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Andre Lacroix - One of the best experts on this subject based on the ideXlab platform.

  • primary bilateral macronodular Adrenal Hyperplasia
    Current Opinion in Endocrinology Diabetes and Obesity, 2014
    Co-Authors: Agostino De Venanzi, Guilherme Asmar Alencar, Isabelle Bourdeau, Maria Candida Barisson Villares Fragoso, Andre Lacroix
    Abstract:

    Purpose of reviewPrimary bilateral macronodular Adrenal Hyperplasia is a rare cause of Cushing's syndrome and is more often diagnosed as bilateral Adrenal incidentalomas with subclinical cortisol production. We summarize the recent insights concerning its epidemiology, diagnosis, genetics, pathophys

  • heredity and cortisol regulation in bilateral macronodular Adrenal Hyperplasia
    The New England Journal of Medicine, 2013
    Co-Authors: Andre Lacroix
    Abstract:

    Cushing's syndrome is a challenging disease in which excess cortisol is secondary to diverse tumors with complex molecular mechanisms. The syndrome has been categorized as corticotropin-dependent or corticotropin-independent. Approximately 20% of cases — mainly cortisol-secreting unilateral adenomas or carcinomas — are considered corticotropin-independent. Cushing's syndrome rarely (in <2% of cases) results from primary bilateral nodular Hyperplasia (either corticotropin-independent macronodular Adrenal Hyperplasia or micronodular Hyperplasia). Bilateral macronodular Adrenal Hyperplasia with subclinical cortisol secretion is more frequent; approximately 10% of incidentally detected Adrenal lesions, which are seen in approximately 4% of adults, are bilateral.1 Despite suppressed levels of circulating corticotropin, excess cortisol . . .

  • acth independent macronodular Adrenal Hyperplasia
    Best Practice & Research Clinical Endocrinology & Metabolism, 2009
    Co-Authors: Andre Lacroix
    Abstract:

    Adrenocorticotropic hormone- (ACTH-)independent macronodular Adrenal Hyperplasia (AIMAH) is an infrequent cause of Cushing's syndrome (CS). AIMAH presents as incidental radiological finding or with subclinical or overt CS, occasionally with secretion of mineralocorticoids or sex steroids. The pathophysiology of this entity is heterogeneous. The aberrant Adrenal expression and function of one or several G-protein-coupled receptors can lead to cell proliferation and abnormal regulation of steroidogenesis. In several familial cases of AIMAH, specific aberrant hormone receptors are functional in the Adrenal of affected members. Additional somatic genetic events related to cell cycle regulation, adhesion and transcription factors occur in addition in the various nodules over time. Other mechanisms, such as Gsp or ACTH receptor mutations and paracrine Adrenal hormonal secretion, have been rarely identified in other cases of AIMAH. The identification of aberrant receptors can offer a specific pharmacological approach to prevent progression and control abnormal steroidogenesis; alternatively, unilateral or bilateral Adrenalectomy becomes the treatment of choice.

Maria I. New - One of the best experts on this subject based on the ideXlab platform.

  • fertility in patients with nonclassical congenital Adrenal Hyperplasia
    Fertility and Sterility, 2019
    Co-Authors: Maria I. New, Ahmed Khattab, David E Reichman, Lucia Ghizzoni, Heino F L Meyerbahlburg, Zev Rosenwaks
    Abstract:

    Nonclassical congenital Adrenal Hyperplasia (NC-CAH) is by far a subtler and milder enzymatic defect to the classical form of the disease. A nuanced understanding of NC-CAH will lead to increased detection of the disorder in those initially misdiagnosed as having polycystic ovary syndrome, will assist in the detection of pregnancies at risk for severe genetic steroid disorders, and will facilitate appropriate ovulation induction and reduction in the hyperandrogenic symptoms which are a cornerstone of the disease. We describe the history of the disease as well as elucidate the pathophysiology, diagnosis, and treatment of the disorder.

  • fertility in patients with congenital Adrenal Hyperplasia
    Fertility and Sterility, 2014
    Co-Authors: David E Reichman, Maria I. New, Perrin C White, Zev Rosenwaks
    Abstract:

    Congenital Adrenal Hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11β-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options.

  • growth hormone therapy to improve adult height in patients with congenital Adrenal Hyperplasia
    Genetic Steroid Disorders, 2014
    Co-Authors: Karen Linsu, Oksana Lekarev, Maria I. New
    Abstract:

    Abstract Many patients with congenital Adrenal Hyperplasia (CAH) do not reach a final adult height within their parentally determined target height range. Our group has reported the effect of growth hormone (GH) alone or in combination with luteinizing hormone releasing hormone analog (LHRHa) on final adult height in 34 patients with CAH. Final adult height was significantly higher than baseline predicted height in both males (172.0 + 4.8 cm versus 162.8 + 7.7 cm, P

  • steroid 21 hydroxylase deficiency congenital Adrenal Hyperplasia
    Pediatric Clinics of North America, 2011
    Co-Authors: Saroj Nimkarn, Karen Linsu, Maria I. New
    Abstract:

    Steroid 21 hydroxylase deficiency is the most common form of congenital Adrenal Hyperplasia (CAH). The severity of this disorder depends on the extent of impaired enzymatic activity, which is caused by various mutations of the 21 hydroxylase gene. This article reviews Adrenal steroidogenesis and the pathophysiology of 21 hydroxylase deficiency. The three forms of CAH are then discussed in terms of clinical presentation, diagnosis and treatment, and genetic basis. Prenatal diagnosis and treatment are also reviewed. The goal of therapy is to correct the deficiency in cortisol secretion and suppress androgen overproduction. Glucocorticoid replacement has been the mainstay of treatment for CAH, but new treatment strategies continue to be developed and studied.

  • An Update of Congenital Adrenal Hyperplasia
    Annals of the New York Academy of Sciences, 2004
    Co-Authors: Maria I. New
    Abstract:

    Publisher Summary Congenital Adrenal Hyperplasia (CAH) is a family of disorders of Adrenal steroidogenesis resulting from an inherited deficiency of one of several enzymes necessary for normal steroid synthesis. This chapter describes the recent advances in congenital Adrenal Hyperplasia. These advances have come from the interdisciplinary collaboration of embryologists, teratologists, enzymologists, immunogeneticists, population geneticists, steroid endocrinologists, and gender psychologists. The chapter describes asimplified scheme of Adrenal steroidogenesis. It provides an overview of the additional evidence that supports the concept that the Adrenal fasciculate and glomerulosa function as two separate glands. This has been gained from the recent study of patients with 21-hydroxylase deficiency. New data shows that in CAH, there is a 21-hydroxylation defect in the zona fasciculata of simple virilizers and salt wasters, whereas zona glomerulosa is defective in salt wasters and not in simple virilizers. The data suggest that there is one enzyme involved in the 21-hydroxylation of the 17-hydroxy and 17-deoxy pathways of Adrenal steroidogenesis in zona fasciculata.

Deborah P. Merke - One of the best experts on this subject based on the ideXlab platform.

  • congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency
    Yearbook of Paediatric Endocrinology, 2021
    Co-Authors: Deborah P. Merke, Richard J Auchus
    Abstract:

    CAH Due to 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia, a common autosomal recessive disorder, is potentially life-threatening in its classic form and may be asymptomatic or cause fema...

  • Modified-release Hydrocortisone in Congenital Adrenal Hyperplasia
    Journal of Clinical Endocrinology and Metabolism, 2021
    Co-Authors: Deborah P. Merke, Wiebke Arlt, Ashwini Mallappa, Aude Brac De La Perriere, Angelica Lindén Hirschberg, Anders Juul, John D. C. Newell-price, Colin G Perry, Alessandro Prete, Aled Rees
    Abstract:

    Background Standard glucocorticoid therapy in congenital Adrenal Hyperplasia regularly fails to control androgen excess, causing glucocorticoid over-exposure and poor health outcomes. We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control. Methods 6-month randomized phase III study, MR-HC versus standard glucocorticoid, followed by single-arm MR-HC extension study. Primary outcomes were change in 24-hour standard deviation score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase III, and efficacy, safety and tolerability of MR-HC for the extension study. Results The phase III study recruited 122 adult CAH patients. While the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P=0.007) and 12 (P=0.019) weeks, and between 07:00h to 15:00h (P=0.044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (

  • genetics of congenital Adrenal Hyperplasia
    Endocrinology and Metabolism Clinics of North America, 2017
    Co-Authors: Fady Hannahshmouni, Wuyan Chen, Deborah P. Merke
    Abstract:

    Congenital Adrenal Hyperplasia (CAH) refers to a group of autosomal recessive disorders due to single-gene defects in the various enzymes required for cortisol biosynthesis. CAH represents a continuous phenotypic spectrum with more than 95% of all cases caused by 21-hydroxylase deficiency. Genotyping is an important tool in confirming the diagnosis or carrier state, provides prognostic information on disease severity, and is essential for genetic counseling. In this article, the authors provide an in-depth discussion on the genetics of CAH, including genetic diagnosis, molecular analysis, genotype-phenotype relationships, and counseling of patients and their families.

  • Congenital Adrenal Hyperplasia
    Lancet (London England), 2017
    Co-Authors: Diala El-maouche, Wiebke Arlt, Deborah P. Merke
    Abstract:

    Summary Congenital Adrenal Hyperplasia is a group of autosomal recessive disorders encompassing enzyme deficiencies in the Adrenal steroidogenesis pathway that lead to impaired cortisol biosynthesis. Depending on the type and severity of steroid block, patients can have various alterations in glucocorticoid, mineralocorticoid, and sex steroid production that require hormone replacement therapy. Presentations vary from neonatal salt wasting and atypical genitalia, to adult presentation of hirsutism and irregular menses. Screening of neonates with elevated 17-hydroxyprogesterone concentrations for classic (severe) 21-hydroxylase deficiency, the most common type of congenital Adrenal Hyperplasia, is in place in many countries, however cosyntropin stimulation testing might be needed to confirm the diagnosis or establish non-classic (milder) subtypes. Challenges in the treatment of congenital Adrenal Hyperplasia include avoidance of glucocorticoid overtreatment and control of sex hormone imbalances. Long-term complications include abnormal growth and development, adverse effects on bone and the cardiovascular system, and infertility. Novel treatments aim to reduce glucocorticoid exposure, improve excess hormone control, and mimic physiological hormone patterns.

  • Management of adolescents with congenital Adrenal Hyperplasia
    The lancet. Diabetes & endocrinology, 2013
    Co-Authors: Deborah P. Merke, Dix P. Poppas
    Abstract:

    Summary The management of congenital Adrenal Hyperplasia involves suppression of Adrenal androgen production, in addition to treatment of Adrenal insufficiency. Management of adolescents with congenital Adrenal Hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of Adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital Adrenal Hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital Adrenal Hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital Adrenal Hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital Adrenal Hyperplasia, common issues include testicular Adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed.

Estelle Louiset - One of the best experts on this subject based on the ideXlab platform.

  • cell to cell communication in bilateral macronodular Adrenal Hyperplasia causing hypercortisolism
    Frontiers in Endocrinology, 2015
    Co-Authors: Herve Lefebvre, Jérôme Bertherat, Celine Duparc, Gaetan Prevost, Estelle Louiset
    Abstract:

    It has been well established that, in the human Adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes and endothelial cells. These different types of cells are present in bilateral macronodular Adrenal Hyperplasia, a rare etiology of primary Adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events which cause the disease favor abnormal Adrenal differenciation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms which are likely to play a role in the pathophysiology of bilateral macronodular Adrenal Hyperplasia-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept.

  • intraAdrenal corticotropin in bilateral macronodular Adrenal Hyperplasia
    The New England Journal of Medicine, 2013
    Co-Authors: Estelle Louiset, Celine Duparc, Jacques Young, Sylvie Renouf, Milene Tetsi Nomigni, Isabelle Boutelet, Rossella Libe, Zakariae Bram, Lionel Groussin, Philippe Caron
    Abstract:

    BACKGROUND 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. METHODS 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-chainreaction 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. RESULTS 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 corticotropinreleasing 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. CONCLUSIONS 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 steroidogenic cells in the hyperplastic Adrenals. Thus, the hypercortisolism associated with bilateral macronodular Adrenal Hyperplasia appears to be corticotropin-dependent. (Funded by the Agence Nationale de la Recherche and others.)

  • acth independent cushing s syndrome with bilateral micronodular Adrenal Hyperplasia and ectopic adrenocortical adenoma
    The Journal of Clinical Endocrinology and Metabolism, 2010
    Co-Authors: Estelle Louiset, Sylvie Renouf, Rossella Libe, Françoise Gobet, Anelia Horvath, Juliette Cariou, Anya Rothenbuhler, Jérôme Bertherat, Eric Clauser, Philippe Grise
    Abstract:

    Context: Bilateral micronodular Adrenal Hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular Adrenal Hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of Adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in Adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcom...

Perrin C White - One of the best experts on this subject based on the ideXlab platform.

  • fertility in patients with congenital Adrenal Hyperplasia
    Fertility and Sterility, 2014
    Co-Authors: David E Reichman, Maria I. New, Perrin C White, Zev Rosenwaks
    Abstract:

    Congenital Adrenal Hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11β-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options.

  • genotype of yupik eskimos with congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency
    Human Genetics, 1992
    Co-Authors: Phyllis W Speisere, Maria I. New, Grace M Tannin, Donald Pickering, Soo Young Yang, Perrin C White
    Abstract:

    An A-to-G transition in the second intron was the sole mutation detected in four Yupik Eskimo patients with salt-wasting congenital Adrenal Hyperplasia due to steroid 21-hydroxylase deficiency. Allele-specific hybridization should be an efficient means of performing prenatal diagnosis of the disease in this highly inbred population.

  • aldosterone synthesis in salt wasting congenital Adrenal Hyperplasia with complete absence of Adrenal 21 hydroxylase
    The New England Journal of Medicine, 1991
    Co-Authors: Phyllis W. Speiser, Levon Agdere, Hajime Ueshiba, Perrin C White, Maria I. New
    Abstract:

    Abstract Background. Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency is a disorder of cortisol and aldosterone biosynthesis that results from mutations in the CYP21 gene encoding the Adrenal 21-hydroxylase P-450c21. It can cause severe salt wasting in newborns that requires long-term treatment with glucocorticoids and mineralocorticoids. We describe a spontaneous partial recovery from this disorder in a 19-year-old woman who had discontinued treatment. Methods. We measured plasma and urinary levels of Adrenal hormones, plasma renin activity, and sodium balance longitudinally in the patient and four other patients in whom Adrenal Hyperplasia had been diagnosed in infancy and in whom DNA analysis had predicted a complete absence of functional P-450c21. The ratio of plasma renin activity to urinary aldosterone was used as a measure of the response of the Adrenal zona glomerulosa. Two patients underwent intravenous infusion of [3H]progesterone for the measurement of extraAdrenal production of ...