岩下窦静脉取血在ACTH依赖性Cushing 综合征鉴别诊断中的应用

目的: 探讨岩下窦静脉取血(IPSS)在鉴别垂体和异位来源的ACTH依赖性Cushing综合征的意义. 方法: 回顾性分析了我院2003/2005年接受此项检查的共10例ACTH依赖性Cushing综合征患者的资料. 结果: 10例ACTH依赖性Cushing综合征的患者,通过IPSS检查仅1例患者与最后结果不符,IPSS诊断符合率90%,不符合率10%. 结论: 岩下窦静脉取血在鉴别诊断垂体和异位ACTH依赖性Cushing综合征中有较高的准确率. 因此,岩下窦静脉取血测ACTH为医生在对根据影像学检查结果无法明确诊断的患者进行治疗时可提供指导意义.     

Ectopic ACTH-secreting syndrome: a single center experience report with a high prevalence of occult tumor

BACKGROUND: Differentiation between the two forms of ACTH-dependent Cushing's syndrome is a challenging task. Although the majority of these cases will be diagnosed as Cushing's disease secondary to an ACTH-secreting pituitary adenoma, 10-15% result from the ectopic ACTH secretion syndrome (EAS), which is usually due to neuroendocrine tumors. In the present study we report our experience with EAS in eight patients evaluated and treated during the past 10 years. METHODS: Our experience in the evaluation and management of EAS was retrospectively reviewed. The latter included a standard biochemical assessment (urinary free cortisol, low- and high-dose dexamethasone suppression tests), petrosal sinus sampling when indicated and imaging techniques such as pituitary MRI, total body CT and somatostatin receptor scintigraphy. RESULTS: The ectopic nature of the ACTH hypersecretion was confirmed with inferior petrosal sinus samplings in all cases. CT scanning localized a putative tumor in 6/8 patients, whereas octreotide scintigraphy was positive in only five. In all cases, the source was traced to the lungs. However, upon performing thoracotomy, a documented ACTH-secreting bronchial carcinoid tumor was found in only four patients. Thus, 4/8 patients with EAS remained "occult." All of these patients underwent adrenalectomy for hypercortisolism control. CONCLUSIONS: EAS is a rare cause of ACTH-dependent Cushing's syndrome. Truly "occult" tumors were frequent and these patients need to be under close surveillance for the detection of neuroendocrine tumors.     

Five cases of cyclical Cushing's syndrome

Reported cases of cyclical Cushing's syndrome are rare. Of 14 successive patients with Cushing's syndrome nine collected sequential urine samples for the estimation of cortisol:creatinine ratio. Five had cyclical Cushing's syndrome while two had considerable variation in urinary cortisol excretion without a cyclical pattern being established. Two of the five patients with a cyclical syndrome had paradoxical responses to dexamethasone. In only one patient with a cyclical pattern did the cortisol:creatinine ratio fall after treatment with bromocriptine or cyproheptadine, or both. The high incidence of the cyclical form of Cushing's syndrome has important clinical implications. A high index of suspicion of the syndrome is required in patients with symptoms or signs of Cushing's syndrome but with normal cortisol values, in patients with fluctuating cortisol values, and in patients with anomalous responses to dexamethasone. Because of possible variations in steroidogenesis the results of drug studies in Cushing's syndrome must be interpreted cautiously.     

Value of computed tomography of the abdomen and chest in investigation of Cushing's syndrome

Computed tomography (CT) scans were performed on 37 patients with biochemically proved Cushing's syndrome to evaluate the role of CT in the investigation of this condition. CT rapidly and correctly identified all 15 adrenocortical tumours, distinguishing five carcinomas from the 10 adenomas. In ACTH-dependent Cushing's syndrome appreciable bilateral adrenal enlargement was common in patients with an ectopic source (6 of 10 cases), while those with a pituitary source usually had normal sized adrenals (9 of 10). Two patients with a history of over seven years had bilateral adrenal nodules. CT was more accurate in locating a primary ectopic source of ACTH (5 of 12 cases) than any other technique and was particularly valuable in detecting small (less than 1.5 cm) peripheral lung carcinoid tumours which may be undetectable by conventional x-ray techniques. Its speed, accuracy, and simplicity make CT the technique of choice both to show the adrenal anatomy and to locate a suspected ectopic ACTH-secreting tumour in patients with proved Cushing's syndrome.     

外周去氨加压素兴奋试验与大剂量地塞米松抑制试验在库欣病中的诊断价值研究

背景　库欣综合征（CS）临床表现复杂,在CS的病因诊断中,库欣病（CD）和异位促肾上腺皮质激素（ACTH）综合征（EAS）难以鉴别诊断。而双侧岩下窦静脉采血（BIPSS）目前是鉴别诊断CD和EAS的金标准,但其在大多数医院无法开展。目前临床通常用大剂量地塞米松抑制试验（HDDST）诊断CD,但其灵敏度较低;有研究证明去氨加压素（DDAVP）具有促肾上腺皮质激素释放激素（CRH）样作用,其可促进垂体ACTH肿瘤分泌ACTH。目的　探究外周DDAVP兴奋试验与HDDST在CD中的诊断价值。方法　回顾性选取2015-01-01至2018-08-30于中国人民解放军总医院明确诊断为ACTH依赖性CS的患者72例为研究对象。收集患者一般资料及外周DDAVP兴奋试验、HDDST结果。计算DDAVP兴奋试验、HDDST诊断CD的灵敏度、特异度。结果　72例ACTH依赖性CS患者中,CD 64例,EAS 8例。有63例ACTH依赖性CS患者进行了外周DDAVP兴奋试验（其中CD 55例,EAS 8例）,其余9例予以剔除;外周DDAVP兴奋试验阳性51例,阴性12例;外周DDAVP兴奋试验诊断CD的灵敏度为92.7%,特异度为100.0%。72例ACTH依赖性CS患者中,HDDST阳性43例,阴性29例;HDDST诊断CD的灵敏度为67.2%,特异度为100.0%。同时行外周DDAVP兴奋试验与HDDST的63例患者中,外周DDAVP兴奋试验与HDDST同时阳性38例（均为CD患者）,外周DDAVP兴奋试验与HDDST同时阴性9例（8例为EAS患者）,外周DDAVP兴奋试验阳性、HDDST阴性16例,外周DDAVP兴奋试验阴性、HDDST阳性0例。同时行外周DDAVP兴奋试验与HDDST的55例CD患者中,外周DDAVP兴奋试验与HDDST同时阳性38例,外周DDAVP兴奋试验与HDDST同时阴性1例,外周DDAVP兴奋试验阳性、HDDST阴性16例,外周DDAVP兴奋试验阴性、HDDST阳性0例。结论　外周DDAVP兴奋试验对CD有较高的诊断价值,临床中疑似CD患者HDDST为阴性时,进一步行外周DDAVP兴奋试验可明显降低漏诊率。     

Melatonin secretion and non-specific immune responses are differentially expressed in corticotropin-dependent and corticotropin-independent Cushing's syndrome.

BACKGROUND: This study was done to clarify the relation between melatonin secretion and the hypothalamic-pituitary-adrenal axis. MATERIAL/METHODS: In this clinical study using a follow-up approach, we investigated the circadian melatonin secretion and immune parameters of patients with corticotropin-dependent (Cushing's disease) and corticotropin-independent Cushing's syndrome. Plasma hormone concentrations, interleukin 1-beta (IL-1beta) and total immunoglobulin E (IgE) were determined before surgical treatment and during remission of the syndrome 1 year later. RESULTS: Patients with Cushing's disease showed mean nocturnal and diurnal melatonin plasma values similar to those of healthy controls. Only the midday level of patients (taken at 12:00) was significantly higher in comparison to controls (35.44+/-19.5 pg/mL vs 17.14+/-3.58 pg/mL; P<0.05). In contrast, patients with corticotropin-independent Cushing's syndrome had significantly lower mean nocturnal and significantly higher mean diurnal melatonin levels (52.8+/-17.7 pg/mL and 59.2+/-28.7 pg/mL, respectively; P<0.05 and P<0.05) as compared with corresponding values for controls (101.4+/-43.1 pg/mL and 28.9+/-11.7 pg/mL, respectively). In the last group of patients, significantly higher mean IL1beta and plasma IgE concentrations (3.30+/-1.72 pg/mL and 527.8+/-474.0 IU/mL, respectively) were observed compared with controls (1.43+/-0.95 pg/mL and 35.7+/-32.1 IU/mL, respectively) (P<0.05). Remission of the hypercortisolism in these patients resulted in restoration of circadian melatonin secretion and significant reductions in plasma IL1beta and total IgE levels. CONCLUSIONS: Our results demonstrate a specific mode of melatonin secretion and different nonspecific immune responses in the 2 investigated forms of hypercortisolism, specifically, corticotropin-dependent and corticotropin-independent Cushing's syndrome.     

肾上腺大结节样增生一例报道

库欣综合征（CS）中15%～20%是由肾上腺原因引起的,其中约10%的患者具有双侧肾上腺增生。肾上腺性CS中皮质醇分泌有时可受肾上腺异常膜受体（包括抑胃肽受体、精氨酸加压素受体、儿茶酚胺类受体、LH/hCG受体和5-羟色胺受体等）的调节。该文报道了1例促肾上腺皮质激素非依赖性大结节样肾上腺增生引起的CS患者,并通过体内试验证实了肾上腺异常膜受体的存在。     

肾上腺大结节样增生一例报道

库欣综合征(CS)中15% ～20%是由肾上腺原因引起的,其中约10%的患者具有双侧肾上腺增生.肾上腺性CS中皮质醇分泌有时可受肾上腺异常膜受体(包括抑胃肽受体、精氨酸加压素受体、儿茶酚胺类受体、LH/hCG受体和5-羟色胺受体等)的调节.该文报道了1例促肾上腺皮质激素非依赖性大结节样肾上腺增生引起的CS患者,并通过体内试验证实了肾上腺异常膜受体的存在.     

MJA Practice Essentials--Endocrinology. 9: Pituitary disease in adults

Pituitary adenomas are found in 10%-25% of unselected autopsy series and are evident in about 10% of asymptomatic individuals by magnetic resonance imaging. Diagnosis of pituitary disorders is often delayed by lack of awareness and the subtlety of symptoms and signs. Hypopituitarism is suspected when peripheral hormone concentrations are low without an elevation in the corresponding pituitary tropic hormone(s). Severe adult-onset growth-hormone deficiency results in reduced muscle mass, increased fat mass and diminished quality of life, which are reversed by growth hormone replacement therapy. While trans-sphenoidal surgery remains first-line treatment for acromegaly, drug treatment has an important role in controlling residual growth-hormone excess and, in some circumstances, as first-line treatment. Dopamine-agonist therapy (cabergoline or bromocriptine) is the treatment of choice for micro- and macroprolactinomas. In patients with suggestive clinical features, elevated 24-hour urine free cortisol level is usually sufficient to diagnose endogenous Cushing's syndrome; careful additional investigation is needed to determine whether the cause is Cushing's disease (pituitary adenoma secreting adrenocorticotropic hormone [ACTH]), ectopic ACTH secretion or adrenal disease. Heightened awareness is needed to detect the sometimes subtle symptoms and signs of pituitary disease     

Severe hypertension secondary to renal artery stenosis and Cushing's syndrome

We present an unusual patient who simultaneously had severe renal artery stenosis RAS and Cushing's syndrome. The case highlights the difficulty of reaching a specific diagnosis of Cushing's syndrome and the possible interaction between Cushing's syndrome and some other concurrent illnesses that this patient had. A 37-year old man presented with severe hypertension HTN and uncontrolled diabetes mellitus DM without clear physical signs of Cushing's syndrome. He was found to have severe osteoporosis, proximal myopathy, several cutaneous warts, tinea versicolor, and chronic viral hepatitis. Captopril-stimulated renal scan and renal artery angiogram revealed severe RAS. Partial balloon dilatation of RAS led to improvement in HTN. Unexpectedly, urine free cortisol 24 hour was found extremely high. Serum adrenocorticotropic hormone ACTH was also elevated and high dose dexamethasone suppression tests were inconclusive. Several imaging studies failed to localize the source of ACTH. Despite normal MRI of the pituitary gland, bilateral inferior petrosal sinus sampling IPSS localized the source of ACTH secretion to the right side of the pituitary gland and right anterior hemihypophysectomy resulted in cure of Cushing's disease, HTN, DM, and tinea versicolor with significant improvement in cutaneous warts, osteoporosis, and chronic hepatitis. In conclusion, RAS and Cushing's syndrome may occur together. Significant hypercortisolemia can occur without clear signs of Cushing's syndrome. Controlling hypercortisolemia is of paramount importance when treating chronic infections in patients with Cushing's syndrome.     

尿游离皮质醇测定在皮质醇症诊断中的价值和意义

本文报告皮质醇症16例,单纯性肥胖70例,主要研究尿游离皮质醇(UFC)在皮质醇症中的珍断价值,结果表明(1)UFC在皮质醇症中的诊断符合率为100％,没有假阴性。(2)UFC水平呈大幅度升高,在诊断上具有特征性.(3)过夜小抑试阴性不能排除皮质醇症,若UFC多次明显升高,结合临床可作进一步的病因学检查。因此UFC测定是皮盾醇症中一项敏感而可靠的诊断试验。     

A clinico-pathological study of Cushing's syndrome at the University Hospital of the West Indies and a review of the literature

Cushing's syndrome is an uncommon but important disease. Twenty-one confirmed cases of spontaneous Cushing's syndrome were documented at the University Hospital of the West Indies over a 21-year period. They were predominantly young females (F:M ratio of 17:4; mean age 25 years and 3 months). The commonest presenting symptoms were amenorrhoea (41%) and obesity (19%). Common clinical features were cushingnoid features (95%), hypertension (76%) and hirsutism (82%). Twenty-nine per cent had frank hyperglycaemia. Cushing's syndrome was due to Cushing's disease in 10 cases, adrenal adenoma in 3 and adrenal carcinoma in 2 cases. In 4 cases with presumed adrenal hyperplasia, the histology was either unavailable or was not consistent with the diagnosis. Two cases appear now to have had the ectopic ACTH Syndrome. Adrenalectomy was the commonest treatment offered. There were no intra-operative or post-operative deaths but recurrence was common after subtotal adrenalectomy in Cushing's disease. Twenty-seven per cent of the patients developed Nelson's syndrome, which was fatal in 50%. Long-term hormone replacement therapy was unnecessary after surgery for adrenal adenomas. Treatment of Cushing's syndrome was well tolerated by the patients.     

血浆ACTH测定在柯兴氏综合征鉴别诊断中的价值

本文报告经手术、病理证实的24例柯兴氏综合征患者血浆 ACTH 水平的改变,并与大剂量地塞米松抑制试验作了比较。结果表明17例柯兴氏病患者中14例血浆 ACTH(8am)水平增高,3例正常高限,0 am ACTH 水平全部增高,且无昼夜节律变化;6例肾上腺皮质腺瘤血浆ACTH 均明显降低;1例异位 ACTH 综合征血浆 ACTH 异常增高。三组之间无一例重叠,与手术、病理的符合率为100%。大剂量地塞米松抑制试验的符合率为67～70.6%。提示血浆 ACTH 测定是鉴别柯兴氏综合征病因十分可靠的方法。     

Successful treatment with ketoconazole of Cushing's syndrome in pregnancy

Patients with Cushing's syndrome rarely become pregnant. This is a high risk situation both for the fetus and the mother, if untreated. We report a patient with Cushing's syndrome due to adrenocortical adenoma who became pregnant and was successfully treated with ketoconazole during the last period of pregnancy.     

Hormone secretion in alcohol-induced pseudo-Cushing's syndrome. Differential diagnosis with Cushing disease.

We describe the clinical and biochemical characteristics of alcohol-induced pseudo-Cushing's syndrome in two patients with signs and symptoms of Cushing's syndrome and slight disturbances in liver function. An insufficient suppression of plasma cortisol to the overnight administration of 1 mg of dexamethasone was accompanied by an absent diurnal rhythm of plasma cortisol and an increased cortisol secretion rate. The plasma cortisol levels at 8 AM normalized during hospital admission (ie, alcohol withdrawal) at the same rate or parallel with the serum gamma-glutamyl transferase concentration. A normal increase of plasma cortisol, adrenocorticotropic hormone, and growth hormone in response to an insulin induced hypoglycemia was not compatible with the diagnosis Cushing's syndrome. However, the result of a differential diagnostic test with metyrapone was compatible with the presence of Cushing's disease. An erroneous diagnosis of Cushing's disease can be easily made in patients with alcohol-induced pseudo-Cushing's syndrome.     

柯兴氏综合症致骨质疏松症28例临床分析

目的探讨柯兴氏综合症患者的首发症状,分析皮质醇增多所致骨质疏松的临床特点,提高对骨痛、骨折为首发表现的柯兴氏综合症的认识,减少误诊率.方法收集近10 a来收治的柯兴氏综合症患者28例,总结其首发症状以及主要临床特点;对28例患者的腰椎、股骨颈进行X线测定,用双能X线吸收仪进行骨密度检测,分析不同类型的柯兴氏综合症所致骨质疏松的临床特点.结果 （1）无论哪种类型的柯兴氏综合症,高血压是最常见的首发症状,占32.1%（9/28）,骨折、骨痛占25%（7/28）;（2）28例患者行X线检查,其中10例骨质疏松,6例肾上腺腺瘤,3例椎体或髋部骨折;对7例有骨折或骨痛症状的患者行骨密度检查提示骨质疏松.结论柯兴氏综合症所致骨质疏松症与病因相关,肾上腺肿瘤引起的肾上腺依赖性柯兴氏综合症较垂体分泌ACTH肿瘤引起的柯兴病更易引起的骨质疏松.     

Metastatic medullary carcinoma of the thyroid complicated by Cushing's syndrome.

A patient with metastatic medullary carcinoma of the thyroid, Cushing's syndrome, and severe diarrhoea is presented. The manifestations of Cushing's syndrome were controlled with a combination of aminogluthethimide and metyrapone. The cause of the diarrhoea has not been found, and it remains resistant to treatment.     

Cushing's syndrome--transitory immune deficiency state?

A 28 year old female patient with Cushing's syndrome due to an adrenal adenoma also suffered from recurrent urinary infections (proteus), tonsillitis (streptococcus), permanent candidiasis and perimandibular abscess (Staphylococcus pyogenes). Suppression of cellular and humoral immunity was confirmed by in vitro tests. After successful right adrenalectomy the clinical signs of Cushing's syndrome disappeared and no evidence of either bacterial or fungal infection were noted one year postoperatively. Immunological tests showed the restitution of both cellular and humoral immunity. The course of the disease in the patient supports the idea that Cushing's syndrome might be considered as a transitory immune deficiency state.     

The clinical response to treatment in adult Cushing's syndrome following remission of hypercortisolaemia

The clinical response of 57 adult patients with Cushing's syndrome due to bilateral adrenocortical hyperplasia or adrenocortical adenoma is documented following resolution of hypercortisolaemia by various forms of treatment. Despite satisfactory biochemical remission of the disease the clinical result was far less satisfactory when assessed by persistence of obesity (55%), menstrual irregularity (41%), hypertension (29%) and insulin-dependent diabetes (22%). Myopathy, hirsuitism and psychological abnormalities persisted to a lesser extent. The mortality rate of the series over a 30 year follow-up period was 4 times that of a general population matched for sex, age and year of entry into the series. Cardiovascular disease was the cause of death in 85%. Irreparable cardiovascular disease is produced early in the course of hypercortisolaemia, emphasizing the vital importance of the earliest possible recognition and treatment of this disease.