Congenital Adrenal Hyperplasia

Mallappa, Ashwini; Merke, Deborah P.

doi:10.1007/978-3-319-44136-8_11

Cited by 3 publications

(3 citation statements)

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“…Eight patients (9%) had an adrenocortical adenoma (median size; 7.5 mm, range 5‐42 mm). One subject had a pheochromocytoma (28 × 23 mm) that was discovered incidentally . He was asymptomatic with markedly elevated 24‐hours total urinary metanephrines 7975 nmol/d (normal 1014‐3113), normetanephrines 8293 nmol/d (normal 606‐2329).…”

Section: Resultsmentioning

confidence: 99%

“…One subject had a pheochromocytoma (28 × 23 mm) that was discovered incidentally. 26 He was asympto- Patients with normal or atrophied adrenals had the highest rates of low BMD. Although the type of comorbidity varied depending on adrenal morphology, CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than CAH patients with normal adrenals (Table 2).…”

Section: Radiographical Characteristicsmentioning

confidence: 91%

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Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia

El‐Maouche

Hannah‐Shmouni

Mallappa

et al. 2019

Clinical Endocrinology

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Objective Adrenonodular hyperplasia and tumour formation are potential long‐term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH. Design This was a cross‐sectional study of 88 patients (mean age 29.2 ± 13 years, 47 females) with classic CAH seen in a tertiary referral centre. Methods CT imaging, performed at study entry or when reaching adulthood, was used to create 3‐dimensional volumetric models. Clinical, genetic and hormonal evaluations were collected and correlated with adrenal morphology and tumour formation. Results Over one‐third of the cohort was obese. 53% had elevated 17‐OH‐progesterone or androstenedione; and 60% had adrenal hyperplasia. Tumours included 11 myelolipomas, 8 benign adrenocortical adenomas, 1 pheochromocytoma and 50% of men had testicular adrenal rest tissue. CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than those with morphologically normal adrenals (P = 0.03). Variables that positively correlated with adrenal volume included hypogonadal/oligomenorrhoeic status, hypertension, androstenedione, aldosterone, and triglyceride levels, and in women, low HDL and insulin resistance. Elevated aldosterone was observed in a subset of patients with simple virilizing CAH. Conclusions Adrenocortical hyperplasia is associated with a number of comorbidities, especially hypogonadism. Aldosterone production associated with adrenal enlargement may play a role in the development of metabolic risk factors. Further studies are needed to assess the long‐term impact of the excess adrenal steroid milieu associated with adrenal enlargement to develop improved management strategies for CAH.

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Section: Resultsmentioning

confidence: 99%

Section: Radiographical Characteristicsmentioning

confidence: 91%

Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia

El‐Maouche

Hannah‐Shmouni

Mallappa

et al. 2019

Clinical Endocrinology

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“…ричиной развития опухолей коры надпочечников может быть врожденная дисфункция коры надпочечников (ВДКН) -генетическое заболевание, чаще всего обусловленное дефицитом 21-гидроксилазы, вызванным мутациями гена CYP21A2, и влияющее на биосинтез кортизола. Ряд авторов показали, что длительные (не менее 5 лет) эпизоды декомпенсации ВДКН с дефицитом 21-гидроксилазы приводят к появлению вторичных новообразований в надпочечниках у 29% больных [1]. Как установили в 2016 г. на основании анализа 36 публикаций H. Falhammar и D.J.…”

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Specific characteristics of metabolomics as assessed by gas chromatography-mass spectrometry in patients with adrenocortical cancer and with adrenal incidentalomas in congenital adrenal hyperplasia

Shafigullina

Великанова

Ворохобина

et al. 2022

Almanac of Clinical Medicine

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Background: Prolonged episodes of uncontrolled congenital adrenal hyperplasia (CAH) have been shown to result in the occurrence of secondary adrenal neoplasms. Prevalence of adrenal incidentalomas in the patients with 21-hydroxylase deficiency ranges from 11% to 82%. As assessed by gas chromatography-mass spectrometry (GC-MS), patients with adrenocortical cancer (ACC) have increased level of steroid hormone precursors due to decreased activity of adrenal steroidogenesis enzymes, mainly that of 21-hydroxylase and 11-hydroxylase. It seems relevant to compare the specific characteristics of steroid metabolism by GC-MS in ACC patients and in patients with adrenal incidentalomas and CAH associated with 21-hydroxylase deficiency (21-OHD). Aim: To identify (by GC-MS) common abnormalities in steroid metabolism and differential diagnostic biomarkers in ACC patients and CAH patients with 21-OHD and adrenal masses. Materials and methods: The study included 41 patients with adrenal cortex neoplasms aged 18 to 65 years without clinical and laboratory signs of endogenous hypercortisolism. Twenty three (23) patients had non-metastatic ACC and 18 patients had CAH due to 21-OHD. The control group included 26 healthy blood donors aged 20 to 59 years. Urine steroid profiles were measured by GC-MS with a gas chromatograph-mass spectrometer (Shimadzu GCMS-QP2020). Results: In the ACC patients, there was an increase in urinary excretion of tetrahydro-11-deoxycortisol, dehydroepiandrosterone, androstenediol-17, etiocholanolone, pregnenediol, and 3,16,20-pregnenetriol (3,16,20-dP3), as well as a decrease in the 3,16,20-dP3/3,16,20-dP3 ratio, compared to the values in the patients with CAH due to 21-OHD. Compared to the healthy control, 21-hydroxylase, 11-hydroxylase, 5-reductase and 11-hydroxysteroid-dehydrogenase (11-HSDH) type 2 activities were lower. Compared to the ACC patients, those with CAH due to 21-OHD had higher urinary excretion of 11-oxo-pregnanetriol (11-oxo-P3) and 21-deoxy-tetrahydrocortisol and lower 5-THF+5-THF+THE)/11-oxo-P3 ratio of 9.0, determination of 11-oxo-dP3, signs higher 5-reductase activity and lower 11-HSDH type 1 activity. The ACC patients and the patients with CAH due to 21-OHD had common abnormalities of steroid metabolism, such as lower activities of 21-hydroxylase, 3-hydroxysteroid-dehydrogenase and 11-hydroxylase, and no differences in urinary excretion of a number of ACC biomarkers (androgens, pregnanediol, and 5-ene-pregnenes). Conclusion: The assessment of urinary excretion of androgens, progestagens, and glucocorticoids by GC-MS made it possible to identify common abnormalities in steroid metabolism in the patients with ACC and CAH due to 21-OHD, which confirms the role of disordered steroidogenesis in the formation of adrenocortical tumors.

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Management challenges and therapeutic advances in congenital adrenal hyperplasia

Mallappa

Merke

2022

Nat Rev Endocrinol

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Treatment for congenital adrenal hyperplasia (CAH) was introduced in the 1950s following the discovery of the structure and function of adrenocortical hormones. Although major advances in molecular biology have delineated steroidogenic mechanisms and the genetics of CAH, management and treatment of this condition continue to present challenges. Management is complicated by a combination of comorbidities that arise from disease-related hormonal derangements and treatment-related adverse effects. The clinical outcomes of CAH can include life-threatening adrenal crises, altered growth and early puberty, and adverse effects on metabolic, cardiovascular, bone and reproductive health. Standard-of-care glucocorticoid formulations fall short of replicating the circadian rhythm of cortisol and controlling efficient adrenocorticotrophic hormone-driven adrenal androgen production. Adrenal-derived 11-oxygenated androgens have emerged as potential new biomarkers for CAH, as traditional biomarkers are subject to variability and are not adrenal-specific, contributing to management challenges. Multiple alternative treatment approaches are being developed with the aim of tailoring therapy for improved patient outcomes. This Review focuses on challenges and advances in the management and treatment of CAH due to 21-hydroxylase deficiency, the most common type of CAH. Furthermore, we examine new therapeutic developments, including treatments designed to replace cortisol in a physiological manner and adjunct agents intended to control excess androgens and thereby enable reductions in glucocorticoid doses.

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Congenital Adrenal Hyperplasia

Cited by 3 publications

References 80 publications

Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia

Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia

Specific characteristics of metabolomics as assessed by gas chromatography-mass spectrometry in patients with adrenocortical cancer and with adrenal incidentalomas in congenital adrenal hyperplasia

Management challenges and therapeutic advances in congenital adrenal hyperplasia

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