unit. The current pregnancy was terminated after the diagnosis, and post mortem examination of the fetus revealed pre-maxilla agenesis, anophthalmia, cerebral ventricular dilatation, adrenal hypoplasia and single umbilical artery. Chromosome analysis resulted in normal karyotypes of the fetus and both parents. The inheritance pattern was regarded as autosomal recessive and the family was informed about the condition and risks during genetic counseling.

Dental Stigmata of Congenital Syphilis: A Historic Review With Present Day Relevance.

PubMed

Nissanka-Jayasuriya, Eranga H; Odell, Edward W; Phillips, Carina

2016-09-01

Syphilis was the first sexually transmitted disease to be diagnosed in childhood. Most developed countries controlled syphilis effectively after the 1950s and congenital syphilis became rare. Since the late 1990s there has been a resurgence of syphilis in developed and developing countries and the WHO estimates that at least half a million infants die of congenital syphilis every year. The earliest reference to the dental manifestations of congenital syphilis was by Sir Jonathan Hutchinson, Assistant Surgeon at The London Hospital in 1861. Three main dental defects are described in congenital syphilis; Hutchinson's incisors, Moon's molars or bud molars, and Fournier's molars or mulberry molars. Although many physicians, dentists, and pathologists in developed countries will be aware of the dental features of syphilis, most will never have seen a case or made the diagnosis. The purpose of this article is to review some of the history of congenital syphilis, remind healthcare professionals of the features, and bring to their attention that the changes are still prevalent and that milder cases can be mistaken for other causes of hypoplasia.

Fetoscopic Therapy for Severe Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: A First in Prenatal Regenerative Medicine at Mayo Clinic.

PubMed

Ruano, Rodrigo; Klinkner, Denise B; Balakrishnan, Karthik; Novoa Y Novoa, Victoria A; Davies, Norman; Potter, Dean D; Carey, William A; Colby, Christopher E; Kolbe, Amy B; Arendt, Katherine W; Segura, Leal; Sviggum, Hans P; Lemens, Maureen A; Famuyide, Abimbola; Terzic, Andre

2018-05-15

To introduce the prenatal regenerative medicine service at Mayo Clinic for fetal endoscopic tracheal occlusion (FETO) care for severe congenital diaphragmatic hernia (CDH). Two cases of prenatal management of severe CDH with FETO between January and August 2017 are reported. Per protocol, FETO was offered for life-threatening severe CDH at between 26 and 29 weeks' gestation. Regenerative outcome end point was fetal lung growth. Gestational age at procedure and maternal and perinatal outcomes were additional monitored parameters. Diagnosis by ultrasonography of severe CDH was based on extremely reduced lung size (observed-to-expected lung area to head circumference ratio [o/e-LHR], eg, o/e-LHR of 20.3% for fetus 1 and 23.0% for fetus 2) along with greater than one-third of the liver herniated into the chest in both fetuses. Both patients underwent successful FETO at 28 weeks. At the time of intervention, no maternal or fetal complications were observed. Postintervention, fetal lung growth was observed in both fetuses, reaching an o/e-LHR of 62.7% at 36 weeks in fetus 1 and 52.4% at 32 weeks in fetus 2. The balloons were removed successfully at 35 weeks and 4 days by ultrasound-guided puncture in the first patient and at 32 weeks and 3 days by ex utero intrapartum therapy-to-airway procedure in the second patient. Postnatal management followed standard of care with patch CDH therapy. At discharge, one patient was breathing normally, whereas the other required minimal nasal cannula oxygen support. The successful launch of the first fetoscopic therapy for CDH at Mayo Clinic reveals its feasibility and safety, with early signs of benefit documented by fetal lung growth and reversal of severe pulmonary hypoplasia. clinicaltrials.gov Identifier: G170062. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Quality of life in adults with congenital adrenal hyperplasia relates to glucocorticoid treatment, adiposity and insulin resistance: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)

PubMed Central

Han, Thang S; Krone, Nils; Willis, Debbie S; Conway, Gerard S; Hahner, Stefanie; Rees, D Aled; Stimson, Roland H; Walker, Brian R; Arlt, Wiebke; Ross, Richard J

2013-01-01

Context Quality of life (QoL) has been variously reported as normal or impaired in adults with congenital adrenal hyperplasia (CAH). To explore the reasons for this discrepancy we investigated the relationship between QoL, glucocorticoid treatment and other health outcomes in CAH adults. Methods Cross-sectional analysis of 151 adults with 21-hydroxylase deficiency aged 18–69 years in whom QoL (assessed using the Short Form Health Survey), glucocorticoid regimen, anthropometric and metabolic measures were recorded. Relationships were examined between QoL, type of glucocorticoid (hydrocortisone, prednisolone and dexamethasone) and dose of glucocorticoid expressed as prednisolone dose equivalent (PreDEq). QoL was expressed as z-scores calculated from matched controls (14 430 subjects from UK population). Principal components analysis (PCA) was undertaken to identify clusters of associated clinical and biochemical features and the principal component (PC) scores used in regression analysis as predictor of QoL. Results QoL scores were associated with type of glucocorticoid treatment for vitality (P=0.002) and mental health (P=0.011), with higher z-scores indicating better QoL in patients on hydrocortisone monotherapy (P<0.05). QoL did not relate to PreDEq or mutation severity. PCA identified three PCs (PC1, disease control; PC2, adiposity and insulin resistance and PC3, blood pressure and mutations) that explained 61% of the variance in observed variables. Stepwise multiple regression analysis demonstrated that PC2, reflecting adiposity and insulin resistance (waist circumference, serum triglycerides, homeostasis model assessment of insulin resistance and HDL-cholesterol), related to QoL scores, specifically impaired physical functioning, bodily pain, general health, Physical Component Summary Score (P<0.001) and vitality (P=0.002). Conclusions Increased adiposity, insulin resistance and use of prednisolone or dexamethasone are associated with impaired QoL in adults

Enamel hypoplasia in the middle pleistocene hominids from Atapuerca (Spain).

PubMed

Bermúdez de Castro, J M; Pérez, P J

1995-03-01

The prevalence and chronology of enamel hypoplasias were studied in a hominid dental sample from the Sima de los Huesos (SH) Middle Pleistocene site at the Sierra de Atapuerca (Burgos, northern Spain). A total of 89 permanent maxillary teeth, 143 permanent mandibular teeth, and one deciduous lower canine, belonging to a minimum of 29 individuals, were examined. Excluding the antimeres (16 maxillary and 37 mandibular cases) from the sample, the prevalence of hypoplasias in the permanent dentition is 12.8% (23/179), whereas the deciduous tooth also showed an enamel defect. No statistically significant differences were found between both arcades and between the anterior and postcanine teeth for the prevalence of hypoplasias. In both the maxilla and the mandible the highest frequency of enamel hypoplasias was recorded in the canines. Only one tooth (a permanent upper canine) showed two different enamel defects, and most of the hypoplasias were expressed as faint linear horizontal defects. Taking into account the limitations that the incompleteness of virtually all permanent dentitions imposes, we have estimated that the frequency by individual in the SH hominid sample was not greater than 40%. Most of the hypoplasias occurred between birth and 7 years (N = 18, X = 3.5, SD = 1.3). Both the prevalence and severity of the hypoplasias of the SH hominid sample are significantly less than those of a large Neandertal sample. Furthermore, prehistoric hunter-gatherers and historic agricultural and industrial populations exhibit a prevalence of hypoplasias generally higher than that of the SH hominids. Implications for the survival strategies and life quality of the SH hominids are also discussed.

Brain stem hypoplasia associated with Cri-du-Chat syndrome.

PubMed

Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

2013-01-01

Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

[Congenital adrenal hyperplasia: a qualitative study on sex definition and redesignation dilation surgery and psychological support (part II)].

PubMed

Telles-Silveira, Mariana; Tonetto-Fernandes, Vânia F; Schiller, Paulo; Kater, Claudio E

2009-12-01

To identify relevant questions related to sex definition and re-designation and reconstructive surgery in patients with congenital adrenal hyperplasia (CAH), and to understand the role of the psychologist in providing care for these patients. We selected 21 subjects: 7 pediatric endocrinologists from 5 Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to a qualitative research model. In this paper, 3 of the studied categories are analyzed: 'sex definition and re-designation', 'reconstructive surgery/vaginal dilation', and 'psychology'. Parents' main anguish relates to the situation of an unnamed sex at birth, whereas sex re-designation was distressful to physicians. A sense of loneliness when dealing with the disease and treatment was a common anguish among patients; dilation procedures were the major complaint. In general, physicians recommend that genital reconstructive surgery be performed early on to avoid future trauma. In such a complex scenario, it is remarkable that not all the reference service staff have a psychologist on duty. Difficulties to deal with questions involving sexuality were evident and dilation procedures are an additional source of trauma for these patients.

Assembling a Functional Clitoris and Vulva from a Pseudo-Penis: A Surgical Technique for an Adult Woman with Congenital Adrenal Hyperplasia.

PubMed

Tjalma, Wiebren A A

2017-06-01

Congenital adrenal hyperplasia (CAH) is associated with a genital deformation that might cause a negative body image. The genital ambiguity is generally "corrected" surgically during early infancy. The advantage is a psychological benefit. The disadvantages are multiple surgical procedures and the loss of orgasm. A 22-year-old woman with CAH consulted for genital reconstructive surgery. She had a pseudopenis of 4 cm and could achieve an orgasm by masturbating. During surgery, the penis was dismantled and with the preserved glans penis and the corpora cavernosa, a clitoris and vestibules were constructed, respectively. On the basis of the anamneses during the follow-up, she had a functional vagina and could still achieve orgasms. Genital correction surgery for CAH at an older age was easier, could be done in 1 step, and enabled the preservation of orgasm. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Banks, Kathryn; Gaviglio, Amy; Hietala, Amy; McCann, Mark; Thomas, William

2012-11-01

Newborn screening (NBS) for the classic forms of congenital adrenal hyperplasia (CAH) is mandated in all states in the United States. Compared with other NBS disorders, the false-positive rate (FPR) of CAH screening remains high and has not been significantly improved by adjusting 17α-hydroxyprogesterone cutoff values for birth weight and/or gestational age. Minnesota was the first state to initiate, and only 1 of 4 states currently performing, second-tier steroid profiling for CAH. False-negative rates (FNRs) for CAH are not well known. This is a population-based study of all Minnesota infants (769,834) born 1999-2009, grouped by screening protocol (one-tier with repeat screen, January 1999 to May 2004; two-tier with second-tier steroid profiling, June 2004 to December 2009). FPR, FNR, and positive predictive value (PPV) were calculated per infant, rather than per sample, and compared between protocols. Overall, 15 false-negatives (4 salt-wasting, 11 simple-virilizing) and 45 true-positives were identified from 1999 to 2009. With two-tier screening, FNR was 32%, FPR increased to 0.065%, and PPV decreased to 8%, but these changes were not statistically significant. Second-tier steroid profiling obviated repeat screens of borderline results (355 per year average). In comparing the 2 screening protocols, the FPR of CAH NBS remains high, the PPV remains low, and false-negatives occur more frequently than has been reported. Physicians should be cautioned that a negative NBS does not necessarily rule out classic CAH; therefore, any patient for whom there is clinical concern for CAH should receive immediate diagnostic testing.

[Clinical and magnetic resonance imaging characteristics of isolated congenital anosmia].

PubMed

Liu, Jian-feng; Wang, Jian; You, Hui; Ni, Dao-feng; Yang, Da-zhang

2010-05-25

To report a series of patients with isolated congenital anosmia and summarize their clinical and magnetic resonance imaging (MRI) characteristics. Twenty patients with isolated congenital anosmia were reviewed retrospectively. A thorough medical and chemosensory history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, sinonasal computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Neither ENT physical examination nor nasal endoscopy was remarkable. Subjective olfactory testing indicated all of them were of anosmia. No olfactory event-related potentials to maximal stimulus were obtained. Computed tomography scan was normal. MRI revealed the absence of olfactory bulbs and tracts in all cases. And hypoplasia or aplasia of olfactory sulcus was found in all cases. All the patients had normal sex hormone level. The diagnosis of isolated congenital anosmia is established on chief complaints, physical examination, olfactory testing and olfactory imaging. MRI of olfactory pathway is indispensable.

Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela.

PubMed

Yepez, Juan B; Murati, Felipe A; Pettito, Michele; Peñaranda, Carlos F; de Yepez, Jazmin; Maestre, Gladys; Arevalo, J Fernando

2017-05-01

The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed. To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. This prospective case series included 43 patients from 2 ophthalmic centers in Colombia and Venezuela who underwent evaluation from October 1, 2015, through June 30, 2016, and were clinically diagnosed with congenital Zika syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native American. Ophthalmic and systemic evaluations and serologic testing were performed on all infants. Patients underwent external ocular examination and dilated ophthalmoscopy. Serologic testing ruled out toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus. Ophthalmic manifestations of congenital Zika syndrome. Of the 43 patients included in this series (28 female and 15 male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all the children had no ophthalmic findings and did not report ocular symptoms during pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve findings included hypoplasia with the double-ring sign, pallor, and increased cup-disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%). Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had a combination of lesions in the posterior pole. Five patients (12%) were

Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela

PubMed Central

Yepez, Juan B.; Murati, Felipe A.; Pettito, Michele; Peñaranda, Carlos F.; de Yepez, Jazmin; Maestre, Gladys

2017-01-01

Importance The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed. Objective To report the ocular manifestations of congenital Zika syndrome with microcephaly in Colombia and Venezuela. Design, Setting, and Participants This prospective case series included 43 patients from 2 ophthalmic centers in Colombia and Venezuela who underwent evaluation from October 1, 2015, through June 30, 2016, and were clinically diagnosed with congenital Zika syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native American. Interventions Ophthalmic and systemic evaluations and serologic testing were performed on all infants. Patients underwent external ocular examination and dilated ophthalmoscopy. Serologic testing ruled out toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency virus. Main Outcomes and Measures Ophthalmic manifestations of congenital Zika syndrome. Results Of the 43 patients included in this series (28 female and 15 male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all the children had no ophthalmic findings and did not report ocular symptoms during pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve findings included hypoplasia with the double-ring sign, pallor, and increased cup-disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%). Chorioretinal scarring was present in 3 patients (7

Prenatal hormones and childhood sex-segregation: Playmate and play style preferences in girls with congenital adrenal hyperplasia

PubMed Central

Pasterski, Vickie; Geffner, Mitchell E.; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

2011-01-01

We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically-developing children, and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. PMID:21338606

Prenatal hormones and childhood sex segregation: playmate and play style preferences in girls with congenital adrenal hyperplasia.

PubMed

Pasterski, Vickie; Geffner, Mitchell E; Brain, Caroline; Hindmarsh, Peter; Brook, Charles; Hines, Melissa

2011-04-01

We investigated playmate and play style preference in children with congenital adrenal hyperplasia (CAH) (26 females, 31 males) and their unaffected siblings (26 females, 17 males) using the Playmate and Play Style Preferences Structured Interview (PPPSI). Both unaffected boys and girls preferred same-sex playmates and sex-typical play styles. In the conflict condition where children chose between a same-sex playmate engaged in an other-sex activity or an other-sex playmate engaged in a same-sex activity, boys (both CAH and unaffected brothers) almost exclusively chose playmates based on the preferred play style of the playmate as opposed to the preferred gender label of the playmate. By contrast, unaffected girls used play style and gender label about equally when choosing playmates. Girls with CAH showed a pattern similar to that of boys: their playmate selections were more masculine than unaffected girls, they preferred a boy-typical play style and, in the conflict condition, chose playmates engaged in a masculine activity. These findings suggest that prenatal androgen exposure contributes to sex differences in playmate selection observed in typically developing children and that, among boys and girls exposed to high levels of androgens prenatally, play style preferences drive sex segregation in play. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular defects of the CYP21A2 gene in Greek-Cypriot patients with congenital adrenal hyperplasia.

PubMed

Skordis, Nicos; Kyriakou, Andreas; Tardy, Véronique; Ioannou, Yiannis S; Varvaresou, Athanasia; Dracopoulou-Vabouli, Maria; Patsalis, Philippos C; Shammas, Christos; Neocleous, Vassos; Phylactou, Leonidas A

2011-01-01

To determine the mutations in the CYP21A2 gene in Greek-Cypriots with congenital adrenal hyperplasia (CAH) and attempt a genotype-phenotype correlation. Molecular analysis was performed by multiplex ligation-dependent probe amplification and direct sequencing of PCR products of the CYP21A2 gene in 32 CAH patients. The most frequent genetic defect in the classic salt-wasting and simple virilizing forms was the IVS2-13A/C>G (55%) mutation, followed by Large lesion (20%) and in the non-classical form, the p.V281L (79.5%). Genotypes were categorized in 4 mutation groups (null, A, B and C). All 3 patients in the null group manifested the salt-wasting form and all 6 patients in mutation group A presented with the classical form. One patient in group B had the simple virilizing form and 22 patients in group C exhibited the non-classical form. The spectrum of mutations of the CYP21A2 gene in our population is comparable to the most common reported in similar ethnic groups. The knowledge of the ethnic specificity of the CYP21A2 mutations represents a valuable diagnostic tool for all forms of CAH. Copyright © 2010 S. Karger AG, Basel.

Congenital hypotrichosis in a Percheron draught horse.

PubMed

Valentine, B A; Hedstrom, O R; Miller, W H; Scott, D W; Mathies, S

2001-08-01

A blue roan Percheron foal was born with poorly circumscribed patchy alopecia of the trunk and legs. Teeth and hoof development were normal. Alopecia was progressive, becoming almost complete by 1 year of age. Histopathological findings in a skin biopsy obtained at 7 months of age were consistent with severe follicular hypoplasia. Sebaceous glands, epitrichial sweat glands and arrector pilae muscles were normal. The horse is alive and otherwise well at 6 years of age, although adult stature is considered small for this breed. The clinical history and histopathological findings are most consistent with a form of congenital hypotrichosis.

From Knowing Nothing to Knowing What, How and Now: Parents' Experiences of Caring for their Children With Congenital Adrenal Hyperplasia.

PubMed

Lundberg, Tove; Lindström, Anders; Roen, Katrina; Hegarty, Peter

2017-06-01

This study investigates various kinds of knowing that European parents use when caring for their children with congenital adrenal hyperplasia (CAH). Semi-structured qualitative interviews with 20 parents of 22 children with CAH. Parents emphasized the importance of knowing what CAH is and what support their child needs, but also knowing how to cope and make sense of the new situation, how to attend to their child's medical needs as well as how to talk to their child. Parents also reported challenges related to connecting with their social network, experiences of emergency care, and how to help their children become independent. These challenges require knowing now : being able to respond appropriately to unique circumstances. Parents experience diverse challenges that may moderate the effects of the diagnosis on children's well-being. Parenting children with CAH requires the development of knowing that goes beyond medical information. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Hepatic encephalomyelopathy in a calf with congenital portosystemic shunt (CPSS)

PubMed Central

Oevermann, Anna; Bley, Tim; Pfister, Patrizia; Miclard, Julien

2008-01-01

A 4-month-old female Holstein Friesian calf was referred to the Veterinary Teaching Hospital, University of Berne, Switzerland for evaluation of ataxia, weakness, apathy and stunted growth. Clinical examination revealed generalized ataxia, propioceptive deficits, decreased menace response and sensibility. Postmortem examination did not reveal macroscopic changes of major organs. Histologically, the brain and the spinal cord lesions were characterized by polymicrocavitation, preferentially affecting the white matter fibers at the junction of grey and white matter and by the presence of Alzheimer type II cells. The liver revealed lesions consistent with a congenital portosystemic shunt, characterized by increased numbers of arteriolar profiles and hypoplasia to absence of portal veins. The pathological investigations along with the animal history and clinical signs indicated a hepatic encephalomyelopathy due to a congenital portosystemic shunt. PMID:18296896

Polarized light and scanning electron microscopic investigation of enamel hypoplasia in primary teeth.

PubMed

Sabel, Nina; Klingberg, Gunilla; Dietz, Wolfram; Nietzsche, Sandor; Norén, Jörgen G

2010-01-01

Enamel hypoplasia is a developmental disturbance during enamel formation, defined as a macroscopic defect in the enamel, with a reduction of the enamel thickness with rounded, smooth borders. Information on the microstructural level is still limited, therefore further studies are of importance to better understand the mechanisms behind enamel hypoplasia. To study enamel hypoplasia in primary teeth by means of polarized light microscopy and scanning electron microscopy. Nineteen primary teeth with enamel hypoplasia were examined in a polarized light microscope and in a scanning electron microscope. The cervical and incisal borders of the enamel hypoplasia had a rounded appearance, as the prisms in the rounded cervical area of the hypoplasia were bent. The rounded borders had a normal surface structure whereas the base of the defects appeared rough and porous. Morphological findings in this study indicate that the aetiological factor has a short duration and affects only certain ameloblasts. The bottom of the enamel hypoplasia is porous and constitutes possible pathways for bacteria into the dentin.

[Clinical management of adrenal incidentalomas: results of a survey].

PubMed

Moreno-Fernández, Jesús; García-Manzanares, Alvaro; Sánchez-Covisa, Miguel Aguirre; García, E Inés Rosa Gómez

2009-12-01

Incidentalomas are clinically silent adrenal masses that are discovered incidentally during diagnostic testing for clinical conditions unrelated to suspicion of adrenal disease. Several decision algorithms are used in the management of adrenal masses. We evaluated the routine use of these algorithms through a clinical activity questionnaire. The questionnaire included data on the work center, initial hormonal and radiological study, imaging and hormonal tests performed to complete the study, surgical indications and clinical follow-up. Thirty-three endocrinologists (79%) attending the annual congress of the Castilla-La Mancha Society of Endocrinology, Nutrition and Diabetes completed the questionnaire. Forty-six percent considered tumoral size to be the most important factor suggesting malignancy in the initial evaluation of adrenal incidentalomas, the limit being 4 cm for 78% of the endocrinologists. Imaging study was completed by magnetic resonance imaging by 39%. All the physicians always performed screening for hypercortisolism and pheochromocytoma. Other assessments always conducted in all incidentalomas included hyperaldosteronism (76%), sex hormone-producing tumor (51%) and congenital adrenal hyperplasia (30%). Seventy-nine percent of respondents began to refer incidentalomas larger than 4 cm for surgical treatment, and 46% referred all tumors larger than 6 cm for surgical treatment. With regard to hormonal function, patients with pheochromocytoma, Cushing's syndrome, hyperaldosteronism with poorly controlled blood pressure or sex hormoneproducing tumors were more frequently referred for surgery. Seventy-six percent of endocrinologists performed clinical follow-up in adrenal incidentalomas larger than 4 cm, preferably through computerized tomography (81%), and repeated studies for hormonal hypercortisolism (97%), primary hyperaldosteronism (42%) and pheochromocytoma (76%) over a 4-5 year period (67%). Clinical practice varied among the endocrinologists

[Bilateral hypoplasia of the internal carotid arteries associated with aneurysm of the right posterior communicating artery. Apropos of a case].

PubMed

el Khamlichi, A; Amrani, F; el Azzusi, M; el Oufir, M; Khamlichi, A M

1989-01-01

The authors report a case of bilateral hypoplasia of the internal carotid arteries associated with aneurysm of the right posterior communicating artery in a 17 year old female patient. This anomaly was discovered following a meningeal haemorrhage, which recurred 18 months later, causing the patient's death. Surgical operation was refused by the patient and her family. Bilateral hypoplasia of the internal carotid arteries is a rare congenital malformation (16 cases have been reported in the literature, our case constitutes the 17th). It is distinguished from aplasia by the presence of a patent but very reduced vascular lumen, while aplasia is associated with vestiges of non-patent vessels. The mechanism of development of such a malformation is unclear: some authors have suggested secondary regression of the internal carotid artery following a phase of normal development, while others consider it to represent arrest of the development of the internal carotid artery, at a given moment in time. The frequency of associated aneurysm would be due to the haemodynamic disruption induced by the malformation, especially as parietal defects are more frequent in a malformed vasculature. Bilateral hypoplasia of the internal carotid arteries may be compatible with normal life for an indefinite period of time due to the development of a large number of collateral vessels. However, the new vasculature is threatened by rupture with meningeal haemorrhage and by acute ischaemia, which would probably involve another aetiological factor.

Health Status of Adults with Congenital Adrenal Hyperplasia: A Cohort Study of 203 Patients

PubMed Central

Arlt, Wiebke; Willis, Debbie S.; Wild, Sarah H.; Krone, Nils; Doherty, Emma J.; Hahner, Stefanie; Han, Thang S.; Carroll, Paul V.; Conway, Gerry S.; Rees, D. Aled; Stimson, Roland H.; Walker, Brian R.; Connell, John M. C.; Ross, Richard J.

2010-01-01

Context: No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity of data from cohorts of meaningful size. Objective: Our objective was to establish the health status of adults with CAH. Design and Setting: We conducted a prospective cross-sectional study of adults with CAH attending specialized endocrine centers across the United Kingdom. Patients: Participants included 203 CAH patients (199 with 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18–69) years. Main Outcome Measures: Anthropometric, metabolic, and subjective health status was evaluated. Anthropometric measurements were compared with Health Survey for England data, and psychometric data were compared with appropriate reference cohorts. Results: Glucocorticoid treatment consisted of hydrocortisone (26%), prednisolone (43%), dexamethasone (19%), or a combination (10%), with reverse circadian administration in 41% of patients. Control of androgens was highly variable with a normal serum androstenedione found in only 36% of patients, whereas 38% had suppressed levels suggesting glucocorticoid overtreatment. In comparison with Health Survey for England participants, CAH patients were significantly shorter and had a higher body mass index, and women with classic CAH had increased diastolic blood pressure. Metabolic abnormalities were common, including obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%), and osteoporosis (7%). Subjective health status was significantly impaired and fertility compromised. Conclusions: Currently, a minority of adult United Kingdom CAH patients appear to be under endocrine specialist care. In the patients studied, glucocorticoid replacement was generally nonphysiological, and androgen levels were poorly controlled. This was associated with an adverse metabolic profile and impaired fertility and quality of life. Improvements in the clinical management of adults with CAH are

How to learn from patients: Fuller Albright's exploration of adrenal function.

PubMed

Schwartz, T B

1995-08-01

Fuller Albright (1900-1969) was acknowledged as the preeminent clinical and investigative endocrinologist of his day by many of his contemporaries, but his many achievements are all but unknown to the present generation of physicians. This article describes how he used his clinical knowledge and a few tools--the measurement of urinary 17-ketosteroid excretion and the administration of methyltestosterone--to elucidate the major hormonal functions of the adrenal cortex and to clarify the pathophysiology of the Cushing syndrome. In addition, in a tour de force of clinical reasoning, he predicted, 5 years before the event, the discovery of a hormone that would reverse the endocrinologic abnormalities of congenital adrenal hyperplasia. Fittingly, he and pioneer pediatric endocrinologist Lawson Wilkins were the first to treat this disease successfully with cortisone.

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study.

PubMed

de Fatima Vasco Aragao, Maria; van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

2016-04-13

To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Retrospective study with a case series. Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

PubMed Central

van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

2016-01-01

Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was

Splicing mutation in CYP21 associated with delayed presentation of salt-wasting congenital adrenal hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohn, B.; Patel, S.V.; Pelczar, J.V.

1995-07-03

Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) most commonly carry an A-G transition at nucleotide 656 (nt 656 A{r_arrow}G), causing abnormal splicing of exons 2 and 3 in CYP21, the gene encoding active steroid 21-hydroxylase. Affected infants are severely deficient in cortisol and aldosterone, and usually come to medical attention during the neonatal period. We report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in early infancy, but suffered salt-wasting crises unusually late in infancy, at 3.5 and 5.5 months, respectively. Laboratory studies at presentation showed hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldosterone was low inmore » spite of markedly elevated plasma renin activity. Basal 17-hydroxyprogesterone levels were only moderately elevated, yet the stimulated levels were more typical of severe, classic CAH due to 21-hydroxylase deficiency. Genomic DNA from the patients was analyzed. Southern blot showed no major deletions or rearrangements. CYP21-specific amplification by polymerase chain reaction, coupled with allele-specific hybridization using wild-type and mutant probes at each of 9 sites for recognized disease-causing mutations, revealed a single, homozygous mutation in each patient: nt 656 A{r_arrow}G. These results were confirmed by sequence analysis. We conclude that the common nt 656 A{r_arrow}G mutation is sometimes associated with delayed phenotypic expression of SW-CAH. We speculate that variable splicing of the mutant CYP21 may modify the clinical manifestation of this disease. 22 refs., 1 fig., 1 tab.« less

Familial intra-areolar polythelia with mammary hypoplasia.

PubMed

Rintala, A; Norio, R

1982-01-01

Dysplastic divided nipples (intra-areolar polythelia) have been found bilaterally in a mother, her two daughters and one son. Two of the patients had mammary hypoplasia, one had unilateral hypoplasia of the pectoral muscle and duplication of the renal pelvis and ureter. The mammary findings are consistent with autosomal dominant inheritance. Whether they represent a new mammo-renal syndrome is uncertain. Reconstructive surgery was performed on two patients. Due to the deformity the mother was unable to nurse her children; following reconstructive surgery the daughter was able to feed her baby normally.

A rare CYP21A2 mutation in a congenital adrenal hyperplasia kindred displaying genotype-phenotype nonconcordance.

PubMed

Khattab, Ahmed; Yuen, Tony; Al-Malki, Sultan; Yau, Mabel; Kazmi, Diya; Sun, Li; Harbison, Madeleine; Haider, Shozeb; Zaidi, Mone; New, Maria I

2016-01-01

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is caused by the autosomal recessive inheritance of mutations in the gene CYP21A2. CYP21A2 mutations lead to variable impairment of the 21-hydroxylase enzyme, which, in turn, is associated with three clinical phenotypes, namely, salt wasting, simple virilizing, and nonclassical CAH. However, it is known that a given mutation can associate with different clinical phenotypes, resulting in a high rate of genotype-phenotype nonconcordance. We aimed to study the genotype-phenotype nonconcordance in a family with three siblings affected with nonclassical CAH. All had hormonal evidence of nonclassical CAH, but this phenotype could not be explained by the genotype obtained from commercial CYP21A2 genetic testing, which revealed heterozygosity for the maternal 30 kb deletion mutation. We performed Sanger sequencing of the entire CYP21A2 gene in this family to search for a rare mutation that was not covered by commercial testing and found in the three siblings a second, rare c.1097G>A (p.R366H) mutation in exon 8. Computational modeling confirmed that this was a mild mutation consistent with nonclassical CAH. We recommend that sequencing of entire genes for rare mutations should be carried out when genotype-phenotype nonconcordance is observed in patients with autosomal recessive monogenic disorders, including CAH. © 2015 New York Academy of Sciences.

Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.

PubMed

Endendijk, Joyce J; Beltz, Adriene M; McHale, Susan M; Bryk, Kristina; Berenbaum, Sheri A

2016-10-01

Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

PubMed

Woelfle, J; Hoepffner, W; Sippell, W G; Brämswig, J H; Heidemann, P; Deiss, D; Bökenkamp, A; Roth, C; Irle, U; Wollmann, H A; Zachmann, M; Kubini, K; Albers, N

2002-02-01

In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in

Adrenal Fatigue

MedlinePlus

... unlikely to cover the costs. What is the theory behind adrenal fatigue? Supporters of adrenal fatigue believe ... by producing hormones like cortisol. According to the theory of adrenal fatigue, when people are faced with ...

Utility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia.

PubMed

Tieh, P Y; Yee, J K; Hicks, R A; Mao, C S; Lee, W-Np

2017-03-01

Screening for congenital adrenal hyperplasia (CAH) caused by 21-α-hydroxylase deficiency is challenging because factors such as prematurity and stress increase intermediate steroid metabolite levels in newborn infants. The objective of this study was to explore the use of the 17-α-hydroxyprogesterone (17-OHP)/11-deoxycortisol ratio as an adjunct measure in the follow-up evaluation of infants with presumptive positive newborn screens for CAH to distinguish between infants with no disorder and those with CAH. This was a retrospective cohort study of infants with presumptive positive newborn screens for CAH. The precursor-to-product ratio of 17-OHP/11-deoxycortisol was compared between infants with no disorder (n=47) and infants with CAH (n=5). The CAH infants had higher 17-OHP/11-deoxycortisol ratios than infants with no disorder: 26 (18 to 58) and 1.05 (0.69 to 1.46), respectively (P<0.05). Among infants with no disorder, higher levels of serum 17-OHP did not reflect higher ratios, indicating sufficient enzyme activity. The results suggest that a low 17-OHP/11-deoxycortisol ratio represents 21-α-hydroxylase sufficiency among presumptive positives in newborn screening of CAH.

Optic Nerve Hypoplasia Syndrome: A Review of the Epidemiology and Clinical Associations

PubMed Central

Garcia-Filion, Pamela; Borchert, Mark

2013-01-01

Opinion statement Background Optic nerve hypoplasia (ONH) has developed into a leading cause of congenital blindness. The frequently associated features of hypopituitarism and absent septum pellucidum were felt to have embryonic linkage as “septo-optic dysplasia” or “de Morsier’s syndrome.” More recent studies have suggested these associations are independent of one another. This review provides an assessment of the historical and recent evidence linking neuroradiologic, endocrinologic and developmental morbidity in patients with ONH. The prenatal risk factors, heritability, and genetic mutations associated with ONH are described. Results Recognition of the critical association of ONH with hypopituitarism should be attributed to William Hoyt, not Georges de Morsier. De Morsier never described a case of ONH or recognized its association with hypopituitarism or missing septum pellucidum. Hypopituitarism is caused by hypothalamic dysfunction. This, and other more recently identified associations with ONH, such as developmental delay and autism, are independent of septum pellucidum development. Other common neuroradiographic associations such as corpus callosum hypoplasia, gyrus dysplasia, and cortical heterotopia may have prognostic significance. The predominant prenatal risk factors for ONH are primiparity and young maternal age. Presumed risk factors such as prenatal exposure to drugs and alcohol are not supported by scrutiny of the literature. Heritability and identified gene mutations in cases of ONH are rare. Conclusion Children with ONH require monitoring for many systemic, developmental, and even life-threatening problems independent of the severity of ONH and presence of brain malformations including abnormalities of the septum pellucidum. “Septo-optic dysplasia” and “de Morsier’s syndrome” are historically inaccurate and clinically misleading terms. PMID:23233151

Internal Carotid Artery Hypoplasia: Role of Color-Coded Carotid Duplex Sonography.

PubMed

Chen, Pei-Ya; Liu, Hung-Yu; Lim, Kun-Eng; Lin, Shinn-Kuang

2015-10-01

The purpose of this study was to determine the role of color-coded carotid duplex sonography for diagnosis of internal carotid artery hypoplasia. We retrospectively reviewed 25,000 color-coded carotid duplex sonograms in our neurosonographic database to establish more diagnostic criteria for internal carotid artery hypoplasia. A definitive diagnosis of internal carotid artery hypoplasia was made in 9 patients. Diagnostic findings on color-coded carotid duplex imaging include a long segmental small-caliber lumen (52% diameter) with markedly decreased flow (13% flow volume) in the affected internal carotid artery relative to the contralateral side but without intraluminal lesions. Indirect findings included markedly increased total flow volume (an increase of 133%) in both vertebral arteries, antegrade ipsilateral ophthalmic arterial flow, and a reduced vessel diameter with increased flow resistance in the ipsilateral common carotid artery. Ten patients with distal internal carotid artery dissection showed a similar color-coded duplex pattern, but the reductions in the internal and common carotid artery diameters and increase in collateral flow from the vertebral artery were less prominent than those in hypoplasia. The ipsilateral ophthalmic arterial flow was retrograde in 40% of patients with distal internal carotid artery dissection. In addition, thin-section axial and sagittal computed tomograms of the skull base could show the small diameter of the carotid canal in internal carotid artery hypoplasia and help distinguish hypoplasia from distal internal carotid artery dissection. Color-coded carotid duplex sonography provides important clues for establishing a diagnosis of internal carotid artery hypoplasia. A hypoplastic carotid canal can be shown by thin-section axial and sagittal skull base computed tomography to confirm the final diagnosis. © 2015 by the American Institute of Ultrasound in Medicine.

A case of adrenal Cushing's syndrome with bilateral adrenal masses.

PubMed

Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

2016-01-01

A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and (131)I-NP-59 scintigraphy are good diagnostic methods for Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

Change in prevalence of congenital defects in children with Prader-Willi syndrome.

PubMed

Torrado, M; Foncuberta, M E; Perez, M F de Castro; Gravina, L P; Araoz, H V; Baialardo, E; Chertkoff, L P

2013-02-01

The aim of this study was to assess the prevalence of congenital defects observed in patients with Prader-Willi syndrome (PWS) and to compare this prevalence with that described in the general population. In addition, these findings were correlated with the different etiologic subtypes. A total of 180 children with PWS followed for 13 years were included in this study. Diagnosis was confirmed by the methylation test, and genetic subtypes were established by using fluorescence in situ hybridization or multiplex ligation-dependent probe amplification and microsatellite analyses. The prevalence of congenital defects was compared with national and international registries of congenital defects in the general population (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas, European Surveillance of Congenital Anomalies, and the New York Registry). Twenty-two percent of the patients presented congenital defects with a risk of 5.4 to 18.7 times higher than that of the general population. The most frequent congenital defects were heart defects, renoureteral malformations, vertebral anomalies, hip dysplasia, clubfoot, and agenesis/hypoplasia of the corpus callosum. Each of these congenital defects was significantly more frequent in the children with PWS than in the general population. The congenital heart defects were more frequent in girls than in boys with PWS. No significant differences were found when the defects were correlated with the different etiologic subtypes. An increased prevalence of congenital defects was found in our PWS patients. This finding suggests the need for further studies in PWS children that allow physicians to detect the congenital defects found in this series and, thus, to anticipate complications, with the ultimate aim of enhancing the management of PWS patients.

Etiological evaluation of primary congenital hypothyroidism cases.

PubMed

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-06-01

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary

Etiological evaluation of primary congenital hypothyroidism cases

PubMed Central

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-01-01

Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital

Are there parental socialization effects on the sex-typed behavior of individuals with congenital adrenal hyperplasia?

PubMed

Wong, Wang I; Pasterski, Vickie; Hindmarsh, Peter C; Geffner, Mitchell E; Hines, Melissa

2013-04-01

Influences of prenatal androgen exposure on human sex-typical behavior have been established largely through studies of individuals with congenital adrenal hyperplasia (CAH). However, evidence that addresses the potential confounding influence of parental socialization is limited. Parental socialization and its relationship to sex-typical toy play and spatial ability were investigated in two samples involving 137 individuals with CAH and 107 healthy controls. Females with CAH showed more boy-typical toy play and better targeting performance than control females, but did not differ in mental rotations performance. Males with CAH showed worse mental rotations performance than control males, but did not differ in sex-typical toy play or targeting. Reported parental encouragement of girl-typical toy play correlated with girl-typical toy play in all four groups. Moreover, parents reported encouraging less girl-typical, and more boy-typical, toy play in females with CAH than in control females and this reported encouragement partially mediated the relationship between CAH status and sex-typical toy play. Other evidence suggests that the reported parental encouragement of sex-atypical toy play in girls with CAH may be a response to the girls' preferences for boys' toys. Nevertheless, this encouragement could further increase boy-typical behavior in girls with CAH. In contrast to the results for toy play, we found no differential parental socialization for spatial activities and little evidence linking parental socialization to spatial ability. Overall, evidence suggests that prenatal androgen exposure and parental socialization both contribute to sex-typical toy play.

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia.

PubMed

Bachelot, Anne; Chakhtoura, Zeina; Plu-Bureau, Geneviève; Coudert, Mathieu; Coussieu, Christiane; Badachi, Yasmina; Dulon, Jérome; Charbit, Beny; Touraine, Philippe

2012-10-01

Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis as in polycystic ovary syndrome (PCOS), but there is no precise evaluation. Our aim was to evaluate the gonadotropic axis and LH pulsatility patterns and to determine factor(s) that could account for the potential abnormality of LH pulsatility. Case/control study. Sixteen CAH women (11 with the salt-wasting form and five with the simple virilizing form), aged from 18 to 40 years, and 16 age-matched women, with regular menstrual cycles (28 ± 3 days), were included. LH pulse patterns over 6 h were determined in patients and controls. No differences were observed between patients and controls in terms of mean LH levels, LH pulse amplitude, or LH frequency. In CAH patients, LH pulsatility patterns were heterogeneous, leading us to perform a clustering analysis of LH data, resulting in a two-cluster partition. Patients in cluster 1 had similar LH pulsatility patterns to the controls. Patients in cluster 2 had: lower LH pulse amplitude and frequency and presented menstrual cycle disturbances more frequently; higher 17-OH progesterone, testosterone, progesterone, and androstenedione levels; and lower FSH levels. LH pulsatility may be normal in CAH women well controlled by hormonal treatment. Undertreatment is responsible for hypogonadotropic hypogonadism, with low LH pulse levels and frequency, but not PCOS. Suppression of progesterone and androgen concentrations during the follicular phase of the menstrual cycle should be a major objective in these patients.

Ossification of the posterior atlantoaxial membrane associated with atlas hypoplasia: A case report.

PubMed

Meng, Yichen; Zhou, Dongxiao; Gao, Rui; Ma, Jun; Wang, Ce; Zhou, Xuhui

2016-11-01

Hypoplasia with an intact posterior arch of the atlas and ossification of the posterior atlantoaxial membrane (PAAM) are individually rare. The patient presented with a 6-month history of progressive weakness and paresthesia of his lower extremities. Cervical myelopathy resulting from atlas hypoplasia and ossification of the posterior atlantoaxial membrane. Laminectomy of the atlas with duroplasty. Preoperative symptoms were alleviated. In most reported cases, either atlas hypoplasia or ossification of the PAAM is responsible for patients' myelopathy. The case illustrated here, to the best of our knowledge, is the first one with coexistent atlas hypoplasia and ossification of the PAAM. And laminectomy of the atlas with duroplasty provided satisfied outcome.

Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

PubMed

Yamanaka, S; Nakao, Kazumasa; Koyama, N; Isobe, Y; Ueda, Y; Kanai, Y; Kondo, E; Fujii, T; Miura, M; Yasoda, A; Nakao, Kazuwa; Bessho, K

2017-12-01

Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3 ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3 ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3 ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3 ach /SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3 ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3 ach mice was significantly ameliorated in Fgfr3 ach /SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic

Prenatal imaging of a fetus with the rare combination of a right congenital diaphragmatic hernia and a giant omphalocele.

PubMed

Nonaka, Ayasa; Hidaka, Nobuhiro; Kido, Saki; Fukushima, Kotaro; Kato, Kiyoko

2014-11-01

A co-existing right congenital diaphragmatic hernia and omphalocele is rare. We present images of a fetus diagnosed with this rare combination of anomalies. Early neonatal death occurred immediately after full-term birth due to severe respiratory insufficiency. In this case, disturbance of chest wall development due to the omphalocele rather than the diaphragmatic hernia was considered as the main cause of lung hypoplasia. Our experience suggests that caution should be exercised for severe respiratory insufficiency in a neonate with an omphalocele and diaphragmatic hernia, even in the absence of an intra-thoracic liver, one of the indicators of poor outcome for congenital diaphragmatic hernia. © 2014 Japanese Teratology Society.

Long term outcomes in 46, XX adult patients with congenital adrenal hyperplasia reared as males.

PubMed

Khattab, A; Yau, M; Qamar, A; Gangishetti, P; Barhen, A; Al-Malki, S; Mistry, H; Anthony, W; Toralles, M B; New, Maria I

2017-01-01

Patients with Congenital Adrenal Hyperplasia (CAH) owing to 21-hydroxylase deficiency and whose karyotype is 46, XX are usually assigned to the female gender. Reported herein are the long term outcomes in three patients with CAH whose karyotype is 46, XX and who were reared as males. A retrospective review of three CAH patients with a 46, XX karyotype who were reared as males was conducted. Gender assignment, clinical and biochemical data, pre and post-genitoplasty genital examinations were reviewed. Gender identity was tested by an extensive questionnaire. Gender role, sexual preference, marital status and sexual satisfaction were evaluated by interview. The three patients were genotyped for the CYP21A2 gene confirming the diagnosis of CAH. Owing to genital virilization, cultural preferences for male gender and the lack of newborn screening programs the three patients reported herein were assigned to the male gender at birth before the diagnosis of CAH was established. In adulthood the patients remained significantly virilized. Thorough psychosexual assessments in adulthood revealed well established male gender identities compatible with their male gender assignments at birth. In all three patients, gender role and behavior were consistent with male gender identity including sexual intercourse with female partners. The three patients reported herein revealed that male gender assignment to CAH patients with a 46, XX karyotype may have a successful outcome providing there is strong parental support and expert endocrine care. No standard guidelines have been published for the gender assignment of CAH patients with a 46, XX karyotype and genital ambiguity. More studies concerning gender assignment in CAH patients with a 46, XX karyotype reared as males are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia Using Cell-Free Fetal DNA in Maternal Plasma

PubMed Central

Tong, Yu K.; Yuen, Tony; Jiang, Peiyong; Pina, Christian; Chan, K. C. Allen; Khattab, Ahmed; Liao, Gary J. W.; Yau, Mabel; Kim, Se-Min; Chiu, Rossa W. K.; Sun, Li; Zaidi, Mone

2014-01-01

Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. Objective: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. Patients: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. Design: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes. Results: In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation. Conclusions: MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders. PMID:24606108

Adrenal venous sampling in a patient with adrenal Cushing syndrome

PubMed Central

Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

2015-01-01

The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

Gene expression analysis in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Burgos, Carmen Mesas; Uggla, Andreas Ringman; Fagerström-Billai, Fredrik; Eklöf, Ann-Christine; Frenckner, Björn; Nord, Magnus

2010-07-01

Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in newborns with congenital diaphragmatic hernia (CDH). Nitrofen is well known to induce CDH and lung hypoplasia in a rat model, but the mechanism remains unknown. To increase the understanding of the underlying pathogenesis of CDH, we performed a global gene expression analysis using microarray technology. Pregnant rats were given 100 mg nitrofen on gestational day 9.5 to create CDH. On day 21, fetuses after nitrofen administration and control fetuses were removed; and lungs were harvested. Global gene expression analysis was performed using Affymetrix Platform and the RAE 230 set arrays. For validation of microarray data, we performed real-time polymerase chain reaction and Western blot analysis. Significantly decreased genes after nitrofen administration included several growth factors and growth factors receptors involved in lung development, transcription factors, water and ion channels, and genes involved in angiogenesis and extracellular matrix. These results could be confirmed with real-time polymerase chain reaction and protein expression studies. The pathogenesis of lung hypoplasia and CDH in the nitrofen model includes alteration at a molecular level of several pathways involved in lung development. The complexity of the nitrofen mechanism of action reminds of human CDH; and the picture is consistent with lung hypoplasia and vascular disease, both important contributors to the high mortality and morbidity in CDH. Increased understanding of the molecular mechanisms that control lung growth may be the key to develop novel therapeutic techniques to stimulate pre- and postnatal lung growth. Copyright 2010 Elsevier Inc. All rights reserved.

Male gender identity in children with 46,XX DSD with congenital adrenal hyperplasia after delayed presentation in mid-childhood.

PubMed

Chowdhury, Tanvir Kabir; Laila, Kamrun; Hutson, John M; Banu, Tahmina

2015-12-01

Girls with congenital adrenal hyperplasia (CAH) diagnosed at birth have some masculine behaviors but rarely convert to male gender. In developing countries, however, diagnosis and treatment (with secondary androgen suppression) are delayed. We aimed to assess effect of delayed treatment of CAH on gender identity. As part of a cross-sectional, case-control study of children with disorders of sex development (DSD), there were 11 patients with CAH. Patients and caregivers answered a questionnaire about gender identity, and behavior was assessed by observing toy play. Patients were examined for Prader score and gender identity. Of 11 CAH patients initially raised as girls, 3 (27%) had converted to male gender at presentation (5, 9, 9years) (Prader 3, 4, 4). Of the remaining 8 patients, one 4-year-old (Prader 2) had a male gender identity score. The remaining girls (2-13years, mean 8.1) (Prader 1-3) had gender identity scores in the female range. One third (4/11) of CAH patients presenting in mid-childhood had male gender identity scores, and ¾ had assumed male gender role. Although social and cultural factors are important in developing countries, this result suggests that delayed treatment may trigger male gender identity, and delayed female genital surgery may be unwise. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

PubMed

Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

1986-08-01

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

A child with hypertension and ambiguous genitalia - an uncommon variant of congenital adrenal hyperplasia: a case report.

PubMed

Pant, Vivek; Baral, Suman; Shrestha, Bishal; Tumbapo, Arjun

2017-06-23

Deficiency in 11β-hydroxylase as a cause of congenital adrenal hyperplasia is uncommon. It should be considered in the differential diagnosis of hypertension with virilization in any prepubescent child. A 12-year-old Asian boy from eastern Nepal presented with pain in his abdomen and hypertension. He was raised as a male but had absent testicles since birth and had precocious puberty. Plasma testosterone, follicle-stimulating hormone, and luteinizing hormone were below baseline level. Basal 17-hydroxyprogesterone was elevated. Magnetic resonance imaging of his pelvis showed presence of Müllerian structures and karyotyping revealed 46,XX genotype. A clinical diagnosis of 11β-hydroxylase deficiency was made in view of hypertension with severe virilization in a 46,XX individual. Our patient's legal guardian was unwilling for our patient to change gender and because our patient is underage, the condition was well explained to his parents. He was managed with steroids and antihypertensive drugs. He was on regular follow-up; after 2 years there was no hypertension but he developed true puberty with functional ovaries. He was prescribed leuprolide (gonadotropin-releasing hormone analogue), letrozole (aromatase inhibitor), and a continuation of antihypertensive drugs. This case highlights the importance of a thorough physical examination of the external genitalia at birth and appropriate referral, and addresses issues in the management of such a disorder. Ethical issues pertaining to consent and who is entitled to give it should be clear so that the affected individual will have optimal psychological development and quality of life.

Sexual orientation and medical history among Iranian people with Complete Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia.

PubMed

Khorashad, Behzad S; Roshan, Ghasem M; Reid, Alistair G; Aghili, Zahra; Hiradfar, Mehran; Afkhamizadeh, Mozhgan; Talaei, Ali; Aarabi, Azadeh; Ghaemi, Nosrat; Taghehchian, Negin; Saberi, Hedieh; Farahi, Nazanin; Abbaszadegan, Mohammad Reza

2017-01-01

To report sexual orientation, relationship status and medical history of Iranian people with Differences of Sex Development (DSD) who were raised female. Our participants consisted of nineteen 46,XY individuals with Complete Androgen Insensitivity Syndrome (CAIS) and eighteen 46,XX individuals with Congenital Adrenal Hyperplasia (CAH) who were raised as females and older than 13years. As well as their relationship status and detailed medical history, an expert psychiatrist assessed their sexual orientation by a semi-structured psychiatric interview with them and, where applicable, their parents. Five percent of CAH participants and 42% of CAIS participants were in a relationship, which was significantly different. All CAH individuals had been diagnosed at birth; 89% of CAIS had been diagnosed after puberty and due to primary amenorrhea and 11% were diagnosed in childhood due to inguinal hernia. Genital reconstructive surgery had been performed in 100% of CAH participants and 37% of CAIS. Regarding sexual contact experiences and sexual fantasies (androphilic, gynephilic or both), no significant differences were found. However, CAH females had significantly more gynephilic dreams (P=0.045). This study, notable as one of the rare from a non-western culture, described sexual, medical and socioeconomic status of 46,XX CAH and 46,XY CAIS individuals living in Iran. Although broadly in line with previous findings from Western cultures, Iranian CAH individuals had fewer romantic relationships, but in contrast to previous studies their sexual orientation was only different from CAIS in the contents of sexual dreams. Copyright © 2016 Elsevier Inc. All rights reserved.

Syndrome-Related Stigma in the General Social Environment as Reported by Women with Classical Congenital Adrenal Hyperplasia.

PubMed

Meyer-Bahlburg, Heino F L; Reyes-Portillo, Jazmin A; Khuri, Jananne; Ehrhardt, Anke A; New, Maria I

2017-02-01

Stigma defined as "undesired differentness" (Goffman, 1963) and subtyped as "experienced" or "enacted," "anticipated," and "internalized" has been documented for patients with diverse chronic diseases. However, no systematic data exist on the association of stigma with somatic intersexuality. The current report concerns women with classical congenital adrenal hyperplasia (CAH), the most prevalent intersex syndrome, and provides descriptive data on CAH-related stigma as experienced in the general social environment (excluding medical settings and romantic/sexual partners) during childhood, adolescence, and adulthood. A total of 62 adult women with classical CAH [41 with the salt-wasting (SW) variant and 21 with the simple-virilizing (SV) variant] underwent a qualitative retrospective interview, which focused on the impact of CAH and its medical treatment on many aspects of women's lives. Deductive content analysis was performed on the transcribed texts. The women's accounts of CAH-related stigma were identified and excerpted as vignettes, and the vignettes categorized according to social context, stigma type, and the associated features of the CAH condition. Nearly two-thirds of women with either variant of CAH provided stigma vignettes. The vignettes included all three stigma types, and most involved some somatic or behavioral feature related to sex or gender. Stigma situations were reported for all ages and all social contexts of everyday life: family, peers, colleagues at work, strangers, and the media. We conclude that there is a need for systematic documentation of stigma in intersexuality as a basis for the development of improved approaches to prevention and intervention.

Role of cerebral ultrasound and magnetic resonance imaging in newborns with congenital cytomegalovirus infection.

PubMed

Capretti, Maria Grazia; Lanari, Marcello; Tani, Giovanni; Ancora, Gina; Sciutti, Rita; Marsico, Concetta; Lazzarotto, Tiziana; Gabrielli, Liliana; Guerra, Brunella; Corvaglia, Luigi; Faldella, Giacomo

2014-03-01

To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Diagnosis of adrenal insufficiency.

PubMed

Dorin, Richard I; Qualls, Clifford R; Crapo, Lawrence M

2003-08-05

The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency. To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency. The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency. Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included. Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs. At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-microg and 1-microg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency. Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and Distinctive Facies

PubMed Central

Stevens, Cathy A.; Lachman, Ralph S.

2011-01-01

We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion. PMID:20602491

Pulmonary hypoplasia in Jarcho-Levin syndrome.

PubMed

Rodríguez, Luis M; García-García, Inés; Correa-Rivas, María S; García-Fragoso, Lourdes

2004-03-01

Jarcho-Levin syndrome, also known as spondylothoracic dysplasia and characterized by short trunk dwarfism, "crab-like" rib cage, with ribs and vertebral defects; it is not uncommon in Puerto Ricans. Many patients die in early infancy due to respiratory compromise associated to lung restriction and the reported cases emphasize mostly the skeletal malformations associated to the syndrome. We report the autopsy findings in a newborn with isolated Jarcho-Levin syndrome emphasizing pulmonary pathology. He was a pre-term male who died of respiratory failure at three hours old and, autopsy findings confirmed the clinical diagnosis. Internal examination showed hypoplastic lungs with normal lobation. The histological structure appeared normal and relatively mature; the diaphragm showed eventration and unilateral absence of musculature. This case shows the worst spectum of the Jarcho-Levin syndrome: pulmonary hypoplasia not compatible with extrauterine life. Since thoracic restriction is present during the fetal period, the degree of pulmonary hypoplasia probably defines survival beyond the neonatal period.

Is there a role for antioxidants in prevention of pulmonary hypoplasia in nitrofen-induced rat model of congenital diaphragmatic hernia?

PubMed

Cigdem, Murat Kemal; Kizil, Goksel; Onen, Abdurrahman; Kizil, Murat; Nergiz, Yusuf; Celik, Yusuf

2010-04-01

Many studies suggest a role for antioxidants in the prevention of lung hypoplasia in nitrofen-induced rat models with congenital diaphragmatic hernia (CDH). This study investigates the oxidative status and the histological outcome of prenatal administration of vitamins E and C with synergistic effect, and effect of N-acetylcysteine (NAC) to improve lung maturation of nitrofen-induced rats. CDH was induced by maternal administration of a single oral dose of nitrofen on day 9.5 of gestation, and the Sprague-Dawley rats were randomly divided into five groups: nitrofen (N), nitrofen + vitamin C (NC), nitrofen + vitamin E (NE), nitrofen + vitamin C + vitamin E (NCE) and nitrofen + NAC (NNAC). A control group in which only vehicle was administered was included. Cesarean section was performed on day 21. Body weight (BW) and total lung weight (LW) of all fetuses with CDH were recorded; lung histological evaluation was performed, and protein content of lungs, determination of thiobarbituric acid reactive substances, and the protein carbonyls in tissue samples were determined. A total of 133 rat fetuses with CDH were investigated. The body weight and the lung weight of fetuses of all groups that were exposed to nitrofen were significantly decreased than of the control group (P < 0.05). The animals exposed to nitrofen with different antioxidants showed increased protein levels in lung tissue. However, in the NCE and the NNAC groups, protein levels were significantly increased than in the others. Malondialdehyde levels significantly decreased in the NCE and the NNAC groups when compared with the NC and the NE groups. In addition, the NCE and NNAC groups decreased protein oxidation to control levels, and no significant difference was observed between control and these two antioxidants groups. The N, NC, NE and NNAC groups showed minimal improvement in lung histology; the NCE groups showed the most improvement in lung histology when compared with the other nitrofen plus

[Addison's disease : Primary adrenal insufficiency].

PubMed

Pulzer, A; Burger-Stritt, S; Hahner, S

2016-05-01

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry.

PubMed

Janzen, Nils; Sander, Stefanie; Terhardt, Michael; Steuerwald, Ulrike; Peter, Michael; Das, Anibh M; Sander, Johannes

2011-12-11

Newborn screening for congenital adrenal hyperplasia (CAH) is usually done by quantifying 17α-hydroxyprogesterone using immunoassay. However, this test produces high rates of false positive results caused by cross reacting steroids. Therefore we have developed a selective and specific method with a short run time (1.25 min) for quantification of 17α-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone and cortisol from dried blood spots. The extraction procedure is very simple and steroid separation is ensured on a BEH C18 column and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Analysis was done in positive ionization mode (ESI+) and recorded in multiple reaction monitoring mode (MRM). The method gave linear results for all steroids over a range of 5-200 (cortisol: 12.5-500)nmol/L with coefficients of regression >0.992. Absolute recovery was >64.1%. Across the analytical range the inter-assay coefficient of variation (CV) was <3%. Newborn blood samples of patients with confirmed 21-CAH and 11-CAH could clearly be distinguished from samples of unaffected newborns falsely positive on immunoassay. The method is not influenced by cross reactions as found on immunoassay. Analysis of dried blood spots shows that this method is sensitive and fast enough to allow rapid analysis and can therefore improve the newborn screening program. Copyright © 2011 Elsevier Inc. All rights reserved.

Adrenal Insufficiency

MedlinePlus

... three types of steroid hormones. In adrenal insufficiency (AI), the cortex does not make enough steroid hormones. ... unlike “adrenal fatigue.” There are two kinds of AI: • Primary AI, also called Addison’s disease. In this ...

Maxillary growth in a congenital cleft palate canine model for surgical research.

PubMed

Paradas-Lara, Irene; Casado-Gómez, Inmaculada; Martín, Conchita; Martínez-Sanz, Elena; López-Gordillo, Yamila; González, Pablo; Rodríguez-Bobada, Cruz; Chamorro, Manuel; Arias, Pablo; Maldonado, Estela; Ortega, Ricardo; Berenguer, Beatriz; Martínez-Álvarez, Concepción

2014-01-01

We have recently presented the Old Spanish Pointer dog, with a 15-20% spontaneous congenital cleft palate rate, as a unique experimental model of this disease. This study aimed to describe the cleft palate of these dogs for surgical research purposes and to determine whether congenital cleft palate influences maxillofacial growth. Seven newborn Old Spanish Pointer dogs of both sexes, comprising a cleft palate group (n = 4) and a normal palate group (n = 3), were fed using the same technique. Macroscopic photographs and plaster casts from the palate, lateral radiographs and computer tomograms of the skull were taken sequentially over 41 weeks, starting at week 5. The cleft morphology, the size and the tissue characteristics in these dogs resembled the human cleft better than current available animal models. During growth, the cleft width varies. Most of the transverse and longitudinal measures of the palate were statistically lower in the cleft palate group. The cleft palate group showed hypoplasia of the naso-maxillary complex. This model of congenital cleft palate seems suitable for surgical research purposes. A reduced maxillofacial pre- and post-natal development is associated to the congenital cleft palate in the Old Spanish Pointer dog. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Linear enamel hypoplasia in the great apes: analysis by genus and locality.

PubMed

Hannibal, Darcy Lee; Guatelli-Steinberg, Debbie

2005-05-01

Most studies report a high prevalence of linear enamel hypoplasia (LEH) in the great apes relative to other nonhuman primates and some human populations. It is unclear if this difference is a direct result of poor health status for the great apes, or if it represents differential incidence due to a lower threshold (sensu Goodman and Rose, 1990 Am. J. Phys. Anthropol. [suppl.] 33:59-110) for the occurrence of enamel hypoplasia among great apes. This study uses the Smithsonian National Museum of Natural History's great ape collection to examine the prevalence of LEH, the most common type of hypoplasia observed. Frequencies of LEH are reported, as well as analyses by taxa and provenience. The study sample consists of 136 specimens and includes 41 gorillas, 25 chimpanzees, and 70 orangutans. Analyses of frequencies are presented for both individuals and teeth by taxonomic category and locality. Among the individuals in this study, 63.97% are affected by LEH. Overall, gorillas (29.27%) exhibit lower frequencies of LEH than chimpanzees (68.00%) and orangutans (82.86%). There is a marked difference in LEH frequencies between mountain and lowland gorillas. There is no difference in LEH frequencies between Sumatran and Bornean orangutans. A range of variation for the great apes in enamel hypoplasia frequencies is found when taxon and locality are considered. It is likely that both biological and environmental factors influence the high frequencies of enamel hypoplasia exhibited in the great apes. Copyright 2004 Wiley-Liss, Inc.

Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

PubMed

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

2018-01-01

Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

Traumatic and non-traumatic adrenal emergencies.

PubMed

Chernyak, Victoria; Patlas, Michael N; Menias, Christine O; Soto, Jorge A; Kielar, Ania Z; Rozenblit, Alla M; Romano, Luigia; Katz, Douglas S

2015-12-01

Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.

Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

PubMed Central

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

2018-01-01

Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

Impact of food, alcohol and pH on modified-release hydrocortisone developed to treat congenital adrenal hyperplasia.

PubMed

Karunasena, Nayananjani; Margetson, Daniel N; Neal, Greg; Whitaker, Martin J; Ross, Richard Jm

2017-04-01

We developed a modified-release hydrocortisone, Chronocort, to replace the cortisol rhythm in patients with congenital adrenal hyperplasia. Food, alcohol and pH affect drug absorption, and it is important to assess their impact when replicating a physiological rhythm. In vitro dissolution to study impact of alcohol and pH on Chronocort. A phase 1, three-period, cross over study in 18 volunteers to assess the impact of food on Chronocort and to compare bioavailability to immediate-release hydrocortisone. In vitro dissolution of Chronocort was not affected by gastrointestinal pH up to 6.0 nor by an alcohol content up to 20% v/v. Food delayed and reduced the rate of absorption of Chronocort as reflected by a longer T max (fed vs fasted: 6.75 h vs 4.5 h, P  = 0005) and lower C max (549.49 nmol/L vs 708.46 nmol/L, ratio 77% with CI 71-85). Cortisol exposure was similar in fed and fasted state: Geo LSmean ratio (CI) AUC 0t for fed/fasted was 108.33% (102.30-114.72%). Cortisol exposure was higher for Chronocort compared to immediate-release hydrocortisone: Geo LSmean ratios (CI) 118.83% (111.58-126.54%); however, derived free cortisol showed cortisol exposure CIs were within 80.0-125.0%: Geo LSmean ratio (CI) for AUC 0t 112.73% (105.33-120.65%). Gastric pH ≤6.0 and alcohol do not affect hydrocortisone release from Chronocort. Food delays Chronocort absorption, but cortisol exposure is similar in the fasted and fed state and exposure as assessed by free cortisol is similar between Chronocort and immediate-release hydrocortisone. © 2017 The authors.

Impact of food, alcohol and pH on modified-release hydrocortisone developed to treat congenital adrenal hyperplasia

PubMed Central

Karunasena, Nayananjani; Margetson, Daniel N; Neal, Greg; Whitaker, Martin J

2017-01-01

Background We developed a modified-release hydrocortisone, Chronocort, to replace the cortisol rhythm in patients with congenital adrenal hyperplasia. Food, alcohol and pH affect drug absorption, and it is important to assess their impact when replicating a physiological rhythm. Subjects and methods In vitro dissolution to study impact of alcohol and pH on Chronocort. A phase 1, three-period, cross over study in 18 volunteers to assess the impact of food on Chronocort and to compare bioavailability to immediate-release hydrocortisone. Results In vitro dissolution of Chronocort was not affected by gastrointestinal pH up to 6.0 nor by an alcohol content up to 20% v/v. Food delayed and reduced the rate of absorption of Chronocort as reflected by a longer Tmax (fed vs fasted: 6.75 h vs 4.5 h, P = 0005) and lower Cmax (549.49 nmol/L vs 708.46 nmol/L, ratio 77% with CI 71–85). Cortisol exposure was similar in fed and fasted state: Geo LSmean ratio (CI) AUC0t for fed/fasted was 108.33% (102.30–114.72%). Cortisol exposure was higher for Chronocort compared to immediate-release hydrocortisone: Geo LSmean ratios (CI) 118.83% (111.58–126.54%); however, derived free cortisol showed cortisol exposure CIs were within 80.0–125.0%: Geo LSmean ratio (CI) for AUC0t 112.73% (105.33–120.65%). Conclusions Gastric pH ≤6.0 and alcohol do not affect hydrocortisone release from Chronocort. Food delays Chronocort absorption, but cortisol exposure is similar in the fasted and fed state and exposure as assessed by free cortisol is similar between Chronocort and immediate-release hydrocortisone. PMID:28100629

Functional studies of novel CYP21A2 mutations detected in Norwegian patients with congenital adrenal hyperplasia

PubMed Central

Brønstad, Ingeborg; Breivik, Lars; Methlie, Paal; Wolff, Anette S B; Bratland, Eirik; Nermoen, Ingrid; Løvås, Kristian; Husebye, Eystein S

2014-01-01

In about 95% of cases, congenital adrenal hyperplasia (CAH) is caused by mutations in CYP21A2 gene encoding steroid 21-hydroxylase (21OH). Recently, we have reported four novel CYP21A2 variants in the Norwegian population of patients with CAH, of which p.L388R and p.E140K were associated with salt wasting (SW), p.P45L with simple virilising (SV) and p.V211M+p.V281L with SV to non-classical (NC) phenotypes. We aimed to characterise the novel variants functionally utilising a newly designed in vitro assay of 21OH enzyme activity and structural simulations and compare the results with clinical phenotypes. CYP21A2 mutations and variants were expressed in vitro. Enzyme activity was assayed by assessing the conversion of 17-hydroxyprogesterone to 11-deoxycortisol by liquid chromatography tandem mass spectroscopy. PyMOL 1.3 was used for structural simulations, and PolyPhen2 and PROVEAN for predicting the severity of the mutants. The CYP21A2 mutants, p.L388R and p.E140K, exhibited 1.1 and 11.3% of wt 21OH enzyme activity, respectively, in vitro. We could not detect any functional deficiency of the p.P45L variant in vitro; although prediction tools suggest p.P45L to be pathogenic. p.V211M displayed enzyme activity equivalent to the wt in vitro, which was supported by in silico analyses. We found good correlations between phenotype and the in vitro enzyme activities of the SW mutants, but not for the SV p.P45L variant. p.V211M might have a synergistic effect together with p.V281L, explaining a phenotype between SV and NC CAH. PMID:24671123

Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Zimmerman, Cheryl L; Gonzalez-Bolanos, Maria T; Willis, Brian A; Brundage, Richard

2015-01-01

Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated. (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters. Thirty-four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6-hour pharmacokinetic studies. Results were analyzed by noncompartmental methods to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone, and androstenedione; maximum concentration and time-to-maximum concentration for cortisol; and minimum and time-to-minimum concentration for 17-hydroxyprogesterone and androstenedione. Mean (SD) cortisol half-life and Cmax were 1.01 (0.20) hours and 24.4 (5.4) μg/dL, respectively. The AUCs for cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) μg hour/dL, 29,490 (23,539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No significant relationships existed between cortisol AUCs and the AUCs of either 17-hydroxyprogesterone (P=0.32) or androstenedione (P=0.99); nor were there differences between the change-from-baseline concentrations for cortisol with either 17-hydroxyprogesterone (P=0.80) or androstenedione (P=0.40). Cortisol simulations indicated that although four daily doses decreased 24-hour hypercortisolemia and hypocortisolemia, substantial periods of each remained. Concentration profiles of cortisol, 17-hydroxyprogesterone, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid half-life and the lack of

Genetics of renal hypoplasia: insights into the mechanisms controlling nephron endowment.

PubMed

Cain, Jason E; Di Giovanni, Valeria; Smeeton, Joanna; Rosenblum, Norman D

2010-08-01

Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice.

BMP4 and LGL1 are Down Regulated in an Ovine Model of Congenital Diaphragmatic Hernia

PubMed Central

Emmerton-Coughlin, Heather M. A.; Martin, K. Kathryn; Chiu, Jacky S. S.; Zhao, Lin; Scott, Leslie A.; Regnault, Timothy R. H.; Bütter, Andreana

2014-01-01

Background/Purpose: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH) remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP) 4 and other factors such as late gestation lung protein 1 (LGL1), are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model. Methods: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was created in seven experimental animals. Lungs were harvested at 136 days (term = 145 days). Lung weight (LW) and mean terminal bronchiole density (MTBD) were measured to determine the degree of pulmonary hypoplasia. Quantitative real time PCR was undertaken to analyze Wnt2, Wnt7b, BMP4, and LGL1 mRNA expression. Results: Total LW was decreased while MTBD was increased in the CDH group (p < 0.05), confirming pulmonary hypoplasia. BMP4 and LGL1 mRNA was significantly reduced in CDH lungs (p < 0.05). Wnt2 mRNA was decreased, although not significantly (p < 0.06). Conclusion: For the first time, down regulation of BMP4 and LGL1 are reported in an ovine CDH model. In contrast to other animal models, these changes are persistent to near term. These findings suggest that mechanical compression from herniated viscera may play a more important role in causing pulmonary hypoplasia in CDH, rather than a primary defect in lung organogenesis. PMID:25593968

Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization.

PubMed

Satani, Nozomi; Ota, Hideki; Seiji, Kazumasa; Morimoto, Ryo; Kudo, Masataka; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Nezu, Masahiro; Omata, Kei; Ito, Sadayoshi; Satoh, Fumitoshi; Takase, Kei

2016-01-01

To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion. The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.9 years ± 11 [standard deviation]). A microcatheter was inserted in first-degree tributary veins. Unilateral aldosterone hypersecretion at the adrenal central vein was determined according to the lateralization index after cosyntropin stimulation. Excess aldosterone secretion at the adrenal tributary vein was considered to be present when the aldosterone/cortisol ratio from this vein exceeded that from the external iliac vein; suppressed secretion was indicated by the opposite pattern. Categoric variables were expressed as numbers and percentages; continuous variables were expressed as means ± standard errors of the mean. The AVS success rate, indicated by a selectivity index of 5 or greater, was 98% (64 of 65). The mean numbers of sampled tributaries on the left and right sides were 2.11 and 1.02, respectively. The following diagnoses were made on the basis of S-AVS results: unilateral aldosterone hypersecretion in 30 patients, bilateral hypersecretion without suppressed segments in 22 patients, and bilateral hypersecretion with at least one suppressed segment in 12 patients. None of the patients experienced severe complications. S-AVS could be used to identify heterogeneous intra-adrenal aldosterone secretion. Patients who have bilateral aldosterone-producing adenomas can be treated with adrenal-sparing surgery or other minimally invasive local therapies if any suppressed segment is identified at S-AVS. © RSNA, 2015.

Gendered Peer Involvement in Girls with Congenital Adrenal Hyperplasia: Effects of Prenatal Androgens, Gendered Activities, and Gender Cognitions.

PubMed

Berenbaum, Sheri A; Beltz, Adriene M; Bryk, Kristina; McHale, Susan

2018-05-01

A key question in understanding gender development concerns the origins of sex segregation. Children's tendencies to interact with same-sex others have been hypothesized to result from gender identity and cognitions, behavioral compatibility, and personal characteristics. We examined whether prenatal androgen exposure was related to time spent with boys and girls, and how that gendered peer involvement was related to sex-typed activities and gender identity and cognitions. We studied 54 girls with congenital adrenal hyperplasia (CAH) aged 10-13 years varying in degree of prenatal androgen exposure: 40 girls with classical CAH (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical CAH (NC-CAH) exposed to low, female-typical, prenatal androgens. Home interviews and questionnaires provided assessments of gendered activity interests and participation, gender identity, and gender cognitions. Daily phone calls over 7 days assessed time spent in gendered activities and with peers. Girls with both C-CAH and NC-CAH interacted more with girls than with boys, with no significant group differences. The groups did not differ significantly in gender identity or gender cognitions, but girls with C-CAH spent more time in male-typed activities and less time in female-typed activities than did girls with NC-CAH. Time spent with girls reflected direct effects of gender identity/cognitions and gender-typed activities, and an indirect effect of prenatal androgens (CAH type) through gender-typed activities. Our results extend findings that prenatal androgens differentially affect gendered characteristics and that gendered peer interactions reflect combined effects of behavioral compatibility and feelings and cognitions about gender. The study also shows the value of natural experiments for testing hypotheses about gender development.

'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial

ClinicalTrials.gov

2018-01-25

Hernia; Hernia, Diaphragmatic; Hernia, DIaphragmatic, Congenital; Pathological Conditions, Anatomical; Congenital Abnormalities; Congenital Diaphragmatic Hernia; Fetal Anomaly; Fetal Surgery; Pulmonary Hypoplasia

Analysis of the enamel hypoplasia using micro-CT scanner versus classical method.

PubMed

Marchewka, Justyna; Skrzat, Janusz; Wróbel, Andrzej

2014-01-01

This article demonstrates the use of micro-CT scanning of the teeth surface for recognizing and evaluating severity of the enamel hypoplasia. To test capabilities of the microtomography versus classical method of evaluation hypoplastic defects of the enamel we selected two human teeth (C, M(2)) showing different types of enamel hypoplasia: linear, pits, and groove. Examined samples derive from archeological material dated on XVII-XVIII AD and excavated in Poland. In the current study we proved that micro-CT scanning is a powerful technique not only for imaging all kinds of the enamel hypoplasia but also allows to perform accurate measurements of the enamel defects. We figure out that contrary to the classical method of scoring enamel defects, the micro-computed tomography yields adequate data which serve for estimating the length of stress episode and length of interval between them.

Adrenal Gland Cancer

MedlinePlus

... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

Congenital Anomaly of Single Dominant Right Coronary Artery with Hypoplastic Left Coronary Artery.

PubMed

Chuang, Cheng-Yen; Chen, Yen-Chou; Cheng, Ho-Shun; Hsieh, Ming-Hsiung

2015-11-01

With the popularization of new imaging technology, more people are deciding to undergo non-invasive studies such as multidetector computerized tomography (MDCT) before receiving coronary angiography. For this reason, coronary anomalies of coronary artery are being encountered more frequently. We here report a 68-year-old male presenting with typical angina. The MDCT images suggested chronic total occlusion of the left anterior descending (LAD) artery with collateral circulation from the right coronary artery (RCA). The patient's coronary angiography showed a congenital coronary anomaly with a single dominant RCA supplying the entire coronary circulation of the heart with both LAD and left circumflex artery hypoplasia. Angiography; Anomaly; Computerized tomography; Coronary artery.

Functional analysis of human cytochrome P450 21A2 variants involved in congenital adrenal hyperplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chunxue; Pallan, Pradeep S.; Zhang, Wei

Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxyprogesterone (17α-OH-progesterone) to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of WT human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH-progesterone). We found that the 17α-OH-progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions. Twelve P450 21A2 variants associated with either salt-wasting or nonclassical forms of CAH were expressed, purified, and analyzed. The catalytic activities of these 12more » variants ranged from 0.00009% to 30% of WT P450 21A2 and the extent of heme incorporation from 10% to 95% of the WT. Substrate dissociation constants (Ks) for four variants were 37–13,000-fold higher than for WT P450 21A2. Cytochrome b5, which augments several P450 activities, inhibited P450 21A2 activity. Similar to the WT enzyme, high noncompetitive intermolecular kinetic deuterium isotope effects (≥ 5.5) were observed for all six P450 21A2 variants examined for 21-hydroxylation of 21-d3-progesterone, indicating that C–H bond breaking is a rate-limiting step over a 104-fold range of catalytic efficiency. Using UV-visible and CD spectroscopy, we found that P450 21A2 thermal stability assessed in bacterial cells and with purified enzymes differed among salt-wasting- and nonclassical-associated variants, but these differences did not correlate with catalytic activity. Our in-depth investigation of CAH-associated P450 21A2 variants reveals critical insight into the effects of disease-causing mutations on this important enzyme.« less

Intertooth patterns of hypoplasia expression: implications for childhood health in the classic Maya collapse.

PubMed

Wright, L E

1997-02-01

Enamel hypoplasias, which record interacting stresses of nutrition and illness during the period of tooth formation, are a key tool in the study of childhood health in prehistory. But interpretation of the age of peak morbidity is complicated by differences in susceptibility to stress both between tooth positions and within a single tooth. Here, hypoplasias are used to evaluate the prevailing ecological model for the collapse of Classic Period Lowland Maya civilization, circa AD 900. Hypoplasias were recorded in the full dentition of 160 adult skeletons from six archaeological sites in the Pasion River region of Guatemala. Instead of constructing a composite scale of stress experience, teeth are considered separately by position in the analysis. No statistical differences are found in the proportion of teeth affected by hypoplasia between "Early," Late Classic, and Terminal Classic Periods for anterior teeth considered to be most susceptible to stress, indicating stability in the overall stress loads affecting children of the three chronological periods. However, hypoplasia trends in posterior teeth may imply a change in the ontogenetic-timing of more severe stress episodes during the final occupation and perhaps herald a shift in child-care practices. These results provide little support for the ecological model of collapse but do call to attention the potential of posterior teeth to reveal subtle changes in childhood morbidity when consideredindividually.

HEAR MAPS a classification for congenital microtia/atresia based on the evaluation of 742 patients.

PubMed

Roberson, Joseph B; Goldsztein, Hernan; Balaker, Ashley; Schendel, Stephen A; Reinisch, John F

2013-09-01

Describe anatomical and radiological findings in 742 patients evaluated for congenital aural atresia and microtia by a multidisciplinary team. Develop a new classification method to enhance multidisciplinary communication regarding patients with congenital aural atresia and microtia. Retrospective chart review with descriptive analysis of findings arising from the evaluation of patients with congenital atresia and microtia between January 2008 and January 2012 at a multidisciplinary tertiary referral center. We developed a classification method based on the acronym HEAR MAPS (Hearing, Ear [microtia], Atresia grade, Remnant earlobe, Mandible development, Asymmetry of soft tissue, Paralysis of the facial nerve and Syndromes). We used this method to evaluate 742 consecutive congenital atresia and microtia patients between 2008 and January of 2012. Grade 3 microtia was the most common external ear malformation (76%). Pre-operative Jahrsdoerfer scale was 9 (19%), 8 (39%), 7 (19%), and 6 or less (22%). Twenty three percent of patients had varying degrees of hypoplasia of the mandible. Less than 10% of patients had an identified associated syndrome. Patients with congenital aural atresia and microtia often require the intervention of audiology, otology, plastic surgery, craniofacial surgery and speech and language professionals to achieve optimal functional and esthetic reconstruction. Good communication between these disciplines is essential for coordination of care. We describe our use of a new classification method that efficiently describes the physical and radiologic findings in microtia/atresia patients to improve communication amongst care providers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

Polycystic ovarian disease: the adrenal connection.

PubMed

Marouliss, George B; Triantafillidis, Ioannis K

2006-01-01

Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders.

PubMed

Dahl, Sara; Wickström, Ronny; Ek, Ulla; Teär Fahnehjelm, Kristina

2018-03-01

Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH. This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests. Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p < 0.001). ASDs were diagnosed in seven of 42 (17%) patients. Children with bilateral ONH had a high risk of neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

[Toe transplantation in congenital malformations of the hand].

PubMed

Foucher, G

1997-11-01

Toe transfer is a well established procedure for thumb and finger reconstruction after mutilation. The indications in congenital malformations are a mater of controversy. Out of a personal series of 209 patients, 42 were children presenting a congenital malformation. Thirty six, with 46 transfers were available for review. There is only one failure at the beginning of our experience. The main indication was absence of pinch either due to absence of thumb (like in congenital band syndrome or some extreme cases of ulnar club hand or cleft hand) or absence of long finger (like in symbrachydactyly monodactylous type) or lack of both thumb and finger (like in peromelic type of symbrachydactyly). In this last type, we have been disappointed by the functional result of the distal implantation of two second toes taken from both feet; we have proposed a "stub" operation consisting in a second toe transfer on the anterior aspect of the radial epiphysis to take advantage of the mobility of the wrist and the availability of plenty tendon transfer (in this proximal situation). When planing to "built" an absent pincer, an early age is mandatory for operation (mean 12 months), to ensure a good cortical integration. A less frequent indication is a partial toe transfer with a vascularized epiphysis to provide growth and mobility in some cases of thumb hypoplasia (like in symbrachydactyly or Blauth and Manske type III b). Results are difficult to assess due to the early operation but if the mobility has been disappointing (mean 32 degrees), sensibility (mean 2PD 5 mm) and growth were excellent.

Use of repeat anterior maxillary distraction to correct residual midface hypoplasia in cleft patients

PubMed Central

2017-01-01

Objectives The study was designed to evaluate the efficacy of performing a second, repeat anterior maxillary distraction (AMD) to treat residual cleft maxillary hypoplasia. Materials and Methods Five patients between the ages of 12 to 15 years with a history of AMD and with residual cleft maxillary hypoplasia were included in the study. Inclusion was irrespective of gender, type of cleft lip and palate, and the amount of advancement needed. Repeat AMD was executed in these patients 4 to 5 years after the primary AMD procedure to correct the cleft maxillary hypoplasia that had developed since the initial procedure. Orthopantomogram (OPG) and lateral cephalograms were taken for evaluation preoperatively, immediately after distraction, after consolidation, and one year postoperatively. The data obtained was tabulated and a Mann Whitney U-test was used for statistical comparisons. Results At the time of presentation, a residual maxillary hypoplasia was observed with a well maintained distraction gap on the OPG which ruled out the occurrence of a relapse. Favorable movement of the segments without any resistance was seen in all patients. Mean maxillary advancement of 10.56 mm was achieved at repeat AMD. Statistically significant increases in midfacial length, SNA angle, and nasion perpendicular to point A distance was achieved (P=0.012, P=0.011, and P=0.012, respectively). Good profile was achieved for all patients. Minimal transient complications, for example anterior open bite and bleeding episodes, were managed. Conclusion Addressing the problem of cleft maxillary hypoplasia at an early age (12–15 years) is beneficial for the child. Residual hypoplasia may develop in some patients, which may require additional corrective procedures. The results of our study show that AMD can be repeated when residual deformity develops with the previous procedure having no negative impact on the results of the repeat procedure. PMID:29333371

Use of repeat anterior maxillary distraction to correct residual midface hypoplasia in cleft patients.

PubMed

Richardson, Sunil; Krishna, Shreya; Bansal, Avi

2017-12-01

The study was designed to evaluate the efficacy of performing a second, repeat anterior maxillary distraction (AMD) to treat residual cleft maxillary hypoplasia. Five patients between the ages of 12 to 15 years with a history of AMD and with residual cleft maxillary hypoplasia were included in the study. Inclusion was irrespective of gender, type of cleft lip and palate, and the amount of advancement needed. Repeat AMD was executed in these patients 4 to 5 years after the primary AMD procedure to correct the cleft maxillary hypoplasia that had developed since the initial procedure. Orthopantomogram (OPG) and lateral cephalograms were taken for evaluation preoperatively, immediately after distraction, after consolidation, and one year postoperatively. The data obtained was tabulated and a Mann Whitney U-test was used for statistical comparisons. At the time of presentation, a residual maxillary hypoplasia was observed with a well maintained distraction gap on the OPG which ruled out the occurrence of a relapse. Favorable movement of the segments without any resistance was seen in all patients. Mean maxillary advancement of 10.56 mm was achieved at repeat AMD. Statistically significant increases in midfacial length, SNA angle, and nasion perpendicular to point A distance was achieved ( P =0.012, P =0.011, and P =0.012, respectively). Good profile was achieved for all patients. Minimal transient complications, for example anterior open bite and bleeding episodes, were managed. Addressing the problem of cleft maxillary hypoplasia at an early age (12-15 years) is beneficial for the child. Residual hypoplasia may develop in some patients, which may require additional corrective procedures. The results of our study show that AMD can be repeated when residual deformity develops with the previous procedure having no negative impact on the results of the repeat procedure.

Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

PubMed

Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

2008-07-01

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

Should we question early feminizing genitoplasty for patients with congenital adrenal hyperplasia and XX karyotype?

PubMed

Binet, A; Lardy, H; Geslin, D; Francois-Fiquet, C; Poli-Merol, M L

2016-03-01

There is a wide difference of opinion between the medical-surgical community and advocacy group regarding Disorders of Sexual Development (DSD) secondary to congenital adrenal hyperplasia (CAH) being ranked in the intersex category. This rupture is even more evident when the issue of genitoplasty is brought up. For physicians it is obvious and unequivocal that a person with CAH and an XX karyotype has a female gender identity, whereas associations tend to rank persons with CAH in the intersex category and advocate holding-off on surgical management. A retrospective case study vs. control group, spanning over 40years, included 21 patients who were treated in 3 different centers. Each patient and their parents were contacted independently and interviewed regarding interpersonal relationships, psychological impact of genitoplasty, gender identity and opinion on optimal care management for this disorder. Three couples controls (parent-child) per CAH patients were used and matched according to age, sex assigned at birth and ethnic origin. Sex assigned at birth seemed to concord with the gender identity perceived by the patients in 85.7% of cases. In fact, 89.7% of patients and 100% of parents felt that feminizing genitoplasty should be performed within the first year of life. There is however a significant difference compared to controls who felt that surgical management should occur later on in life. No difference was highlighted during childhood regarding parents-child relationships or social integration. However, during adolescence, the parents-child relationship tended to be significantly more painful for the CAH group. Integrating their parenting role was significantly harder for patients in the CAH-DSD group. In the population of CAH-DSD patients who had genitoplasty the level of sexual fulfillment was not lower to the one reported by the control group. Female sex assignment seems legitimate according to this study and the development of gender identity in these

Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

PubMed

Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

2012-06-01

A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

Thromboembolism and congenital malformations: from Duane syndrome to thalidomide embryopathy.

PubMed

Parsa, Cameron F; Robert, Matthieu P

2013-04-01

To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations. Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis. Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemodynamic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide. Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.

Case Report: Congenital Erythroleukemia in a Premature Infant with Dysmorphic Features.

PubMed

Helin, Heidi; van der Walt, Jon; Holder, Muriel; George, Simi

2016-01-01

We present a case of pure erythroleukemia, diagnosed at autopsy, in a dysmorphic premature infant who died of multiorgan failure within 24 hours of birth. Dysmorphic features included facial and limb abnormalities with long philtrum, microagnathia, downturned mouth, short neck as well as abnormal and missing nails, missing distal phalanx from the second toe, and overlapping toes. Internal findings included gross hepatomegaly and patchy hemorrhages in the liver, splenomegaly, and cardiomegaly; and subdural, intracerebral, and intraventricular hemorrhages. Histology revealed infiltration of bone marrow, kidney, heart, liver, adrenal, lung, spleen, pancreas, thyroid, testis, thymus, and placenta by pure erythroleukemia. Only 6 cases of congenital erythroleukemia have been previously reported with autopsy findings similar to those of this case. The dysmorphic features, although not fitting any specific syndrome, make this case unique. Congenital erythroleukemia and possible syndromes suggested by the dysmorphic features are discussed.

Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PubMed

Ajish, T P; Praveen, V P; Nisha, B; Kumar, Harish

2014-11-01

There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen. Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed. The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m(2) total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens. The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone. There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

Cushing's syndrome and the nodular adrenal gland.

PubMed

Samuels, M H; Loriaux, D L

1994-09-01

This article examines Cushing's syndrome in four main categories as associated with nodular adrenal glands: adrenal adenoma, adrenal carcinoma, primary pigmented nodular adrenal dysplasia, and macronodular adrenal hyperplasia. A summary of clinical features of these four categories is presented.

Prenatal androgenization affects gender-related behavior but not gender identity in 5-12-year-old girls with congenital adrenal hyperplasia.

PubMed

Meyer-Bahlburg, Heino F L; Dolezal, Curtis; Baker, Susan W; Carlson, Ann D; Obeid, Jihad S; New, Maria I

2004-04-01

Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones-indicated by the degree of genital masculinization-as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30 control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.

Sodium Chloride Supplementation Is Not Routinely Performed in the Majority of German and Austrian Infants with Classic Salt-Wasting Congenital Adrenal Hyperplasia and Has No Effect on Linear Growth and Hydrocortisone or Fludrocortisone Dose.

PubMed

Bonfig, Walter; Roehl, Friedhelm; Riedl, Stefan; Brämswig, Jürgen; Richter-Unruh, Annette; Fricke-Otto, Susanne; Hübner, Angela; Bettendorf, Markus; Schönau, Eckhard; Dörr, Helmut; Holl, Reinhard W; Mohnike, Klaus

2018-01-01

Sodium chloride supplementation in salt-wasting congenital adrenal hyperplasia (CAH) is generally recommended in infants, but its implementation in routine care is very heterogeneous. To evaluate oral sodium chloride supplementation, growth, and hydrocortisone and fludrocortisone dose in infants with salt-wasting CAH due to 21-hydroxylase in 311 infants from the AQUAPE CAH database. Of 358 patients with classic CAH born between 1999 and 2015, 311 patients had salt-wasting CAH (133 females, 178 males). Of these, 86 patients (27.7%) received oral sodium chloride supplementation in a mean dose of 0.9 ± 1.4 mmol/kg/day (excluding nutritional sodium content) during the first year of life. 225 patients (72.3%) were not treated with sodium chloride. The percentage of sodium chloride-supplemented patients rose from 15.2% in children born 1999-2004 to 37.5% in children born 2011-2015. Sodium chloride-supplemented and -unsupplemented infants did not significantly differ in hydrocortisone and fludrocortisone dose, target height-corrected height-SDS, and BMI-SDS during the first 2 years of life. In the AQUAPE CAH database, approximately one-third of infants with salt-wasting CAH receive sodium chloride supplementation. Sodium chloride supplementation is performed more frequently in recent years. However, salt supplementation had no influence on growth, daily fludrocortisone and hydrocortisone dose, and frequency of adrenal crisis. © 2017 S. Karger AG, Basel.

Hepatic arteriovenous fistulae and portal vein hypoplasia in a Labrador retriever.

PubMed

Schaeffer, I G; Kirpensteijn, J; Wolvekamp, W T; Van den Ingh, T S; Rothuizen, J

2001-03-01

An 18-month-old male Labrador retriever was referred for investigation of chronic intermittent diarrhoea and vomiting of two months duration. A diagnosis of hepatic arteriovenous fistulae was made. These are extremely rare hepatic vascular anomalies which confer arterial pressure to the portal vein. Liver atrophy, portal vein hypoplasia, portal hypertension and multiple acquired portosystemic collateral vessels are the main complications. Surgical excision is a challenge as resection of large lesions may be associated with significant blood loss. In this dog, persistence of portal vein hypoplasia and extensive collateral pathways following surgery led to a reserved prognosis.

Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

PubMed

Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

2013-11-28

Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

PubMed

Domenice, S; Latronico, A C; Brito, V N; Arnhold, I J; Kok, F; Mendonca, B B

2001-09-01

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

Unlikely culprit: congenital middle aortic syndrome diagnosed in the sixth decade of life.

PubMed

Ali, Muhammad Sajawal; Tchernodrinski, Stefan; Mohananey, Divyanshu; Ali, Ahya Sajawal

2016-08-16

A 58-year-old woman was admitted with acute heart failure. She had a long history of resistant hypertension, with an unremarkable work up for secondary causes in the past. Her brachial blood pressure was 210/70 mm Hg, with ankle blood pressure of 100/70 mm Hg. CT angiogram revealed marked narrowing of the descending thoracic aorta between the left subclavian artery and the diaphragm, consistent with middle aortic syndrome (MAS). She was initially managed with diuretics and antihypertensives. Subsequently thoracotomy revealed a severely hypoplastic segment of the descending aorta. The diseased segment was resected and aortic reconstruction performed. Histopathology showed fragmentation of the medial elastic fibres and fibrosis of the medial and intimal layers. These findings along with gross aortic hypoplasia and absence of features of Takayasu's arteritis, suggest that our patient had congenital MAS. The patient has done well since her surgery. We believe this is the first case of congenital MAS reported in the sixth decade of life. 2016 BMJ Publishing Group Ltd.

Prenatal evaluation of the middle ear and diagnosis of middle ear hypoplasia using MRI.

PubMed

Katorza, Eldad; Nahama-Allouche, Catherine; Castaigne, Vanina; Gonzales, Marie; Galliani, Eva; Marlin, Sandrine; Jouannic, Jean-Marie; Rosenblatt, Jonathan; le Pointe, Hubert Ducou; Garel, Catherine

2011-05-01

Analysis of the middle ear with fetal MRI has not been previously reported. To show the contribution of fetal MRI to middle ear imaging. The tympanic cavity was evaluated in 108 fetal cerebral MRI examinations (facial and/or cerebral malformation excluded) and in two cases, one of Treacher Collins syndrome (case 1) and the other of oculo-auriculo-vertebral (OUV) spectrum (case 2) with middle ear hypoplasia identified by MRI at 27 and 36 weeks' gestation, respectively. In all 108 fetuses (mean gestational age 32.5 weeks), the tympanic cavity and T2 hypointensity related to the ossicles were well visualised on both sides. Case 1 had micro/retrognathia and bilateral external ear deformity and case 2 had retrognathism with a left low-set and deformed ear. MRI made it possible to recognize the marked hypoplasia of the tympanic cavity, which was bilateral in case 1 and unilateral in case 2. Both syndromes are characterized by craniofacial abnormalities including middle ear hypoplasia, which cannot be diagnosed with US. The middle ear cavity can be visualized with fetal MRI. We emphasize the use of this imaging modality in the diagnosis of middle ear hypoplasia.

Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

PubMed

Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

2017-03-01

Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

Reduced short term memory in congenital adrenal hyperplasia (CAH) and its relationship to spatial and quantitative performance.

PubMed

Collaer, Marcia L; Hindmarsh, Peter C; Pasterski, Vickie; Fane, Briony A; Hines, Melissa

2016-02-01

Girls and women with classical congenital adrenal hyperplasia (CAH) experience elevated androgens prenatally and show increased male-typical development for certain behaviors. Further, individuals with CAH receive glucocorticoid (GC) treatment postnatally, and this GC treatment could have negative cognitive consequences. We investigated two alternative hypotheses, that: (a) early androgen exposure in females with CAH masculinizes (improves) spatial perception and quantitative abilities at which males typically outperform females, or (b) CAH is associated with performance decrements in these domains, perhaps due to reduced short-term-memory (STM). Adolescent and adult individuals with CAH (40 female and 29 male) were compared with relative controls (29 female and 30 male) on spatial perception and quantitative abilities as well as on Digit Span (DS) to assess STM and on Vocabulary to assess general intelligence. Females with CAH did not perform better (more male-typical) on spatial perception or quantitative abilities than control females, failing to support the hypothesis of cognitive masculinization. Rather, in the sample as a whole individuals with CAH scored lower on spatial perception (p ≤ .009), a quantitative composite (p ≤ .036), and DS (p ≤ .001), despite no differences in general intelligence. Separate analyses of adolescent and adult participants suggested the spatial and quantitative effects might be present only in adult patients with CAH; however, reduced DS performance was found in patients with CAH regardless of age group. Separate regression analyses showed that DS predicted both spatial perception and quantitative performance (both p ≤ .001), when age, sex, and diagnosis status were controlled. Thus, reduced STM in CAH patients versus controls may have more general cognitive consequences, potentially reducing spatial perception and quantitative skills. Although hyponatremia or other aspects of salt-wasting crises or additional hormone

Aldosterone hypersecretion in “non-salt-losing” congenital adrenal hyperplasia

PubMed Central

Bartter, Frederic C.; Henkin, Robert I.; Bryan, George T.

1968-01-01

Patients with the “non-salt-losing” form of the adrenogenital syndrome were studied before and after suppression of adrenal cortical activity with carbohydrate-active steroids. The response of aldosterone secretion to sodium deprivation was measured; in some patients response to adrenocorticotropic hormone (ACTH) was measured as well. The aldosterone secretion was normal and responded normally to sodium deprivation in all patients studied during suppression with carbohydrate-active steroids. This finding suggests that 21-hydroxylation of progesterone is normal in this syndrome. The sole abnormality in the production of aldosterone in these patients was found to be excessive secretion of aldosterone while they were not receiving suppressive doses of carbohydrate-active steroids. This finding strongly supports the view that the biogenetic pathways through which aldosterone is produced from progesterone are intact in this syndrome. No patient showed hypertension or hypokalemic alkalosis despite very high aldosterone secretion rates. This observation suggests that the hyper-aldosteronism is secondary to a tendency to sodium loss in the patient whose ACTH production is not suppressed. These studies provide additional evidence in support of the hypothesis that the salt-losing and “non-salt-losing” forms of adrenogenital syndrome are genetically and biochemically distinct. PMID:4299011

Adrenal Gland Tumors: Statistics

MedlinePlus

... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism.

PubMed

Mattioli, Francesca; Piton, Amelie; Gérard, Bénédicte; Superti-Furga, Andrea; Mandel, Jean-Louis; Unger, Sheila

2016-06-01

The cardinal features of Primrose syndrome (MIM 259050) are dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. A variety of neurological signs and symptoms have been reported including hearing loss, autism, behavioral abormalities, hypotonia, cerebral calcifications, and hypoplasia of the corpus callosum. Recently, heterozygous de novo missense mutations in ZBTB20, coding for a zing finger protein, have been identified in Primrose syndrome patients. We report a boy with intellectual disability carrying two de novo missense mutations in the last exon of ZBTB20 (Ser616Phe and Gly741Arg; both previously unreported). One of them, Ser616Phe, affects an amino acid located in one of the C2H2 zing-fingers involved in DNA-binding and close to other missense mutations already described. Reverse phenotyping showed that this patient presents with classic features of Primrose syndrome (dysmorphic facies, macrocephaly, hearing loss, hypotonia, hypoplasia of the corpus callosum) and, in addition, congenital hypothyroidism. Review of the literature reveals another Primrose syndrome patient with hypothyroidism and thus, this may represent an under recognized component that should be investigated in other patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Bilateral renal dysplasia with nephron hypoplasia in a foal.

PubMed

Zicker, S C; Marty, G D; Carlson, G P; Madigan, J E; Smith, J M; Goetzman, B W

1990-06-15

Bilateral renal dysplasia and nephron hypoplasia was diagnosed in a Quarter Horse foal with clinical signs of lethargy, convulsions, and diarrhea. Laboratory evaluation revealed anemia, hypoproteinemia, leukopenia, hyponatremia, hypochloremia, and hyposmolality. The foal also had high concentrations of serum creatinine, BUN, and phosphorus. Evaluation of urinary indices revealed a high ratio of urinary gamma-glutamyl-transferase activity to concentration of creatinine, as well as a high fractional clearance ratio of sodium and potassium. Intravenous treatment with saline solution (0.9% NaCl) and antimicrobials provided only temporary resolution of some of the abnormalities. Diagnosis was partly established by histologic evaluation of renal tissue obtained via an ultrasonographically guided biopsy and was confirmed at necropsy. Pathologic changes in the kidney were unique in that the size of the kidneys, along with the appearance and number of glomeruli, were essentially normal despite marked hypoplasia of nephron tubules in the medulla.

Bone marrow morphology and disease progression in congenital thrombocytopenia: a detailed clinicopathologic and genetic study of eight cases.

PubMed

Tsang, Hamilton C; Bussel, James B; Mathew, Susan; Liu, Yen-Chun; Imahiyerobo, Allison A; Orazi, Attilio; Geyer, Julia T

2017-04-01

Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed. Six adult and two pediatric patients were identified (six male, two female). Age range at first biopsy was 1-47 (median, 31) years. Underlying diseases included thrombocytopenia-absent radius syndrome, congenital thrombocytopenia with radial-ulnar synostosis, MYH9-related disorder, shortened telomere syndrome, congenital thrombocytopenia with ANKRD26 mutation, and familial platelet disorder with predisposition to acute myeloid leukemia. Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis. Two patients had marrow hypoplasia and two had unremarkable marrow morphology. Three patients-all in the myelodysplastic/myeloproliferative neoplasm-like group-developed disease progression characterized by erythroid and myeloid dysplasia, elevated bone marrow blasts, and new cytogenetic abnormalities. Unlike non-familial myeloid neoplasms, congenital thrombocytopenia patients in the myelodysplastic/myeloproliferative neoplasm-like group had a long and indolent clinical course (average age at disease progression, 47 years). In summary, three distinct morphologic types of congenital thrombocytopenia were identified: a hyperplastic myelodysplastic/myeloproliferative neoplasm-like group, a hypoplastic bone marrow failure-like group, and a group with relatively normal marrow

[Adrenal tumours in childhood].

PubMed

Martos-Moreno, G A; Pozo-Román, J; Argente, J

2013-09-01

This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Adrenal hormones before and after venography during adrenal venous sampling: a self-controlled study.

PubMed

Koike, Yuya; Matsui, Seishi; Omura, Masao; Makita, Kohzoh; Obara, Alfonso W D; Moriya, Nobukazu; Nishikawa, Tetsuo

2017-03-01

A stress reaction involving increased adrenal hormone release occurs when starting adrenal venous sampling (AVS). The purpose of the present study was to investigate the effect of single shot venography on adrenal hormone production during AVS. This was a prospective self-controlled study. We enrolled 54 consecutive patients (21 men, 33 women; mean age 52 ± 11 years) with primary aldosteronism who underwent AVS from May 2014 to February 2015. Under non-stimulated conditions, blood samples were obtained from a common trunk of the left adrenal vein before and after single shot venography. The initial plasma aldosterone and cortisol concentration (PAC and PCC) were compared with those measured after venography for each patient. PAC and PCC were slightly but significantly decreased between before and after venography (after log transformation 2.12 ± 0.73 vs 2.07 ± 0.72, P = 0.00066, 1.89 ± 0.52 vs 1.83 ± 0.53, P = 0.00031, respectively). During non-stimulated left AVS, adrenal hormone secretion was slightly but significantly decreased after venography, similar to the normal time-related stress reaction. Venography did not increase the adrenal hormone secretion.

Extracorporeal Membrane Oxygenation in Premature Infants With Congenital Diaphragmatic Hernia.

PubMed

Cuevas Guamán, Milenka; Akinkuotu, Adesola C; Cruz, Stephanie M; Griffiths, Pamela A; Welty, Stephen E; Lee, Timothy C; Olutoye, Oluyinka O

2017-11-14

Prematurity and low birth weight have been exclusion criteria for extracorporeal membrane oxygenation (ECMO); however, these criteria are not evidence based. With advances in anticoagulation, improved technology, and surgical expertise, it is difficult to deny a potential therapy based on these criteria alone. We report the outcome of three neonates who were ineligible based on traditional criteria but were offered ECMO as a life-saving measure. We highlight the interdisciplinary nature of modern decision-making. All three neonates had severe congenital diaphragmatic hernia diagnosed prenatally, had normal fetal karyotypes, were born prematurely, and weighed less than 2 kg. All three neonates underwent cervical venoarterial cannulation, stabilization on ECMO, and repair of their congenital diaphragmatic hernia early in their ECMO courses. All three infants had long courses of respiratory support attributable to lung hypoplasia, but there were no short- or long-term complications attributable to ECMO support directly. All three are alive at 2 years of age and were making progress developmentally. In conclusion, with interdisciplinary collaboration and clinical guidelines uniformly implemented, low birth weight infants may benefit from ECMO and should not be denied the therapy arbitrarily based on gestational age or size alone. Further research is essential to determine appropriate patient selection in premature infants.

Congenital heart defects in oculodentodigital dysplasia: Report of two cases.

PubMed

Izumi, Kosuke; Lippa, Andrew M; Wilkens, Alisha; Feret, Holly A; McDonald-McGinn, Donna M; Zackai, Elaine H

2013-12-01

Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations. © 2013 Wiley Periodicals, Inc.

Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia.

PubMed

Quintos, J B; Vogiatzi, M G; Harbison, M D; New, M I

2001-04-01

Short stature in the adult patient with congenital adrenal hyperplasia (CAH) is commonly seen, even among patients in excellent adrenal control during childhood and puberty. In this study we examine the effect of GH therapy on height prediction in children with both CAH and compromised height prediction. Leuprolide acetate, a GnRH analog (GnRHa), was given to patients with evidence of early puberty. GH (n = 12) or the combination of GH and GnRHa (n = 8) was administered to 20 patients with CAH while they continued therapy with glucocorticoids. Each patient in the treatment group was matched according to age, sex, bone age, puberty, and type of CAH with another CAH patient treated only with glucocorticoid replacement. The match was made at the start of GH treatment. Of the 20 patients, 12 have completed 2 yr of therapy. After 1 yr of GH or combination GH and GnRHa therapy, the mean growth rate increased from 5 +/- 1.9 to 7.8 +/- 1.6 cm/yr vs. 5.4 +/- 1.7 to 5 +/- 2 cm/yr in the group not receiving GH (P < 0.0001). During the second year of treatment, the mean growth rate was 6 +/- 1.6 vs. 4.2 +/- 2.1 cm/yr in the group not receiving GH (P < 0.001). The height SD score for chronological age in the treatment group at the end of 1 and 2 yr of treatment improved significantly more than the nontreatment group (P < 0.01). A similar improvement in the height SD score for bone age was found in the treatment group after 1 (-1.4 +/- 0.9 vs. -1.7 +/- 0.9; P < 0.0001) and 2 yr of therapy (-0.67 +/- 0.68 vs. -1.7 +/- 1.2; P < 0.0004). The mean predicted adult height improved from 159 +/- 11 (baseline) to 170 +/- 7.5 cm (after 2 yr of therapy) closely approximating target height (173 +/- 8 cm). All patients continued the hydrocortisone treatment. In patients with CAH and compromised height prediction, treatment with GH or the combination of GH and GnRHa results in an improvement of growth rate and height prediction and a reduction in height deficit for bone age.

The genetics of congenital aniridia-a guide for the ophthalmologist.

PubMed

Landsend, Erlend S; Utheim, Øygunn A; Pedersen, Hilde R; Lagali, Neil; Baraas, Rigmor C; Utheim, Tor P

Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications. Copyright © 2017 Elsevier Inc. All rights reserved.

The case for early use of rapid whole genome sequencing in management of critically ill infants: Late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease and recurrent infections.

PubMed

Sweeney, Nathaly M; Nahas, Shareef A; Chowdhury, Shimul; Del Campo, Miguel; Jones, Marilyn C; Dimmock, David P; Kingsmore, Stephen F; Investigators, Rcigm

2018-03-16

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy number variants, and single gene mutations. CDH is the most expensive non-cardiac congenital defect: Management frequently requires implementation of Extracorporeal Membrane Oxygenation (ECMO), which increases management expenditures 2.4 - 3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in hospital survival of 80-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including post-cardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections and developmental delay. Rapid whole genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day. Had rWGS been performed as a neonate, eight months of suffering and futile healthcare utilization may have been avoided. Cold Spring Harbor Laboratory Press.

Treatment of enamel hypoplasia in a patient with Usher syndrome.

PubMed

de la Peña, Victor Alonso; Valea, Martín Caserío

2011-08-01

Usher syndrome (USH) is a group of autosomal recessive diseases characterized by the association of retinitis pigmentosa with sensorineural hearing loss. There are three types of USH. In addition, in people with USH and hypoplasia, the thickness of the enamel is reduced. The authors describe a case of a patient with USH type II associated with severe enamel hypoplasia and multiple unerupted teeth. The authors placed direct composite crowns and extracted severely affected and impacted molars. There is little information available on the oral pathologies of USH. Because the authors did not know how the patient's condition would progress and the patient still was growing, the authors treated the patient conservatively by placing direct composite crowns. The treatment has met both esthetic and functional expectations for 10 years. Copyright © 2011 American Dental Association. All rights reserved.

[Risk factors for teeth aplasia and hypoplasia in cleft lip and palate children].

PubMed

Korolenkova, M V; Starikova, N V; Ageeva, L V

2016-01-01

The aim of the study was to assess the significance of environmental risk factors for teeth aplasia and hypoplasia in cleft lip and palate children. Two hundred and forty-seven cleft lip and palate (CLP) children were enrolled in the study including 105 (42.5%) with bilateral CLP and 57.5% with unilateral CLP. The mean age was 11.2±4.9 years. Teeth condition was assessed clinically and radiologically. The impact of risk factors for teeth anomalies was analyzed by retrospective data obtained from computer database (absence of preoperative orthopedic treatment, palatal defects after primary palatoplasty and type of primary procedures). Surgical trauma by early periosteoplasty (at the age of 3-4 months), excessive scarring and tissue traction due to absence of early orthopedic treatment and palatal defect were associated with significantly higher incidence of incisors hypoplasia (both developmental enamel defects and microdentia) and aplasia of central incisors not seen in the other study subgroups. Incisors aplasia and hypoplasia in CLP patients do not always have disembryogenic origin but may depend on external environmental factors, including surgical trauma.

Congenital Zika syndrome with arthrogryposis: retrospective case series study.

PubMed

van der Linden, Vanessa; Filho, Epitacio Leite Rolim; Lins, Otavio Gomes; van der Linden, Ana; Aragão, Maria de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Rocha, Maria Angela Wanderley; Sobral da Silva, Paula Fabiana; Carvalho, Maria Durce Costa Gomes; do Amaral, Fernando José; Gomes, Joelma Arruda; Ribeiro de Medeiros, Igor Colaço; Ventura, Camila V; Ramos, Regina Coeli

2016-08-09

To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Retrospective case series study. Association for Assistance of Disabled Children, Pernambuco state, Brazil. Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis. The arthrogryposis was unrelated to the abnormalities

Congenital Zika syndrome with arthrogryposis: retrospective case series study

PubMed Central

Filho, Epitacio Leite Rolim; Lins, Otavio Gomes; Aragão, Maria de Fátima Viana Vasco; Brainer-Lima, Alessandra Mertens; Cruz, Danielle Di Cavalcanti Sousa; Rocha, Maria Angela Wanderley; Sobral da Silva, Paula Fabiana; Carvalho, Maria Durce Costa Gomes; do Amaral, Fernando José; Gomes, Joelma Arruda; Ribeiro de Medeiros, Igor Colaço; Ventura, Camila V; Ramos, Regina Coeli

2016-01-01

Objective To describe the clinical, radiological, and electromyographic features in a series of children with joint contractures (arthrogryposis) associated with congenital infection presumably caused by Zika virus. Design Retrospective case series study. Setting Association for Assistance of Disabled Children, Pernambuco state, Brazil. Participants Seven children with arthrogryposis and a diagnosis of congenital infection presumably caused by Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Main clinical, radiological, and electromyographic findings, and likely correlation between clinical and primary neurological abnormalities. Results The brain images of all seven children were characteristic of congenital infection and arthrogryposis. Two children tested positive for IgM to Zika virus in the cerebrospinal fluid. Arthrogryposis was present in the arms and legs of six children (86%) and the legs of one child (14%). Hip radiographs showed bilateral dislocation in seven children, subluxation of the knee associated with genu valgus in three children (43%), which was bilateral in two (29%). All the children underwent high definition ultrasonography of the joints, and there was no evidence of abnormalities. Moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography (monopolar). Five of the children underwent brain computed tomography (CT) and magnetic resonance imaging (MRI) and the remaining two CT only. All presented malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter (especially in the junction between the cortex and white matter), reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. MRI of the spine in four children showed apparent thinning of the cord and reduced ventral roots. Conclusions Congenital Zika syndrome should be added to the differential diagnosis of congenital

The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency.

PubMed

di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna; Secco, Andrea; Calandra, Erika; Calcagno, AnnaLisa; Frassinetti, Costanza; Ghezzi, Michele; Ambrosini, Linda; Parodi, Stefano; Gastaldi, Roberto; Loche, Sandro; Maghnie, Mohamad

2010-05-01

The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.

Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos.

PubMed

Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

2015-10-01

Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. Copyright © 2015 Elsevier B.V. All rights reserved.

Autonomic control of adrenal function.

PubMed Central

Edwards, A V; Jones, C T

1993-01-01

Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

PubMed

Carvalho, Luciane Carneiro de; Brito, Vinicius Nahime; Martin, Regina Matsunaga; Zamboni, Aline Machado; Gomes, Larissa Garcia; Inácio, Marlene; Mermejo, Livia Mara; Coeli-Lacchini, Fernanda; Teixeira, Virginia Ribeiro; Gonçalves, Fabrícia Torres; Carrilho, Alexandre José Faria; Del Toro Camargo, Kenny Yelena; Finkielstain, Gabriela Paula; Taboada, Giselle Fernandes; Frade Costa, Elaine Maria; Domenice, Sorahia; Mendonca, Berenice Bilharinho

2016-06-01

To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Retrospective study. Tertiary care center. Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. None. Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency.

PubMed

Frisén, Louise; Nordenström, Anna; Falhammar, Henrik; Filipsson, Helena; Holmdahl, Gundela; Janson, Per Olof; Thorén, Marja; Hagenfeldt, Kerstin; Möller, Anders; Nordenskjöld, Agneta

2009-09-01

Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.

Obesity in children with congenital adrenal hyperplasia in the Minnesota cohort: importance of adjusting body mass index for height-age.

PubMed

Sarafoglou, Kyriakie; Forlenza, Gregory P; Yaw Addo, O; Kyllo, Jennifer; Lteif, Aida; Hindmarsh, P C; Petryk, Anna; Gonzalez-Bolanos, Maria Teresa; Miller, Bradley S; Thomas, William

2017-05-01

To evaluate obesity and overweight in children with congenital adrenal hyperplasia (CAH) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index-for-height-age (BMI HA ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall-for-age stature. Longitudinal. One hundred and ninety-four children with CAH seen from 1970 to 2013: 124 salt wasting (SW); 70 simple virilizing (SV); 102 females. Body mass index (BMI) end-points were overweight (85-94 percentile) and obese (≥95 percentile). Approximately 50% of the children had at least one BMI measurement ≥95 percentile and about 70% had at least one ≥85 percentile. Using BMI HA percentiles, obesity incidence decreased slightly in SW children (47-43%) and markedly in SV children (50-33%); however, overweight status was not reduced. Only 6% of SW and 1% of SV children were persistently obese (≥3 clinic visits) when BMI HA was applied, whereas overweight status persisted in 35% of SW and 33% of SV children. Most obesity or overweight when using BMI HA occurred before age 10 and there was no association with hydrocortisone (HC) or fludrocortisone dosing. Adiposity rebound for SW children occurred by 3·3 years and in SV females by age 3·8 years, over a year earlier than the adiposity rebound for healthy children. Children with CAH are at higher risk for early onset obesity and overweight with or without using BMI HA but rates of persistent obesity were lower than previously reported. Careful HC dosing during early childhood is needed to prevent increased weight gain and an early adiposity rebound. © 2017 John Wiley & Sons Ltd.

A novel pipeline for adrenal tumour segmentation.

PubMed

Koyuncu, Hasan; Ceylan, Rahime; Erdogan, Hasan; Sivri, Mesut

2018-06-01

Adrenal tumours occur on adrenal glands surrounded by organs and osteoid. These tumours can be categorized as either functional, non-functional, malign, or benign. Depending on their appearance in the abdomen, adrenal tumours can arise from one adrenal gland (unilateral) or from both adrenal glands (bilateral) and can connect with other organs, including the liver, spleen, pancreas, etc. This connection phenomenon constitutes the most important handicap against adrenal tumour segmentation. Size change, variety of shape, diverse location, and low contrast (similar grey values between the various tissues) are other disadvantages compounding segmentation difficulty. Few studies have considered adrenal tumour segmentation, and no significant improvement has been achieved for unilateral, bilateral, adherent, or noncohesive tumour segmentation. There is also no recognised segmentation pipeline or method for adrenal tumours including different shape, size, or location information. This study proposes an adrenal tumour segmentation (ATUS) pipeline designed to eliminate the above disadvantages for adrenal tumour segmentation. ATUS incorporates a number of image methods, including contrast limited adaptive histogram equalization, split and merge based on quadtree decomposition, mean shift segmentation, large grey level eliminator, and region growing. Performance assessment of ATUS was realised on 32 arterial and portal phase computed tomography images using six metrics: dice, jaccard, sensitivity, specificity, accuracy, and structural similarity index. ATUS achieved remarkable segmentation performance, and was not affected by the discussed handicaps, on particularly adherence to other organs, with success rates of 83.06%, 71.44%, 86.44%, 99.66%, 99.43%, and 98.51% for the metrics, respectively, for images including sufficient contrast uptake. The proposed ATUS system realises detailed adrenal tumour segmentation, and avoids known disadvantages preventing accurate

Congenital Diaphragmatic Hernia

PubMed Central

2012-01-01

Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted. PMID:22214468

Monogenic Disorders of Adrenal Steroidogenesis.

PubMed

Baranowski, Elizabeth S; Arlt, Wiebke; Idkowiak, Jan

2018-06-06

Disorders of adrenal steroidogenesis comprise autosomal recessive conditions affecting steroidogenic enzymes of the adrenal cortex. Those are located within the 3 major branches of the steroidogenic machinery involved in the production of mineralocorticoids, glucocorticoids, and androgens. This mini review describes the principles of adrenal steroidogenesis, including the newly appreciated 11-oxygenated androgen pathway. This is followed by a description of pathophysiology, biochemistry, and clinical implications of steroidogenic disorders, including mutations affecting cholesterol import and steroid synthesis, the latter comprising both mutations affecting steroidogenic enzymes and co-factors required for efficient catalysis. A good understanding of adrenal steroidogenic pathways and their regulation is crucial as the basis for sound management of these disorders, which in the majority present in early childhood. © 2018 The Author(s) Published by S. Karger AG, Basel.

Internal jugular vein thrombosis associated with venous hypoplasia and protein S deficiency revealed by ultrasonography.

PubMed

Lim, Byung Gun; Kim, Young Min; Kim, Heezoo; Lim, Sang Ho; Lee, Mi Kyoung

2011-12-01

A 41-year-old woman, who had no thrombotic risk factors and past history except congenital scoliosis, underwent central venous catheterization (CVC) before correction of the scoliosis. When internal jugular vein (IJV) catheterization using the anatomical landmark technique failed, CVC under ultrasound guidance was tried. As a consequence, thrombosis and hypoplasia of the right IJV were incidentally detected by ultrasonography. Central venous catheters were then successfully placed in other veins under ultrasound guidance. Also, after examinations to rule out the possibility of pulmonary embolism and to clarify the causes of the IJV thrombosis, the patient was found to have protein S deficiency. CVC under ultrasound guidance should be recommended to prevent the failure of cannulation and complications such as thromboembolism in patients who could possibly have anomalies of vessels as a result of anatomical deformities caused by severe scoliosis, even if patients do not have thrombotic risk factors such as a history of central catheter insertion or intravenous drug abuse, cancer, advanced age, cerebral infarction, and left ventricular dysfunction. Also, if venous thrombosis is found in patients without predisposing risk factors, one should ascertain the cause of the hypercoagulable state, for example protein S deficiency, and perform appropriate treatment and prevention of venous thromboembolism.

Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

PubMed

Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E

2013-01-01

Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.

Genetics Home Reference: 21-hydroxylase deficiency

MedlinePlus

... Urinary Tract Defects Orphanet: Congenital adrenal hyperplasia Screening, Technology, and Research in Genetics (PDF) Vanderbilt Childrens Hospital: Congenital Adrenal Hyperplasia (PDF) Virginia Department of ...

Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts, unlinked to the LAMA2, FCMD, MEB and CMD1B loci, in three Tunisian patients.

PubMed

Triki, Chahnez; Louhichi, Nacim; Méziou, Mériam; Choyakh, Fakher; Kéchaou, Mohamed Salah; Jlidi, Rachid; Mhiri, Chokri; Fakhfakh, Faiza; Ayadi, Hamadi

2003-01-01

We report three Tunisian patients affected by congenital muscular dystrophy with mental retardation and cerebellar cysts on cranial magnetic resonance imaging. The clinical features were characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absence of speech, inability to walk in three patients, but calf hypertrophy was noted only in two patients. Brain magnetic resonance imaging showed several cerebellar cysts and vermis hypoplasia in all of the patients. Abnormality of the white matter was present in two patients. The pattern of gyration was normal in all cases. Serum creatine kinase was elevated in all three cases and their muscle biopsy showed dystrophic changes compatible with congenital muscular dystrophy. The immunohistochemical analysis of the skeletal muscle revealed partial merosin deficiency, more pronounced for the N-terminal antibody. Linkage analysis excluded congenital muscular dystrophy loci on chromosomes 6q22, 9q31, 1p32 and 1q42. These patients constituted a particular form of congenital muscular dystrophy with a combination of severe motor delay, mental retardation, partial merosin deficiency and cerebellar cysts. Two patients showed white matter abnormalities on magnetic resonance imaging and hypertrophy of the calves. These cases, in addition to those reported previously, confirmed the large phenotypic variability in the group of secondary merosin deficiency congenital muscular dystrophy.

TBX15 mutations cause craniofacial dysmorphism, hypoplasia of scapula and pelvis, and short stature in Cousin syndrome.

PubMed

Lausch, Ekkehart; Hermanns, Pia; Farin, Henner F; Alanay, Yasemin; Unger, Sheila; Nikkel, Sarah; Steinwender, Christoph; Scherer, Gerd; Spranger, Jürgen; Zabel, Bernhard; Kispert, Andreas; Superti-Furga, Andrea

2008-11-01

Members of the evolutionarily conserved T-box family of transcription factors are important players in developmental processes that include mesoderm formation and patterning and organogenesis both in vertebrates and invertebrates. The importance of T-box genes for human development is illustrated by the association between mutations in several of the 17 human family members and congenital errors of morphogenesis that include cardiac, craniofacial, and limb malformations. We identified two unrelated individuals with a complex cranial, cervical, auricular, and skeletal malformation syndrome with scapular and pelvic hypoplasia (Cousin syndrome) that recapitulates the dysmorphic phenotype seen in the Tbx15-deficient mice, droopy ear. Both affected individuals were homozygous for genomic TBX15 mutations that resulted in truncation of the protein and addition of a stretch of missense amino acids. Although the mutant proteins had an intact T-box and were able to bind to their target DNA sequence in vitro, the missense amino acid sequence directed them to early degradation, and cellular levels were markedly reduced. We conclude that Cousin syndrome is caused by TBX15 insufficiency and is thus the human counterpart of the droopy ear mouse.

Steroid Profiling by Gas Chromatography–Mass Spectrometry and High Performance Liquid Chromatography–Mass Spectrometry for Adrenal Diseases

PubMed Central

McDonald, Jeffrey G.; Matthew, Susan

2012-01-01

The ability to measure steroid hormone concentrations in blood and urine specimens is central to the diagnosis and proper treatment of adrenal diseases. The traditional approach has been to assay each steroid hormone, precursor, or metabolite using individual aliquots of serum, each with a separate immunoassay. For complex diseases, such as congenital adrenal hyperplasia and adrenocortical cancer, in which the assay of several steroids is essential for management, this approach is time consuming and costly, in addition to using large amounts of serum. Gas chromatography/mass spectrometry profiling of steroid metabolites in urine has been employed for many years but only in a small number of specialized laboratories and suffers from slow throughput. The advent of commercial high-performance liquid chromatography instruments coupled to tandem mass spectrometers offers the potential for medium- to high-throughput profiling of serum steroids using small quantities of sample. Here, we review the physical principles of mass spectrometry, the instrumentation used for these techniques, the terminology used in this field and applications to steroid analysis. PMID:22170384

Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

PubMed Central

Gehrand, Ashley; Bruder, Eric D.; Hoffman, Matthew J.; Engeland, William C.; Moreno, Carol

2014-01-01

The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. PMID:25394830

Equine fetal adrenal, gonadal and placental steroidogenesis.

PubMed

Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

2017-10-01

Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

Turner's hypoplasia and non-vitality: A case report of sequelae in permanent tooth

PubMed Central

Geetha Priya, P. R.; John, John B.; Elango, Indumathi

2010-01-01

Hypoplasia is the result of disruption in the process of enamel matrix formation, which in turn causes defect in quality and thickness of enamel. Four cases of Turner's hypoplastic teeth with a previous history of trauma/infection in their primary predecessors at the age of 2-3 years have been reported. These hypoplastic teeth had turned non-vital without any carious insult, cavitation or further trauma. This article thereby stresses the importance of early detection of enamel hypoplasia and proper management at the earliest possible stage to enable an efficient prevention from clinically non-evident microbial invasion in the dentinal tubules and concomitant pulp pathosis. PMID:22114432

Severe hypoplasia of the omasal laminae in a Japanese Black steer with chronic bloat--a case report.

PubMed

Takagi, Mitsuhiro; Mukai, Shuhei; Fushimi, Yasuo; Matsushita, Kouhei; Miyoshi, Nobuaki; Yasuda, Nobuhiro; Kitajima, Hideo; Takamure, Senro; Matsushita, Toshihiko; Kitamura, Nobuo; Deguchi, Eisaburo

2007-12-01

An 11-month-old Japanese Black steer with chronic bloat underwent clinical and histological analyses. During the observation period, it showed normal appetite and fecal volume but persistent chronic bloat symptoms. Compared to controls, the steer's feces contained undigested large straws. Necropsy revealed normal rumen, reticulum, and abomasum but a small omasum. The rumen, reticulum, and abomasum mucosa was normal, with well-developed ruminal papillae. However, severe hypoplasia of the omasal laminae was observed along with hypoplasia reticular groove and ruminoreticular fold. The contents of the reticulum, omasum, and abomasums comprised undigested large sized hay particles. The omasum papillae showed no pathological abnormalities. This is a rare case of a steer with chronic bloat probably caused by severe hypoplasia of the omasal laminae.

Bone lengthening for congenital differences of the hands and digits in children.

PubMed

Matsuno, Takahiro; Ishida, Osamu; Sunagawa, Toru; Ichikawa, Makoto; Ikuta, Yoshikazu; Ochi, Mitsuo

2004-07-01

We investigated the growth of bones after lengthening to evaluate the effectiveness and usefulness of bone lengthening in congenital hand deficiencies. Bone lengthening was performed to treat congenital hand deficiencies including hypoplastic thumb, hypoplasia of the small finger, cleft hand, metacarpal synostosis, brachymetacarpia, symbrachydactyly, and amniotic band syndrome. A total of 15 patients (1-13 years old) underwent lengthening of 23 bones. The average of distraction was 10 mm. The mean follow-up period was 59 months. The length of the bones at follow-up evaluation was measured and then compared with the length of the bones immediately after lengthening. The bone growth after lengthening, the percentage of growth after lengthening, and the growth rate were compared among diagnostic groups. In the cases involving older patients the bone length changed little and the growth plates of these patients closed naturally soon after lengthening. In contrast, in the cases in which the patients were younger than 7 years old the lengthened bones grew continuously. The amount of bone growth was different for each disease in the younger patients. In patients with amniotic band syndrome the lengthened bones grew at the same rate as the bones in the hand. Other diagnoses such as symbrachydactyly had a different growth pattern in the hand. We conclude that bone lengthening is a reliable method for the correction of congenital differences of the hand. The indications for this procedure must be determined while considering the relationship between the specific disease and subsequent bone growth.

Variant adrenal venous anatomy in 546 laparoscopic adrenalectomies.

PubMed

Scholten, Anouk; Cisco, Robin M; Vriens, Menno R; Shen, Wen T; Duh, Quan-Yang

2013-04-01

Knowing the types and frequency of adrenal vein variants would help surgeons identify and control the adrenal vein during laparoscopic adrenalectomy. To establish the surgical anatomy of the main vein and its variants for laparoscopic adrenalectomy and to analyze the relationship between variant adrenal venous anatomy and tumor size, pathologic diagnosis, and operative outcomes. In a retrospective review of patients at a tertiary referral hospital, 506 patients underwent 546 consecutive laparoscopic adrenalectomies between April 22, 1993, and October 21, 2011. Patients with variant adrenal venous anatomy were compared with patients with normal adrenal venous anatomy regarding preoperative variables (patient and tumor characteristics [size and location] and clinical diagnosis), intraoperative variables (details on the main adrenal venous drainage, any variant venous anatomy, duration of operation, rate of conversion to hand-assisted or open procedure, and estimated blood loss), and postoperative variables (transfusion requirement, reoperation for bleeding, duration of hospital stay, and histologic diagnosis). Laparoscopic adrenalectomy. Prevalence of variant adrenal venous anatomy and its relationship to tumor characteristics, pathologic diagnosis, and operative outcomes. Variant venous anatomy was encountered in 70 of 546 adrenalectomies (13%). Variants included no main adrenal vein identifiable (n = 18), 1 main adrenal vein with additional small veins (n = 11), 2 adrenal veins (n = 20), more than 2 adrenal veins (n = 14), and variants of the adrenal vein drainage to the inferior vena cava and hepatic vein or of the inferior phrenic vein (n = 7). Variants occurred more often on the right side than on the left side (42 of 250 glands [17%] vs. 28 of 296 glands [9%], respectively; P = .02). Patients with variant anatomy compared with those with normal anatomy had larger tumors (mean, 5.1 vs 3.3 cm, respectively; P < .001), more pheochromocytomas (24 of 70 [35%] vs

A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia.

PubMed

Mallappa, Ashwini; Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J; Daley, Lori-Ann; Digweed, Dena; Eckland, David J A; Van Ryzin, Carol; Nieman, Lynnette K; Arlt, Wiebke; Ross, Richard J; Merke, Deborah P

2015-03-01

Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700-1500 h; P = .002), and afternoon (1500-2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700-1500 h; P = .02) 17-OHP AUC. Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.

Two-year pilot study of newborn screening for congenital adrenal hyperplasia in New South Wales compared with nationwide case surveillance in Australia.

PubMed

Gleeson, Helena K; Wiley, Veronica; Wilcken, Bridget; Elliott, Elizabeth; Cowell, Christopher; Thonsett, Michael; Byrne, Geoffrey; Ambler, Geoffrey

2008-10-01

To assess the benefits and practicalities of setting up a newborn screening (NBS) program in Australia for congenital adrenal hyperplasia (CAH) through a 2 year pilot screening in ACT/NSW and comparing with case surveillance in other states. The pilot newborn screening occurred between 1/10/95 and 30/9/97 in NSW/ACT. Concurrently, case reporting for all new CAH cases occurred through the Australian Paediatric Surveillance Unit (APSU) across Australia. Details of clinical presentation, re-sampling and laboratory performance were assessed. 185,854 newborn infants were screened for CAH in NSW/ACT. Concurrently, 30 cases of CAH were reported to APSU, twelve of which were from NSW/ACT. CAH incidence was 1 in 15 488 (screened population) vs 1 in 18,034 births (unscreened) (difference not significant). Median age of initial notification was day 8 with confirmed diagnosis at 13(5-23) days in the screened population vs 16(7-37) days in the unscreened population (not significant). Of the 5 clinically unsuspected males in the screened population, one had mild salt-wasting by the time of notification, compared with salt-wasting crisis in all 6 males from the unscreened population. 96% of results were reported by day 10. Resampling was requested in 637 (0.4%) and median re-sampling delay was 11(0-28) days with higher resample rates in males (p < 0.0001). The within-laboratory cost per case of clinically unsuspected cases was A$42 717. There seems good justification for NBS for CAH based on clear prevention of salt-wasting crises and their potential long-term consequences. Also, prospects exist for enhancing screening performance.

Bilateral adrenal masses: a single-centre experience

PubMed Central

Bandgar, Tushar; Khare, Shruti; Jadhav, Swati; Lila, Anurag; Goroshi, Manjunath; Kasaliwal, Rajeev; Khadilkar, Kranti; Shah, Nalini S

2016-01-01

Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies. PMID:27037294

[Hemorrhagic adrenal pseudocyst: case report].

PubMed

Basile, G; Buffone, A; Cicciarella, G; di Mari, P; Cirino, E

2004-01-01

Adrenal cysts are usually asymptomatic; they are usually identified occasionally during ultrasound or C.T. scans (incidentaloma). Among adrenal cysts the most common types are epithelial cysts and pseudocysts. Intracystic haemorrhage is one of the possible complications of adrenal pseudocysts. We report a case of a young woman with right superior abdominal pain, fever and acute anemia. A C.T. scan showed a 10 cm. mass between the liver and the right kidney. To be sure of the nature of this mass also M.R., urography and C.T.-guided biopsy were carried out. This latter only let us make the final diagnosis of hemorrhagic adrenal pseudocyst. Thereafter, a laparotomic right adrenalectomy was performed, with full recovery of the patient. Adrenal cysts may cause differential diagnostic problems with masses of contiguous organs like kidney, liver and gallbladder. For this reason, ultrasound and C.T. scans may not be sufficient and must be completed by M.R., urography and/or C.T.-guided biopsy. Intracystic hamorrhage, spontaneous or post-traumatic, may cause to the patient acute anemia which, as soon as the diagnosis is confirmed, indicates surgery. The operation usually is a laparotomic adrenalectomy, since the laparoscopic approach is not sufficient to control large masses with active bleeding inside.

The effect of in vitro tracheal occlusion on branching morphogenesis in fetal lung explants from the rat nitrofen model of congenital diaphragmatic hernia.

PubMed

Grushka, Jeremy R; Al-Abbad, Saleh; Baird, Robert; Puligandla, Pramod; Kaplan, Feige; Laberge, Jean-Martin

2010-05-01

Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia. Tracheal occlusion has been shown to accelerate lung growth, but its effect on bronchial branching is unknown. In this study, we characterize the effects of in vitro TO on bronchial branch development in fetal lung explants derived from the nitrofen rat model of congenital diaphragmatic hernia. Rat dams were gavaged nitrofen on gestational day 9.5, and fetal lungs were harvested for explant culture on gestational day 14 (term, 22 days). Four experimental groups were investigated, with TO performed ex vivo using cautery: control, control + TO, nitrofen, and nitrofen + TO. Explants were incubated for 72 hours. Representative photographs were taken at 0, 24, 48, and 72 hours from the time of culture, and the number of distal branches was counted for each explant. The Student t test was used to compare distal branch measurements. A minimum of 12 fetal lung explants were cultured for each group. By 24 hours, all explants undergoing TO had more branch iterations than explants that did not. Moreover, TO in nitrofen-exposed explants increased bronchial branching to control levels by 24 hours in culture. Our results suggest that TO at day 14 increases branching in normal and nitrofen-exposed lung explants. In addition, TO increases airway branching in nitrofen-exposed explants to control levels suggesting that early TO reverses the lung hypoplasia seen in this model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Hernandez, Karen Gomez; Mete, Ozgur

2015-06-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

2015-03-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Progress in diagnosis and treatment of adrenal metastases tumor].

PubMed

Wu, Chu-jun; Qiu, Min; Ma, Lu-lin

2015-08-18

The adrenal gland is a common site of metastases, only second to pulmonary, liver and bone. The prevalence of adrenal metastases in patients with a history of cancer is between 10%-25%.The most common sites of origin are cancers of the lung, kidney, breast, gastrointestinal tract, and skin (melanoma).The mainstays of adrenal metastases diagnosis are computerized tomogramphy (CT), magnetic resonance imaging (MRI), and positron emission tomogramphy (PET). All patients should undergo complete hormonal evaluation to rule out functional adrenal tumors. Adrenal biopsy should be reserved for cases in which the results of non-invasive techniques are equivocal. In patients with isolated adrenal metastases, adrenalectomy is recommended, because of improved overall survival. For the patient with unresectable adrenal metastases tumor, radiotherapy and ablative therapy are feasible and useful methods for controlling adrenal metastases and offer patients opportunities for improved survival.

European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

PubMed

Ekman, Bertil; Fitts, David; Marelli, Claudio; Murray, Robert D; Quinkler, Marcus; Zelissen, Pierre M J

2014-05-09

Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK

Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

PubMed

Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

2015-02-01

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

Image-Guided Ablation of Adrenal Lesions

PubMed Central

Yamakado, Koichiro

2014-01-01

Although laparoscopic adrenalectomy has remained the standard of care for the treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation, has been shown to be clinically useful in many nonsurgical candidates. Ablation therapy has been used to treat both functioning adenomas and malignant tumors, including primary adrenal carcinoma and metastasis. For patients with functioning adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after ablation; for patients with malignant adrenal neoplasms, however, the survival benefit from ablation therapy remains unclear, though good initial results have been reported. This article outlines the current role of ablation therapy for adrenal lesions, as well as identifying some of the technical considerations for this procedure. PMID:25049444

Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

USDA-ARS?s Scientific Manuscript database

Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

CONGENITAL ABNORMALITIES OF CRANIAL NERVE DEVELOPMENT: OVERVIEW, MOLECULAR MECHANISMS, AND FURTHER EVIDENCE OF HETEROGENEITY AND COMPLEXITY OF SYNDROMES WITH CONGENITAL LIMITATION OF EYE MOVEMENTS

PubMed Central

Traboulsi, Elias I

2004-01-01

ABSTRACT Purpose The clinical and molecular genetic classification of syndromes with congenital limitation of eye movements and evidence of cranial nerve dysgenesis continues to evolve. This monograph details clinical and molecular genetic data on a number of families and isolated patients with congenital fibrosis of the extraocular muscles (CFEOM) and related disorders, and presents an overview of the mechanisms of abnormal patterns of motor and sensory cranial nerve development in these rare syndromes. Methods Clinical examination of one patient with CFEOM1, one family with clinical features of CFEOM2, one family with recessive CFEOM3, one family with horizontal gaze palsy and progressive scoliosis (HGPPS), and four patients with various combinations of congenital cranial nerve abnormalities. Genotyping of families with CFEOM and HGPPS for polymorphic markers in the regions of the three known CFEOM loci and in the HGPPS region, and mutation analysis of the ARIX and KIF21A genes in patients with CFEOM were performed according to standard published protocols. Results The patient with CFEOM1 had the second most common mutation in KIF21A, a 2861 G>A mutation that resulted in an R954Q substitution. The family with CFEOM2 phenotype did not map to the CFEOM2 locus. The family with recessive CFEOM3 did not map to any of the known loci. The HGPPS family mapped to 11q23–q25. One patient had optic nerve hypoplasia and fifth nerve dysfunction. Two patients had the rare combination of Möbius syndrome and CFEOM. One patient had Möbius syndrome and fifth nerve dysfunction. Conclusions There is genetic heterogeneity in CFEOM2 and CFEOM3. Abnormalities in sensory nerves can also accompany abnormalities of motor nerves, further substantiating the effect of individual mutations on developing motor as well as sensory cranial nerve nuclei. PMID:15747768

Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: A new X-linked multiple congenital anomalies/mental retardation syndrome: Clinical description and molecular studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamel, B.C.J.; Mariman, E.C.M.; Beersum, S.E.C. van

1994-07-15

We report on two brothers and their two maternal uncles with severe mental retardation, congenital heart defect, cleft or highly arched palate, short stature and craniofacial anomalies consisting of microcephaly, abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, and micro-gnathia. Three of the four patients died at an early age. The mother of the two brothers had an atrial septal defect. She is assumed to be manifesting carrier of a mutant gene, which is expressed in her two sons and two brothers. By multipoint linkage analysis it is found that the most likely location of the responsible gene ismore » the pericentromeric region Xp21.3-q21.3 with DMD and DXS3 as flanking markers. Maximum information is obtained with marker DXS453 (Z = 1.20 at {theta} = 0.0). 24 refs., 12 figs., 1 tab.« less

Diagnosis and classification of Addison's disease (autoimmune adrenalitis).

PubMed

Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire

2014-01-01

Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.

Prenatal determinants of optic nerve hypoplasia: Review of suggested correlates and future focus

PubMed Central

Garcia-Filion, Pamela; Borchert, Mark

2013-01-01

Optic nerve hypoplasia (ONH), a congenital malformation characterized by an underdeveloped optic nerve, is a seemingly epidemic cause of childhood blindness and visual impairment with associated lifelong morbidity. While the prenatal determinants of ONH are unknown, early case reports have led to a longstanding speculation that risky health behaviors (e.g. recreational drugs, alcohol) are a likely culprit. There has yet to be a systematic review of the epidemiology of ONH to assess the common prenatal features that may help focus research efforts in the identification of likely prenatal correlates. A review of the past 50 years of epidemiologic research was conducted to examine the prenatal features linked with ONH and provide direction for future research. There are select prominent prenatal features associated with ONH: young maternal age and primiparity. Commonly implicated prenatal exposures (e.g., recreational or pharmaceutical drugs, viral infection, etc.) were rare or uncommon in large cohort studies of ONH and therefore unlikely to be major contributors to ONH. Familial cases and gene mutations are rare. The preponderance of young mothers and primiparity among cases of ONH is striking, although the significance is unclear. Recent research suggests a potential role for prenatal nutrition, weight gain, and factors of deprivation. With the rapidly increasing prevalence of ONH, future research should focus on investigating the relevance of young maternal age and primiparity and exploring the recently suggested etiologic correlates in epidemic clusters of ONH. PMID:24160732

Radioguided Adrenal Surgery

PubMed Central

Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

2015-01-01

Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

Challenging embryological theories on congenital diaphragmatic hernia: future therapeutic implications for paediatric surgery.

PubMed Central

Jesudason, E. C.

2002-01-01

Lung hypoplasia is central to the poor prognosis of babies with congenital diaphragmatic hernia (CDH). Prolapse of abdominal organs through a diaphragmatic defect has traditionally been thought to impair lung growth by compression. The precise developmental biology of CDH remains unresolved. Refractory to fetal correction, lung hypoplasia in CDH may instead originate during embryogenesis and before visceral herniation. Resolving these conflicting hypotheses may lead to reappraisal of current clinical strategies. Genetic studies in murine models and the fruitfly, Drosophila melanogaster are elucidating the control of normal respiratory organogenesis. Branchless and breathless are Drosophila mutants lacking fibroblast growth factor (FGF) and its cognate receptor (FGFR), respectively. Sugarless and sulphateless mutants lack enzymes essential for heparan sulphate (HS) biosynthesis. Phenotypically, all these mutants share abrogated airway branching. Mammalian organ culture and transgenic models confirm the essential interaction of FGFs and HS during airway ramification. Embryonic airway development (branching morphogenesis) occurs in a defined spatiotemporal sequence. Unlike the surgically-created lamb model, the nitrofen rat model permits investigation of embryonic lung growth in CDH. Microdissecting embryonic lung primordia from the nitrofen CDH model and normal controls, we demonstrated that disruption of stereotyped airway branching correlates with and precedes subsequent CDH formation. To examine disturbed branching morphogenesis longitudinally, we characterised a system that preserves lung hypoplasia in organ culture. We tested FGFs and heparin (an HS analogue) as potential therapies on normal and hypoplastic lungs. Observing striking differences in morphological response to FGFs between normal and hypoplastic lung primordia, we postulated abnormalities of FGF/HS signalling in the embryonic CDH lung. Evaluating this hypothesis further, we examined effects of an HS

Short limbed dwarfism, genital hypoplasia, sparse hair, and vertebral anomalies: a variant of Ellis-van Creveld syndrome?

PubMed Central

Fryns, J P; Moerman, P

1993-01-01

A male newborn with acromesomelic short limbed dwarfism, genital hypoplasia, and vertebral anomalies is reported. As the child had an important number of clinical and radiological symptoms seen in patients with Ellis-van Creveld syndrome, we raise the question of whether he may represent a variant example of this syndrome despite the absence of cardinal symptoms such as postaxial polydactyly and ectodermal changes (nail hypoplasia). Images PMID:8487282

WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

PubMed

Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

2017-01-01

Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.

PubMed

Melo, Adriana Suely de Oliveira; Aguiar, Renato Santana; Amorim, Melania Maria Ramos; Arruda, Monica B; Melo, Fabiana de Oliveira; Ribeiro, Suelem Taís Clementino; Batista, Alba Gean Medeiros; Ferreira, Thales; Dos Santos, Mayra Pereira; Sampaio, Virgínia Vilar; Moura, Sarah Rogéria Martins; Rabello, Luciana Portela; Gonzaga, Clarissa Emanuelle; Malinger, Gustavo; Ximenes, Renato; de Oliveira-Szejnfeld, Patricia Soares; Tovar-Moll, Fernanda; Chimelli, Leila; Silveira, Paola Paz; Delvechio, Rodrigo; Higa, Luiza; Campanati, Loraine; Nogueira, Rita M R; Filippis, Ana Maria Bispo; Szejnfeld, Jacob; Voloch, Carolina Moreira; Ferreira, Orlando C; Brindeiro, Rodrigo M; Tanuri, Amilcar

2016-12-01

Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. Description of the major lesions caused by ZIKV congenital infection. Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

PubMed

Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing's syndrome in patients with bilateral adrenal disease.

PubMed

Lowery, Aoife J; Seeliger, Barbara; Alesina, Pier F; Walz, Martin K

2017-08-01

The treatment of hypercortisolism for patients with bilateral adrenal disease (BAD) is controversial. Bilateral total adrenalectomy results in permanent hypocortisolaemia requiring lifelong steroid replacement. A more conservative surgical approach, with less than bilateral total adrenalectomy (leaving functional adrenal tissue either unilaterally or bilaterally), represents an alternative option; however, long-term outcome or recurrence data are limited. We report our experience with the surgical management of hypercortisolism caused by BAD. Between 2004 and 2016, 42 patients (12 male, 30 female; mean age 58 ± 10 years) with clinical or subclinical Cushing's syndrome (CS/sCS) caused by BAD underwent adrenal surgery via the posterior retroperitoneoscopic approach. Adrenal surgery was defined as "adrenalectomy" when total gland excision was performed or "resection" when a partial or subtotal adrenal resection was performed. Clinical, radiological and biochemical parameters were evaluated preoperatively and postoperatively. Seventy adrenal operations performed in total included unilateral resection (n = 3), unilateral adrenalectomy (n = 15), bilateral resection (n = 9), adrenalectomy and contralateral resection (n = 14) and bilateral total adrenalectomy (n = 3). Median operating time was 47.5 min (30-150) with no difference between unilateral and bilateral (synchronous included) procedures (p = 0.15). Mortality was zero. Clavien-Dindo grade of postoperative complications was I (n = 5) and IV (n = 3). All but one patient with CS and 17/31 patients with sCS received postoperative steroid supplementation for a median duration of 20 (1.5-129) months. After median follow-up of 40 months (3-129), the remission rate was 92%; 11 patients required ongoing steroid supplementation. There were three biochemical recurrences (two underwent contralateral resection); two patients with new/progressive radiological nodularity are biochemically eucortisolaemic. A

Adrenal Incidentaloma

MedlinePlus

... or subclinical hypercortisolism: conditions caused by too much cortisol Hyperaldosteronism : too much aldosterone A pheochromocytoma: a rare ... in which the adrenal glands make too little cortisol and aldosterone, and too much androgen Cancer of ...

Experience with long-term glucocorticoid treatment in congenital adrenal hyperplasia: growth pattern compared with genetic height potential.

PubMed

Aycan, Zehra; Ocal, Gonul; Berberoglu, Merih; Cetinkaya, Ergun; Adiyaman, Pelin; Evliyaoglu, Olcay

2006-03-01

Long-term replacement treatment with high doses of steroids in congenital adrenal hyperplasia (CAH) is known to have a negative influence on growth. We evaluated the effects of long-term steroid treatment in patients with classical CAH on height development in relation to genetic height potential. Twenty-three patients with CAH (16 females, 7 males, mean age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of steroid treatment on growth was determined by monitoring patients for 8.61 +/- 3.46 years (2-17 years) while they were treated with hydrocortisone at a mean dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht-SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for all patients. Predicted adult height according to bone age was calculated and it was determined whether height was developing according to the genetic height potential. In addition, patients were grouped as 'tight control' or 'poor control' according to their mean serum 17OH-progesterone or ACTH levels while on treatment. We evaluated whether height development was different for the tight and poor control groups. The mean chronological age of our patients at the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH) 157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14. There was no significant difference between the actual Ht-SDS and TH-SDS of our patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our patients had normal height according to their genetic potential while 71.5% were shorter than their genetic height potential. While the Ht-SDS and corrected Ht-SDS were similar in the tight and poor metabolic control groups, the predicted height was significantly greater in the tight control group. We demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical CAH had

Laparoscopic Adrenalectomy for Adrenal Tumors

PubMed Central

Chuan-yu, Sun; Yat-faat, Ho; Wei-hong, Ding; Yuan-cheng, Gou; Qing-feng, Hu; Ke, Xu; Bin, Gu; Guo-wei, Xia

2014-01-01

Objective. To evaluate the indication and the clinical value of laparoscopic adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we performed laparoscopic adrenalectomy. The laparoscopic approach has been the procedure of choice for surgery of benign adrenal tumors, and the upper limit of tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful; only one was converted to open surgery due to bleeding. The average operating time and intraoperative blood loss of pheochromocytoma were significantly more than the benign tumors (P < 0.05). After 3 months of follow-up, the preoperative symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic adrenalectomy has the advantages of minimal invasion, less blood loss, fewer complications, quicker recovery, and shorter hospital stay. The full preparation before operation can decrease the average operating time and intraoperative blood loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the first choice treatment for the resection of adrenal benign tumor. PMID:25132851

Diagnosis and management of pediatric adrenal insufficiency.

PubMed

Uçar, Ahmet; Baş, Firdevs; Saka, Nurçin

2016-08-01

Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

PubMed Central

Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

2016-01-01

Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal

Changing the facial features of patients with Treacher Collins syndrome: protocol for 3-stage treatment of hard and soft tissue hypoplasia in the upper half of the face.

PubMed

Mitsukawa, Nobuyuki; Saiga, Atsuomi; Satoh, Kaneshige

2014-07-01

Treacher Collins syndrome is a disorder characterized by various congenital soft tissue anomalies involving hypoplasia of the zygoma, maxilla, and mandible. A variety of treatments have been reported to date. These treatments can be classified into 2 major types. The first type involves osteotomy for hard tissue such as the zygoma and mandible. The second type involves plastic surgery using bone grafting in the malar region and soft tissue repair of eyelid deformities. We devised a new treatment to comprehensively correct hard and soft tissue deformities in the upper half of the face of Treacher Collins patients. The aim was to "change facial features and make it difficult to tell that the patients have this disorder." This innovative treatment strategy consists of 3 stages: (1) placement of dermal fat graft from the lower eyelid to the malar subcutaneous area, (2) custom-made synthetic zygomatic bone grafting, and (3) Z-plasty flap transposition from the upper to the lower eyelid and superior repositioning and fixation of the lateral canthal tendon using a Mitek anchor system. This method was used on 4 patients with Treacher Collins syndrome who had moderate to severe hypoplasia of the zygomas and the lower eyelids. Facial features of these patients were markedly improved and very good results were obtained. There were no major complications intraoperatively or postoperatively in any of the patients during the series of treatments. In synthetic bone grafting in the second stage, the implant in some patients was in the way of the infraorbital nerve. Thus, the nerve was detached and then sutured under the microscope. Postoperatively, patients had almost full restoration of sensory nerve torpor within 5 to 6 months. We devised a 3-stage treatment to "change facial features" of patients with hypoplasia of the upper half of the face due to Treacher Collins syndrome. The treatment protocol provided a very effective way to treat deformities of the upper half of the face

[Adrenal tumors. Principles of diagnostics and operative treatment].

PubMed

Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

2010-05-01

Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

A Phase 2 Study of Chronocort, a Modified-Release Formulation of Hydrocortisone, in the Treatment of Adults With Classic Congenital Adrenal Hyperplasia

PubMed Central

Sinaii, Ninet; Kumar, Parag; Whitaker, Martin J.; Daley, Lori-Ann; Digweed, Dena; Eckland, David J. A.; Van Ryzin, Carol; Nieman, Lynnette K.; Arlt, Wiebke; Merke, Deborah P.

2015-01-01

Context: Treatment of congenital adrenal hyperplasia (CAH) is suboptimal. Inadequate suppression of androgens and glucocorticoid excess are common and current glucocorticoid formulations cannot replace the cortisol circadian rhythm. Objectives: The primary objective was to characterize the pharmacokinetic profile of Chronocort, a modified-release hydrocortisone formulation, in adults with CAH. Secondary objectives included examining disease control following 6 months of Chronocort with dose titration. Design, Setting, and Patients: Sixteen adults (eight females) with classic CAH participated in an open-label, nonrandomized, Phase 2 study at the National Institutes of Health Clinical Center. Twenty-four-hour blood sampling was performed on conventional glucocorticoids and following 6 months of Chronocort. Chronocort was initiated at 10 mg (0700 h) and 20 mg (2300 h). Dose titration was performed based on androstenedione and 17-hydroxyprogresterone (17-OHP) levels and clinical symptomatology. Main Outcome Measures: The primary outcome was cortisol pharmacokinetics of Chronocort and secondary outcomes included biomarkers of CAH control (androstenedione and 17-OHP). Results: In patients with CAH, Chronocort cortisol profiles were similar to physiologic cortisol secretion. Compared with conventional therapy, 6 months of Chronocort resulted in a decrease in hydrocortisone dose equivalent (28 ± 11.8 vs 25.9 ± 7.1 mg/d), with lower 24-hour (P = .004), morning (0700–1500 h; P = .002), and afternoon (1500–2300 h; P = .011) androstenedione area under the curve (AUC) and lower 24-hour (P = .023) and morning (0700–1500 h; P = .02) 17-OHP AUC. Conclusions: Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH. PMID:25494662

Study of adrenal function in patients with tuberculosis.

PubMed

Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

2018-07-01

Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal

[Analysis of 180 patients with sensory defect nystagmus (SDN) and congenital idiopathic nystagmus (CIN)].

PubMed

Lorenz, B; Gampe, E

2001-01-01

Analysis of the diseases underlying congenital nystagmus in a series of patients registered during 6 years as a prerequisite for adequate counselling of the families. Retrospective study of all patients that presented between 1992 and 1998 with congenital nystagmus not related to visual deprivation or acquired pathologies of the visual pathways. The patients were examined clinically and in dependence on the findings also by electrophysiological (Ganzfeld ERG and VEP, Albino-flash-VEP), psychophysical (colour vision, dark adaptation, spectral sensitivity), and molecular genetic methods. When estimated necessary, family members affected by history and unaffected family members were also examined. In cases of complex neuroophthalmological diseases a neuropaediatric examination including neuroimaging was initiated. In total, 180 patients could be analysed. A sensory defect nystagmus (SDN) was present in 142 patients (79%). The diagnoses were as follows: albinism (any form) in 56 patients (30%), progressive photoreceptor dystrophy in 20 patients (11%), stationary cone dysfunction in 18 patients (10%), bilateral optic nerve hypoplasia in 15 patients (8%), chorioretinal or optic nerve colobomata in 10 patients (6%), aniridia and its variants in 10 patients (6%), familial isolated nystagmus in 8 patients (5%), and congenital stationary night blindness in 5 patients (3%). 38 patients (21%) could not (yet) be classified. The prevalence of SDN as the manifesting symptom of a variety of well defined diseases in the present series of at least 79% is similar to that of 90% reported earlier. The precise diagnosis is a prerequisite for counselling the families as to functional prognosis and recurrence risk. Unnecessary neurological examinations including neuroimaging can be avoided.

Magnetic Resonance Imaging of Malformations of Midbrain-Hindbrain.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Castillo, Mauricio

2016-01-01

We aim to review the magnetic resonance imaging appearance of malformations of midbrain and hindbrain. These can be classified as predominantly cerebellar malformations, combined cerebellar and brain stem malformations, and predominantly brain stem malformations. The diagnostic criteria for the majority of these morphological malformations are based on neuroimaging findings. The predominantly cerebellar malformations include predominantly vermian hypoplasia seen in Dandy-Walker malformation and rhombencephalosynapsis, global cerebellar hypoplasia reported in lissencephaly and microlissencephaly, and unilateral cerebellar hypoplasia seen in PHACES, vanishing cerebellum, and cerebellar cleft. Cerebellar dysplasias are seen in Chudley-McCullough syndrome, associated with LAMA1 mutations and GPR56 mutations; Lhermitte-Duclos disease; and focal cerebellar dysplasias. Cerebellar hyperplasias are seen in megalencephaly-related syndromes and hemimegalencephaly with ipsilateral cerebellomegaly. Cerebellar and brain stem malformations include tubulinopathies, Joubert syndrome, cobblestone malformations, pontocerebellar hypoplasias, and congenital disorders of glycosylation type Ia. Predominantly brain stem malformations include congenital innervation dysgenesis syndrome, pontine tegmental cap dysplasia, diencephalic-mesencephalic junction dysplasia, disconnection syndrome, and pontine clefts.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Therapeutic patient education in adrenal insufficiency.

PubMed

Guignat, Laurence

2018-06-01

It is essential to encourage patient autonomy in the management of their illness, and notably their participation in treatment education programs; specific programs target avoidance or early preventive treatment of acute adrenal insufficiency, which is a life-threatening complication. Therapeutic patient education is recommended by the two international consensus statements on the management of primary adrenal insufficiency and the French consensus on adrenal insufficiency. Although there is no common international reference framework to date, the objective of the French consensus was to provide a frame of reference to facilitate the development of therapeutic education for patients with adrenal insufficiency. The principal educational objectives were: for the patient to always carry the necessary emergency equipment; be able to identify situations of increased risk and the early signs of adrenal crisis; know how to adjust oral glucocorticoid treatment; be capable of administering hydrocortisone by subcutaneous injection; be able to adjust treatment to different situations (heat, physical exercise, travel); and be able to appropriately use the resources of the healthcare services. Other programs could also be developed to respond to patients' needs and expectations, notably concerning hydrocortisone dose adjustment to avoid overdose in the context of chronic fatigue syndrome. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Occult spinal canal stenosis due to C-1 hypoplasia in children with Down syndrome.

PubMed

Matsunaga, Shunji; Imakiire, Takanori; Koga, Hiroaki; Ishidou, Yasuhiro; Sasaki, Hiromi; Taketomi, Eiji; Higo, Masaru; Tanaka, Hiroshi; Komiya, Setsuro

2007-12-01

Little has been published about subclinical spinal canal stenosis due to C-1 hypoplasia in patients with Down syndrome. In this paper the authors performed a matched comparison study with cross-sectional survey to investigate occult spinal canal stenosis due to C-1 hypoplasia in children with Down syndrome. A total of 102 children with Down syndrome ranging in age from 10 to 15 years were matched according to age and physique with 176 normal children. In all participants, the anteroposterior (AP) diameter of C-1 and the atlas-dens interval (ADI) were measured on plain lateral x-ray images of the cervical spine. The cross-sectional area of the atlas was also measured from a cross-sectional computed tomography image of C-1. Eight children (6.7%) with Down syndrome developed atlantoaxial subluxation associated with myelopathy. The difference in the ADI between the patients and controls was not statistically significant. The average AP diameter of the atlas and the spinal canal area along the cross-section of the atlas were significantly smaller in children with Down syndrome than those in the control group. Atlantoaxial instability and occult spinal canal stenosis due to C-1 hypoplasia in patients with Down syndrome may significantly increase the risk of myelopathy.

Urethral hydrodistension for management of urethral hypoplasia in prune belly syndrome: long-term results.

PubMed

Kajbafzadeh, Abdol-Mohammad; Rasouli, Mohammad Reza; Dianat, SeyedSaeid; Nezami, Behtash G; Mahboubi, Amir Hassan; Sina, Alireza

2010-11-01

The aim of the study was to evaluate the efficacy and safety of urethral hydrodistension for management of urethral hypoplasia in prune belly syndrome (PBS). During a 10-year period, 7 infants with PBS and urethral hypoplasia presented either with open urachus or surgically created urinary diversion referred to our hospital. Five milliliters of normal saline was pushed via a 22-gauge plastic angiocatheter into the urethra with simultaneous finger pressure on the perineum to occlude the proximal urethra that was repeated with higher volumes of the solution (up to 20 mL). The procedure was continued until a 6F or 8F feeding tube catheter confirmed the urethral patency. Hydrodistension was repeated in 3-month intervals till complete patency was confirmed by imaging. Median age of the infants was 6 (1-8) months. All urethral hydrodistension were successful after 1 to 3 sessions. Follow-up imaging studies showed significant improvement in all patients except one. Natural and surgically created urinary diversions were closed in 6 infants. The hydrodistension create an equal and constant pressure into the urethral wall without any urethral damage. This technique can be considered along with the other available methods for management of urethral hypoplasia in selected cases of PBS. Copyright © 2010 Elsevier Inc. All rights reserved.

Sepsis risk factors in infants with congenital diaphragmatic hernia.

PubMed

Levy, Michaël; Le Sache, Nolwenn; Mokhtari, Mostafa; Fagherazzi, Guy; Cuzon, Gaelle; Bueno, Benjamin; Fouquet, Virginie; Benachi, Alexandra; Eleni Dit Trolli, Sergio; Tissieres, Pierre

2017-12-01

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly and remains among the most challenging ICU-managed disease. Beside severe pulmonary hypertension, lung hypoplasia and major abdominal surgery, infective complications remain major determinants of outcome. However, the specific incidence of sepsis as well as associated risk factors is unknown. This prospective, 4-year observational study took place in the pediatric intensive care and neonatal medicine department of the Paris South University Hospitals (Le Kremlin-Bicêtre, France), CDH national referral center and involved 62 neonates with CDH. During their ICU stay, 28 patients (45%) developed 38 sepsis episodes. Ventilator-associated pneumonia (VAP: 23/38; 31.9 VAP per 1000 days of mechanical ventilation) and central line-associated blood stream infections (CLABSI: 5/38; 5.5 per 1000 line days) were the most frequently encountered infections. Multivariate analysis showed that gestational age at birth and intra-thoracic position of liver were significantly associated with the occurrence of sepsis. Infected patients had longer duration of mechanical and noninvasive ventilation (16.2 and 5.8 days, respectively), longer delay to first feeding (1.2 days) and a longer length of stay in ICU (23 days), but there was no difference in mortality. Healthcare-associated infections, and more specifically VAP, are the main infective threat in children with CDH. Sepsis has a significant impact on the duration of ventilator support and ICU length of stay but does not impact mortality. Low gestational age and intra-thoracic localization of the liver are two independent risk factors associated with sepsis.

The use of internal maxillary distraction for maxillary hypoplasia: a preliminary report.

PubMed

Van Sickels, Joseph E; Madsen, Mathew J; Cunningham, Larry L; Bird, Douglas

2006-12-01

Distraction osteogenesis is a useful alternative to advance the maxilla in complicated cases of maxillary hypoplasia. The purpose of this article is to review the workup, experience, and preliminary results with the use of internal distraction osteogenesis for maxillary hypoplasia at one teaching institution. Over a 5-year period, more than 300 patients with craniofacial and dentofacial defects have undergone oral and maxillofacial surgery at our center to correct their skeletal discrepancies. Of these, 10 have had maxillary distraction osteogenesis done with internal distractors. Follow-up of 6 months or more was available for 8 patients. Stereolithographic models were used to bend distractors prior to surgery in 6 patients. Latency prior to the start of distraction was 3 to 7 days and varied with the age of the patient. Distraction occurred at approximately 1 mm per day with an average distraction length of 8.5 mm (range, 6-10 mm). Excellent occlusal results were obtained in 5 patients. Major complications including nonunion and failure to achieve acceptable occlusal results were observed in 3 patients. Minor complications including pain and loosening of the distracter devices were observed in 2 patients, but did not appear to affect the esthetic and functional results. Distraction osteogenesis is a useful alternative to traditional orthognathic surgery to treat maxillary hypoplasia. Internal distractions are attractive to patients, but are more difficult to place and can cause discomfort to patients when trying to achieve an ideal primary vector of distraction. Stereolithographic models can help with placement of the device. Changes in design of distractors may help with patient discomfort.

Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

PubMed

Fassnacht, Martin; Arlt, Wiebke; Bancos, Irina; Dralle, Henning; Newell-Price, John; Sahdev, Anju; Tabarin, Antoine; Terzolo, Massimo; Tsagarakis, Stylianos; Dekkers, Olaf M

2016-08-01

: By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

PubMed

Macchiaroli, Annamaria; Kelberman, Daniel; Auriemma, Renata Simona; Drury, Suzanne; Islam, Lily; Giangiobbe, Sara; Ironi, Gabriele; Lench, Nicholas; Sowden, Jane C; Colao, Annamaria; Pivonello, Rosario; Cavallo, Luciano; Gasperi, Maurizio; Faienza, Maria Felicia

2014-01-25

Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management. Copyright © 2013 Elsevier B.V. All rights reserved.

Androgen and psychosexual development: core gender identity, sexual orientation and recalled childhood gender role behavior in women and men with congenital adrenal hyperplasia (CAH).

PubMed

Hines, Melissa; Brook, Charles; Conway, Gerard S

2004-02-01

We assessed core gender identity, sexual orientation, and recalled childhood gender role behavior in 16 women and 9 men with CAH and in 15 unaffected female and 10 unaffected male relatives, all between the ages of 18 and 44 years. Women with congenital adrenal hyperplasia (CAH) recalled significantly more male-typical play behavior as children than did unaffected women, whereas men with and without CAH did not differ. Women with CAH also reported significantly less satisfaction with the female sex of assignment and less heterosexual interest than did unaffected women. Again, men with CAH did not differ significantly from unaffected men in these respects. Our results for women with CAH are consistent with numerous prior reports indicating that girls with CAH show increased male-typical play behavior. They also support the hypotheses that these women show reduced heterosexual interest and reduced satisfaction with the female sex of assignment. Our results for males are consistent with most prior reports that boys with CAH do not show a general alteration in childhood play behavior. In addition, they provide initial evidence that core gender identity and sexual orientation are unaffected in men with CAH. Finally, among women with CAH, we found that recalled male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood. Although prospective studies are needed, these results suggest that those girls with CAH who show the greatest alterations in childhood play behavior may be the most likely to develop a bisexual or homosexual orientation as adults and to be dissatisfied with the female sex of assignment.

Complement component 4 copy number variation and CYP21A2 genotype associations in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

PubMed

Chen, Wuyan; Xu, Zhi; Nishitani, Miki; Van Ryzin, Carol; McDonnell, Nazli B; Merke, Deborah P

2012-12-01

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of cortisol biosynthesis caused by CYP21A2 mutations. An increase in gene copy number variation (CNV) exists at the CYP21A2 locus. CNV of C4, a neighboring gene that encodes complement component 4, is associated with autoimmune disease susceptibility. In this study, we performed comprehensive genetic analysis of the RP-C4-CYP21-TNX (RCCX) region in 127 unrelated 21-OHD patients (100 classic, 27 nonclassic). C4 copy number was determined by Southern blot. C4 CNV and serum C4 levels were evaluated in relation to CYP21A2 mutations and relevant phenotypes. We found that the most common CYP21A2 mutation associated with the nonclassic form of CAH, V281L, was associated with high C4 copy number (p = 7.13 × 10(-16)). Large CYP21A2 deletion, a common mutation associated with the classic form of CAH, was associated with low C4 copy number (p = 1.61 × 10(-14)). Monomodular RCCX with a short C4 gene, a risk factor for autoimmune disease, was significantly less frequent in CAH patients compared to population estimates (2.8 vs. 10.6 %; p = 1.08 × 10(-4)). In conclusion, CAH patients have increased C4 CNV, with mutation-specific associations that may be protective for autoimmune disease. The study of CYP21A2 in relation to neighboring genes provides insight into the genetics of CNV hotspots, an important determinant of human health.

Adrenal tuberculosis in Cushing's disease with bilateral macronodular adrenocortical hyperplasia.

PubMed

Kwon, Hyuk-Sang; Kim, Sang-Il; Yoo, Soon-Jib; Yoon, Kun-Ho; Lee, Kwang-Woo; Kang, Moon-Won; Son, Ho-Young; Kang, Sung-Koo; Cha, Bong-Yun

2006-04-01

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

Unilateral hypoplasia with contralateral hypertrophy of anterior belly of digastric muscle: a case report.

PubMed

Ochoa-Escudero, Martin; Juliano, Amy F

2016-10-01

Anomalies of the anterior belly of the digastric muscle (DM) are uncommon. We present a case of hypoplasia of the anterior belly of the left DM with hypertrophy of the anterior belly of the contralateral DM. The importance of recognizing this finding is to differentiate hypoplasia of the anterior belly of the DM from denervation atrophy, and not to confuse contralateral hypertrophy with a submental mass or lymphadenopathy. In denervation atrophy of the anterior belly of the DM, associated atrophy of the ipsilateral mylohyoid muscle is present. Hypertrophy of the anterior belly of the contralateral DM can be differentiated from a submental mass or lymphadenopathy by recognizing its isodensity on computed tomography and isointensity on magnetic resonance imaging to other muscles, without abnormal contrast enhancement.

Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.

PubMed

Santos, Marta; Bastos, Pedro; Gonzaga, Silvia; Roriz, José-Mário; Baptista, Maria J; Nogueira-Silva, Cristina; Melo-Rocha, Gustavo; Henriques-Coelho, Tiago; Roncon-Albuquerque, Roberto; Leite-Moreira, Adelino F; De Krijger, Ronald R; Tibboel, Dick; Rottier, Robbert; Correia-Pinto, Jorge

2006-04-01

Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.

C-Arm Computed Tomography-Assisted Adrenal Venous Sampling Improved Right Adrenal Vein Cannulation and Sampling Quality in Primary Aldosteronism.

PubMed

Park, Chung Hyun; Hong, Namki; Han, Kichang; Kang, Sang Wook; Lee, Cho Rok; Park, Sungha; Rhee, Yumie

2018-05-04

Adrenal venous sampling (AVS) is a gold standard for subtype classification of primary aldosteronism (PA). However, this procedure has a high failure rate because of the anatomical difficulties in accessing the right adrenal vein. We investigated whether C-arm computed tomography-assisted AVS (C-AVS) could improve the success rate of adrenal sampling. A total of 156 patients, diagnosed with PA who underwent AVS from May 2004 through April 2017, were included. Based on the medical records, we retrospectively compared the overall, left, and right catheterization success rates of adrenal veins during the periods without C-AVS (2004 to 2010, n=32) and with C-AVS (2011 to 2016, n=134). The primary outcome was adequate bilateral sampling defined as a selectivity index (SI) >5. With C-AVS, the rates of adequate bilateral AVS increased from 40.6% to 88.7% (P<0.001), with substantial decreases in failure rates (43.7% to 0.8%, P<0.001). There were significant increases in adequate sampling rates from right (43.7% to 91.9%, P<0.001) and left adrenal veins (53.1% to 95.9%, P<0.001) as well as decreases in catheterization failure from right adrenal vein (9.3% to 0.0%, P<0.001). Net improvement of SI on right side remained significant after adjustment for left side (adjusted SI, 1.1 to 9.0; P=0.038). C-AVS was an independent predictor of adequate bilateral sampling in the multivariate model (odds ratio, 9.01; P<0.001). C-AVS improved the overall success rate of AVS, possibly as a result of better catheterization of right adrenal vein. Copyright © 2018 Korean Endocrine Society.

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

PubMed

Gallo-Payet, Nicole

2016-05-01

The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. © 2016 Society for Endocrinology.

[Diagnosis and surgical treatment of cystic pulmonary hypoplasia with aortic blood supply].

PubMed

Opanasenko, N S; Klimenko, V I; Kshanovskiĭ, A É; Tereshkovich, A V; Kalenichenko, M I; Konik, B N; Demus, R S; Obremskaia, O K; Levanda, L I; Kononenko, V A; Mikitenko, I Iu

2013-12-01

Cystic pulmonary hypoplasia with aortic blood supply--it is a rare inborn failure, in which the part of pulmonary tissue is developing separately from tracheo-bronchial tree and takes blood supply from systemic blood circulation. Diagnosis of the disease is a complicated, and it is necessary to apply modern radiological methods of visualization. The results of treatment of 27 patients, suffering cystic pulmonary hypoplasia with aortic blood supply, in the clinic through 50 yrs, were analyzed. All the patients were operated on.In 17 (63%) patients lobectomy was performed, in 4 (14.8%)--the left-sided lower lobe pyramid was excised, in 1 (3.7%)--the left-sided wedge resection of C(X), in 1 (3.7%)--the left-sided pulmonectomy, in 1 (3.7%)--left-sided resection of C(VIII) - C(IX). The rate of intraoperative complications--14.8%, and postoperative--7.4%. Efficacy of surgical treatment for this period constitutes 100%.

Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.

PubMed

Engberg, Hedvig; Butwicka, Agnieszka; Nordenström, Anna; Hirschberg, Angelica Lindén; Falhammar, Henrik; Lichtenstein, Paul; Nordenskjöld, Agneta; Frisén, Louise; Landén, Mikael

2015-10-01

Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n = 335) born between January 1915 and January 2010 were compared with aged-matched female (n = 33500) and male controls (n = 33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded. Copyright © 2015 Elsevier Ltd. All rights reserved.

Percutaneous interstitial brachytherapy for adrenal metastasis: technical report.

PubMed

Kishi, Kazushi; Tamura, Shinji; Mabuchi, Yasushi; Sonomura, Tetsuo; Noda, Yasutaka; Nakai, Motoki; Sato, Morio; Ino, Kazuhiko; Yamanaka, Noboru

2012-09-01

We developed and evaluated the feasibility of a brachytherapy technique as a safe and effective treatment for adrenal metastasis. Adapting a paravertebral insertion technique in radiofrequency ablation of adrenal tumors, we developed an interstitial brachytherapy for adrenal metastasis achievable on an outpatient basis. Under local anesthesia and under X-ray CT guidance, brachytherapy applicator needles were percutaneously inserted into the target. A treatment plan was created to eradicate the tumor while preserving normal organs including the spinal cord and kidney. We applied this interstitial brachytherapy technique to two patients: one who developed adrenal metastasis as the third recurrence of uterine cervical cancer after reirradiation, and one who developed metachronous multiple metastases from malignant melanoma. The whole procedure was completed in 2.5 hours. There were no procedure-related or radiation-related early/late complications. FDG PET-CT images at two and three months after treatment showed absence of FDG uptake, and no recurrence of the adrenal tumor was observed for over seven months until expiration, and for six months until the present, respectively. This interventional interstitial brachytherapy procedure may be useful as a safe and eradicative treatment for adrenal metastasis.

Congenital Adrenal Hyperplasia

MedlinePlus

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Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation.

PubMed

Thomas, Shery; Thomas, Mervyn G; Andrews, Caroline; Chan, Wai-Man; Proudlock, Frank A; McLean, Rebecca J; Pradeep, Archana; Engle, Elizabeth C; Gottlob, Irene

2014-03-01

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.

Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

PubMed

Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

2015-01-01

In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

Growth, nutritional, and gastrointestinal aspects of focal dermal hypoplasia (Goltz-Gorlin syndrome)

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X-chromosome. In the present study, we characterized the pattern of growth, body composition, and the nutritional and gastrointestinal aspects of children and adults (n'='19) affected with t...

Ultrasonographic adrenal gland findings in healthy semi-captive cheetahs (Acinonyx jubatus).

PubMed

Kirberger, Robert M; Tordiffe, Adrian S W

2016-05-01

Cheetahs in captivity are believed to suffer from stress predisposing them to poor health. To date fecal glucocorticoids have been used as a non-invasive indicator of chronic stress. This study examines, the feasibility of transabdominal adrenal gland ultrasonography in cheetahs and determined normal adrenal measurements that can potentially be used as a more reliable indicator of chronic stress and/or adrenal function. Thirty-three adult cheetahs, aged between 2 and 13 years, accommodated in large off-display camps were examined over 9 days under general anesthesia. The adrenals were readily identified, with the right adrenal being more difficult to find and measure than the left, and were smaller than those expected in similar sized dogs. The left adrenal was shorter and slightly more oval shaped than the right with a length and cranial pole width at a 95% prediction interval of 16.3-22.4 and 4.1-8.7 mm. The same measurements for the right adrenal were 16.8-26.2 and 3.4-10.8 mm, respectively. Corticomedullary ratios were larger for the left adrenal. When corrected for body size, females had significantly longer and greater left adrenal corticomedullary ratios than males. Adrenal measurements did not correlate with left renal length, body size measurements, or enclosure size. Measurements that increased with age included the cortical and total adrenal widths. Adrenal ultrasonography offers potential benefits in assessment of individual cheetah adrenal pathology or the evaluation of stress induced adrenomegally especially in combination with other evaluations such as non-invasive fecal glucocorticoid analyses. Zoo Biol. 35:260-268, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Adrenal Ewing's Sarcoma in an Elderly Man.

PubMed

Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

2018-02-15

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

Adrenal tuberculosis after a pheochromocytoma: a misleading tumoral presentation.

PubMed

Hiéronimus, S; Bernard, J-L; Chevallier, P; Chevallier, A; Chyderiotis, G; Fenichel, P; Landraud, L

2007-06-01

Adrenal gland involvement could account for 6% of active tuberculosis. The diagnosis of this extrapulmonary form of tuberculosis is difficult, especially when presenting as unilateral adrenal tumor. This report describes an unusual case of adrenal tuberculosis presenting as a tumor occurring shortly after surgical removal of an adrenal pheochromocytoma located in the opposite gland, in a 63-year-old woman with a previous history of breast cancer. At initial presentation, the patient suffered from symptomatic paroxysmal hypertension. A pheochromocytoma in the left adrenal was diagnosed and resected. One year later, while physical examination and biological parameters were unremarkable, an enhanced adrenal computed tomography (CT) scan showed a right adrenal mass mimicking the CT features of the resected pheochromocytoma. A peripheral tissular rim delineating a central hypodensity characterized this tumor. Magnetic resonance imaging (MRI) showed the same findings on gadolinium-enhanced T1-weighted slices, while the mass was not seen on T2-weighted images. No tumoral signal loss was observed on out of phase images when using the in phase-out of phase T1-weighted sequence. Because of the tumoral evolution and the uncertainty of the nature of that lesion, the patient underwent a second adrenalectomy. Definitive diagnosis was provided by culture of tissue sample, which resulted in the identification of Mycobacterium tuberculosis. In an era of tuberculosis resurgence, this unusual case underscores the necessity of keeping in mind adrenal tuberculosis as a possible differential diagnosis in adrenal tumors of uncertainty nature. It stresses the importance of culture of biopsy tumor, whenever feasible, to avoid unnecessary operations. In the near future, interferon-gamma assay could be a valuable means to recognize extrapulmonary forms of tuberculosis.

Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Sakai, Kohei; Kimura, Osamu; Furukawa, Taizo; Fumino, Shigehisa; Higuchi, Koji; Wakao, Junko; Kimura, Koseki; Aoi, Shigeyoshi; Masumoto, Kouji; Tajiri, Tatsuro

2014-12-01

Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Pregnant rats were administered with nitrofen (100mg) on gestation day 9.5 (E9.5). BBS (50mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH. Copyright © 2014 Elsevier Inc. All rights reserved.

Incidence and Cause of Hypertension During Adrenal Radiofrequency Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Yamada, Tomomi

Purpose: To evaluate the incidence and cause of hypertension prospectively during adrenal radiofrequency ablation (RFA). Methods: For this study, approved by our institutional review board, written informed consent was obtained from all patients. Patients who received RFA for adrenal tumors (adrenal ablation) and other abdominal tumors (nonadrenal ablation) were included in this prospective study. Blood pressure was monitored during RFA. Serum adrenal hormone levels including epinephrine, norepinephrine, dopamine, and cortisol levels were measured before and during RFA. The respective incidences of procedural hypertension (systolic blood pressure >200 mmHg) of the two patient groups were compared. Factors correlating with procedural systolicmore » blood pressure were evaluated by regression analysis.ResultsNine patients underwent adrenal RFA and another 9 patients liver (n = 5) and renal (n = 4) RFA. Asymptomatic procedural hypertension that returned to the baseline by injecting calcium blocker was found in 7 (38.9%) of 18 patients. The incidence of procedural hypertension was significantly higher in the adrenal ablation group (66.7%, 6/9) than in the nonadrenal ablation group (11.1%, 1/9, P < 0.0498). Procedural systolic blood pressure was significantly correlated with serum epinephrine (R{sup 2} = 0.68, P < 0.0001) and norepinephrine (R{sup 2} = 0.72, P < 0.0001) levels during RFA. The other adrenal hormones did not show correlation with procedural systolic blood pressure. Conclusion: Hypertension occurs frequently during adrenal RFA because of the release of catecholamine.« less

Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1980-01-01

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

Standards of ultrasound imaging of the adrenal glands

PubMed Central

Jakubowski, Wiesław S.; Dobruch-Sobczak, Katarzyna; Kasperlik-Załuska, Anna A.

2015-01-01

Adrenal glands are paired endocrine glands located over the upper renal poles. Adrenal pathologies have various clinical presentations. They can coexist with the hyperfunction of individual cortical zones or the medulla, insufficiency of the adrenal cortex or retained normal hormonal function. The most common adrenal masses are tumors incidentally detected in imaging examinations (ultrasound, tomography, magnetic resonance imaging), referred to as incidentalomas. They include a range of histopathological entities but cortical adenomas without hormonal hyperfunction are the most common. Each abdominal ultrasound scan of a child or adult should include the assessment of the suprarenal areas. If a previously non-reported, incidental solid focal lesion exceeding 1 cm (incidentaloma) is detected in the suprarenal area, computed tomography or magnetic resonance imaging should be conducted to confirm its presence and for differentiation and the tumor functional status should be determined. Ultrasound imaging is also used to monitor adrenal incidentaloma that is not eligible for a surgery. The paper presents recommendations concerning the performance and assessment of ultrasound examinations of the adrenal glands and their pathological lesions. The article includes new ultrasound techniques, such as tissue harmonic imaging, spatial compound imaging, three-dimensional ultrasound, elastography, contrast-enhanced ultrasound and parametric imaging. The guidelines presented above are consistent with the recommendations of the Polish Ultrasound Society. PMID:26807295

Hypoplasia-associated Severe Early Childhood Caries – A Proposed Definition

PubMed Central

Caufield, P.W.; Li, Y.; Bromage, T.G.

2012-01-01

We propose a new classification of severe early childhood caries (S-ECC): hypoplasia-associated severe early childhood caries (HAS-ECC). This form of caries affects mostly young children living at or below poverty, characterized by structurally damaged primary teeth that are particularly vulnerable to dental caries. These predisposing developmental dental defects are mainly permutations of enamel hypoplasia (EHP). Anthropologists and dental researchers consider EHP an indicator for infant and maternal stresses including malnutrition, a variety of illnesses, and adverse birthing conditions. Differentiation of HAS-ECC from other forms of early childhood caries is warranted because of its distinct etiology, clinical presentation, and eventual management. Defining HAS-ECC has important clinical implications: Therapies that control or prevent other types of caries are likely to be less effective with HAS-ECC because the structural integrity of the teeth is compromised prior to their emergence into the oral cavity. By the time these children present to the dentist, the treatment options often become limited to surgical management under general anesthesia. To prevent HAS-ECC, dentists must partner with other health providers to develop interventions that begin with pregnant mothers, with the aim of eliminating or ameliorating the covariates accompanying poverty, including better pre- and post-natal care and nutrition. PMID:22529242

Acute adrenal crisis

MedlinePlus

... condition that occurs when there is not enough cortisol. This is a hormone produced by the adrenal ... parts. The outer portion, called the cortex, produces cortisol. This is an important hormone for controlling blood ...

A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery

PubMed Central

Morimoto, R; Satani, N; Iwakura, Y; Ono, Y; Kudo, M; Nezu, M; Omata, K; Tezuka, Y; Seiji, K; Ota, H; Kawasaki, Y; Ishidoya, S; Nakamura, Y; Arai, Y; Takase, K; Sasano, H; Ito, S; Satoh, F

2016-01-01

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl−1 and aldosterone renin activity ratio of 90.2 (ng dl−1 per ng ml−1 h−1), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl−1 confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production. PMID:26538381

Expression of Iroquois genes is up-regulated during early lung development in the nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Lukošiūtė, Aušra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family. Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls. Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia

PubMed Central

Chock, Valerie Y.; Van Meurs, Krisa P.; Hintz, Susan R.; Ehrenkranz, Richard A.; Lemons, James A.; Kendrick, Douglas E.; Stevenson, David K.

2008-01-01

We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO2 response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO2 of 39±50 mm Hg versus a mean decrease of 11±15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population. PMID:19067285

Principles and management of adrenal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javadpour, N.

1987-01-01

This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imagingmore » techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.« less

Partial Agenesis and Hypoplasia of the Corpus Callosum in Idiopathic Autism

PubMed Central

Wegiel, Jarek; Flory, Michael; Kaczmarski, Wojciech; Brown, W. Ted; Chadman, Kathryn; Wisniewski, Thomas; Nowicki, Krzysztof; Kuchna, Izabela; Ma, Shuang Yong; Wegiel, Jerzy

2017-01-01

Abstract To test the hypothesis that developmental anomalies of the corpus callosum (CC), contribute to the pathogenesis of autism, we characterized the type, topography, and severity of CC pathology corresponding to reduced CC areas that are detected by magnetic resonance imaging in the brains of 11 individuals with autism and 11 controls. In the brains of 3 autistic subjects, partial CC agenesis resulted in complete or partial lack of interhemispheric axonal connections in CC segments III–V. In these cases, a combination of focal agenesis and uniform axonal deficit caused reduction of CC areas by 37%, of axon numbers by 62%, and of the numerical density of axons by 39%. In the CC of 8 autistic subjects without agenesis, there was an 18% deficit of the midsagittal CC area, 48.4% deficit of axon numbers, and 37% reduction of the numerical density of axons. The significantly thinner CC, reduced CC area, and uniform axonal deficit in all autistic subjects were classified as CC hypoplasia. Thus, the byproduct of partial CC agenesis and hypoplasia is reduction of axonal connections between cortical areas known to be involved in behavioral alterations observed in people with autism. PMID:28395085

Purkinje cell heterotopy with cerebellar hypoplasia in two free-living American kestrels (Falco sparverius)

USDA-ARS?s Scientific Manuscript database

Two wild fledgling kestrels exhibited lack of motor coordination, postural reaction deficits, and abnormal propioception. At necropsy, the cerebellum and brainstem were markedly underdeveloped. Microscopically, there was Purkinje cells heterotopy, abnormal circuitry, and hypoplasia with defective fo...

The clinical manifestations, diagnosis, and treatment of adrenal emergencies.

PubMed

Tucci, Veronica; Sokari, Telematé

2014-05-01

Emergency medicine physicians should be able to identify and treat patients whose clinical presentations, including key historical, physical examination, and laboratory findings are consistent with diagnoses of primary, secondary, and tertiary adrenal insufficiency, adrenal crisis, and pheochromocytoma. Failure to make a timely diagnosis leads to increased morbidity and mortality. As great mimickers, adrenal emergencies often present with a constellation of nonspecific signs and symptoms that can lead even the most diligent emergency physician astray. The emergency physician must include adrenal emergencies in the differential diagnosis when encountering such clinical pictures. Copyright © 2014 Elsevier Inc. All rights reserved.

[Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].

PubMed

Rubio-Puchol, O; Garzón-Pastor, S; Salom-Vendrell, C; Hernández-Mijares, A

Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Mortality of Septic Mice Strongly Correlates With Adrenal Gland Inflammation.

PubMed

Jennewein, Carla; Tran, Nguyen; Kanczkowski, Waldemar; Heerdegen, Lars; Kantharajah, Ajith; Dröse, Stefan; Bornstein, Stefan; Scheller, Bertram; Zacharowski, Kai

2016-04-01

Sepsis and septic shock are commonly present in the ICU and accompanied by significant morbidity, mortality, and cost. The frequency of secondary adrenal insufficiency in sepsis remains open to debate and a challenge to identify and treat appropriately. Animal models of sepsis using genetic or surgical initiation of adrenal insufficiency resulted in increased mortality, but the mechanisms are still unclear. The present study investigates the impact of adrenal inflammation in septic mice challenged with cecal ligation and puncture. Prospective experimental study. University laboratory. C57BL/6N wild-type mice. Sepsis, induced by cecal ligation and puncture for 24 and 48 hours. Both septic and control mice were carefully monitored (every 30 min) for up to 48 hours and divided into survivors and nonsurvivors. We observed a significant and massive increase of interleukin-6, interleukin-1β, and tumor necrosis factor-α in adrenal protein extracts of nonsurvivors compared with sham animals and survivors. This pattern was partly reflected in liver and lung but not in plasma samples. Notably, a significant increase in nonsurvivors compared with survivors was only found for lung interleukin-6. In line with these findings, we detected a higher degree of leukocyte infiltration and hemorrhage in the adrenal glands of deceased mice. Evaluation of the hypothalamic-pituitary-adrenal axis response in these animals revealed an increase of adrenocorticotropic hormone, which was only partly reflected in the corticosterone level. Notably, using the adrenocorticotropic hormone stimulation test, we found an impaired adrenocorticotropic hormone response, particularly in nonsurvivors, which significantly correlated with the number of infiltrated leukocytes. Cecal ligation and puncture-induced murine sepsis induces a strong inflammatory response in the adrenal glands, which is accompanied by cell death and hemorrhage. Our data suggest that mortality and adrenal incapacitation are

A review of the anatomy and clinical significance of adrenal veins.

PubMed

Cesmebasi, Alper; Du Plessis, Maira; Iannatuono, Mark; Shah, Sameer; Tubbs, R Shane; Loukas, Marios

2014-11-01

The adrenal veins may present with a multitude of anatomical variants, which surgeons must be aware of when performing adrenalectomies. The adrenal veins originate during the formation of the prerenal inferior vena cava (IVC) and are remnants of the caudal portion of the subcardinal veins, cranial to the subcardinal sinus in the embryo. The many communications between the posterior cardinal, supracardinal, and subcardinal veins of the primordial venous system provide an explanation for the variable anatomy. Most commonly, one central vein drains each adrenal gland. The long left adrenal vein joins the inferior phrenic vein and drains into the left renal vein, while the short right adrenal vein drains immediately into the IVC. Multiple variations exist bilaterally and may pose the risk of surgical complications. Due to the potential for collaterals and accessory adrenal vessels, great caution must be taken during an adrenalectomy. Adrenal venous sampling, the gold standard in diagnosing primary hyperaldosteronism, also requires the clinician to have a thorough knowledge of the adrenal vein anatomy to avoid iatrogenic injury. The adrenal vein acts as an important conduit in portosystemic shunts, thus the nature of the anatomy and hypercoagulable states pose the risk of thrombosis. © 2014 Wiley Periodicals, Inc.

Laser autofluorescent spectroscopy in adrenal tumor surgery

NASA Astrophysics Data System (ADS)

Vetshev, Petr S.; Ippolitov, Leonid I.; Loschenov, Victor B.; Kazaryan, Airazat M.; Minnibaev, Marat T.; Vetshev, Sergei P.

1999-12-01

Determination of a histological type of adrenal lesion at the preoperative or intraoperative stage allows to choose the optimal volume of surgery and in the short time effectively correct the postoperative hormonal therapy. 12 patients with different adrenal tumours (3 - lightcellular adenoma, 3 - mixedcellular adenoma, 1 - darkcellular adenoma, 1 - trabecular adenoma, 1 - malignant lymphoma, 3 - aldosteroma, 1 - pheochromocytoma, including the chance of combination of mixedcellular adenoma and aldosteroma of left adrenal) were operated on. The patients' aged varied from 33 to 62 years. For the first time we made intraoperative laser autofluorescent spectroscopy (IOLAS). The laser ve1ength was 632.8 nm. We defined a autofluorescent intensity. Portable equipment was used. The duration of the procedure did not exceed 2mm. The autofluorescent peak of adrenal tissue was 1.33+/-0.05 relativistic unit (RU) at 685 nm. The autofiurescent peaks of adrenal adenomas were 1 .07 RU, 0.9-1 .15 RU, 1.7-1 .9 RU, 3.4 RU accordingly for trabecular adenoma, lightcellular adenoma, mixedcellular adenoma, darkcellular adenoma Besides greater contribution of longwave component to auflurescence is characteristic for mixecellular adenoma and especially for darkcellular adenoma. The autofiurescent peaks of aldosteroma and pheochromocytoma were accordingly 1.2-1.4 RU and 2.2 RU. Spectral distribution of intensity was like mixedcellular adenoma's one. In the case of malignant lymphoma the autofiurescence peak was 2,3 RU and we also noted displacement of maximum of autoflurescence (-15 nm, from 685 nm to 670 nm).The results of IOLAS application as a adjuvant diagnosticmethod point to promise for intraoperative rapid diagnostics of adrenal tumours.

Characterization of novel StAR (steroidogenic acute regulatory protein) mutations causing non-classic lipoid adrenal hyperplasia.

PubMed

Flück, Christa E; Pandey, Amit V; Dick, Bernhard; Camats, Núria; Fernández-Cancio, Mónica; Clemente, María; Gussinyé, Miquel; Carrascosa, Antonio; Mullis, Primus E; Audi, Laura

2011-01-01

Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH). StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

Characterization of Novel StAR (Steroidogenic Acute Regulatory Protein) Mutations Causing Non-Classic Lipoid Adrenal Hyperplasia

PubMed Central

Flück, Christa E.; Pandey, Amit V.; Dick, Bernhard; Camats, Núria; Fernández-Cancio, Mónica; Clemente, María; Gussinyé, Miquel; Carrascosa, Antonio; Mullis, Primus E.; Audi, Laura

2011-01-01

Context Steroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH). Objective StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. Design To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. Setting Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. Patients Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. Results StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. Conclusions StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed. PMID:21647419

Adrenal venous sampling for stratifying patients for surgery of adrenal nodules detected using dynamic contrast enhanced CT

PubMed Central

Kim, Jin Young; Kim, See Hyung; Lee, Hee Jung; Kim, Young Hwan; Kim, Mi Jeong; Cho, Seung Hyun

2014-01-01

PURPOSE We aimed to assess the value of adrenal venous sampling (AVS) for diagnosing primary aldosteronism (PA) subtypes in patients with a unilateral nodule detected on adrenal computed tomography (CT) and scheduled for adrenalectomy. MATERIALS AND METHODS This retrospective study included 80 consecutive patients with PA undergoing CT and AVS. Different lateralization indices were assessed, and a cutoff established using receiver operating characteristic curve analysis. The value of CT alone versus CT with AVS for differentiating PA subtypes was compared. The adrenalectomy outcome was assessed, and predictors of cure were determined using univariate analysis. RESULTS AVS was successful in 68 patients. A cortisol-corrected aldosterone affected-to-unaffected ratio cutoff of 2.0 and affected-to-inferior vena cava ratio cutoff of 1.4 were the best lateralization indices, with accuracies of 82.5% and 80.4%, respectively. CT and AVS diagnosed 38 patients with aldosterone-producing adenomas, five patients with unilateral adrenal hyperplasia, and 25 patients with bilateral adrenal hyperplasia. Of the 52 patients with a nodule detected on CT, subsequent AVS diagnosed bilateral adrenal hyperplasia in 14 patients (27%). Compared to the results of combining CT with AVS, the accuracy of CT alone for diagnosing aldosterone-producing adenomas was 71.1% (P < 0.001). The cure rate for hypertension after adrenalectomy was 39.2%, with improvement in 53.5% of patients. On univariate analysis, predictors of persistent hypertension were male gender and preoperative systolic blood pressure. CONCLUSION To avoid inappropriate surgery, AVS is necessary for diagnosing unilateral nodules with aldosterone hypersecretion detected by CT. PMID:24047720

Prenatal surgery for congenital diaphragmatic hernia.

PubMed

Au-Yeung, Jeff Ying-Kit; Chan, Kwong-Leung

2003-10-01

Congenital diaphragmatic hernia (CDH) has a mortality rate of up to 77% despite optimal pre- and postnatal care. Fetuses with liver herniation, a low lung-to-head ratio, and an early diagnosis before 24 weeks have a particularly poor prognosis. In utero open repair of these fetuses does not improve patient survival. The PLUG (Plug the Lung Until it Grows) technique was reported to be able to reverse pulmonary hypoplasia in CDH. A foam plug or a titanium clip is used and the trachea can be unplugged using Ex Utero Intrapartum Tracheoplasty (EXIT) at birth. Since hysterotomy causes premature labour, a video-fetoscopic intrauterine technique of tracheal occlusion called Fetendo-PLUG was developed. Compared to those who receive standard postnatal care or fetal tracheal occlusion via open hysterotomy, patients who undergo Fetendo-PLUG are reported to have a higher survival rate of 75% and fewer fetal and maternal complications. A recent refinement is to use a detachable balloon for intratracheal occlusion through a single 5 mm port under real-time ultrasound guidance. Without the need for neck dissection, injury to the recurrent laryngeal nerves and trachea and vocal cord paresis can be minimized. The result of this form of treatment for CDH is promising, but further refinement of fetal instrumentation and development of effective tocolytic drugs are still required.

Adrenal Function Status in Patients with Paracoccidioidomycosis after Prolonged Post-Therapy Follow-Up

PubMed Central

Tobón, Angela M.; Agudelo, Carlos A.; Restrepo, Carlos A.; Villa, Carlos A.; Quiceno, William; Estrada, Santiago; Restrepo, Angela

2010-01-01

This study assessed adrenal function in patients with paracoccididioidomycosis who had been treated to determine a possible connection between high antibody titers and adrenal dysfunction attributable to persistence of the fungus in adrenal gland. Adrenal gland function was studied in 28 previously treated patients, 2 (7.1%) of whom were shown to have adrenal insufficiency and 7 (259%) who showed a below normal response to stimuli by adrenocorticotropic hormone. Paracoccidioides brasiliensis was detected in the adrenal gland from one of the patients with adrenal insufficiency. Although the study failed to demonstrate a significant difference between high antibody titers and low cortisol levels, the proportion of adrenal insufficiency detected and the subnormal response to adrenocorticotropic hormone confirmed that adrenal damage is an important sequela of paracoccidioidomycosis. Studies with a larger number of patients should be conducted to confirm the hypothesis of persistence of P. brasiliensis in adrenal gland after therapy. PMID:20595488

A novel mutation (C1425Y) in the FBN2 gene in a father and son with congenital contractural arachnodactyly.

PubMed

Chen, Ying; Lei, Yun-Ping; Zheng, Hong-Xiang; Wang, Wei; Cheng, Hong-Bo; Zhang, Jing; Wang, Hong-Yan; Jin, Li; Li, Hong

2009-06-01

Congenital contractural arachnodactyly (Beals syndrome) is a rare autosomal dominantly inherited connective tissue disorder characterized by flexion contractures, arachnodactyly, crumpled ears, and mild muscular hypoplasia. Here, a father and son with congenital contractural arachnodactyly features were identified. After sequencing 15 exons (22 to 36) of the FBN2 gene, a novel mutation (C1425Y) was found in exon 33. This de novo mutation presented first in the father and was transmitted to his son, but not in the other 14 unaffected family members and 365 normal people. The C1425Y mutation occurs at the 19th cbEGF domain. Cysteines in this cbEGF domain are rather conserved in species, from human down to ascidian. The cbEGF12-13 in human FBN1 was employed as the template to perform homology modeling of cbEGF18-19 of human FBN2 protein. The mutation has also been evaluated by further prediction tools, for example, SIFT, Blosum62, biochemical Yu's matrice, and UMD-Predictor tool. In all analysis, the mutation is predicted to be pathogenic. Thus, the structure destabilization by C1425Y might be the cause of the disorder.

Characterization of Adrenal Adenoma by Gaussian Model-Based Algorithm.

PubMed

Hsu, Larson D; Wang, Carolyn L; Clark, Toshimasa J

2016-01-01

We confirmed that computed tomography (CT) attenuation values of pixels in an adrenal nodule approximate a Gaussian distribution. Building on this and the previously described histogram analysis method, we created an algorithm that uses mean and standard deviation to estimate the percentage of negative attenuation pixels in an adrenal nodule, thereby allowing differentiation of adenomas and nonadenomas. The institutional review board approved both components of this study in which we developed and then validated our criteria. In the first, we retrospectively assessed CT attenuation values of adrenal nodules for normality using a 2-sample Kolmogorov-Smirnov test. In the second, we evaluated a separate cohort of patients with adrenal nodules using both the conventional 10HU unit mean attenuation method and our Gaussian model-based algorithm. We compared the sensitivities of the 2 methods using McNemar's test. A total of 183 of 185 observations (98.9%) demonstrated a Gaussian distribution in adrenal nodule pixel attenuation values. The sensitivity and specificity of our Gaussian model-based algorithm for identifying adrenal adenoma were 86.1% and 83.3%, respectively. The sensitivity and specificity of the mean attenuation method were 53.2% and 94.4%, respectively. The sensitivities of the 2 methods were significantly different (P value < 0.001). In conclusion, the CT attenuation values within an adrenal nodule follow a Gaussian distribution. Our Gaussian model-based algorithm can characterize adrenal adenomas with higher sensitivity than the conventional mean attenuation method. The use of our algorithm, which does not require additional postprocessing, may increase workflow efficiency and reduce unnecessary workup of benign nodules. Copyright © 2016 Elsevier Inc. All rights reserved.

Inherited neuroaxonal dystrophy in dogs causing lethal, fetal-onset motor system dysfunction and cerebellar hypoplasia

PubMed Central

Fyfe, John C.; Al-Tamimi, Raba' A.; Castellani, Rudy J.; Rosenstein, Diana; Goldowitz, Daniel; Henthorn, Paula S.

2010-01-01

Neuroaxonal dystrophy in brainstem, spinal cord tracts, and spinal nerves accompanied by cerebellar hypoplasia was observed in a colony of laboratory dogs. Fetal akinesia was documented by ultrasonographic examination. At birth, affected puppies exhibited stereotypical positioning of limbs, scoliosis, arthrogryposis, pulmonary hypoplasia, and respiratory failure. Regional hypoplasia in the central nervous system was apparent grossly, most strikingly as underdeveloped cerebellum and spinal cord. Histopathologic abnormalities included swollen axons and spheroids in brainstem and spinal cord tracts; reduced cerebellar foliation, patchy loss of Purkinje cells, multifocal thinning of the external granular cell layer, and loss of neurons in the deep cerebellar nuclei; spheroids and loss of myelinated axons in spinal roots and peripheral nerves; increased myocyte apoptosis in skeletal muscle; and fibrofatty connective tissue proliferation around joints. Breeding studies demonstrated that the canine disorder is a fully penetrant, simple autosomal recessive trait. The disorder demonstrated a type and distribution of lesions homologous to that of human infantile neuroaxonal dystrophy (INAD), most commonly caused by mutations of PLA2G6, but alleles of informative markers flanking the canine PLA2G6 locus did not associate with the canine disorder. Thus, fetal-onset neuroaxonal dystrophy in dogs, a species with well-developed genome mapping resources, provides a unique opportunity for additional disease gene discovery and understanding of this pathology. PMID:20653033

A Unique Way of Learning: Teaching Young Children with Optic Nerve Hypoplasia

ERIC Educational Resources Information Center

Mendiola, Rosalinda; Bahar, Cheryl; Brody, Jill; Slott, Gayle L.

2005-01-01

This booklet was inspired by the need of educators and therapists of preschool students who are blind and visually impaired to share their observations of children with Optic Nerve Hypoplasia (ONH) and the therapies found to be helpful when working with these children. The work done at the Blind Childrens Center is very rewarding, and these…

Defining and predicting 'intrauterine fetal renal failure' in congenital lower urinary tract obstruction.

PubMed

Ruano, Rodrigo; Safdar, Adnan; Au, Jason; Koh, Chester J; Gargollo, Patricio; Shamshirsaz, Alireza A; Espinoza, Jimmy; Cass, Darrell L; Olutoye, Oluyinka O; Olutoye, Olutoyin A; Welty, Stephen; Roth, David R; Belfort, Michael A; Braun, Michael C

2016-04-01

The aim of this study was to identify predictors of 'intrauterine fetal renal failure' in fetuses with severe congenital lower urinary tract obstruction (LUTO). We undertook a retrospective study of 31 consecutive fetuses with a diagnosis of LUTO in a tertiary Fetal Center between April 2013 and April 2015. Predictors of 'intrauterine fetal renal failure' were evaluated in those infants with severe LUTO who had either a primary composite outcome measure of neonatal death in the first 24 h of life due to severe pulmonary hypoplasia or a need for renal replacement therapy within 7 days of life. The following variables were analyzed: fetal bladder re-expansion 48 h after vesicocentesis, fetal renal ultrasound characteristics, fetal urinary indices, and amniotic fluid volume. Of the 31 fetuses included in the study, eight met the criteria for 'intrauterine fetal renal failure'. All of the latter had composite poor postnatal outcomes based on death within 24 h of life (n = 6) or need for dialysis within 1 week of life (n = 2). The percentage of fetal bladder refilling after vesicocentesis at time of initial evaluation was the only predictor of 'intrauterine fetal renal failure' (cut-off <27 %, area under the time-concentration curve 0.86, 95 % confidence interval 0.68-0.99; p = 0.009). We propose the concept of 'intrauterine fetal renal failure' in fetuses with the most severe forms of LUTO. Fetal bladder refilling can be used to reliably predict 'intrauterine fetal renal failure', which is associated with severe pulmonary hypoplasia or the need for dialysis within a few days of life.

Case report of a bilateral adrenal myelolipoma associated with Cushing disease.

PubMed

Park, Se Yoon; Kwak, Mi Kyung; Kim, Hye Jeong; Park, Hyeong Kyu; Suh, Kyo-Il; Yoo, Myung Hi; Jin, So Young; Yun, Sumi; Byun, Dong Won

2017-12-01

Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Adrenal incidentaloma caused by extramedullary haematopoiesis: conservative management is optimal.

PubMed

Sekar, Suganya; Burad, Deepak; Abraham, Aby; Paul, Mazhuvanchary Jacob

2015-09-21

We present a thalassaemic patient with extramedullary haematopoiesis in the adrenal gland, which is one of the rare sites of involvement. A 29-year-old man presented with a history of anaemia since childhood which required blood transfusion recently. On examination, he had pallor, icterus and splenomegaly with no other palpable abdominal mass. He was diagnosed to have β-thalassaemia. Ultrasonography of the abdomen showed an incidental right adrenal mass with splenomegaly; CT revealed a large right adrenal mass with heterogeneous density. Adrenal adenoma, carcinoma and extramedullary haematopoiesis were considered in the differential diagnosis. After excluding a functioning tumour, the diagnosis was confirmed by ultrasound-guided biopsy. Since the patient was asymptomatic, the adrenal lesion was managed conservatively. 2015 BMJ Publishing Group Ltd.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

PubMed

Akturk, Halis Kaan; Chindris, Ana Maria; Hines, Jolaine M; Singh, Ravinder J; Bernet, Victor J

2018-03-01

To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Effect of Space Flight on Adrenal Medullary Function

NASA Technical Reports Server (NTRS)

Lelkes, Peter I.

1999-01-01

We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

Angiotensin II receptors in cortical and medullary adrenal tumors.

PubMed

Opocher, G; Rocco, S; Cimolato, M; Vianello, B; Arnaldi, G; Mantero, F

1997-03-01

Several pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing's adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 +/- 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 +/- 8.4 fmol/mg). In Cush, the receptor density (27.6 +/- 8.2 fmol/mg; P < 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed. In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.

Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids.

PubMed

Holme, J; Tomlinson, J W; Stockley, R A; Stewart, P M; Barlow, N; Sullivan, A L

2008-10-01

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

Thyroid and adrenal relationships

PubMed Central

Parsons, Victor; Ramsay, Ian

1968-01-01

A brief review of the actions of adrenal medullary and thyroid hormones is presented and the ways in which they interact are examined. It is concluded that thyroid hormone produces the necessary intracellular environment without which the steady state and emergency actions of cathecholamines would be vitiated. In hyperthyroidism the increased concentration of thyroid hormones results in a lowering of the threshold for catecholamine action. For this reason it is possible to alleviate many of the symptoms of thyrotoxicosis by means of drugs which block β-adrenergic receptors. Attention is also drawn to the simultaneous occurrence of thyroid and adrenal disease, in the hope that this will encourage the search for further links in this field of endocrinology. PMID:5655216

STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.

PubMed

Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina

2018-01-01

Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.

Comparison of cortisol exposures and pharmacodynamic adrenal steroid responses to hydrocortisone suspension vs. commercial tablets.

PubMed

Sarafoglou, Kyriakie; Gonzalez-Bolanos, Maria T; Zimmerman, Cheryl L; Boonstra, Timothy; Yaw Addo, O; Brundage, Richard

2015-04-01

The Endocrine Society Clinical Practice Guidelines on congenital adrenal hyperplasia (CAH) recommend against using hydrocortisone suspension based on a study that examined a commercial suspension. Our objective was to examine the absorption of an extemporaneously prepared hydrocortisone suspension and compare it to tablets. Secondary objectives were to evaluate the 17-hydroxyprogesterone and androstenedione adrenal steroid responses. Using a parallel design, 34 children diagnosed with CAH received either suspension (n = 9; median age 1.8 years) or tablets (n = 25; median age 7.5 years). Patients were given their usual morning hydrocortisone formulation and dose; 12 serial blood samples were obtained and the area under the curve (AUC) was calculated. The mg/m(2) dose-normalized cortisol AUCs were no different in the suspension and tablet groups (P = ·06), nor was there a significant difference in the C(max) or T(max) (P = .08 and P = .41, respectively). Although there were no differences in the 17-hydroxyprogesterone change-from-baseline AUCs, baseline concentrations, or the nadir concentrations when comparing suspension and tablet formulations, the androstenedione values were significantly lower as expected in the younger aged suspension group. Our results offer compelling evidence that an extemporaneously prepared hydrocortisone suspension provides comparable cortisol exposures to commercially available tablet formulations in children and can be used to safely and effectively treat CAH. © 2014, The American College of Clinical Pharmacology.

Adrenal trauma: Elvis Presley Memorial Trauma Center experience.

PubMed

Mehrazin, Reza; Derweesh, Ithaar H; Kincade, Matthew C; Thomas, Adam C; Gold, Robert; Wake, Robert W

2007-11-01

Adrenal gland injury is a potentially devastating event if unrecognized in the treatment course of a trauma patient. We reviewed our single-center experience and outcomes in patients with adrenal gland trauma. We performed a retrospective review of all patients presenting with trauma to the Regional Medical Center at Memphis who had adrenal gland injuries from January 1991 through March 2006. Each chart was reviewed with attention to the demographics, associated injuries, complications, and outcomes. Patients were stratified into two subgroups according to age (35 years or younger and older than 35 years) to allow for an age-based comparison between the two groups. Of 58,000 patients presenting with trauma, 130 (0.22%) were identified with adrenal injuries, of which 8 (6.2%) were isolated and 122 (93.8%) were not. Of these 130 patients, 125 (96.2%) had their injury diagnosed by computed tomography and 5 (3.8%) had their injury diagnosed during exploratory laparotomy. Right-sided injuries predominated (78.5%), with six (4.6%) bilateral. Four patients (3.1%) underwent adrenalectomy. Seven patients (5.4%) with adrenal injuries died. One patient (0.77%) required chronic steroid therapy. Patients older than 35 years were more likely to have complications such as deep venous thrombosis, pneumonia, and urinary tract infections. Patient age of 35 years or younger was associated with a significantly increased incidence of liver lacerations. Adrenal gland injury is uncommon, although mostly associated with greater injury severity. Although adding to morbidity, most are self-limited and do not require intervention.

Adrenal collision tumor (parachordoma and ganglioneuroma): A case report.

PubMed

Lai, Yulin; Zhou, Liang; Hu, Jia; Li, Wenhua; Cui, Lin; Lai, Yongqing; Ni, Liangchao

2018-06-01

Adrenal collision tumors (ACTs) are distinct tumors that occur simultaneously in the same adrenal gland and are very rare. We herein report the case of a 56-year-old woman who was admitted to the hospital for medical imaging. The findings of the physical and laboratory examinations, including endocrine function, were unremarkable. Contrast-enhanced computed tomography of the abdomen revealed a 28×20×33-mm mass in the left adrenal medial limb, for which a laparoscopic surgery was performed. Postoperative pathological examination revealed two distinct tumors, namely a parachordoma and a ganglioneuroma. To the best of our knowledge, and following a thorough literature search, this is the first report of coexisting parachordoma and ganglioneuroma in the same adrenal gland.

Exploring the relationship between hypoplasia and odontometric asymmetry in Isola Sacra, an imperial Roman necropolis.

PubMed

Hoover, Kara C; Corruccini, Robert S; Bondioli, Luca; Macchiarelli, Roberto

2005-01-01

Anthropological studies reporting odontometric asymmetry values or dental enamel hypoplasia frequencies use these markers as a record of physiological perturbations occurring during dental development. While both markers indirectly suggest the amount of relative stress a population might have experienced, a relationship between the two has been explored only recently in the literature. In this study, we address the possibility of such a relationship in two ways. First, Kendall's tau B correlations test the degree of relationship on the level of the individual between hypoplasia presence/absence (P/A) and severity of hypoplasia appearance (PS) data for the anterior dentition and directional (DA) and fluctuating asymmetry (FA) data for concurrently developing molars pairs. Second, an F-test explores between-group (ranked hypoplastic individuals and non-hypoplastic individuals) variance about the mean, expecting the hypoplastic individuals to be more variable. The sample consists of 72 individuals from the Isola Sacra necropolis, which is associated with Portus, the port city of ancient Rome. Results indicated only a very weak predictive relationship between some variables and few significant differences in variation. However, variance follows trends in published literature. Possible explanations for the lack of interaction on the level of the individual include both etiological and genetic susceptibility factors that are significant in and of themselves as they suggest a more complex reading of the hard tissue evidence for stress in archaeological populations. Copyright 2005 Wiley-Liss, Inc

Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Alvarez, Luis A J; Corcionivoschi, Nicolae; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050±0.01 vs. 0.3125±0.01; P<.0001) and with CDH (0.1671±0.01 vs. 0.3125±0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. © 2013.

Slide tracheoplasty outcomes in children with congenital pulmonary malformations.

PubMed

DeMarcantonio, Michael A; Hart, Catherine K; Yang, Christina J; Tabangin, Meredith; Rutter, Michael J; Bryant, Roosevelt; Manning, Peter B; de Alarcón, Alessandro

2017-06-01

Evaluate and compare surgical outcomes of slide tracheoplasty for the treatment of congenital tracheal stenosis in children with and without pulmonary malformations. Retrospective chart review at a tertiary care pediatric medical center. We identified patients with tracheal stenosis who underwent slide tracheoplasty from 2001 to 2014, and a subset of these patients who were diagnosed with congenital pulmonary malformations. Hospital course and preoperative and postoperative complications were recorded. One hundred thirty patients (18 with pulmonary malformations, 112 with normal pulmonary anatomy) were included. Pulmonary malformations included unilateral pulmonary agenesis (61%) and hypoplasia (39%). Children with pulmonary malformations had a greater median age compared to their normal lung anatomy counterparts. Preoperatively, patients with pulmonary malformations more frequently required preoperative mechanical ventilation (55.6% vs. 21.3%, P = .007), extracorporeal membrane oxygenation (ECMO) (11% vs. 0.9%, P = .05), and tracheostomy (22.2% vs. 3.6%, P = .01). Postoperatively, patients with pulmonary malformations more frequently required mechanical ventilation >48 hours (78% vs. 37%, P =.005) and ECMO use (11% vs. 0.9%, P = .05). Pulmonary malformation patients and children with normal anatomy did not differ in terms of postoperative tracheostomy (16.7% vs. 4.4%, P > .05), dehiscence (6% vs. 0%, P > .05%), restenosis (11% vs. 6%, P > .05) or postoperative figure 8 deformity (6% vs. 3%, P > .05). Mortality, however, was significantly increased (22.2% vs. 3.6%, P = .01) in children with pulmonary malformations. Although slide tracheoplasty can be successfully performed in patients with abnormal pulmonary anatomy, surgeons and families should anticipate a more difficult postoperative course, with possible associated prolonged mechanical ventilation, ECMO use, and higher mortality than in children with tracheal stenosis alone. 4. Laryngoscope, 127:1283-1287, 2017

The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis.

PubMed

Ambroziak, Urszula; Kępczyńska-Nyk, Anna; Kuryłowicz, Alina; Małunowicz, Ewa Maria; Wójcicka, Anna; Miśkiewicz, Piotr; Macech, Magdalena

2016-01-01

As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing. © 2015 John Wiley & Sons Ltd.

Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities.

PubMed

Gill, W B; Schumacher, G F; Bibbo, M; Straus, F H; Schoenberg, H W

1979-07-01

Epididymal cysts and/or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero, compared to 7.8 per cent of 307 placebo-exposed controls. Analyses of the spermatozoa have revealed severe pathological changes (Eliasson score greater than 10) in 134 diethylstilbestrol-exposed men (18 per cent) and 87 placebo-exposed men (8 per cent). Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism. Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent. Although none of our Diekmann's lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid. A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism.

Imaging of adrenal masses with emphasis on adrenocortical tumors.

PubMed

Sundin, Anders

2012-01-01

Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings ("incidentalomas"). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [(18)F]fluoro-deoxy-glucose ((18)FDG), is able to differentiate benign from malignant adrenal tumors in many patients. (11)C-metomidate ((11)C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

Successful Adrenal Venous Sampling by Non-experts with Reference to CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morita, Satoru, E-mail: i@imodey.com; Yamazaki, Hiroshi; Sonoyama, Yasuyuki

PurposeTo establish technical success rates and safety of adrenal venous sampling (AVS) performed by non-experts with reference to CT images.Materials and Methods104 AVS procedures with adrenocorticotropic hormone stimulation were performed for patients with suspected primary aldosteronism. One of three radiology residents with 2nd, 5th, and 5th grade experience undertook the procedure under the guidance of an experienced, board-certified interventional radiologist with reference to contrast-enhanced CT images obtained in 102 cases. Successful catheterization of the adrenal veins was assessed using three criteria: an adrenal venous cortisol concentration of more than 200 μg/dL (criterion A); an adrenal vein/inferior vena cava cortisol ratio ofmore » more than 5:1 (criterion B); and an adrenal vein/inferior vena cava cortisol ratio of more than 10:1 (criterion C).ResultsThe operators were aware of the anatomy of the left adrenal veins in 102 cases (98 %) and of the right adrenal veins in 99 cases (95 %) prior to the procedure. CT identified the correct position of the right adrenal vein orifice in 82 of 99 cases (83 %). The overall technical success rates for AVS from the right adrenal vein according to criteria A, B, and C, were 96, 96, and 94 %, respectively. Those for the left adrenal vein were 97, 98, and 94 %, respectively. No significant differences in success rates were observed between the operators (p = 0.922–0.984). No major complications, including adrenal vein rupture, were observed.ConclusionsWhen CT images are used to guide AVS, the procedure can be performed successfully and safely even by non-experts.« less

Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study.

PubMed

Hahner, Stefanie; Spinnler, Christina; Fassnacht, Martin; Burger-Stritt, Stephanie; Lang, Katharina; Milovanovic, Danijela; Beuschlein, Felix; Willenberg, Holger S; Quinkler, Marcus; Allolio, Bruno

2015-02-01

Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI), which according to retrospective data represents a significant clinical complication. Here we aimed to prospectively assess incidence of AC and mortality associated with AC in patients with chronic AI. A total of 423 patients with AI (primary AI, n = 221; secondary AI, n = 202) were prospectively followed up for 2 years. Baseline assessment included a general questionnaire and detailed written instructions on glucocorticoid dose adaptation during stress. Patients received follow-up questionnaires every 6 months and were contacted by phone in case of reported adrenal crisis. A total of 423 data sets were available for baseline analysis, and 364 patients (86%) completed the whole study. Sixy-four AC in 767.5 patient-years were documented (8.3 crises per 100 patient-years). Precipitating causes were mainly gastrointestinal infection, fever, and emotional stress (20%, respectively) but also other stressful events (eg, major pain, surgery, strenuous physical activity, heat, pregnancy) or unexplained sudden onset of AC (7%) were documented. Patients with a previous AC were at higher risk of crisis (odds ratio 2.85, 95% confidence interval 1.5-5.5, P < .01). However, no further risk factors could be identified. Ten patients died during follow-up; in four cases death was associated with AC (0.5 AC related deaths per 100 patient-years). Even in educated patients with chronic adrenal insufficiency, AC occurs in a substantial proportion of cases. Furthermore, we identified AC-associated mortality in approximately 6% of AC. Our findings further emphasize the need for improved management of AC in patients with chronic AI.

Adrenal maturation, nutritional status, and mucosal immunity in Bolivian youth.

PubMed

Hodges-Simeon, Carolyn R; Prall, Sean P; Blackwell, Aaron D; Gurven, Michael; Gaulin, Steven J C

2017-09-10

Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosterone-sulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development. © 2017 Wiley Periodicals, Inc.

Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency.

PubMed

Hershkovitz, Eli; Arafat, Maram; Loewenthal, Neta; Haim, Alon; Parvari, Ruti

2015-09-01

The nicotinamide nucleotide transhydrogenase (NNT) enzyme is the main generator of nicotinamide adenine dinucleotide phosphate-oxidase in the mitochondrion. Mutations of the NNT gene have been recently implicated in familial glucocorticoid deficiency. We describe the long-term clinical course of a NNT-deficient 20-year-old patient with combined adrenal failure who had developed a testicular adrenal rest tumor and precocious puberty. The patient's medical records were reviewed. Whole-exome sequencing was performed on DNA obtained from the patient and family members. The patient experienced Addisonian crisis at 10 months of age. Enlarged testicular volume and precocious puberty, accompanied by increased testosterone levels, were noted at 6 years. Testicular biopsy revealed a adrenal rest tumor, which regressed after intensification of glucocorticoid treatment. Genetic studies disclosed a c.1163A>C, p.Tyr388Ser substitution on the NNT gene. This mutation is predicted to be damaging to NNT function. We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.

Robotic Radiosurgery for Adrenal Gland Metastases

PubMed Central

Heidorn, Sarah-Charlotta; Kremer, Nikolaus; Muacevic, Alexander; Fürweger, Christoph

2017-01-01

Introduction The purpose of this study was to investigate the safety and efficacy of CyberKnife (CK) robotic radiosurgery for treatment of adrenal metastases. Methods We performed a retrospective analysis of 23 patients with adrenal metastases who had been treated with CK between October 2006 and December 2015. Fifteen patients received chemotherapy prior to radiosurgery, all patients underwent computer tomography (CT) fluoroscopically guided percutaneous placement of one to three gold fiducials into the adrenal gland. Nineteen patients were selected for single-fraction radiosurgery with a median dose of 22 Gy, four patients were treated in three fractions with a median dose of 13.5 Gy. Results Median follow-up time was 23.6 months. Four patients (17%) experienced local relapse during the evaluation period with a mean time of 19 months to tumor progression. The actuarial local tumor control rate was 95% after one year and 81% after two years. Three of the four patients with local recurrence were retreated with CK radiosurgery. Dynamic tumor tracking enabled accurate treatment with correlation errors less than 2 mm, despite extensive respiration-induced target motion up to 22 mm. Apart from nausea directly after treatment in five patients, we observed no early or late treatment-related side effects. Conclusions Single fraction robotic radiosurgery for adrenal gland metastases is a safe and effective treatment option for patients who are not eligible for surgical resection. PMID:28451479

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis)

PubMed Central

Doherty, D; Parisi, M A; Finn, L S; Gunay-Aygun, M; Al-Mateen, M; Bates, D; Clericuzio, C; Demir, H; Dorschner, M; van Essen, A J; Gahl, W A; Gentile, M; Gorden, N T; Hikida, A; Knutzen, D; Özyurek, H; Phelps, I; Rosenthal, P; Verloes, A; Weigand, H; Chance, P F; Dobyns, W B; Glass, I A

2011-01-01

Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. PMID:19574260

Neglected issues concerning teaching human adrenal steroidogenesis in popular biochemistry textbooks.

PubMed

Han, Zhiyong; Elliott, Mark S

2017-11-01

In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand health consequences caused by deficiencies of enzymes in the adrenal steroidogenic pathways. However, popular biochemistry textbooks contain insufficient information and may sometimes give students a misimpression about certain aspects of human adrenal steroidogenesis. This article highlights two neglected issues in teaching human adrenal steroidogenesis in popular biochemistry textbooks. The purpose of this article is to draw attention to these issues. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):469-474, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

A Novel Method of Adrenal Venous Sampling via an Antecubital Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xiongjing, E-mail: jxj103@hotmail.com; Dong, Hui; Peng, Meng

PurposeCurrently, almost all adrenal venous sampling (AVS) procedures are performed by femoral vein access. The purpose of this study was to establish the technique of AVS via an antecubital approach and evaluate its safety and feasibility.Materials and MethodsFrom January 2012 to June 2015, 194 consecutive patients diagnosed as primary aldosteronism underwent AVS via an antecubital approach without ACTH simulation. Catheters used for bilateral adrenal cannulations were recorded. The success rate of bilateral adrenal sampling, operation time, fluoroscopy time, dosage of contrast, and incidence of complications were calculated.ResultsA 5F MPA1 catheter was first used to attempt right adrenal cannulation in all patients.more » Cannulation of the right adrenal vein was successfully performed in 164 (84.5%) patients. The 5F JR5, Cobra2, and TIG catheters were the ultimate catheters for right adrenal cannulation in 16 (8.2%), 5 (2.6%), and 9 (4.6%) patients, respectively. For left adrenal cannulation, JR5 and Cobra2 catheters were used in 19 (9.8%) and 10 (5.2%) patients, respectively, while only TIG catheters were used in the remaining 165 (85.1%) patients. The rate of successful adrenal sampling on the right, left, and bilateral sides was 91.8%, 93.3%, and 87.6%, respectively. The mean time of operation was (16.3 ± 4.3) minutes, mean fluoroscopy time was (4.7 ± 1.3) minutes, and the mean use of contrast was (14.3 ± 4.7) ml. The incidence of adrenal hematoma was 1.0%.ConclusionsThis study showed that AVS via an antecubital approach was safe and feasible, with a high rate of successful sampling.« less

Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia.

PubMed

Besnard, Marianne; Eyrolle-Guignot, Dominique; Guillemette-Artur, Prisca; Lastère, Stéphane; Bost-Bezeaud, Frédérique; Marcelis, Ludivine; Abadie, Véronique; Garel, Catherine; Moutard, Marie-Laure; Jouannic, Jean-Marie; Rozenberg, Flore; Leparc-Goffart, Isabelle; Mallet, Henri-Pierre

2016-01-01

We detected an unusual increase in congenital cerebral malformations and dysfunction in fetuses and newborns in French Polynesia, following an epidemic of Zika virus (ZIKV), from October 2013 to March 2014. A retrospective review identified 19 cases, including eight with major brain lesions and severe microcephaly, six with severe cerebral lesions without microcephaly and five with brainstem dysfunction without visible malformations. Imaging revealed profound neurological lesions (septal and callosal disruption, ventriculomegaly, abnormal neuronal migration, cerebellar hypoplasia, occipital pseudocysts, brain calcifications). Amniotic fluid was drawn from seven cases at gestation weeks 20 to 29. ZIKV RNA was detected by RT-PCR and infectious ZIKV isolates were obtained in four of five microcephalic, but not in two non-microcephalic cases with severe brain lesions. Medical termination of pregnancy was performed in eleven cases; two cases with brainstem dysfunction died in the first months of life; six cases are alive, with severe neurological impairment. The results show that four of seven tested fetuses with major neurological injuries were infected with ZIKV in utero. For other non-microcephalic, congenital abnormalities we were not able to prove or exclude ZIKV infection retrospectively. The unusual occurrence of brain malformations or dysfunction without microcephaly following a ZIKV outbreak needs further studies.

Liver segment IV hypoplasia as a risk factor for bile duct injury.

PubMed

Mercado, Miguel Angel; Franssen, Bernardo; Arriola, Juan Carlos; Garcia-Badiola, Artemio; Arámburo, Rigoberto; Elnecavé, Alejandro; Cortés-González, Rubén

2011-09-01

Bile duct injury remains constant in the era of laparoscopic cholecystectomy and misidentification of structures remains one of the most common causes of such injuries. Abnormalities in liver segment IV, which is fully visible during laparoscopic cholecystectomy, may contribute to misidentification as proposed herein. We describe the case of a 36-year-old female who had a bile duct injury during a laparoscopic cholecystectomy where the surgeon noticed an unusually small distance between the gallbladder and the round ligament. We define hypoplasia of liver segment IV as well as describe the variation of the biliary anatomy in the case. We also intend to fit it in a broader spectrum of developmental anomalies that have both hyopoplasia of some portion of the liver and variations in gallbladder and bile duct anatomy that may contribute to bile duct injury. To our knowledge, hypoplasia of liver segment IV has not been suggested in the literature as a risk factor for bile duct injury except in the extreme case of a left-sided gallbladder. Surgeons should be vigilant during laparoscopic cholecystectomy when they become aware of an unusually small distance between the gallbladder bed and the round ligament prior to beginning their dissection, variations in the common bile duct and cystic duct should be expected.

A previously undescribed autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome with fronto-nasal dysostosis, cleft lip/palate, limb hypoplasia, and postaxial poly-syndactyly: acro-fronto-facio-nasal dysostosis syndrome.

PubMed

Richieri-Costa, A; Colletto, G M; Gollop, T R; Masiero, D

1985-04-01

We describe two sibs born to a consanguineous couple. Among other clinical findings both have mental retardation, short stature, facial and skeletal abnormalities characterized by hypertelorism, broad notched nasal tip, cleft lip/palate, campto-brachy-poly-syndactyly, fibular hypoplasia, and marked anomalies of foot structures. Facial signs of the reported patients resemble those present in the fronto-nasal "dysplasia" syndrome; however, the whole clinical picture in the present patients suggests a true MCA/MR syndrome, most likely inherited as an autosomal recessive trait. Clinical and genetic aspects of the present family are discussed.

The possible correlation between dental enamel hypoplasia and a historic natural disaster in the Roman population of Herculaneum (79 AD - central Italy).

PubMed

D'Anastasio, R; Cesana, D T; Viciano, J; Sciubba, M; Nibaruta, P; Capasso, L

2013-01-01

Dental enamel hypoplasia is usually read as a sign of a systematic growth disturbance during childhood. Following the analysis of human teeth from Herculaneum (79 AD, Central Italy), the authors focused on linear enamel hypoplasia (LEH) manifestations in order to delineate a possible correlation between their frequency and distribution and the earthquake that occurred in 62 AD, which is well documented in historical literature. The human remains from Herculaneum were buried at the same time as the Vesuvius eruption and represent an exceptional snapshot of life in the Roman Imperial Age. The Goodman and Rose method (1990) was used for attributing an "age at the moment of stress" for every skeleton in order to delineate the epidemiology of the enamel hypoplasia. When LEH frequency was analysed by age, two different age groups showed relevant patterns of hypoplasia: the first peak was evident in individuals between 14 and 20 years who were younger than 6 years at the time of the 62 AD earthquake, and a second peak was noted in adults of 30 +/- 5 years old, which suggests the presence of another stressful event that occurred 10 years before the earthquake, around 53 AD. The bimodal distribution of enamel hypoplasia could be the consequence of two different historical periods characterized by instability in the food supply, unhygienic conditions, and epidemic episodes; our data suggest that the first peak could be related to a decline in health status as an effect of the 62 AD earthquake. The relationship between recent natural disasters and variations in health status in modern populations is well documented in scientific literature. Our research represents the first attempt to correlate the status of health to an earthquake of known date in an archaeological population.

Anterior maxillary segmental distraction in the treatment of severe maxillary hypoplasia secondary to cleft lip and palate

PubMed Central

Li, Hongliang; Dai, Jiewen; Si, Jiawen; Zhang, Jianfei; Wang, Minjiao; Shen, Steve Guofang; Yu, Hongbo

2015-01-01

Anterior maxillary segmental distraction (AMSD) is an effective surgical procedure in the treatment of maxillary hypoplasia secondary to cleft lip and palate. Its unique advantage of preserving velopharyngeal function makes this procedure widely applied. In this study, the application of AMSD was described and its long-term stability was explored. Eight patients with severe maxillary hypoplasia secondary to CLP were included in this study. They were treated with AMSD using rigid external distraction (RED) device. Cephalometric analysis was performed twice at three time points for evaluation: before surgery (T1), after distraction (T2), and 2 years after treatment (T3). One-way analysis of variance was used to assess the differences statistically. All the distractions completed smoothly, and maxilla was distracted efficiently. The value of SNA, NA-FH, Ptm-A, U1-PP, overjet and PP (ANS-PNS) increased significantly after the AMSD procedure (P < 0.05), with the mean overjet increased by 14.28 mm. However, comparison of cephalometric analysis between T2 and T3 showed no significant difference (P > 0.05). Changes of palatopharyngeal depth and soft palatal length were insignificant. AMSD with RED device provided an effective way to correct maxillary hypoplasia secondary to CLP, extended the palatal and arch length, avoided damage on velopharyngeal closure function and reduced the relapse rate. It is a promising and valuable technique in this potentially complicated procedure. PMID:26629107

Anterior maxillary segmental distraction in the treatment of severe maxillary hypoplasia secondary to cleft lip and palate.

PubMed

Li, Hongliang; Dai, Jiewen; Si, Jiawen; Zhang, Jianfei; Wang, Minjiao; Shen, Steve Guofang; Yu, Hongbo

2015-01-01

Anterior maxillary segmental distraction (AMSD) is an effective surgical procedure in the treatment of maxillary hypoplasia secondary to cleft lip and palate. Its unique advantage of preserving velopharyngeal function makes this procedure widely applied. In this study, the application of AMSD was described and its long-term stability was explored. Eight patients with severe maxillary hypoplasia secondary to CLP were included in this study. They were treated with AMSD using rigid external distraction (RED) device. Cephalometric analysis was performed twice at three time points for evaluation: before surgery (T1), after distraction (T2), and 2 years after treatment (T3). One-way analysis of variance was used to assess the differences statistically. All the distractions completed smoothly, and maxilla was distracted efficiently. The value of SNA, NA-FH, Ptm-A, U1-PP, overjet and PP (ANS-PNS) increased significantly after the AMSD procedure (P < 0.05), with the mean overjet increased by 14.28 mm. However, comparison of cephalometric analysis between T2 and T3 showed no significant difference (P > 0.05). Changes of palatopharyngeal depth and soft palatal length were insignificant. AMSD with RED device provided an effective way to correct maxillary hypoplasia secondary to CLP, extended the palatal and arch length, avoided damage on velopharyngeal closure function and reduced the relapse rate. It is a promising and valuable technique in this potentially complicated procedure.

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism.

PubMed

Babaya, Naru; Makutani, Yukako; Noso, Shinsuke; Hiromine, Yoshihisa; Ito, Hiroyuki; Taketomo, Yasunori; Ueda, Kazuki; Ushijima, Hokuto; Komoike, Yoshifumi; Yamazaki, Yuto; Sasano, Hironobu; Kawabata, Yumiko; Ikegami, Hiroshi

2017-12-06

We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

Renal and adrenal tumours in children

PubMed Central

2007-01-01

The differential diagnosis of renal and supra-renal masses firstly depends on the age of the child. Neuroblastoma (NBL) may be seen antenatally or in the newborn period; this tumour has a good prognosis unlike NBL seen in older children (particularly NBL in those aged 2–4 years). Benign renal masses predominate in early infancy but beyond the first year of life Wilms' tumour is the most common renal malignancy, until adolescence when renal cell carcinoma has similar or increased frequency as children get older. Adrenal adenomas and carcinomas also occur in childhood; these tumours are indistinguishable on imaging but criteria for the diagnosis of adrenal carcinoma include size larger than 5 cm, a tendency to invade the inferior vena cava and to metastasise. The most topical dilemmas in the radiological assessment of renal and adrenal tumours are presented. Topics covered include a proposed revision to the staging of NBL, the problems inherent in distinguishing nephrogenic rests from Wilms' tumour and the current recently altered approach regarding small lung nodules in children with Wilms' tumour. PMID:17339140

Adrenal crisis in treated Addison's disease: a predictable but under-managed event.

PubMed

White, Katherine; Arlt, Wiebke

2010-01-01

Adrenal crisis is a life-threatening event that occurs regularly in Addison's patients receiving standard replacement therapy. Patient reports suggest that it is an underestimated and under-managed event. To assess the frequency of adrenal crisis in diagnosed patients and to understand the factors contributing to the risks of adrenal crisis. We conducted a postal survey of Addison's patients in four countries, UK (n=485), Canada (n=148), Australia (n=123) and New Zealand (n=85) in 2003, asking about patients' experiences of adrenal crisis and their demographic characteristics. In 2006, a shorter follow-up survey was conducted in the UK (n=261). The frequency and causes of adrenal crisis were compared across both surveys. Demographic data from the 2003 survey were analysed to establish the main variables associated with an elevated risk of crisis. Around 8% of diagnosed cases can be expected to need hospital treatment for adrenal crisis annually. Exposure to gastric infection is the single most important factor predicting the likelihood of adrenal crisis. Concomitant diabetes and/or asthma increase the frequency of adrenal crises reported by patients. The endocrinologist has a responsibility to ensure that Addison's patients have adequate access to life-saving emergency injection materials and repeated, practical training sessions in how to use them, while the general practitioner plays a vital role as in arranging prompt emergency admissions.

Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.

PubMed

Grayson, Jessica; Tipirneni, Kiranya E; Skinner, Daniel F; Fort, Matthew; Cho, Do-Yeon; Zhang, Shaoyan; Prince, Andrew C; Lim, Dong-Jin; Mackey, Calvin; Woodworth, Bradford A

2017-09-01

Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model. Sinus development was evaluated in CFTR -/- and CFTR +/+ rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified. At birth, sinus volumes were decreased in CFTR -/- rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm 3 vs 14.5 ± 0.73 mm 3 ; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR +/+ animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection. CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection. © 2017 ARS-AAOA, LLC.

Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy–Walker malformation

PubMed Central

Patnaik, Ashis; Mishra, Sudhansu Sekhar; Das, Srikanta

2017-01-01

Pseudo-TORCH syndrome or congenital infection-like syndrome is a group of conditions which resemble congenital infections such as those caused by toxoplasmosis, rubella, cytomegalovirus (CMV), herpes (TORCH) group of organisms, clinico-radiologically, but serological tests are negative for the organisms. One of the variety shows features such as microcephaly, extensive intracranial calcification showing gross resemblance to congenital CMV infection, making its other name as microcephaly intracranial calcification syndrome (MICS). Dandy–Walker malformation (DWM), in addition to posterior fossa large cyst, cerebellar vermis hypoplasia, and hydrocephalus is often associated with agenesis of the corpus callosum and callosal lipomas, dysplasia of the brainstem, and cerebellar hypoplasia or dysgenesis. But radiological features of DWM with microcephaly and intracranial calcification are very unusual and have been rarely reported in the literature.[1] We report a case of infant showing clinical features suggestive of congenital CMV infection with negative serology and radiological imaging suggestive of DWM with extensive intracranial calcification. Pseudo-TORCH syndrome with radiological features of DWM is a congenital developmental abnormality. Inspite of hydrocephalus, it does not require cerebrospinal fluid (CSF) diversionary procedure due to lack of increased intracranial pressure. Conservative management for seizure disorder is the optimal therapy. PMID:28761539

Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy-Walker malformation.

PubMed

Patnaik, Ashis; Mishra, Sudhansu Sekhar; Das, Srikanta

2017-01-01

Pseudo-TORCH syndrome or congenital infection-like syndrome is a group of conditions which resemble congenital infections such as those caused by toxoplasmosis, rubella, cytomegalovirus (CMV), herpes (TORCH) group of organisms, clinico-radiologically, but serological tests are negative for the organisms. One of the variety shows features such as microcephaly, extensive intracranial calcification showing gross resemblance to congenital CMV infection, making its other name as microcephaly intracranial calcification syndrome (MICS). Dandy-Walker malformation (DWM), in addition to posterior fossa large cyst, cerebellar vermis hypoplasia, and hydrocephalus is often associated with agenesis of the corpus callosum and callosal lipomas, dysplasia of the brainstem, and cerebellar hypoplasia or dysgenesis. But radiological features of DWM with microcephaly and intracranial calcification are very unusual and have been rarely reported in the literature.[1] We report a case of infant showing clinical features suggestive of congenital CMV infection with negative serology and radiological imaging suggestive of DWM with extensive intracranial calcification. Pseudo-TORCH syndrome with radiological features of DWM is a congenital developmental abnormality. Inspite of hydrocephalus, it does not require cerebrospinal fluid (CSF) diversionary procedure due to lack of increased intracranial pressure. Conservative management for seizure disorder is the optimal therapy.

Trans-sinusal maxillary distraction for correction of midfacial hypoplasia: long-term clinical results.

PubMed

Nadjmi, N; Schutyser, F; Van Erum, R

2006-10-01

Maxillary distraction osteogenesis is indicated in severe angle class III malocclusions, and severe maxillary hypoplasia among some cleft patients and other craniofacial deformities. Twenty patients, aged 8-48 years (mean 17.8+/-10.5 SD) with maxillary and midfacial hypoplasia were treated. The follow-up period was 13-65 months (mean 35+/-16.3 SD). A trans-sinusal maxillary distractor was placed intraorally at each side of the maxilla. The distraction vector was predicted using specialist software, and was transferred to the patients using stereolithographic models and individual templates. A (high) Le Fort I type osteotomy was performed. The amount of activation varied from 8 to 17.5 mm (mean 13.1+/-2.9 SD). Soft and hard tissue formation resulted in complete healing across the distraction gaps. The distractors are almost completely submerged, and can be left in place as long as necessary to avoid relapse. Wit's appraisal was used to measure the stability of the long-term distraction results. Results up to 5 years after distraction showed considerable maxillary advancement with long-term stability. Ongoing growth of the facial skeleton must be considered when distraction osteogenesis is chosen in growing patients.

The Role of Nuclear Receptor Coactivators in Recurrent Prostate Cancer

DTIC Science & Technology

2006-02-01

hyp- oplasia congenita and hypogonadotropic hypogonadism (34). From an evolutionary perspective, the AR AF2 region of the ligand binding domain is more...linked adrenal hypoplasia congenita and hypogo- nadotropic hypogonadism . Nature 372:672–676. 35. Muscatelli, F., A. P. Walker, E. De Plaen, A. N

Principles and clinical applications of liquid chromatography - tandem mass spectrometry for the determination of adrenal and gonadal steroid hormones.

PubMed

Kulle, A E; Welzel, M; Holterhus, P-M; Riepe, F G

2011-10-01

Liquid-chromatography - tandem mass spectrometry (LC-MS/MS) is becoming the method of choice for clinical steroid analysis. In most instances, it has the advantage of higher sensitivity, better reproducibility and greater specificity than commercial immunoassay techniques. The method requires only minimal sample preparation and a small sample volume. Furthermore, it has the potential to analyze multiple steroids simultaneously. Modern instruments guarantee high throughput, allowing an affordable price for the individual assay. All this makes LC-MS/MS an attractive method for use in a clinical setting. Reliable reference ranges for the detected analytes are the pre-requisite for their clinical use. If these are available, LC-MS/MS can find application in congenital disorders of steroid metabolism, such as congenital adrenal hyperplasia, disorders of sex development and disorders of salt homeostasis, as well as in acquired disorders of steroid metabolism, such as primary aldosteronism, Cushing's disease, Addison's disease, and hyperandrogenemia, as well as in psychiatric disease states such as depression or anxiety disorders. The principles of LC-MS/MS for steroid measurement, the pros and cons of LC-MS/MS compared with conventional immunoassays and the possible applications in clinical routine, with a special focus on pediatric endocrinology needs, are discussed here.

The effect of bedrest on adrenal function

NASA Technical Reports Server (NTRS)

Leach, C. S.; Hulley, S. B.; Rambaut, P. C.; Dietlein, L. F.

1973-01-01

Eight male subjects were subjected to continuous bedrest for 24-80 weeks for the purpose of studying metabolic responses. Three of the subjects did supine exercises daily during part of the study. Adrenal function was examined in relation to adrenal cortical and medullary excretions. The results reveal an increase in hydrocortisone throughout the test period, a decrease in norepinephrine and no change in epinephrine. These data suggest that exercise could decrease the severity of deconditioning caused by bedrest.

[Adrenal incidentaloma: a clinical problem related to imaging].

PubMed

de Bruijne, E L E; Burgmans, J P J; Krestin, G P; Pols, H A P; van den Meiracker, A H; de Herder, W W

2005-08-13

Two female patients, 68 and 67 years of age, were referred for right abdominal pain and pyelonephritis, respectively. During the diagnostic work-up, an unsuspected adrenal mass was found in both patients. Hormonal evaluation and imaging showed a benign non-hyperactive functioning adenoma in one patient and a pheochromocytoma in the other. Both patients were successfully treated with endoscopic adrenalectomy. Wider application and improvement of abdominal imaging procedures have caused an increase of incidentally detected adrenal masses, posing a common clinical problem. Typically, a diagnosis can be made on the basis of the characteristic radiological image. The exact nature of the defect is often unclear and further evaluation is required to determine functionality and possible malignancy. An algorithm is presented for the management of adrenal incidentalomas.

Regulation of the Adrenal Cortex Function During Stress

NASA Technical Reports Server (NTRS)

Soliman, K. F. A.

1978-01-01

A proposal to study the function of the adrenal gland in the rat during stress is presented. In the proposed project, three different phases of experimentation will be undertaken. The first phase includes establishment of the circadian rhythm of both brain amines and glucocoticoids, under normal conditions and under chronic and acute stressful conditions. The second phase includes the study of the pharmacokinetics of glucocorticoid binding under normal and stress conditions. The third phase includes brain uptake and binding under different experimental conditions. In the outlined experiments brain biogenic amines will be evaluated, adrenal functions will be measured and stress effect on those parameters will be studied. It is hoped that this investigation can explain some of the complex relationships between the brain neurotransmitter and adrenal function.

VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

PubMed Central

Sbragia, L.; Nassr, A.C.C.; Gonçalves, F.L.L.; Schmidt, A.F.; Zuliani, C.C.; Garcia, P.V.; Gallindo, R.M.; Pereira, L.A.V.

2014-01-01

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression. PMID:24519134

Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation

PubMed Central

Gregory, L. C.; Humayun, K. N.; Turton, J. P. G.; McCabe, M. J.; Rhodes, S. J.

2015-01-01

Background: LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies. Objective/Hypothesis: To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients. Method: We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants. Results: We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype. Conclusion: We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life. PMID:25871839

Cri-du-chat (5p-) syndrome presenting with cerebellar hypoplasia and hypospadias: prenatal diagnosis and aCGH characterization using uncultured amniocytes.

PubMed

Chen, Chih-Ping; Huang, Ming-Chao; Chen, Yi-Yung; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Town, Dai-Dyi; Wang, Wayseen

2013-07-25

We present prenatal diagnosis of a de novo distal deletion involving 5p(5p15.1→pter) using uncultured amniocytes in a pregnancy with cerebellar hypoplasia, hypospadias and facial dysmorphisms in the fetus. We discuss the genotype-phenotype correlation and the consequence of haploinsufficiency of CTNND2, SEMA5A, TERT, SRD5A1 and TPPP. We speculate that haploinsufficiency of SRD5A1 and TPPP may be responsible for hypospadias and cerebellar hypoplasia, respectively, in this case. Copyright © 2013 Elsevier B.V. All rights reserved.

[Adrenal incidentaloma and nuclear medicine examination].

PubMed

Tenenbaum, F

2009-03-01

In the setting of adrenal incidentaloma, nuclear medicine evaluation is only indicated after biological and imaging work-up has been completed. MIBG scintigraphy is helpful to characterize pheochromocytomas. In lesions without MIBG uptake, 18F FDG or 18F DOPA PET can be considered to characterize chromaffin cell tumours. To characterize lesions of the adrenal cortex, iodocholesterol scintigraphy is performed to confirm the origin of the adenoma and the benign or malignant nature of the lesion since benign adenomas show tracer uptake and malignant lesions show no tracer uptake. 18F FDG PET only characterizes the lesion as benign or malignant.

Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma

PubMed Central

Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

2011-01-01

Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5–6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement. PMID:22679235

Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma.

PubMed

Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

2011-09-13

Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5-6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement.

Ca(2+) signaling mechanisms in bovine adrenal chromaffin cells.

PubMed

Weiss, Jamie L

2012-01-01

Calcium (Ca(2+)) is a crucial intracellular messenger in physiological aspects of cell signaling. Adrenal chromaffin cells are the secretory cells from the adrenal gland medulla that secrete catecholamines, which include epinephrine and norepinephrine important in the 'fight or flight' response. Bovine adrenal chromaffin cells have long been used as an important model for secretion -(exocytosis) not only due to their importance in the short-term stress response, but also as a neuroendocrine model of neurotransmtter release, as they have all the same exocytotic proteins as neurons but are easier to prepare, culture and use in functional assays. The components of the Ca(2+) signal transduction cascade and it role in secretion has been extensively characterized in bovine adrenal chromaffin cells. The Ca(2+) sources, signaling molecules and how this relates to the short-term stress response are reviewed in this book chapter in an endeavor to generally -overview these mechanisms in a concise and uncomplicated manner.

Congenital malformations and other reproductive losses in goats due to poisoning by Poincianella pyramidalis (Tul.) L.P. Queiroz (=Caesalpinia pyramidalis Tul.).

PubMed

Santos Dos Reis, Suélen Dias; de Oliveira, Ricardo Santana; Correia Marcelino, Sóstenes Apolo; Silva Almeida E Macêdo, Juliana Targino; Riet-Correa, Franklin; da Anunciação Pimentel, Luciano; Ocampos Pedroso, Pedro Miguel

2016-08-01

In the semiarid region of Brazil, in areas with vegetation composed mainly of Poincianella pyramidalis, several cases of congenital malformation and reproductive losses were observed in goats and sheep from 2012 to 2014. To determine the teratogenic effect of P. pyramidalis, two groups of eight goats each were used. Goats from Group 1 received fresh P. pyramidalis, harvested daily, as the only roughage during the whole breeding and pregnancy period. Goats in Group 2 (control) received Cynodon dactylon (tifton) hay free choice. Ultrasound examination for pregnancy diagnosis was performed every 28 days. Four goats from Group 1 were pregnant on day 28 but not on day 56, suggesting embryonic death or abortion. Another goat from Group 1 died at day 70 of pregnancy, and the fetuses exhibited micrognathia. The other three goats bore six kids, three of which showed bone malformations in the limbs, spine, ribs, sternum, and head, including arthrogryposis, scoliosis and micrognathia. One kid also showed hypoplasia of the left pulmonary lobes. In the control group, all goats bore a total of 13 kids and none of them exhibited malformations. These results demonstrated that P. pyramidalis causes congenital malformations and other reproductive losses in goats. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

[Effect of drinking boron on microtructure of adrenal gland in rats].

PubMed

Li, Shenghe; Wang, Jue; Zhou, Jinxing; Jin, Guangming; Gu, Youfang; Xu, Wanxiang

2012-09-01

The effects of drinking boron exposure on the mass, organ indexes and structure of adrenal gland were studied in the paper. Methods 192 Sprague-Dawley rats (28 +/- 2 days) with no bacteria infecting were divided into six groups (n = 32, male = female) randomly. Treated rats drunk the distilled water which supplemented with boron of 0, 40, 80, 160, 320 and 640 mg/L, respectively, for 60 days. At the 30th and the 60th day of experiment, 16 rats (n = 8, male = female) of each group were selected and made into narcosis with 10% Chloral Hydrate. The adrenal glands were obtained, weighted and fixed after dissection, then the samples were made into paraffin sections, stained with HE stain and chromaffin, observed and photographed by Olympus CH-30 microphotograph system. Compared with control group, the average mass of adrenal gland of male rats in each experiment group decreased significantly or most significantly at the 30th day of experiment (P < 0.05 or P < 0.01), but the index of adrenal gland of male rats in the group of 640 mg/L boron at 60th day of experiment increased significantly (P < 0.05). Under the microscope, the microstructure of adrenal gland of rats in the group of 40 mg/L boron were better obviously than control group, and the numbers of chromaffin granules in chromaffin cell increased obviously. The histopathological changes of different degree could be observed in the group of 80 to 640 mg/L boron, and they became remarkable with the boron supplementation. By comparative observation, the damage of cells in adrenal medulla appeared ahead of them in adrenal cortex, and the pathological change of adrenal gland in male rats were obvious than female rats. Drinking supplemented with 40 mg/L boron could prompt the structure of adrenal gland in rats, but could cause different degree damage, or even obvious toxic effect when the concentration of boron supplementation in drinking from 80 to 640 mg/L.

Congenital Spondylolytic Spondylolisthesis of C2 Vertebra Associated With Atlanto-Axial Dislocation, Chiari Type I Malformation, and Anomalous Vertebral Artery: Case Report With Review Literature.

PubMed

Sardhara, Jayesh; Pavaman, Sindgikar; Das, Kuntal; Srivastava, Arun; Mehrotra, Anant; Behari, Sanjay

2016-11-01

Congenital spondylolytic spondylolisthesis of C2 vertebra resulting from deficient posterior element of the axis is rarely described in the literature. We describe a unique case of agenesis of posterior elements of C2 with craniovertebral junction anomalies consisting of osseous, vascular, and soft tissue anomalies. A 26-year-old man presented with symptoms of upper cervical myelopathy of 12 months' duration. A computed tomography scan of the cervical spine including the craniovertebral junction revealed spondylolisthesis of C2 over C3, atlantoaxial dislocation, occipitalization of the atlas, hypoplasia of the odontoid, and cleft posterior C1 arch. Additionally, the axis vertebra was found devoid of its posterior elements except bilaterally rudimentary pedicles. Magnetic resonance imaging revealed tonsilar herniation, suggesting associated Chiari type I malformation. CT angiogram of the vertebral arteries displayed persistent bilateral first intersegmental arteries crossing the posterior aspect of the C1/2 facet joint. This patient underwent foramen magnum decompression, C3 laminectomy with occipito-C3/C4 posterior fusion using screw and rod to maintain the cervical alignment and stability. We report this rare constellation of congenital craniovertebral junction anomaly and review the relevant literature. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute adrenal insufficiency: an aide-memoire of the critical importance of its recognition and prevention.

PubMed

Gargya, A; Chua, E; Hetherington, J; Sommer, K; Cooper, M

2016-03-01

Adrenal crisis is a life-threatening emergency that causes significant excess mortality in patients with adrenal insufficiency. Delayed recognition by medical staff of an impending adrenal crisis and failure to give timely hydrocortisone therapy within the emergency department continue to be commonly encountered, even in metropolitan teaching hospitals. Within the authors' institutions, several cases of poorly handled adrenal crises have occurred over the last 2 years. Anecdotal accounts from members of the Addison's support group suggest that these issues are common in Australia. This manuscript is a timely reminder for clinical staff on the critical importance of the recognition, treatment and prevention of adrenal crisis. The manuscript: (i) outlines a case and the clinical outcome of sub-optimally managed adrenal crisis, (ii) summarises the clinical features and acute management of adrenal crisis, (iii) provides recommendations on the prevention of adrenal crisis and (iv) provides guidance on the management of 'sick days' in patients with adrenal insufficiency. © 2016 Royal Australasian College of Physicians.

Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

PubMed Central

Mello, Marcelo F.; Faria, Alvaro A.; Mello, Andrea F.; Carpenter, Linda L.; Tyrka, Audrey R.; Price, Lawrence H.

2015-01-01

Objective The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. Method A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. Results There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. Discussion The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. Conclusion Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses. PMID:19967199

[Association between Williams syndrome and adrenal insufficiency].

PubMed

Rchachi, Meryem; Larwanou, Maazou Mahamane; El Ouahabi, Hanan; Ajdi, Farida

2017-01-01

Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease.

PubMed

Venizelos, I; Venizelos, J; Tamiolakis, D; Lambropoulou, M; Alexiadis, G; Petrakis, G; Papadopoulos, N

2007-08-01

We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.

Treatment of Severe Maxillary Hypoplasia With Combined Orthodontics and Distraction Osteogenesis.

PubMed

Lucchese, Alessandra; Albertini, Paolo; Asperio, Paolo; Manuelli, Maurizio; Gastaldi, Giorgio

2018-01-05

Distraction osteogenesis (DO) is a technique that allows the generation of new bone in a gap between 2 vascularized bone surfaces in response to the application of graduated tensile stress across the bone gap.Distraction osteogenesis has become a routine treatment of choice to correct skeletal deformities and severe bone defects in the craniofacial complex over the past decade. Distraction osteogenesis has been successfully chosen in lengthening the maxilla and the mandible; in the maxilla and recently in the mandible, the jawbones have been distracted and widened transversely to relieve severe anterior dental crowding and transverse discrepancies between the dental arches.Distraction osteogenesis for maxillary advancement started in 1993 and is now widely used, especially in patients with skeletal Class III malocclusion caused by maxillary hypoplasia.The aim of this study was to present the efficiency of combined orthodontic and DO in the severe maxillary hypoplasia.A 35-year-old Italian man presented to our clinical practice with the chief complaint of esthetic and functionally problems because of skeletal Class III malocclusion with anterior crossbite.Considering that the severity of the skeletal discrepancy is remarkable but compensated by the DO potential, the combined orthodontic and DO treatment was considered adequate, like less invasive and equally effective.It was obtained a good alignment with the upper and lower arch dental alveolar maxillary advancement that allowed to correct the sagittal relationships.The patient was satisfied for the treatment results and had considerable improvement in his self-esteem.

Congenital toxoplasmosis

MedlinePlus

... page: //medlineplus.gov/ency/article/001360.htm Congenital toxoplasmosis To use the sharing features on this page, please enable JavaScript. Congenital toxoplasmosis is a group of symptoms that occur when ...

Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

PubMed Central

Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

2018-01-01

Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

PubMed

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

PubMed Central

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-01-01

Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692

8D.04: CLINICAL BENEFITS OF ADMINISTERING SUPER-SELECTIVE SEGMENTAL ADRENAL VENOUS SAMPLING AND PERFORMING ADRENAL SPARING SURGERY IN THE PATIENTS WITH PRIMARY ALDOSTERONISM.

PubMed

Satoh, F; Morimoto, R; Ono, Y; Iwakura, Y; Omata, K; Kudo, M; Satani, N; Ota, H; Seiji, K; Takase, K; Nakamura, Y; Sasano, H; Ito, S

2015-06-01

Adrenal venous sampling (AVS) has been well known to play pivotal roles in clinical differential diagnosis of unilateral aldosterone producing adenoma (APA) from bilateral idiopathic hyperaldosteronism (IHA). However, it is also true that a central vein AVS or c-AVS which collects the blood from right and left central adrenal veins can by no means discriminate bilateral APA from BHA. There have been no published studies reporting the reliable clinical differential diagnosis between bilateral APA and IHA, especially IHA cases with bilateral non-functioning adenomas (NFA), which has been considered practically impossible in clinical differential diagnosis. As an attempt to this clinical dilemma, segmental AVS (S-AVS), which could evaluate segmental effluents from adrenal tributary veins, has been recently developed. We have performed S-AVS in these patients above following C-AVS, via the insertion of a microcatheter in up to three intra-adrenal first-degree tributary veins on bilateral adrenals. S-AVS did enable us to evaluate the intra-adrenal localization of corticosteroidogenesis. These data did indicate that S-AVS should be performed in the PA patients who had increased aldosterone levels in bilateral central vein and demonstrated space occupying lesions in the bilateral adrenals in order to avoid bilateral adrenalectomy or long lasting medical treatment toward persistent PA. In addition to the situations above, we have administere S-AVS to the following patients; those who had clinically suspected APA but not sufficiently high lateralization indexes according to the results of C-AVS, very young ones with higher clinical probability of recurrence and those who could benefit from partial adrenalectomy by demonstrating the sites of specific steroidogenesis. However, it is also entirely true that S-AVS is more expensive, time-consuming and labor-intensive compared to C-AVS.(Figure is included in full-text article.)The angiography during S-AVS (A, B), the coronal CT

Reduced ventral cingulum integrity and increased behavioral problems in children with isolated optic nerve hypoplasia and mild to moderate or no visual impairment.

PubMed

Webb, Emma A; O'Reilly, Michelle A; Clayden, Jonathan D; Seunarine, Kiran K; Dale, Naomi; Salt, Alison; Clark, Chris A; Dattani, Mehul T

2013-01-01

To assess the prevalence of behavioral problems in children with isolated optic nerve hypoplasia, mild to moderate or no visual impairment, and no developmental delay. To identify white matter abnormalities that may provide neural correlates for any behavioral abnormalities identified. Eleven children with isolated optic nerve hypoplasia (mean age 5.9 years) underwent behavioral assessment and brain diffusion tensor imaging, Twenty four controls with isolated short stature (mean age 6.4 years) underwent MRI, 11 of whom also completed behavioral assessments. Fractional anisotropy images were processed using tract-based spatial statistics. Partial correlation between ventral cingulum, corpus callosum and optic radiation fractional anisotropy, and child behavioral checklist scores (controlled for age at scan and sex) was performed. Children with optic nerve hypoplasia had significantly higher scores on the child behavioral checklist (p<0.05) than controls (4 had scores in the clinically significant range). Ventral cingulum, corpus callosum and optic radiation fractional anisotropy were significantly reduced in children with optic nerve hypoplasia. Right ventral cingulum fractional anisotropy correlated with total and externalising child behavioral checklist scores (r = -0.52, p<0.02, r = -0.46, p<0.049 respectively). There were no significant correlations between left ventral cingulum, corpus callosum or optic radiation fractional anisotropy and behavioral scores. Our findings suggest that children with optic nerve hypoplasia and mild to moderate or no visual impairment require behavioral assessment to determine the presence of clinically significant behavioral problems. Reduced structural integrity of the ventral cingulum correlated with behavioral scores, suggesting that these white matter abnormalities may be clinically significant. The presence of reduced fractional anisotropy in the optic radiations of children with mild to moderate or no visual impairment raises

Massive adrenal vein aneurysm mimicking an adrenal tumor in a patient with hemophilia A: a case report and review of the literature.

PubMed

Sleightholm, Richard; Wahlmeier, Steven; Carson, Jeffrey S; Drincic, Andjela; Lazenby, Audrey; Foster, Jason M

2016-12-01

Visceral venous aneurysms are exceedingly rare, and until now, there have been no reports of this phenomenon in the adrenal vasculature. This report details the first adrenal venous aneurysm reported in the literature. The aneurysm presented as an 18-cm mass that was initially suspected to be a hematoma or tumor on the basis of the complex medical history of the patient, which included hemophilia A and testicular cancer. After surgical excision, pathologic examination confirmed this mass to be a 15.9-cm adrenal vein aneurysm, the largest aneurysm of any type or location recorded in the medical literature. A 58-year-old caucasian male with hemophilia A presented to the emergency room of another institution with abdominal pain, blood in the stool, and a history of diverticulosis and symptomatic hemorrhoids. A large, left-sided adrenal mass was detected by computed tomography, and because of the patient's hemophilia A and imaging consistent with a hemorrhagic mass, a hematoma was initially suspected. The patient was transferred to our institution, monitored for further bleeding with a stable hospital course, and discharged from the hospital under close monitoring. After 7-8 weeks with no change in the size of the mass, concerns grew regarding increasing symptoms of both satiety and mass effects from the large anomaly, as well as about the patient's complicated medical history, which also included cancer. Surgical excision was recommended because of the concerns about increasing symptoms and the possibility of a malignancy. Correction and maintenance of factor VIII levels were incorporated pre-, intra-, and postoperatively, and en bloc surgical resection was performed to minimize bleeding and provide oncologic extirpation of the mass. A bowling ball-sized mass was removed, and careful pathologic examination revealed the mass to be a venous adrenal aneurysm. After a brief hospital stay, the patient made a full recovery. Extensive review of the literature revealed 11

Heterogeneous levels of oxidative phosphorylation enzymes in rat adrenal glands.

PubMed

Ogawa, Koichi; Harada, Keita; Endo, Yutaka; Sagawa, Sueko; Inoue, Masumi

2011-01-01

Mitochondria are organelles that produce ATP and reactive oxygen species, which are thought to be responsible for a decline in physiological function with aging. In this study, we morphologically and biochemically examined mitochondria in the rat adrenal gland. Immunohistochemistry showed that the rank order for intensity of immunolabelling for complex IV was zona reticularis > zona fasciculata > adrenal medulla, whereas for complex V α and β subunits, it was zona fasciculata > zona reticularis and adrenal medulla. The immunolabelling for complex I was homogeneous in the adrenal gland. The difference in immunolabelling between complexes I and IV indicates that the ratio of levels of complex I to that of complex IV in the zona reticularis was smaller than that in the zona fasciculata and the adrenal medulla. Electron microscopy revealed that aging rats had zona reticularis cells with many lysosomes and irregular nuclei. The result suggests that the level of proteins involved in oxidative phosphorylation is coordinated within the complex, but differs between the complexes. This might be responsible for degeneration of zona reticularis cells with aging. Copyright © 2009 Elsevier GmbH. All rights reserved.

Dental caries and its relationship to bacterial infection, hypoplasia, diet, and oral hygiene in 6- to 36-month-old children.

PubMed

Milgrom, P; Riedy, C A; Weinstein, P; Tanner, A C; Manibusan, L; Bruss, J

2000-08-01

Caufield et al. (1) have suggested that the acquisition of mutans streptococci in young children most likely takes place during a "window of infectivity" from 19 to 31 months of age. This study determined the prevalence of dental caries and bacterial infection in a randomly selected sample of 199 children 6 to 36 months old from the island of Saipan in the Common-wealth of the Northern Mariana Islands, USA. The relationships between caries and Streptococcus mutans infection, hypoplasia, diet and oral hygiene behavior were investigated. The overall estimated prevalence of caries was high: 46.8% of the children had white spot lesions and 39.1% had enamel cavitation. Colonization was seen in very young children; S. mutans was detected in 25% of the predentate children. The results of multi-variable modeling support the hypothesis that bacterial infection, diet, and hypoplasia are important in the etiology of dental caries in this population. Adjusted for age and ethnicity, children with a high level of S. mutans detected were 5 times more likely to have dental caries than children with a lower level of S. mutans detected. Hypoplasia and a high cariogenicity score (diet) were also significant independent predictors. The odds of having any white spot lesions or enamel cavitation were 9.6 times greater for children with any hypoplasia, and 7.8 times greater for children with high cariogenicity scores relative to those with lower scores after adjusting for level of S. mutans, age and ethnicity. Sleeping with a bottle, maternal sharing of utensils, and high snacking frequency were not significant predictors of caries in this population.

Genetics of congenital hypogonadotropic hypogonadism in Denmark.

PubMed

Tommiska, Johanna; Känsäkoski, Johanna; Christiansen, Peter; Jørgensen, Niels; Lawaetz, Jacob Gerner; Juul, Anders; Raivio, Taneli

2014-07-01

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterized by incomplete/absent puberty caused by deficiency or defective action of gonadotropin-releasing hormone (GnRH). The phenotypic features of patients with CHH vary from genital hypoplasia and absent puberty to reversal of HH later in life. We examined the genetics and clinical features of CHH in Denmark. Forty-one male patients were screened for mutations in KAL1, FGFR1, FGF8, PROK2, PROKR2, GNRHR, TAC3, TACR3, and KISS1R. CHD7 was screened in two patients with hearing loss. In 12 patients, a molecular genetic cause for CHH was found. Four patients had mutations in KAL1 (C105VfsX13, C53X, ex5-8del, R257X), and five in FGFR1 (G97S, R209C, A512V, R646W, and c.1614C>T, (p.I538I), predicted to affect splicing). All 9 had severe HH (cryptorchidism and/or micropenis), and 2 had cleft lip/palate. One patient with a previously reported homozygous R262Q mutation in GNRHR displayed fascinating temporal variation in his phenotype. Two patients with hearing loss had CHD7 mutations (c.7832_7841del (p.K2611MfsX25) and c.2443-2A>C), confirming that CHH patients with CHARGE syndrome-associated features should be screened for mutations in CHD7. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Anatomical Variations of the Right Adrenal Vein: Concordance Between Multidetector Computed Tomography and Catheter Venography.

PubMed

Omura, Kensuke; Ota, Hideki; Takahashi, Yuuki; Matsuura, Tomonori; Seiji, Kazumasa; Arai, Yoichi; Morimoto, Ryo; Satoh, Fumitoshi; Takase, Kei

2017-03-01

Adrenal venous sampling is the most reliable diagnostic procedure to determine surgical indications in primary aldosteronism. Because guidelines recommend multidetector computed tomography (CT) to evaluate the adrenal gland, some past reports used multidetector CT as a guide for adrenal venous sampling. However, the detailed anatomy of the right adrenal vein and its relationship with an accessory hepatic vein remains uncertain. The purpose of this study was to describe detailed anatomical variations of the right adrenal vein and to determine the concordance between CT and catheter venography in patients with primary aldosteronism. In total, 440 consecutive patients who underwent adrenal venous sampling were included. Four-phase dynamic CT was performed. Anatomical locations and variations of the right adrenal vein and its relationship with the accessory hepatic vein were compared with catheter venographic findings. Successful catheterization was achieved in 437 patients (99%). The right adrenal vein was visualized in the late arterial phase with CT in 420 patients (95%). The right adrenal vein formed a common trunk with the accessory hepatic vein in 87 patients (20%). CT identified the correct craniocaudal level of the orifice in 354 patients (84%). Anatomical variations, location, and angle of inflow of the right adrenal vein based on CT demonstrated high concordance with catheter venography. CT may provide useful information for preparation before adrenal venous sampling. © 2017 American Heart Association, Inc.

Hypertensive crisis caused by electrocauterization of the adrenal gland during hepatectomy.

PubMed

Doo, A Ram; Son, Ji-Seon; Han, Young-Jin; Yu, Hee Chul; Ko, Seonghoon

2015-02-14

Hypertensive crisis (i.e., systolic blood pressure over 300 mmHg) is very rare during operation except pheochromocytoma, but it can be a fatal and embarrassing to surgeons and anesthesiologists. The right adrenal gland can be electrocauterized during a right hemi-hepatectomy. We report a case of hypertensive crisis during right hemi-hepatectomy in which the right adrenal gland was stimulated by monopolar electrocautery in a patient with normal neuroendocrine function. A 73-year-old man with hepatocellular carcinoma was scheduled to undergo right hemi-hepatectomy. Three hours into the surgery, the patient's blood pressure increased abruptly from 100/40 to over 350/130 mmHg (the maximum measurement pressure of the monitor; 350 mmHg). The surgeon had cauterized the right adrenal gland using monopolar electrocautery to separate the liver from the adrenal gland immediately prior to the event. Approximately 3 minutes after suspending the operation, blood pressure returned to baseline levels. After the event, the operation was successfully completed without any complication. Hormonal studies and iodine-123 meta-iodobenzylguanidine scintigraphy revealed no neuroendocrine tumor such as a pheochromocytoma. Operations such as hepatectomy that stimulate the adrenal gland may lead to an unexpected catecholamine surge and result in hypertensive crisis, even if neuroendocrine function of the adrenal gland is normal.

Brain serotonin and pituitary-adrenal functions

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

1973-01-01

It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

The classification based on intrahepatic portal system for congenital portosystemic shunts.

PubMed

Kanazawa, Hiroyuki; Nosaka, Shunsuke; Miyazaki, Osamu; Sakamoto, Seisuke; Fukuda, Akinari; Shigeta, Takanobu; Nakazawa, Atsuko; Kasahara, Mureo

2015-04-01

Liver transplantation was previously indicated as a curative operation for congenital absence of portal vein. Recent advances in radiological interventional techniques can precisely visualize the architecture of the intrahepatic portal system (IHPS). Therefore, the therapeutic approach for congenital portosystemic shunt (CPS) needs to be reevaluated from a viewpoint of radiological appearances. The aim of this study was to propose the IHPS classification which could explain the pathophysiological characteristics and play a complementary role of a therapeutic approach and management for CPS. Nineteen patients with CPS were retrospectively reviewed. The median age at diagnosis was 6.8 years old. Eighteen of these patients underwent angiography with a shunt occlusion test and were classified based of the severity of the hypoplasia of IHPS. The eighteen cases who could undergo the shunt occlusion test were classified into mild (n=7), moderate (n=6) and severe types (n=5) according to the IHPS classification. The IHPS classification correlated with the portal venous pressure under shunt occlusion, the histopathological findings, postoperative portal venous flow and liver regeneration. Shunt closure resulted in dramatic improvement in the laboratory data and subclinical encephalopathy. Two patients with the severe type suffered from sepsis associated with portal hypertension after treatment, and from the portal flow steal phenomenon because of the development of unexpected collateral vessels. The patients with the severe type had a high risk of postoperative complications after shunt closure in one step, even if the PVP was relatively low during the shunt occlusion test. The IHPS could be visualized by the shunt occlusion test. The IHPS classification reflected the clinicopathological features of CPS, and was useful to determine the therapeutic approach and management for CPS. Copyright © 2015 Elsevier Inc. All rights reserved.

A new CYP21A1P/CYP21A2 chimeric gene identified in an Italian woman suffering from classical congenital adrenal hyperplasia form

PubMed Central

Concolino, Paola; Mello, Enrica; Minucci, Angelo; Giardina, Emiliano; Zuppi, Cecilia; Toscano, Vincenzo; Capoluongo, Ettore

2009-01-01

Background More than 90% of Congenital Adrenal Hyperplasia (CAH) cases are associated with mutations in the 21-hydroxylase gene (CYP21A2) in the HLA class III area on the short arm of chromosome 6p21.3. In this region, a 30 kb deletion produces a non functional chimeric gene with its 5' and 3' ends corresponding to CYP21A1P pseudogene and CYP21A2, respectively. To date, five different CYP21A1P/CYP21A2 chimeric genes have been found and characterized in recent studies. In this paper, we describe a new CYP21A1P/CYP21A2 chimera (CH-6) found in an Italian CAH patient. Methods Southern blot analysis and CYP21A2 sequencing were performed on the patient. In addition, in order to isolate the new CH-6 chimeric gene, two different strategies were used. Results The CYP21A2 sequencing analysis showed that the patient was homozygote for the g.655C/A>G mutation and heterozygote for the p.P30L missense mutation. In addition, the promoter sequence revealed the presence, in heterozygosis, of 13 SNPs generally produced by microconversion events between gene and pseudogene. Southern blot analysis showed that the woman was heterozygote for the classic 30-kb deletion producing a new CYP21A1P/CYP21A2 chimeric gene (CH-6). The hybrid junction site was located between the end of intron 2 pseudogene, after the g.656C/A>G mutation, and the beginning of exon 3, before the 8 bp deletion. Consequently, CH-6 carries three mutations: the weak pseudogene promoter region, the p.P30L and the g.655C/A>G splice mutation. Conclusion We describe a new CYP21A1P/CYP21A2 chimera (CH-6), associated with the HLA-B15, DR13 haplotype, in a young Italian CAH patient. PMID:19624807

Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas.

PubMed

Kann, Peter Herbert

2016-01-01

Endoscopic ultrasound (EUS) imaging of adrenal glands and its application to diagnostic procedures of adrenal diseases has been reported since 1998. It can be considered a relevant advantage in the field of adrenal diseases. Indeed, EUS allows the detection of adrenal lesions (even very small ones) and their characterization, the assessment of malignancy criteria, the early detection of neoplastic recurrences, the preoperative identification of morphologically healthy parts of the glands, the differentiation of extra-adrenal from adrenal tumors, and of the pathological entities associated with adrenal insufficiency, and the fine-needle aspiration biopsy (EUS-FNA) of suspicious lesions. At the same time, its clinical relevance depends on the experience of the endosonographer. Moreover, EUS is also by far the best and most sensitive imaging technique to detect and assess the follow-up of pancreatic manifestation of MEN1 disease. It furthermore enables the preoperatively localization of insulinomas and critical structures in their neighborhood, and may be relevant in planning surgical strategy. A positive EUS in a case of insulinoma furthermore confirms the endocrine diagnosis, especially considering the differential diagnosis of hypoglycemia factitia by oral antidiabetics. It can be supplemented by EUS-FNA. Again, it has to be considered that EUS may reveal false positive and false negative results, and the quality of the findings largely depends on the endosonographer's skills and experience. The most important technical details together with the advantages and limitations of EUS, and the pathognomonic characteristic of benign and malignant disorders of the adrenals and pancreas are presented here. © 2016 S. Karger AG, Basel.

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Takahashi, Hiromizu; Hofmann, Alejandro; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition associated with congenital diaphragmatic hernia (CDH), characterized by defective lung development. Sproutys and Sprouty-related proteins (SPREDs) play a key role in lung branching morphogenesis through modification of epithelial-mesenchymal interactions. During the pseudoglandular stage, Sproutys are highly expressed in distal airway epithelium, while SPREDs within the surrounding mesenchyme. Sprouty2/4 knockouts show severe defects in branching morphogenesis with reduced number of distal airways. SPRED-1 and SPRED-2 are strongly expressed in regions of new airway formation, highlighting their important function in branching pattern. We hypothesized that expression of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 is decreased during lung branching morphogenesis in nitrofen-induced PH. Timed-pregnant rats received either nitrofen or vehicle on E9.5. On E15.5 (n = 16), fetal lungs were micro-dissected and divided into controls and PH, while on E18.5 (n = 24) groups were: control, PH without CDH [CDH(-)], and PH with CDH [CDH(+)]. Pulmonary gene expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were analyzed by qRT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution. On E18.5, relative mRNA expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were significantly decreased in CDH(-) and CDH(+) groups compared to controls (P < 0.05). Immunoreactivity of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 was markedly diminished on E18.5 in nitrofen-induced PH. Decreased expression of Sproutys and SPREDs during the terminal pseudoglandular stage may disrupt lung branching morphogenesis by interfering with epithelial-mesenchymal interactions contributing to PH.

Congenital Hypothyroidism

MedlinePlus

... Disease Featured Resource Find an Endocrinologist Search Congenital Hypothyroidism March 2012 Download PDFs English Espanol Editors Rosalind S. ... Resources MedlinePlus (NIH) Mayo Clinic What is congenital hypothyroidism? Newborn babies who are unable to make enough ...

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids.

PubMed

Yarnell, Kelly; Purcell, Rebecca S; Walker, Susan L

2016-04-25

Adrenal activity can be assessed in the equine species by analysis of feces for corticosterone metabolites. During a potentially aversive situation, corticotrophin releasing hormone (CRH) is released from the hypothalamus in the brain. This stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, which in turn stimulates release of glucocorticoids from the adrenal gland. In horses the glucocorticoid corticosterone is responsible for several adaptations needed to support equine flight behaviour and subsequent removal from the aversive situation. Corticosterone metabolites can be detected in the feces of horses and assessment offers a non-invasive option to evaluate long term patterns of adrenal activity. Fecal assessment offers advantages over other techniques that monitor adrenal activity including blood plasma and saliva analysis. The non-invasive nature of the method avoids sampling stress which can confound results. It also allows the opportunity for repeated sampling over time and is ideal for studies in free ranging horses. This protocol describes the enzyme linked immunoassay (EIA) used to assess feces for corticosterone, in addition to the associated biochemical validation.

Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation.

PubMed

Seo, Ja Young; Park, Hyung-Doo; Kim, Jong Won; Oh, Hyeon Ju; Yang, Jeong Soo; Chang, Yun Sil; Park, Won Soon; Lee, Soo-Youn

2014-01-01

Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

Bone marrow hypoplasia associated with fenbendazole administration in a dog.

PubMed

Gary, Anthony T; Kerl, Marie E; Wiedmeyer, Charles E; Turnquist, Susan E; Cohn, Leah A

2004-01-01

A 1.5-year-old Doberman pinscher was presented with sudden-onset of fever and malaise. Twelve days prior to presentation, fenbendazole therapy was initiated for a suspected lungworm infection. Results of a complete blood count on presentation showed pancytopenia, while histopathological evaluation of a bone marrow core sample revealed bone marrow hypoplasia of undetermined etiology. Bactericidal antibiotics and fluid therapy, as well as discontinuation of fenbendazole administration, led to a complete resolution of clinical and hematological abnormalities within 15 days. An idiosyncratic reaction to fenbendazole was suspected based on the absence of infectious, neoplastic, autoimmune, and toxic etiologies, as well as resolution of clinical signs and pancytopenia upon drug withdrawal.

Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?

PubMed

Satoh, Fumitoshi; Morimoto, Ryo; Seiji, Kazumasa; Satani, Nozomi; Ota, Hideki; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Kudo, Masataka; Nezu, Masahiro; Omata, Kei; Tezuka, Yuta; Kawasaki, Yoshihide; Ishidoya, Shigeto; Arai, Yoichi; Takase, Kei; Nakamura, Yasuhiro; McNamara, Keely; Sasano, Hironobu; Ito, Sadayoshi

2015-10-01

Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the collection of effluents from bilateral adrenal central veins (CV)--sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction. We then evaluated the clinical utility of this novel approach in the diagnosis and treatment of PA. We performed C-AVS and/or S-AVS in 297 PA patients and assessed the accuracy of diagnosis based on the results of C-AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of clinicopathological evaluation of resected specimens. S-AVS demonstrated both elevated and attenuated secretion of aldosterone from APA and non-tumorous segments, respectively, in patients with bilateral APA and recurrent APA. These findings were completely confirmed by detailed histopathological examination after surgery. S-AVS, but not C-AVS, also served to identify APA located distal from the CV. Compared to C-AVS, S-AVS served to identify APA in some patients, and its use should expand the pool of patients eligible for adrenal sparing surgery through the identification of unaffected segments, despite the fact that S-AVS requires more expertise and time. Especially, this new technique could enormously benefit patients with bilateral or recurrent APA because of the preservation of non-tumorous glandular tissue. © 2015 European Society of Endocrinology.

Adrenal venous sampling in primary aldosteronism: multinomial regression modeling to detect aldosterone secretion lateralization when right adrenal sampling is missing.

PubMed

Durivage, Camille; Blanchette, Rémi; Soulez, Gilles; Chagnon, Miguel; Gilbert, Patrick; Giroux, Marie-France; Bourdeau, Isabelle; Oliva, Vincent L; Lacroix, André; Therasse, Eric

2017-02-01

Difficulty to recognize or canulate the right adrenal vein is the most frequent cause of adrenal venous sampling (AVS) failure. We aimed to assess multinomial regression modeling (MRM) of peripheral and left adrenal vein samplings to detect lateralization of aldosterone secretion when the right AVS is missing. Simultaneous bilateral AVS samplings were performed before (basal) and after intravenous cosyntropin injection in 188 consecutive patients between December 1989 and September 2015. Different reference standards for lateralization of aldosterone secretion were defined for basal and for postcosyntropin AVS and according to lateralization index cutoffs at least 2 and at least 4. MRMs were built to detect lateralization of aldosterone secretion according to these reference standards using only peripheral and left adrenal veins samplings (without the right AVS). Detection accuracy was assessed by the area under the receiver operating characteristic (AUROC) curves and detection sensitivities were reported for specificity at least 95%. For basal AVS with lateralization index at least 2, AUROC were respectively 0.931 [95% confidence interval (CI) 0.894-0.968] and 0.922 (95% CI 0.882-0.962) for right and left lateralization of aldosterone secretion detection and MRM could detect respectively 65.5 and 62.7% of the right and left lateralization of aldosterone secretion. For AVS after cosyntropin with lateralization index at least 4, AUROC were respectively 0.964 (95% CI: 0.940-0.987) and 0.955 (95% CI: 0.927-0.983) for right and left lateralization of aldosterone secretion, and MRM could detect respectively 77.2 and 72.9% of the right and left lateralization of aldosterone secretion. MRM can detect lateralization of aldosterone secretion without the right AVS in most patients and could eliminate the need for repeat AVS when right adrenal vein canulation is nonselective or impossible.

Severe polyuria after the resection of adrenal pheochromocytoma.

PubMed

Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

2010-12-01

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

Modulating the pituitary-adrenal response to stress

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.

1975-01-01

Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

Adrenal 11-beta hydroxysteroid dehydrogenase activity in response to stress.

PubMed

Zallocchi, Marisa; Matković, Laura; Damasco, María C

2004-06-01

This work studied the effect of stresses produced by simulated gavage or gavage with 200 mmol/L HCl two hours before adrenal extraction, on the activities of the 11beta-hydroxysteroid dehydrogenase 1 and 11beta-hydroxysteroid dehydrogenase 2 isoforms present in the rat adrenal gland. These activities were determined on immediately prepared adrenal microsomes following incubations with 3H-corticosterone and NAD+ or NADP+. 11-dehydrocorticosterone was measured as an end-product by TLC, and controls were adrenal microsomes from rats kept under basal (unstressed) conditions. 11beta-hydroxysteroid dehydrogenase 1 activity, but not 11beta-hydroxysteroid dehydrogenase 2 activity, was increased under both stress-conditions. Homeostatically, the stimulation of 11beta-hydroxysteroid dehydrogenase 1 activity would increase the supply of glucocorticoids. These, in turn, would activate the enzyme phenylethanolamine N-methyl transferase, thereby improving the synthesis of epinephrine as part of the stress-response.

Megalourethra: a case report managed with a single intrauterine bladder aspiration.

PubMed

Asma, Basha; Jumana, Baramki

2012-02-01

Congenital megalourethra is a rare mesenchymal anomaly of the male urethra, characterised by severe dilatation of the penile urethra due to congenital absence of the corpus spongiosum and/or corpus cavernosum. Postnatal complications include voiding and erectile dysfunction as well as renal insufficiency and pulmonary hypoplasia. We present a unique case of congenital megalourethra diagnosed prenatally in the early second trimester. The parents opted to continue pregnancy and vaginal delivery of a live neonate occurred with a favourable outcome.

Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

PubMed

Prüss, Harald; Tedeschi, Andrea; Thiriot, Aude; Lynch, Lydia; Loughhead, Scott M; Stutte, Susanne; Mazo, Irina B; Kopp, Marcel A; Brommer, Benedikt; Blex, Christian; Geurtz, Laura-Christin; Liebscher, Thomas; Niedeggen, Andreas; Dirnagl, Ulrich; Bradke, Frank; Volz, Magdalena S; DeVivo, Michael J; Chen, Yuying; von Andrian, Ulrich H; Schwab, Jan M

2017-11-01

Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

Aldo-Keto Reductases 1B in Adrenal Cortex Physiology

PubMed Central

Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A. Marie

2016-01-01

Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

Abnormal gel flotation caused by contrast media during adrenal vein sampling.

PubMed

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Gelati, Matteo; Bassi, Antonella; Contro, Alberto; Pizzolo, Francesca; Guidi, Gian Cesare

2016-10-15

During adrenal venous sampling (AVS) procedure, radiologists administer a contrast agent via the catheter to visualize the proper catheter position. A patient with primary aldosteronism diagnostic-hypothesis was admitted for AVS. A venogram was performed to
confirm the catheter's position with 2mL of Iopamidol 300 mg/mL. Samples were collected with syringe connected to a hydrophilic coated catheter by low-pressure aspiration from each of the four collection sites: inferior vena cava in the suprarenal portion, inferior vena cava in the infrarenal portion, left adrenal vein, and right adrenal vein; then immediately transferred from syringe to tubes with gel separator. All tubes were centrifuged at 1200 x g for 10 minutes. At the end of centrifugation process, primary blood tubes containing blood from inferior vena cava and left adrenal vein exhibited the standard gel separator barrier, while tubes from right adrenal vein showed abnormal flotation of gel separator. The radiologist confirmed the usage of 2.6 mL instead of 2.0 mL of Iopamidol 300 mg/mL. This iodinated contrast media, with 1.33 g/cm 3 of density, was used close to the right adrenal vein due to some difficulty to access it. The abnormal flotation of gel separator in samples taken from right adrenal vein can be explained by the usage of the iodinated
contrast media. We suggest using plain-tubes (without gel separator) for AVS in order to avoid preanalytical nonconformities. Moreover, a blood volume equivalent to twice the catheter extension should be discarded to eliminate residual contrast media before collection of samples for laboratory assays.

Abnormal gel flotation caused by contrast media during adrenal vein sampling

PubMed Central

Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Gelati, Matteo; Bassi, Antonella; Contro, Alberto; Pizzolo, Francesca; Guidi, Gian Cesare

2016-01-01

Introduction During adrenal venous sampling (AVS) procedure, radiologists administer a contrast agent via the catheter to visualize the proper catheter position. Materials and methods A patient with primary aldosteronism diagnostic-hypothesis was admitted for AVS. A venogram was performed to
confirm the catheter’s position with 2mL of Iopamidol 300 mg/mL. Samples were collected with syringe connected to a hydrophilic coated catheter by low-pressure aspiration from each of the four collection sites: inferior vena cava in the suprarenal portion, inferior vena cava in the infrarenal portion, left adrenal vein, and right adrenal vein; then immediately transferred from syringe to tubes with gel separator. All tubes were centrifuged at 1200 x g for 10 minutes. Results At the end of centrifugation process, primary blood tubes containing blood from inferior vena cava and left adrenal vein exhibited the standard gel separator barrier, while tubes from right adrenal vein showed abnormal flotation of gel separator. The radiologist confirmed the usage of 2.6 mL instead of 2.0 mL of Iopamidol 300 mg/mL. This iodinated contrast media, with 1.33 g/cm3 of density, was used close to the right adrenal vein due to some difficulty to access it. Conclusion The abnormal flotation of gel separator in samples taken from right adrenal vein can be explained by the usage of the iodinated
contrast media. We suggest using plain-tubes (without gel separator) for AVS in order to avoid preanalytical nonconformities. Moreover, a blood volume equivalent to twice the catheter extension should be discarded to eliminate residual contrast media before collection of samples for laboratory assays. PMID:27812311

CLINICAL FACTORS ASSOCIATED WITH BIOCHEMICAL ADRENAL-CORTISOL INSUFFICIENCY IN HOSPITALIZED PATIENTS

PubMed Central

Ben-Shlomo, Anat; Mirocha, James; Liu, Ning-Ai; Sheinin, Renee C.; Melmed, Shlomo

2014-01-01

Background Diagnosis of adrenal-cortisol insufficiency is often misleading in hospitalized patients as clinical and biochemical features overlap with co-morbidities. We analyzed clinical determinants associated with a biochemical diagnosis of adrenal-cortisol insufficiency in non-ICU hospitalized patients. Methods In a retrospective cohort study we reviewed 4668 inpatients with random morning cortisol levels ≤15 μg/dL hospitalized in our center between 2003 and 2010. Using serum cortisol threshold level of 18 μg/dL 30 and/or 60 minutes after cortrosyn (250 μg) injection to define biochemical adrenal-cortisol status, we characterized and compared insufficient (n=108, serum cortisol ≤18 μg/dL) and sufficient ( n=394; serum cortisol >18 μg/dL) non-ICU hospitalized patients. Results Commonly reported clinical and routine biochemical adrenal-cortisol insufficiency features were similar between insufficient and sufficient inpatients. Biochemical adrenal-cortisol insufficiency was associated with increased frequency of liver disease, specifically hepatitis C (p=0.01) and prior orthotopic liver transplantation (p<0.001), HIV (p=0.005) and reported preexisting male hypogonadism (p<0.001) as compared to biochemical adrenal-cortisol sufficiency group. Forty percent of insufficient inpatients were not treated with glucocorticoids after diagnosis. Multivariable logistic analysis demonstrated that inpatients with higher cortisol levels (p=0.0001), higher diastolic blood pressure (p=0.05) and females (p=0.009) were more likely not to be treated, while those with previous short-term glucocorticoid treatment (p=0.002), had other co-existing endocrine diseases (p=0.005) or received an inhospital endocrinology consultation (p<0.0001) were more likely to be replaced with glucocorticoids. Conclusions Commonly reported adrenal-cortisol insufficiency features do not reliably identify hospitalized patients biochemically confirmed to have this disorder. Co-morbidities including

[Vascular adrenal cyst causing difficult to control high blood pressure].

PubMed

García Escudero, D; Torres Roca, M; Hernández Contreras, M E; Sánchez Rodríguez, C; Oñate Celdrán, J

Hypertension is a prevalent disease in developed countries. Adrenal masses, and especially adrenal cysts, are a rare and usually asymptomatic finding, which can go unnoticed or be detected as incidental findings in imaging tests. These circumstances make the multidisciplinary approach mandatory. The case is presented on a 72 year-old woman with uncontrolled high blood pressure referred to the Urology Department due to the incidental finding of a right retroperitoneal mass. A functional and imaging study was performed, establishing a diagnosis of adrenal cyst causing hypertensive symptoms. A literature search was performed in order to assess diagnostic and therapeutic approaches. With the diagnosis of adrenal cyst causing uncontrolled high blood pressure, a right laparoscopic adrenalectomy was performed. After surgery the patient has maintained blood pressure within the normal range. A multidisciplinary approach is necessary for the management of rare diseases. The surgical approach, if possible, should be laparoscopic. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Simultaneous peritoneal and retroperitoneal splenosis mimics metastatic right adrenal mass.

PubMed

Hashem, Abdelwahab; Elbaset, M A; Zahran, Mohamed H; Osman, Yasser

2018-06-05

Right retroperitoneal splenosis is rare with few reported cases. We report, here, the case of simultaneous peritoneal and retroperitoneal splenosis mimics metastatic right adrenal mass. A 28-year-old man who had previously undergone post traumatic splenectomy at childhood and subsequently presented with an large incidental non-functioning right adrenal mass with presence of extra-hepatic peritoneal focal lesion diagnosed as metastasis by magnetic resonance imaging (MRI). Adrenalectomy with metatstectomy was performed, and both masses were identified to be splenosis. Adrenal incidentalomas (AIs) is defined as asymptomatic masses >1 cm. on cross-sectional imaging studies. AIs have significant malignant potential for masses > 6 cm. Splenosis are found most frequently in the left retroperitoneum in cases involving retroperitoneal splenosis. However, right retroperitoneal splenosis have been reported. Traditional imaging techniques cannot differentiate splenosis from malignancy. Large right adrenal incidentalomas present with other abdominal, peritoneal masses could be splenosis in patient following post-traumatic splenectomy. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.