Are Cushing's disease patients curable?

Treatment of Cushing's disease remains a challenge. Whereas pituitary surgery can “cure” the patient and restore a completely normal pituitary adrenal axis, there are immediate failures and late recurrences which ultimately require alternate therapeutic approaches. These are numerous, but so are their drawbacks, and all appear to be “default options”. For the future, pituitary adenoma has to remain the “reasonable obsession” of efficient and optimistic therapists…     

Low basal serum cortisol in patients with severe atopic dermatitis: potent topical corticosteroids wrongfully accused

BACKGROUND: Topical corticosteroids are used extensively to treat inflammatory skin disorders including atopic dermatitis (AD). Several studies have described temporary reversible suppression of hypothalamic-pituitary-adrenal function. However, sound evidence of permanent disturbance of adrenal gland function is lacking. OBJECTIVES: To relate basal cortisol levels to prior use of topical corticosteroids and disease activity in patients with moderate to severe AD and to investigate the effect on basal serum cortisol levels of topical corticosteroid treatment during hospitalization. METHODS: Two groups of patients with AD were evaluated: 25 inpatients with severe AD who required hospitalization (group 1) and 28 outpatients with moderate to severe AD (group 2). In group 1, morning basal serum cortisol levels were measured twice, at admission and at discharge; in group 2, morning basal serum cortisol levels were measured once. Use of topical corticosteroids in the 3 months prior to the cortisol measurement was recorded and disease activity was monitored using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score and serum thymus and activation-regulated chemokine (TARC) levels. RESULTS: On admission, basal cortisol levels in group 1 were significantly (P < 0.001) decreased in 80% of the patients. In group 2, the basal cortisol levels were normal in all but three patients. Comparing the two groups, group 1 on admission had a significantly lower cortisol level than that of group 2 (P < 0.001). Disease activity in group 1 on admission was significantly higher than that of group 2 (P < 0.001). There was no difference in use of topical corticosteroids in the 3 months before cortisol measurement. At discharge in group 1 there was a significant increase (P < 0.0001) of basal cortisol levels and a significant (P < 0.001) decrease in disease activity reflected by the decrease in serum TARC levels and SASSAD score. CONCLUSIONS: Disease activity, rather than the use of topical corticosteroids, is responsible for the low basal cortisol values in patients with severe AD.     

Comparison of the effects of 2-deoxyglucose and immobilization on secretion and synthesis rate of catecholamines in the adrenal gland: a microdialysis study in conscious rats

Using microdialysis, extracellular 3,4-dihydroxyphenylalanine (DOPA), noradrenaline (NA) and adrenaline (AD) concentrations in the adrenal gland were monitored in conscious rats during and after 60 min of immobilization (IMM) as well as after injection of 500 mg kg^-1 2-deoxyglucose (2-DG). IMM produced a rapid and transient increase in secretion of AD (20-fold), NA (13-fold) and DOPA (3.6-fold). This was accompanied by an increase in blood pressure (+ 18 mmHg) and heart rate (- 146 b. p.m.). Repeated exposure to IMM (daily 60 min, for 5 days) had no influence on either catecholamine secretion of haemodynamic profiles, indicating the lack of habituation to stressful conditions. Unlike IMM, the stress of 2-DG-induced centralneuroglucopenia stimulated the release of AD without affecting NA secretion. AD levels peaked (5.1-fold increase) 4&60 min after 2-DG injection and then slowly declined. 2-DG induced no changes in blood pressure but reduced the heart rate (-48 b. p.m.). In separate experiments, steady-state dialysate DOPA levels, reached during continuous infusion of decarboxylase inhibitor NSD 1015 into adrenal gland tissue through the dialysis probe, served as an index of adrenomedullary tyrosine hydroxylase (TH) activity. IMM evoked a marked increase in TH activity (DOPA formation increased 2.7-fold), which remained elevated 60 min after the cessation of stress when AD and NA secretion had already fallen to baseline. After 2-DG, despite significant hormonal response, adrenal TH activity was unchanged. These results give clear evidence that IMM and 2-DG-induced neuroglucopenia may be considered as two different types of stressful stimuli.     

Fine‐needle aspiration of a presacral myelolipoma: A case presentation with flow cytometry and immunohistochemical studies

Myelolipomas are benign soft‐tissue tumors predominantly found in the adrenal gland. Extra‐adrenal myelolipomas are rare, with about 30 previous cases reported. Approximately half of the reported cases were located in the presacral region. These were usually found at autopsy or during the workup of vague abdominal symptoms. Histologically, these lesions show bone marrow elements, with adipose tissue and scattered lymphoid aggregates. Radiologically‐guided fine‐needle aspiration (FNA) is helpful in establishing the diagnosis, thus obviating resection in some patients. We report on a case of an incidental presacral myelolipoma that underwent examination by computer tomography, magnetic resonance imaging, FNA, and immunohistochemical staining. This lesion was also analyzed by flow cytometry. To our knowledge, the use of the latter technique in the characterization of such tumors has not been previously reported. Diagn. Cytopathol. 1999;20:47–51. © 1999 Wiley‐Liss, Inc.     

Effects of Estrous Cycle and of in vivo Unilateral or Bilateral Adrenal Demedullation on the Distribution of Norepinephrine and Epinephrine Between Different Zones of the Adrenal

The distribution of norepinephrine (NE) and epinephrine (E) between the capsule/glomerular zone and the remainder of the adrenal was studied in the adult female rat. Both catecholamines were present in these two parts of the gland. The concentration of E was higher than that of NE. In the capsule/glomerular zone the catecholamine concentrations were more than twenty to thirty times lower than in the inner part of the gland. The circulating levels of catecholamines were always very low. The present data also support very weak or no changes in catecholamine concentrations in both parts of the adrenal during the different stages of the estrous cycle. The plasma levels of both aldosterone and corticosterone, like those of catecholamines, did not vary significantly throughout the estrous cycle. One week after unilateral or bilateral demedullation, both E content and concentration were reduced in the whole capsule/glomerular zone of the adrenal although the NE content did not change. The reduction of NE concentration could be related to the drastic weight increase of this part of the gland on the operated side. Moreover, unilateral demedullation was unable to significantly modify the plasma levels of both E and NE. In contrast bilateral demedullation suppressed circulating E and induced a significant reduction (about 50%) of NE plasma level. The present data suggest: 1) an extra-adrenal origin for the NE innervation of the capsule/glomerular zone of the adrenal cortex, and 2) a dual origin for E in the capsule/glomerular zone; part of E could arise from the adrenal medulla and part from an extra-adrenal site.     

原发性高血压合并无功能肾上腺意外瘤患者代谢综合征患病情况分析

目的：探讨原发性高血压合并无功能肾上腺意外瘤（NFAI）患者代谢综合征（MS）发生情况及其与皮质醇分泌水平的相关性。方法：复旦大学附属中山医院内分泌科2014年10月至2015年4月收治的原发性高血压合并NFAI患者56例（NFAI组）,原发性高血压肾上腺形态正常者58例（EH组）。收集身高、体质量、腹围、血压等体格检查参数;测定电解质,血脂谱,空腹及餐后2 h血糖水平,以及隔夜1 mg地塞米松试验（ONDST）后皮质醇水平。根据有无代谢综合征（MS）,分别将NFAI组和EH组患者分为MS组（MS组）和非MS组（NMS组）,比较各组ONDST后皮质醇水平。结果：NFAI组患者舒张压、体质指数（BMI）、腹围、餐后2 h 血糖、三酰甘油、ONDST后皮质醇水平高于EH组患者（P<0.05）。56例NFAI组患者中,22例（39.2%）合并MS,高于EH组患者（14例,24.1%,P<0.05）。NFAI组患者中,MS亚组患者ONDST后皮质醇水平高于NMS亚组患者（P<0.05）。随着NFAI组患者MS组分数量异常增加,ONDST后皮质醇水平逐渐升高。结论：原发性高血压合并NFAI患者MS患病率较高,其MS发生与ONDST后皮质醇水平相关。     

Devastating salt‐wasting crisis in a four‐month‐old male child with congenital adrenal hyperplasia,highlighting the essence of neonatal screening

Congenital adrenal hyperplasia (CAH) is a rare condition usually referred to as a group of genetic disorders resulting due to a deficiency of steroid enzymes required by adrenal glands to produce cortisol and mineralocorticoid hormones. It has an autosomal recessive mode of inheritance and is further categorized into two types—Classic and Non‐Classic. Non‐Classic CAH is a more common milder form that presents late after puberty. Classic CAH, although more severe, is rare and detected at birth and is associated with the life‐threatening adrenal crisis in both sexes and virilization of the external genitalia in females (46, XX) patients, whereas in males, no overt abnormality of the external genitalia is present. We present a case of a four‐month‐old male child with the classic form of CAH who was brought with complaints of loose stools, projectile non bilious vomiting, decreased urine output, and failure to feed for 3 days. The child had a clinical presentation of salt wasting with hypoglycemia and hyperpigmentation of his genitalia. The USG findings revealed increased anteroposterior diameter of renal pelvis indicative of a growth in the suprarenal area. 17‐hydroxyprogesterone (17‐OHP) was found to be elevated confirming the diagnosis. He was treated with hydrocortisone with gradual improvement in his glucose and electrolytes. The patient was discharged home on replacement therapy consisting of oral prednisolone and fludrocortisone acetate and followed up as outpatient with significant improvement in the clinical findings. The fact that the child was not screened for CAH at birth led to the critical consequences of the disease in this case. To prevent life‐threatening adrenal crisis and help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH should be made mandatory even in low‐ and middle‐income countries.     

消疲怡神口服液对应激大鼠下丘脑—垂体—肾上腺—胸腺轴？…

目的：探讨消疲怡神口服液抗应激的作用机理。方法：观察了消疲怡神口服液对强制冷水游泳大鼠模型血清单胺类物质、肾上腺抗坏血酸和下丘脑垂体单胺类递质含量及胸腺指数的影响。结果：消疲怡神口服液可以拮抗应激所致血清多巴胺、５－羟色胺含量升高和肾上腺抗坏血酸含量降低,使降低的下丘脑垂体去甲肾上腺素、５－羟色胺含量回升,但对胸腺旨数无明显影响。结论：消疲怡神口服液的作用机制与其对机体下丘脑－垂体－肾上腺－胸腺轴     

淫羊藿总黄酮拮抗皮质酮大鼠肾上腺皮质细胞凋亡的研究

目的:研究淫洋藿总黄酮(EF)拮抗糖皮质激素副作用,保护肾上腺皮质功能的机制。方法:采用肾上腺重量指数评价EF应用后萎缩的肾上腺皮质恢复情况;分离肾上腺细胞,流式细胞仪检测细胞凋亡率;并用末端脱氧核苷酸转移酶介导缺口末端标记法(TUNEL)原位检测细胞凋亡;用大鼠全基因组表达谱芯片检测凋亡相关基因表达。结果:与正常组相比,皮质酮组肾上腺重量指数显著下降,肾上腺细胞凋亡率明显上升,P<0.05;EF治疗后,肾上腺重量指数升高,细胞凋亡率明显下降,P<0.05。TUNEL显示正常组、皮质酮组、EF组每张切片平均凋亡细胞数分别为4.67±1.53、70.67±9.29、18.67±7.64;基因芯片发现正常大鼠肾上腺有53个凋亡相关基因表达,其中39个具有促凋亡活性,14个基因具有抗凋亡活性,促凋亡基因和抗凋亡基因组成了一个网络,皮质酮使3个具有抗凋亡活性的基因下调,EF治疗使具有抗凋亡活性AMP激活蛋白激酶α1催化亚单位基因和丝裂原激活蛋白激酶8相互作用蛋白基因显著上调。结论:EF拮抗皮质酮诱导的大鼠肾上腺皮质过度凋亡是其拮抗糖皮质激素对HPA轴的抑制,保护肾上腺皮质功能的机制。     

肾上腺囊肿的误诊分析

目的提高对肾上腺囊肿的诊断水平。方法回顾性分析9例经手术和病理证实被误诊的肾上腺囊肿的临床资料,复习文献并讨论肾上腺囊肿的误诊原因。结果误诊原因主要有四点：①对肾上腺囊肿的认识和重视程度不足;②B超作为初步诊断对术前诊断的影响较大;③B超和CT本身的局限性,对病灶来源判断不清;④部分肾上腺囊肿CT值较高,使得对病灶性质造成误判。结论提高对肾上腺囊肿的认识和重视程度对减少误诊率非常重要,合理地联合应用B超、CT、MRI能显著提高肾上腺囊肿的诊断正确率。