Cushing's syndrome with cortisol hypersecretion from one of bilateral adrenocortical adenomas: Report of a case

We report herein the case of a 40-year-old man with Cushing's syndrome, diagnosed by clinical manifestations and endocrinological studies, who was found to have bilateral adrenocortical adenomas, one of which hypersecreted cortisol. The Cushing's syndrome was therefore attributed to primary adrenocortical disease, and the right adrenal tumor was resected and histologically diagnosed as a so-called black adenoma. After resection of the right tumor, the left adrenal tumor showed no signs of cortisol hypersecretion for the 23 months of follow-up until the patient died of peritonitis subsequent to the rupture of a duodenal ulcer. The left adrenal tumor was examined at autopsy and found to be a cortical adenoma. These data imply that the adrenal adenomas developed primarily from the adrenal gland itself, and that one of the tumors was well differentiated and secreted excess hormones, while the other remained in cell proliferation without hypersecretion.     

Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study

It is unclear whether a random plasma cortisol measurement and the corticotropin (ACTH) test adequately reflect glucocorticoid secretory capacity in critical illness. This study aimed to determine whether these tests provide information representative of the 24 hour period. Plasma cortisol was measured hourly for 24 hours in 21 critically ill septic patients followed by a corticotropin test with 1 microg dose administered intravenously. Serum and urine were analysed for ACTH and free cortisol respectively. Marked hourly variability in plasma cortisol was evident (coefficient of variation 8-30%) with no demonstrable circadian rhythm. The individual mean plasma cortisol concentrations ranged from 286 +/- 59 nmol/l to 796 +/- 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated with both random plasma cortisol (r2 0.9, P < 0.0001) and the cortisol response to corticotropin (r2 0.72, P < 0.001). Only nine percent of patients increased their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response). However, 35% of non-responders had spontaneous hourly rises > 250 nmol/l thus highlighting the limitations of a single point corticotropin test. Urinary free cortisol was elevated (865 +/- 937 nmol) in both corticotropin responders and non-responders suggesting elevated plasma free cortisol. No significant relationship was demonstrable between plasma cortisol and ACTH. We conclude that although random cortisol measurements and the low dose corticotropin tests reliably reflect the 24 hour mean cortisol in critical illness, they do not take into account the pulsatile nature of cortisol secretion. Consequently, there is the potential for erroneous conclusions about adrenal function based on a single measurement. We suggest that caution be exercised when drawing conclusions on the adequacy of adrenal function based on a single random plasma cortisol or the corticotropin test.     

Early post-operative ACTH and cortisol as predictors of remission in Cushing's disease

AIM: To study the value of early (24 h) post-operative ACTH and serum cortisol as predictors of remission after transsphenoidal surgery in Cushing's disease. METHODS: We prospectively studied 44 patients who underwent transsphenoidal surgery for Cushing's disease between 1997 and 2005. The mean follow-up period of patients after surgery was 49 months (19-102 months). The predictive value of clinical characteristics, pre-operative hormonal studies, radiological, surgical and histological findings, and post-operative hormonal studies were analysed. For the post-operative hormonal study plasma ACTH and serum cortisol were determined at 8.00 a.m. the day after surgery. RESULTS: After surgery, Cushing's disease remitted in 39 patients (89%) and persisted in 5 patients (11%). Three patients relapsed during the follow-up period. Only three study variables were predictive of persistence of Cushing's disease after surgery: the non identification of the adenoma in histology (an adenoma was found in 87% of the patients in remission, and in 20% of treatment failures, p = 0.01), the early post-operative plasma ACTH (patients in remission: 2 pmol/L (1.1-10.8 pmol/L), treatment failures: 8.2 pmol/L (1.1-12 pmol/L), p = 0.019), and the early post-operative serum cortisol (patients in remission: 128.4 nmol/L (27.6-4644 nmol/L), treatment failures: 797 nmol/L (606-1037 nmol/L), p = 0.003). ROC curves indicated that plasma ACTH < or = 7.55 pmol/L distinguished patients in remission from treatment failures with 80% sensitivity and 97.4% specificity, and serum cortisol < or = 585 nmol/L with 100% sensitivity and 90% specificity. CONCLUSIONS: Twenty-four hours after transsesphenoidal surgery for Cushing's disease, and without glucocorticoids replacement, patients with serum cortisol concentrations higher than 585 nmol/L, and/or plasma ACTH higher than 7.55 pmol/L, and/or those in which an adenoma is not identified in the histological study, have a high risk of treatment failure.     

Cortisol and its metabolites in the plasma and urine in Cushing's syndrome with chronic renal failure (CRF), compared to Cushing's syndrome without CRF

A 48-year-old man was admitted for treatment of Cushing's syndrome due to right adrenal adenoma, associated with chronic renal failure (CRF) with a blood urea nitrogen level of 64.2 and serum creatinine level of 3.9 mg/dl. After removal of the adrenal adenoma, the CRF deteriorated with progressive symptoms of anorexia, vomiting and hypertension, and the patient was placed on hemodialysis. Prior to adrenalectomy, the 17 OHCS and 17 KGS in the urine were not so high. However, the urinary 17 KS was high with an elevated 11-oxy fraction. In comparison with 2 patients suffering from adrenal Cushing's syndrome with normal renal function, there were no large accumulated quantities of glucuronic conjugated and unconjugated metabolites in the plasma of the CRF Cushing's syndrome, with confirmation ascribable to the radioimmunoassayable cross-reactivity of the cortisol antiserum used in the radioimmunoassay kit. In the Cushing's syndrome with CRF, almost all the cortisol, which was hypersecreted from the adenoma, was presumed to be converted to the 11-oxy fraction of 17 KS, possibly by activation of hepatic enzymes.     

术后3 h血清淀粉酶检测对ERCP术后胰腺炎的预测价值

目的 评估ERCP术后3 h血清淀粉酶值对ERCP术后胰腺炎（post-ERCP pancreatitis,PEP）的预测价值。方法 收集2011年10月1日至2014年12月1日我院328例连续行ERCP的患者术后3 h和24 h血清淀粉酶值,并统计PEP的发生情况。将是否发生PEP作为状态变量,两个时间点的血清淀粉酶作为检验变量,采用SPSS13.0系统作ROC曲线,分析术后3 h和24 h血清淀粉酶对PEP的预测价值。结果 328例患者中诊断PEP共17例（5.18%）。术后3 h血清淀粉酶值≤200 U/L共194例（59.15%）,其中PEP 2例（1.03%）;术后3 h血清淀粉酶值>200 U/L共134例（40.85%）,其中PEP 15例（11.19%）;两者比较有统计学差异（x²=19.731;P<0.001）。术后3 h血清淀粉酶值ROC曲线下面积为0.845,诊断准确度良好,最佳Cut-off值为280 U/L,灵敏度82.4%,特异度74.3%,阳性预测值14.7%,阴性预测值98.7%,准确度74.4%,Youden指数56.4%。术后24 h血清淀粉酶值≤600 U/L共284例（86.59%）,其中PEP 1例（0.35%）;术后24 h血清淀粉酶值>600 U/L共44例（13.41%）,其中PEP 16例（36.36%）;两者比较有统计学差异（x²=93.341;P<0.001）。术后24 h血清淀粉酶值ROC曲线下面积为0.977,诊断价值高,最佳Cut-off值为534.5 U/L,灵敏度100%,特异度89.1%,阳性预测值33.3%,阴性预测值100%,准确度89.6%,Youden指数89.1%。结论 ERCP术后3 h血清淀粉酶值对PEP有较好的早期预测价值,特别是有很好的阴性预测价值;当术后3 h血清淀粉酶值>200 U/L并且有胰管插管时,需高度警惕PEP的发生。     

Spontaneous rupture of the ureter of a patient with Cushing's syndrome

A case of spontaneous rupture of the ureter with Cushing's syndrome is presented. The fragility of the tissue in Cushing's syndrome is thought to render the ureter more susceptible to rupture.     

Scanning of the adrenals in Cushing's syndrome

131I-19-iodocholesterol adrenal scans were obtained in seven patients with Cushing's syndrome. Characteristic imaging patterns were seen in three patients with bilateral adrenal hyperplasia with symmetrical uptake of the isotope. Two patients with adrenocortical adenoma and one patient with a well-differentiated adrenocortical carcinoma showed intense activity in one adrenal gland and absent activity in the contralateral gland. In one patient with adrenal nodular hyperplasia asymmetrical uptake was found with increased activity in the right adrenal gland where a larger adenomatous nodule was found at histologic examination. Adrenal imaging with radioactive cholesterol is a useful noninvasive technique for the diagnosis and treatment of Cushing's syndrome.     

Adrenal incidentaloma: a case of subclinical Cushing's syndrome

The authors describe a case of adrenal incidentaloma that was the cause of subclinical Cushing's syndrome and take the opportunity to weigh up some of the clinical, diagnostic and therapeutic aspects. Besides the particular expression of the symptoms which were difficult to interpret before reaching a diagnosis, the authors describe the diagnostic work-up adopted, aimed at precisely identifying the type of tumour and the surgical procedure implemented laparoscopically, the outstanding validity of which is confirmed compared to traditional adrenalectomy techniques.     

The repeatability of the 24-hour pad test

A prospective observational study was conducted in a tertiary urogynaecology unit in women with the primary symptom of urinary incontinence to assess the repeatability of the 24-hour pad test. One hundred and eight women undertook seven 24-hour pad tests over 7 consecutive days together with 7 simultaneous fluid and activity charts. The results were analysed collectively and according to urodynamic subsets. Repeatability was assessed by repeated measures analysis of variance and univariate analysis of variance for each urodynamic diagnosis group (USI, mixed and no USI). Variation between pad test weights over the 7 days was low, supporting good repeatability. The number of days of pad testing required to approximate the 7-day average was 3 days. However, a single 24-hour pad test correlated highly with the 7-day average (r=0.881) and was considered sufficient to gauge leakage severity.     

Severe hypertension and massive osteoporosis as presenting symptoms of Cushing's syndrome.

Though Cushing's syndrome is a well-known clinical problem in terms of side effects of steroid therapy, endogenous Cushing's syndrome is a relatively rare diagnosis. We treated a 27-year-old patient who presented with severe hypertension and massive osteoporosis. We could diagnose a central Cushing syndrome by endocrinological function tests which, in retrospect, existed undiagnosed for more than 5 years. However, magnetic resonance imaging did not display an adenoma neither of the hypophysis nor of the adrenal glands. During explorative surgery, a cylindric microadenoma of the pituary gland was found and excised. After surgery, the blood pressure returned to normal, making further antihypertensive treatment unnecessary.     

Anesthetic management for laparoscopic adrenalectomy in a pregnant patient with Cushing's syndrome

Cushing's syndrome is extremely rare during pregnancy, because it often causes amenorrhea and infertility. We experienced a case of Cushing's syndrome in the 23rd week of pregnancy receiving laparoscopic surgery. It was difficult to control the blood pressure and heart rate, but we succeeded in the safe management of both mother and fetus.     

Criteria for surgical therapy of hypothalamo-hypophyseal Cushing's syndrome]

This article tries to give criteria for the two possible modes of treatment of the pituitary-dependent Cushing's syndrome. Patients (n = 6) who show no secondary complications on Cushing's disease should undergo implantation of 90Y and/or 192Ir into the pituitary gland. After implantation, the excessive secretion of ACTH is suppressed to normal values. The symptoms of Cushing's syndrome disappear. Following the operation, certain patients must also receive hormonal replacement therapy. Fertility is not always preserved. Total adrenalectomy as the alternative procedure is performed in adults with advanced symptoms of the disease (n = 3) and in children (n = 3). Following removal of the adrenal glands, the symptoms of Cushing's syndrome disappear. The appearance of Nelson's tumor after adrenalectomy (10% in the literature) is discussed.     

Carpal tunnel syndrome. Evaluation of a quantitative provocational diagnostic test

A diagnostic test combining the sensitivity of the Semmes-Weinstein monofilament measurement and the specificity of the wrist flexion provocational test has been evaluated in a group of 21 patients (33 hands) with electrodiagnostically verified carpal tunnel syndrome and 30 asymptomatic hands (controls). Semmes-Weinstein monofilament testing consisted of several sensory threshold measurements obtained by the application of force-calibrated Semmes-Weinstein monofilaments to each digit in the hand with the wrist in neutral position. The quantitative provocational diagnostic test employed Semmes-Weinstein measurements obtained with the wrist both in the neutral and flexed positions. The sensitivity (82%) and specificity (86%) of the combined test were calculated. It was more sensitive and specific than the wrist flexion test alone and more specific than the Semmes-Weinstein sensibility test. The combined test is recommended as the most accurate and sensitive quantitative clinical test for median nerve compression evaluated by the authors to date.     

自体肾上腺移植治疗难治性库欣病临床疗效分析

目的 探讨垂体肿瘤切除术后难治性库欣病行双侧肾上腺全切并带血管自体肾上腺移植的临床疗效. 方法 回顾性分析4例难治性库欣病患者行带血管自体肾上腺移植的远期疗效,男1例,女3例.年龄14~36岁.4例肾上腺移植前均行经鼻经蝶窦垂体肿瘤切除术,术后效果不佳;肾上腺移植术式为左侧肾上腺全切,取30%～50%肾上腺组织移植于左侧髂窝,游离腹壁下动脉并与肾上腺中央静脉吻合,游离大隐静脉并套入式吻合在肾上腺切开的包膜上,术后逐渐减少激素替代用量.分别随访1.0、1.5、8.0、10.0年,观察患者l临床症状.检测血皮质醇,24 h尿游离皮质醇,促肾上腺皮质激素(ACTH),调整激素替代用量. 结果 4例患者自体肾上腺移植患者术后库欣病症状消失,无Nelson综合征发生,仅l例皮肤轻度变黑.影像学、手术、临床表现和内分泌检查证实,4例移植肾上腺均存活,并可减少激素替代用量.移植术后1年,肾上腺功能和激素替代用量保持稳定,存活的移植肾上腺在高ACTH刺激下无明显增生. 结论 双侧肾上腺全切并自体肾上腺移植远期疗效明确,可作为难治性库欣病治疗的可选方案.     

Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias

BACKGROUND: A definitive diagnosis of primary hyperoxaluria type 1 (PH1) and primary hyperoxaluria type 2 (PH2) requires the measurement of alanine:glyoxylate aminotransferase (AGT) and glyoxylate reductase (GR) activities, respectively, in a liver biopsy. We have evaluated a molecular genetic approach for the diagnosis of these autosomal-recessive diseases. METHODS: Polymerase chain reaction (PCR) was used to detect three common mutations in the AGXT gene (c.33_34insC, c.508G>A, and c.731T>C) and one, c.103delG, in the GRHPR gene in DNA samples from 365 unrelated individuals referred for diagnosis of PH1 and/or PH2 by liver enzyme analysis. RESULTS: One or more of these mutations was found in 183 (68.8%) biopsy proven cases of PH1 and PH2 with a test negative predictive value of 62% and 2%, respectively. 102 (34.1%) patients were homozygous or compound heterozygous, making a molecular diagnosis possible. Age of onset and presenting features were similar in patients homozygous for any of the four mutations. Of the AGXT homozygotes, only the c.508G>A mutant was associated with significant AGT catalytic activity and in two of these activity was in the low normal range, possibly reflecting variation in mitochondrial content of the biopsy as this particular mutation is associated with mitochondrial mistargeting. CONCLUSION: Limited mutation analysis can provide a useful first line test for PH1 and PH2 in patients in whom primary hyperoxaluria is suspected and in whom secondary causes have been excluded. Those patients in whom a single mutation, or no mutation, is found can then be selectively targeted for liver biopsy.