CRF IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING''S SYNDROME: A COMPARISON WITH THE DEXAMETHASONE SUPPRESSION TEST

Accurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin-releasing factor (CRF-41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high-dose dexamethasone suppression test (8 mg/day for 48 h). Of 20 patients with confirmed Cushing's disease (pituitary-dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high-dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF-41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high-dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high-dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.     

THE OVERNIGHT DEXAMETHASONE TEST IS A WORTHWHILE SCREENING PROCEDURE

The overnight low-dose dexamethasone test is a convenient screening procedure for Cushing's syndrome. Claims that the test is associated with a high incidence of 'false positives', rendering it of little value particularly in obese and hospital in-patients, have been investigated in the present study. The data from 100 consecutive subjects undergoing overnight low-dose dexamethasone tests to examine for the possibility of Cushing's syndrome, were reviewed. Cushing's syndrome was identified in four patients, normal suppression of cortisol values occurred in 84 patients and 12 patients exhibited false positive results. Differences in body weights, body mass indices or in-patient status did not distinguish between those subjects with normal suppression of plasma cortisol and those subjects who yielded false positive results. These data indicate that the simple overnight dexamethasone test substituted for the more cumbersome traditional 48-h dexamethasone test in 84 of 96 patients who did not have Cushing's syndrome. Thus the overnight test provides a useful screening procedure but a small percentage of patients, approximately 12.5%, will require additional procedures to exclude Cushing's syndrome.     

EXPERIENCE WITH TRILOSTANE IN THE TREATMENT OF CUSHING'S SYNDROME

Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3β-hydroxysteroid dehydrogenase Δ4,Δ5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.     

AN EVALUATION OF LABORATORY TESTS FOR THE DETECTION AND DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME

1. Results of tests for the diagnosis of Cushing's syndrome of various aetiologies are discussed for twenty-five patients in whom the pathology was established by operation or autopsy. 2. Control values for the urinary excretion of free Cortisol, 17-OHCS, Porter-Silber chromogens (P-SC) and 17-OS and plasma levels of P-SC are compared with those for normal subjects. 3. The results indicated that urinary values are within the normal range for some patients with Cushing's syndrome. 4. Plasma levels of P-SC in the morning were within the normal range for the majority and elevated for the rest. 5. Some patients showed day-night variation of plasma P-SC but evening values were above the normal range. 6. The expected response for low dosage dexamethasone was found in all patients tested but unexpected responses followed high dosage in some. 7. Plasma 11-OHCS in the five patients tested failed to respond to insulin induced hypoglycaemia. 8. Metyrapone administration and corticotrophin infusion tests had limited usefulness in establishing the aetiology of the disease. The 17-OHCS excretion became raised in the response to corticotrophin and the elevation was prolonged beyond normal responsiveness.     

OVERNIGHT URINARY GROWTH HORMONE MEASUREMENT IN THE DIAGNOSIS OF ACROMEGALY

Several studies report higher urinary GH excretion in acromegalic patients compared to control subjects. We investigated the diagnostic potential of overnight urinary GH excretion in acromegaly, using a recently developed enzyme-linked immunosorbent assay. Overnight urine samples were obtained from 117 control subjects and nine patients with untreated acromegaly. GH excretion was higher in acromegalic patients compared to control subjects, with geometric mean total overnight values of 46.35 and 5.73 microU respectively. The range for total overnight urinary GH in control subjects was 0.75-21.75 microU and two of the nine patients with untreated acromegaly had GH measurements within this range. Urinary GH measurements were corrected using predictive clinical variables but this resulted in minimal improvement in discrimination between control subjects and acromegalic patients. Lack of complete discrimination between control subjects and acromegalic patients limits the usefulness of a single overnight urinary GH measurement as a screening test for acromegaly.     

THROMBOEMBOLIC COMPLICATIONS IN CUSHING'S SYNDROME

Thromboembolic events are thought to occur with increased frequency in Cushing's syndrome due to the predisposing factors, obesity, hypertension, a raised haematocrit and major surgery plus a ‘hypercoagulable state’. To examine this postulate further we have studied 43 patients with Cushing's syndrome retrospectively and 10 patients prospectively to determine the incidence of arterial and venous thrombosis, both spontaneous and post-operative. Arterial events were noted in four cases (9%) and deep vein thrombosis or pulmonary thromboembolism (PTE) occurred in six cases (11%). Post-operative PTE occurred in 2-7% of all operations. These vascular complications tended to occur in the older patients with Cushing's syndrome. In our series, clinically significant thromboembolic episodes appear no more common than expected and the indications for prophylactic anticoagulation (the older and more obese patients) may not be different from other patients undergoing major surgery. An incidental finding was of a greater frequency of hypertension in Cushing's patients due to an adrenal adenoma.     

CUSHING'S SYNDROME OF NINETEEN YEARS' DURATION

A case of Cushing's syndrome of 19 years' duration is described. The disease began at the age of 12 years and caused an abrupt cessation of growth. The adrenals were responsive to stimulation with corticotrophin and suppression with dexamethasone. After irradiation of the pituitary gland had failed to improve the patients' condition, bilateral adrenalectomy was performed. Postoperatively exfoliation and skin itching caused much trouble, and it was 14 months before his corticosteroid requirements reached the usual maintenance level.     

SHORT-TERM FLUCTUATIONS IN PLASMA CORTISOL IN CUSHING'S SYNDROME

Short-term fluctuations in plasma cortisol were determined overnight in twelve patients with Cushing's syndrome: eight patients with bilateral adrenal hyperplasia of hypothalamic-pituitary origin, three patients with a cortisol producing adenoma and one patient with a carcinoma of the adrenal cortex. While either secretory episodes in plasma cortisol or a fixed pattern of cortisol secretion were observed both in patients with pituitary dependent and in those with pituitary independent hypercorticism, a typical night-day variation in plasma cortisol was only found in one of the eight patients with Cushing's syndrome of hypothalamic-pituitary origin. The patient with a cortisol producing carcinoma showed only minor fluctuations in plasma cortisol throughout the test period. The results indicate that no discrimination can be made between patients with pituitary dependent or independent Cushing's syndrome by demonstrating an episodic or a fixed secretion of cortisol. It seems, however, that the finding of a typical night-day variation in hormone secretion points to hypercorticism of hypothalamic-pituitary origin.     

唇腺活检对诊断干燥综合征的意义

对１９６例可疑的干燥综合征（ＳＳ），患者作了唇腺活检（ＬＳＧ－Ｂ）和Ｓｃｈｉｒｍｅｒ试验、角膜荧光染色和ＳＳ－Ａ／ｓＳ－Ｂ抗体等免疫学检查。１９６例中１１７例ＬＳＧ－Ｂ≥２个灶／４ｍｍ￣２，其中９２例同时有干燥性角膜结膜炎（ＫＣＳ），符合Ｔａｌａｌ的ＳＳ诊断标准。余２５例ＬＳＧ－Ｂ阳性而不伴有ＫＣＳ者，１６例符合继发性ＳＳ（２°ＳＳ），９例有ＳＳ的临床特征表现和ＳＳ一Ａ／ＳＳ－Ｂ阳性而不能排除ＳＳ。此外ＬＳＧ－Ｂ（－）而有ＫＣＳ阳性者１１例均符合原发性ＳＳ（１°ＳＳ）或２°ＳＳ。本组１２８例ＳＳ中ＬＳＧ－Ｂ的阳性率为９１％。我们还发现２°ＳＳ在ＬＳＧ－Ｂ中的灶性涎腺炎严重程度明显轻于１°ＳＳ，而在１°ＳＳ中灶性涎腺炎的严重程度与系统累及呈正相关。     

THE DIAGNOSIS OF CUSHING'S SYNDROME USING 131I-19-IODOCHOLESTEROL UPTAKE AND ADRENAL IMAGING

Uptake measurements and visualization of the adrenal glands were performed using ¹³¹I-19-iodocholesterol in ten healthy subjects and fourteen patient suffering from Cushing's syndrome (nine hyperplasias and five adenomas). The normal range in healthy subjects (average uptake value ± 2 SD) is 0·12–0·27% for both adrenals. In patients with Cushing's syndrome the uptake values ranged from 0·321 to 1·497 %. Normal bilateral images were obtained in all the healthy subjects as well as in eight of the patients with hyperplasia, whilst the remaining patient with hyperplasia showed distinctly enlarged glands. In contrast, an image of the diseased side only was obtained in patients with adrenal adenomas. We conclude that radiocholesterol studies in Cushing's syndrome allow confirmation of the diagnosis, definition of the pathophysiologic type of disease and lateralization of adrenal adenomas.     

CUSHING'S SYNDROME IN PREGNANCY—TREATMENT WITH METYRAPONE

A 23-year-old female presented with severe Cushing's syndrome in the 23rd week of pregnancy. Investigations showed plasma cortisol 770 nmol/l (08.00 h) and 850 nmol/l (23.00 h); plasma ACTH was 10 ng/l (08.00 h) and 27 ng/l (23.00 h); urinary free cortisol excretion was 2460 nmol/24 h. Dexamethasone 2 mg 6-hourly for 48 h suppressed the 08.00 h plasma cortisol only to 680 nmol/l. Abdominal C.T. scan showed a right adrenal adenoma. The patient was treated with metyrapone and a good clinical improvement ensued. Plasma cortisol was reduced to 300–500 nmol/l. Despite ultrasonographic evidence of normal fetal growth, urinary oestriol excretion was markedly deficient. Prior to the spontaneous onset of labour, there was a marked rise in plasma cortisol despite continuous metyrapone treatment. A normal female infant was born at 37 weeks' gestation. The maternal adrenal adenoma was subsequently removed. The deficiency of oestriol synthesis during the pregnancy may be explained by metyrapone-induced inhibition of C19-hydroxylation.     

应用固相补体结合试验诊断家畜布鲁氏菌病的试验报告

本报告指出虽然液相补体结合试验诊断家畜布病的特异性较强,灵敏度较高,但其操作不如固相补体结合试验简便,而且耗材料量大,不利于在基层兽医部门直接应用。因此,在保持液相补体结合试验特异性强,灵敏度高的基础上,作者建立了固相补体结合试验诊断家畜布病的操作程序和判定标准。用固相和液相补体结合试验检测牛羊血清519份,其阳性检出率固相为2.3～71.4％,液相为2.3～65.3％,无显著差异(P>0.05)。两种检测方法的阳性一致率为88.6～100％,亦显示较高水平。     

THE DEVELOPMENT OF CUSHING'S SYNDROME FROM A PREVIOUSLY SILENT PITUITARY TUMOUR

Abstract A 60 year old woman originally presented with headache. Investigations revealed a pituitary tumour and endocrine investigations at that time showed normal plasma Cortisol levels. Seven years after removal of this tumour, the patient developed the clinical and biochemical features of Cushing's disease. Immunoperoxidase staining of the original tumour was positive for adrenocor-ticotrophic hormone. This report suggests that immunocytochemistry may have an important role in the routine evaluation of pituitary tumours.     

24 HOUR MELATONIN SECRETORY PATTERN IN CUSHING'S SYNDROME

The concentrations of plasma melatonin and cortisol were determined every 20 min during a 24 h period in 6 women aged 24 to 45 years with Cushing's syndrome of differing aetiologies (4 adrenal adenomas, 2 adrenal hyperplasia). Melatonin was assayed after chloroform extraction according to the method of Rollag and Niswender (1976). Abnormal melatonin secretory patterns were found in all the patients; 24 h melatonin concentration means varied from 130 to 413 pg/ml and were not significantly higher than the 24 h mean in 4 controls (215 ± 126 pg/ml). All six subjects however showed a significant increase of melatonin during the day period (302 ± 109 as compared with controls 129 ± 65 mg/ml, mean ± SD; P<0.005). No relationship could be found between abnormal melatonin levels and the sexual status of the patients (4 with amenorrhoea, 2 normally menstruating women). An alteration of melatonin secretory pattern is present in Cushing's syndrome, whatever the aetiology. It is suggested that hypercortisolism, by itself, may modify the pattern of melatonin secretion.     

PATHOGENESIS OF THE URETHRAL SYNDROME IN WOMEN AND ITS DIAGNOSIS IN GENERAL PRACTICE

Women with the urethral syndrome have been studied in general practice. When Kass's criterion was applied 67 (49%) of 138 women with symptoms had significant bacteriuria, but 66% of the remaining 71 had bacteriuria which was not significant, compared with only 9% of a control series. These organisms are probably related to the patients' symptoms and should not be thought of as contaminants. Sexual intercourse, the menopause, cold weather, emotional stress, catheterisation, allergy, and menstruation may alter the urethral defence mechanisms and enable urinary pathogens to become established.     

快速免疫色谱测试卡诊断恶性疟和间日疟的效果评价

目的： 评价快速免疫色谱测试卡（ Ｉ Ｃ Ｔ） 在疟区诊断恶性疟和间日疟的效果。方法： 以疟原虫镜检结果为标准, 用 Ｉ Ｃ Ｔ 检测门诊“四热”病人中的恶性疟和间日疟。结果： Ｉ Ｃ Ｔ 检测恶性疟与间日疟的敏感性分别为９６７ ％ 和９０４ ％ , 特异性为９８６ ％ 。与原虫镜检结果的符合率为９４７ ％ 。恶性疟与间日疟之间无交叉反应。结论： 免疫色谱测试卡可同时检测恶性疟和间日疟, 较镜检法快速、简易。