Abstract Background Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. ...Objectives This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). Methods A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery ShMOLLI). Results Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. Conclusions This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.
Genetics of congenital adrenal hyperplasia Krone, Nils, MD; Arlt, Wiebke, MD, DSc, FRCP
Best Practice & Research Clinical Endocrinology & Metabolism,
04/2009, Letnik:
23, Številka:
2
Journal Article
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Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. It comprises a group of autosomal recessive disorders caused by the deficiency of one of four ...steroidogenic enzymes involved in cortisol biosynthesis or in the electron donor enzyme P450 oxidoreductase (POR) that serves as electron donor to steroidogenic cytochrome P450 (CYP) type II enzymes. The biochemical and clinical phenotype depends on the specific enzymatic defect and the impairment of specific enzyme activity. Defects of steroid 21-hydroxylase (CYP21A2) and 11β-hydroxylase (CYP11B1) only affect adrenal steroidogenesis, whereas 17α-hydroxylase (CYP17A1) and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) deficiency also impact on gonadal steroid biosynthesis. Inactivating POR gene mutations are the cause of CAH manifesting with apparent combined CYP17A1–CYP21A2 deficiency. P450 oxidoreductase deficiency (ORD) has a complex phenotype including two unique features not observed in any other CAH variant: skeletal malformations and severe genital ambiguity in both sexes.
Despite treatment with glucocorticoids and mineralocorticoids, the ability to work and quality of life of patients who have adrenal insufficiency remains low. There are no helpful objective measures ...of optimal glucocorticoid replacement, so this is best achieved by careful clinical assessment. Adequacy of mineralocorticoid replacement may be judged by assessing postural change in blood pressure, serum electrolytes, and plasma renin activity. Novel delayed-release and sustained-release formulations of hydrocortisone seem to more closely mimic diurnal serum cortisol rhythms than conventional hydrocortisone tablets. Such preparations are currently being evaluated and may play a role in management of patients who have adrenal insufficiency.
Normal male sex development requires the SRY gene on the Y chromosome, the regression of Müllerian structures via anti-Müllerian hormone (AMH) signalling, the development of the Wolffian duct system ...into normal male internal genital structures consequent to testosterone secretion by the testicular Leydig cells, and finally, sufficient activation of testosterone to dihydrotestosterone by 5α-reductase. All these events take place during weeks 8–12 of gestation, a narrow window of sexual differentiation. Recent studies in human fetal development have demonstrated the early fetal expression of the adrenocorticotrophic hormone (ACTH) receptor and all steroidogenic components necessary for the biosynthesis of cortisol. These findings provide compelling evidence for the assumed pathogenesis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, diminished feedback to the pituitary due to glucocorticoid deficiency, subsequent ACTH excess, and up-regulation of adrenal androgen production with subsequent virilization. Another CAH variant, P450 oxidoreductase deficiency, manifests with 46,XX disorder of sex development (DSD), i.e., virilized female genitalia, despite concurrently low circulating androgens. This CAH variant illustrates the existence of an alternative pathway toward the biosynthesis of active androgens in humans which is active in human fetal life only. Thus CAH teaches important lessons from nature, providing privileged insights into the window of human sexual differentiation, and particularly highlighting the importance of steroidogenesis in the process of human sexual differentiation.
To characterize large adrenal tumors (≥4 cm in diameter) and to identify features associated with malignancy.
We investigated the clinical, biochemical, and imaging characteristics in a large ...retrospective single-center cohort of patients with adrenal tumors of 4 cm or more in diameter during the period of January 1, 2000, through December 31, 2014.
Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 31%), pheochromocytomas (n=158 22%), other benign adrenal tumors (n=116 16%), adrenocortical carcinomas (n=88 13%), and other malignant tumors (n=127 18%). Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm range, 4-24.4 cm vs 5 cm range, 4-20 cm), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units HU range, 14.1-75.5 HU vs 11.5 HU range, −110 to 71.3 HU; P<.001). On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy.
The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.
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