Serum bone Gla protein and carboxyterminal cross-linked telopeptide of type I collagen in patients with Cushing's syndrome.

Serum bone Gla protein, a marker of bone formation, and carboxyterminal cross-linked telopeptide of type I collagen levels, an index of bone resorption, were evaluated in eight patients with active Cushing''s syndrome and in four with ''preclinical'' Cushing''s syndrome, before and after surgery. In basal conditions, serum bone Gla protein levels were significantly lower (p < 0.0001) in patients with active Cushing''s syndrome (1.0 +/- 0.35 ng/ml) than in controls (5.4 +/- 0.15 ng/ml); two out of four patients with the ''preclinical'' form had reduced bone Gla protein levels, while in the other two cases levels were in the normal range. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (3.0 +/- 0.4 ng/ml), although slightly reduced, were similar to those recorded in controls (4.1 +/- 0.3 ng ml), both in patients with active and with preclinical Cushing''s syndrome. After surgery serum levels of both marker proteins significantly increased in seven out of eight patients with active Cushing''s syndrome; in one patient, who was not cured after surgery, bone Gla proteins levels remained lower than in normals, while levels of carboxyterminal cross-linked telopeptide of type I collagen had a transient increase after six months. In the two patients with a ''preclinical'' Cushing''s syndrome who underwent surgery, a significant rise of the levels of both marker proteins was observed, similar to that observed in patients with active Cushing''s syndrome. It was concluded that serial determinations of these new markers of bone formation and resorption may be usefully employed to follow-up the clinical course of Cushing''s syndrome and provide information on the rate of bone turnover in response to medical and/or surgical therapies. Moreover, the evaluation of these markers in preclinical states of Cushing''s syndrome might suggest the need for surgery.     

Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In-DTPA-D-Phe1]octreotide.

The differential diagnosis and management of Cushing''s syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing''s syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing''s syndrome and the procedure for localisation of an ACTH source are discussed.     

Diagnostic difficulties in periodic Cushing's syndrome.

A 22-year-old black woman presented with symptoms suggestive of Cushing''s syndrome three years after chemotherapy for a presumed teratoma with cervical lymphadenopathy. Initially, the absence of clinical signs and the demonstration of two normal 24 h urinary free cortisols appeared to exclude the diagnosis, but an ectopic adrenocorticotropin-producing thymic carcinoid was subsequently removed surgically. Cushing''s syndrome due to ectopic adrenocorticotropin production can be difficult to diagnose, particularly if there is periodic hormonogenesis.     

双侧肾上腺高功能皮质腺瘤致ACTH非依赖性库欣综合征3例临床诊疗探索

目的 探讨双侧肾上腺高功能皮质腺瘤致促肾上腺皮质激素（ACTH）非依赖性库欣综合征的临床特点、诊治思路,提高对该疾病的认知。 方法 收集2016～2021年四川大学华西医院内分泌代谢科收治的3例双侧肾上腺功能性皮质腺瘤致ACTH非依赖性库欣综合征患者行回顾性分析,分析患者的一般情况、症状及体征、辅助检查、诊治过程等临床资料,并结合文献进行复习和讨论。 结果 3例患者均表现为典型且严重的库欣综合征,并伴有显著的心脏和代谢并发症,影像学提示双侧肾上腺单发腺瘤;2例患者行双侧肾上腺静脉采血,均提示双侧肾上腺皮质醇高分泌且无优势侧;1例患者行双侧肾上腺肿物切除术,另外2例患者因为心功能不全严重,行分期双侧肾上腺肿物切除术,术后病理结果3例均提示双侧肾上腺皮质腺瘤,术后皮质醇浓度均明显降低,均给长期予糖激素替代治疗。 结论 双侧肾上腺高功能皮质腺瘤致ACTH非依赖性库欣综合征非常罕见,明确诊断并判断双侧功能定位非常重要,治疗上应根据患者的病情及并发症情况个体化的选择最适合患者的手术方式,术后应严密随访,及时给予并调整糖皮质激素替代治疗,并终身随访。     

Iatrogenic Cushing's syndrome due to nasal betamethasone: a problem not to be sniffed at!

Nasal steroid drops for the treatment of allergic rhinitis can cause iatrogenic Cushing''s syndrome and care should be taken with their use in clinical practice.     

Anomalous responses to stimulation and suppression tests in Cushing's syndrome due to a calcified adrenal adenoma

A case of Cushing''s syndrome, due to an adrenal adenoma, which responded to dexamethasone with a rise in plasma urinary steroids is described. Further unusual features were radiologically visible calcification and a response to ACTH stimulation.     

Adrenocorticotropin-secreting carcinoid tumour identified and treated 12 years after presentation with Cushing's syndrome.

A case of Cushing''s syndrome due to an adrenocorticotropin (ACTH) secreting bronchial carcinoid tumour is described. Endocrine assessment suggested ectopic ACTH syndrome, but imaging revealed no tumour. Bilateral adrenalectomy was performed, and computed tomographic scans of chest and abdomen were performed annually. A small nodule became apparent in the right lung 12 years after the presentation, which postoperatively was confirmed as the bronchial carcinoid tumour responsible for the ectopic ACTH syndrome.     

Treatment of an adrenal cortical carcinoma with a combination of o,p��-DDD and aminoglutethimide

A patient with Cushing''s syndrome due to an adrenocortical carcinoma is described. Treatment of residual disease and functional metastases was attempted with o,p′-DDD and later aminoglutethimide. Aminoglutethimide in a daily dose of 1 g appeared to have little effect additional to o,p′-DDD. It is important to maintain replacement therapy with cortico-steroids throughout the use of these drugs.     

Secretory symptoms from metastatic adrenal cortical carcinoma responding to octreotide.

The prognosis of patients with metastatic adrenal cortical carcinoma is poor, and their disabling symptoms are usually unresponsive to conventional therapy. A patient with Cushing''s syndrome secondary to a secretory adrenal cortical carcinoma was treated with octreotide, endocrine therapy and chemotherapy having failed. Treatment led to a dramatic relief of her symptoms with a fall in corticosteroid secretion. Somatostatin analogue therapy for this tumour should be encouraged in view of the lack of alternative palliative treatment.     

Benign intracranial hypertension after pituitary surgery for Cushing's disease.

An 11 year old girl underwent successful transsphenoidal pituitary adenomectomy for pituitary-dependent Cushing''s syndrome. Three months after operation, just after stopping glucocorticoid replacement therapy, she developed benign intracranial hypertension. This resolved when exogenous glucocorticoids were restarted but occurred again when they were later stopped. On restarting glucocorticoids again, this second episode of intracranial hypertension resolved. This complication may have been due to the large fall in endogenous cortisol production after removal of her adenoma and subsequent persistent mild endogenous hypocortisolism.     

Diabetic retinopathy in Cushing's disease

A patient with proliferative diabetic retinopathy in long-standing Cushing''s disease is described.     

Lung carcinoid related Cushing's syndrome: report of three cases and review of the literature

Three patients with lung carcinoid related Cushing''s syndrome (LCRCS) treated at Frenchay Hospital, Bristol between 1984 and 1994 are described. The first patient presented with hyperpigmentation 13 years after bilateral adrenalectomy. The second patient had no recurrence or metastases 14 years after removal of a typical carcinoid tumour. The last patient survived nine years after diagnosis of liver metastasis. The possibility of LCRCS should be considered in every patient proved to have Cushing''s disease and bilateral adrenal enlargement on abdominal computed tomography. Biochemical sets of investigation (for example, adrenocorticotrophic hormone (ACTH) stimulation, dexamethasone suppression, and metyrapone response) could be misleading and should not be relied upon solely. Search for an ectopic ACTH source should be called off only when ACTH has been demonstrated in the surgically removed specimen, and most importantly, when the serum ACTH concentration returns to normal after surgery. Lung carcinoid tumours are compatible with long survival, and liver metastasis could prove indolent and slowly growing.


     

Post-thymectomy collapse: an unusual case of acute adrenal insufficiency.

A 54-year-old man who had an appearance strongly suggestive of Cushing''s syndrome, collapsed after the removal of a carcinoid tumour of the thymus. The clinical suspicion of acute adrenal insufficiency was supported by invasive haemodynamic data and the diagnosis was subsequently confirmed biochemically. These post-operative events were subsequently ignored and a further crisis was probably prevented by tumour recurrence (and hence resumption of adrenocorticotropic hormone (ACTH) production). The ectopic production of ACTH from a carcinoid tumour of the thymus is recognised but a report of acute adrenal insufficiency from its removal is probably unique.     

Somatostatin analogue treatment of neuroendocrine tumours.

The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically ''nonfunctioning'' pituitary tumours are still uncertain. Somatostatin analogues are not useful in the treatment of patients with prolactinomas, or adrenocorticotropin (ACTH)-secreting adenomas. However, the somatostatin analogue octreotide suppressed pathological ACTH release in some patients with Nelson''s syndrome and ACTH and cortisol secretion in several patients with Cushing''s syndrome caused by ectopic ACTH secretion. Somatostatin analogues are effective in the sympatomatic treatment of most (metastatic) pancreatic islet cell tumours and most (metastatic) carcinoids. In some of these patients, they also induce tumour stabilisation or reduction. In some patients with (metastatic) medullary thyroid carcinomas, continuous treatment with very high doses of octreotide can be of temporary relief. The clinical effectiveness of somatostatin analogues in patients with small cell lung cancer is currently under investigation. Long-term therapy with somatostatin analogues of catecholamine-secreting (malignant) paragangliomas and phaeochromocytomas has not shown clinical benefits.     

促肾上腺皮质激素非依赖性库欣综合征患者肾周及皮下脂肪组织的炎症及纤维化

目的 探讨促肾上腺皮质激素(ACTH)非依赖性库欣综合征患者不同部位脂肪组织炎症及纤维化程度.方法 收集行后腹腔镜下肾上腺肿物切除术的ACTH非依赖性库欣综合征患者的肾脏周围及皮下脂肪组织,RT-PCR检测白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及基质金属蛋白酶-2(MMP-2)、金属蛋白酶类组织抑制剂1(TIMP1)、早期生长反应因子1(EGR1)及脂肪因子CCAAT增强子结合蛋白β(CEBPβ)、解耦联蛋白-1(UCP-1)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)及细胞死亡介导的DNA碎片因子样受体a(CIDEA)mRNA的表达.结果 ACTH非依赖性库欣综合征患者肾周脂肪组织中CIDEA mRNA的表达显著高于皮下脂肪组织(P<0.05).而脂肪因子CEBPβ、UCP-1及PGC1αmRNA的表达在肾脏周围脂肪及皮下脂肪组织中差异无统计学意义.皮下脂肪组织IL-6、TIMP1及EGR1 mRNA的表达显著高于肾脏周围脂肪组织(P<0.05).肾周脂肪组织及皮下脂肪中TNF-α及MMP-2 mRNA的表达相似.结论 库欣综合征患者的皮下脂肪组织中的炎症及纤维化程度高于肾脏周围脂肪.提示不同部位脂肪组织具有不同的生物学特性,长时间较高水平的皮质醇刺激可能导致皮下脂肪炎症.     

Anterior pituitary function after adrenalectomy in patients with Cushing's syndrome.

We assessed anterior pituitary function in five patients with Cushing''s syndrome before and after the removal of cortisol-secreting adrenal adenomas. Before surgery, all patients lacked response of growth hormone to hypoglycaemia, four had low responses of thyrotrophin to thyrotrophin releasing hormone, three had hypogonadism and two had low prolactin reserve. After successful removal of the adrenal adenoma, all patients developed postoperative hypoadrenocorticism and recovered all impaired anterior pituitary hormones within a period of 3 months. Our results point to a direct inhibiting action of glucocorticoids at the pituitary level as the explanation for the impaired anterior pituitary function. Moreover, direct gonadal suppression by glucocorticoids may be an additional mechanism of hypogonadism in some patients.     

腹部CT检查发现的939例肾上腺病变患者的临床分析

目的 探讨腹部CT检查发现的肾上腺病变的检出率、病因构成、临床特点及诊治现状.方法 回顾性分析2014年7月~2015年6月于南方医科大学南方医院影像中心行腹部CT检查报告提示肾上腺有异常改变的门诊和住院患者的病历资料,包括患者性别、年龄、影像特征、生化检验、临床诊断、治疗方式、术后病理、发现病变的原因等.结果(1)本院1年内行腹部CT检查的患者共19004例,检查提示存在肾上腺病变的患者共939例,检出率为4.9%.其中男性560例(59.6%),女性379例(40.4%),平均就诊年龄为53.2岁.肾上腺占位在总体肾上腺病变中所占比例随年龄递增呈有上升趋势.行内分泌功能评估的患者有270例(28.8%),无功能性病变占38.9%,功能性病变中原发性醛固酮增多症比例最高,占16.3%;库欣综合征和亚临床库欣综合征各占4.1%和7.0%;嗜铬细胞瘤占7.0%.(2)共发现肾上腺意外瘤191例,检出率为1.0%,其中良性腺瘤占70.3%,肾上腺皮质癌和肾上腺转移癌的比例分别为2.4%和0.5%.只有76例(39.8%)患者进行了内分泌功能评估,其中无功能瘤34例,占44.7%;功能性病变以嗜铬细胞瘤最常见,占22.4%,而原发性醛固酮增多症和亚临床库欣综合征各占9.2%和6.6%.结论 我院所有腹部CT检查中肾上腺病变的检出率达4.9%,肾上腺意外瘤的检出率1.0%.虽然大多数肾上腺病变为良性无功能病变,但仍有部分具有内分泌功能或为恶性病变.临床上约有60%的肾上腺意外瘤患者未进行内分泌功能的评估,功能亢进的病变极易被漏诊.临床医生需要进一步提高对肾上腺意外瘤的认识并规范其诊疗流程.     

基于生物信息学分析库欣综合征核心基因与互作miRNA

目的利用生物信息学筛选库欣综合征(CS)的核心基因及通路,并预测其相互作用的微小核糖核酸(miRNA)及小分子药物。 方法从GEO数据库下载CS基因芯片数据集并筛选出差异表达基因(DEG),随后对差异基因进行功能富集分析、蛋白互作分析、核心基因筛选,预测互作miRNA及小分子药物并进行验证。 结果共筛选出10个核心基因并预测出479个互作miRNA,相关通路集中在PI3K-Akt、cAMP、CS及MAPK信号通路等,奥那司匹、拉帕替尼是较为显著的小分子药物。 结论利用生物信息学方法筛选出参与CS发生发展的前5条信号通路、10个核心基因及479个互作miRNA,并预测出奥那司匹、拉帕替尼等小分子药物。     

Adrenal incidentaloma: subclinical Cushing's syndrome.

Adrenal incidentalomas present a significant differential diagnostic challenge. All patients with an incidentally discovered adrenal lesion should be carefully considered and re-evaluated to exclude extra-adrenal malignancy. Tumours with hypersecretory syndromes require excision, whilst those tumours more than 6 cm in size, particularly if they exhibit other features of malignancy on computed tomography (CT), magnetic resonance imaging (MRI) or scintigraphy, should also be excised. In all cases screening for phaeochromocytomas should be performed, and in the context of hypertension and spontaneous hypokalaemia, a primary aldosterone-secreting tumour requires exclusion. However, the natural history and treatment regimens for those individuals demonstrating ''subclinical Cushing''s syndrome'' is far from clear. Size, as determined by CT or MR scanning, does not in itself reliably distinguish benign from malignant disease. Scintigraphy may be a useful adjunct, with discordant patterns suggesting malignant disease. Fine needle aspiration should not routinely be used but may be useful in cases of doubt about other extra adrenal malignancy.     

蔡慎初从郁论治雷诺综合征经验

正雷诺综合征是指由血管神经功能紊乱所引起,遇冷或情绪紧张后出现阵发性肢端小动脉强烈收缩,从而导致肢端缺血改变的临床综合征。发病时,肢端皮肤出现阵发性、对称性的苍白-紫绀-潮红性改变,并伴有手脚冰凉、麻木或疼痛。女性发病率可达3%,病情缠绵难愈~([1])。蔡慎初教授为国家级名老中医药专家,从事中医相关临床、科研工作50余载,对雷诺综合征的诊治有丰富和独到的经验。笔者有幸侍诊于侧,现将蔡老师治疗雷诺综合征经验介绍如下,与同道共飨。